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Answers and Critiques Item 1 Answer: A Item 2 Answer: B Educational Objective: Treat mucocutaneous Educational Objective: Treat familial Mediterranean fever. ulcerations in Behqet syndrome with apremilast. The most appropriate treatment is colchicine (Option B). The most appropriate treatment is apremilast (Option A). Autoinflammatory syndromes are monogenic diseases that Behqet syndrome is a systemic vasculitis characterized by result in periodic episodes of system inflammation. This recurrent oral aphthae. Other manifestations include gen, patient demonstrates multiple episodes of a systemic inflam- ital aphthae, ocular disease, skin lesions, gastrointestinal matory syndrome characterized by fever, abdominal pain, Ut (t, involvement, neurologic disease, vascular disease, and rash, and arthritis, each lasting only several days. This constel ET arthritis. The treatment of oral and genital ulcers is guided by lation is characteristic of familial Mediterranean f'ever (FMF), the severity of symptoms and the presence of other disease a disease driven by several mutations in the MEFV gene. tJ .C, manifestations. This patient's disease does not seem to be This gene encodes pyrin, a protein important to the pro responding adequately to colchicine, which is an appropriate duction and/or overproduction of interleukin 1B. Although C, vl flrst line therapy for mucocutaneous ulcerations. Hence, an the genetics continue to be studied, from a clinical point of (l, alternate or additional treatment should be tried. Apremilast view the disease is most commonly found in Jewish, Arab, Ul is an oral phosphodiesterase 4 inhibitor approved for treat and Turkish populations and follows an autosomal recessive = ment of psoriasis, psoriatic arthritis, and prevention of oral pattern. Other symptoms may include other forms of serositis, ulcers in Behget syndrome. It is a reasonable alternative to including pericarditis. During episodes, inflammatory mark colchicine as a glucocorticoid-sparing agent for patients ers are elevated; in between episodes the physical examina with recurrent oral ulcers. Apremilast must be started at a tion and laboratory results may be normal. Diagnosis is made low dose and uptitrated over a few days to achieve a main clinically and can be confirmed definitively in most patients tenance dosage of 30 mg twice daily. Clinical trial data also through genetic testing. One long term consequence of the suggest a positive impact on genital ulcers, with a trend episodic inflammation of FMF is amyloidosis, including of the toward improvement, but the studies were not powered to kidneysr this patient's low level proteinuria may be an early assess this outcome. Apremilast is usually well tolerated but manifestation. Other autoinflammatory syndrornes are rarer is associated with adverse events, such as diarrhea, nausea, and have similar but nonidentical features that allow them to and headache. It should be used cautiously in patients with be distinguished from FMF. First-line treatment oIFMF is lile depression. Systemic glucocorticoids in tapering doses can long daily prophylaxis u,'ith colchicine. which in most cases be used in patients who are refractory to colchicine and prevents attacks, prevents renal amyloidosis, and can inhibit apremilast. However, if the patient requires continued sys neutrophils and suppress interleukin 1 B generation. temic glucocorlicoid therapy, azathioprine. thalidomide, or Canakinumab (Option A) is a monoclonal antibody to tumor necrosis factor inhibitors are most appropriate. interleukin-lB that has been reported to successfully treat Ixekizumab (Option B) is an interleukin-l7a inhibitor patients with FMF, including those in whom colchicine has approved for psoriasis, psoriatic arthritis, and ankylosing spon- failed. However, canakinumab is expensive and immuno dylitis. It has not been studied for or shown to be eflective in suppressive and has not been FDA approved for FMF treat treating mucocutaneous manifestations of Behqet syndrome. ment. Given the long experience with colchicine and its There are no data on use of leflunomide (Option C) in efficacy, canakinumab should be reserved for patients with the treatment of mucocutaneous manifestations of Behget FMF in whom colchicine has failed or is not tolerated. syndrome. NSAIDs, such as indomethacin (Option C), may alle- Mycophenolate mofetil (Option D) is not effective in viate symptoms during FMF attacks but do not address the the treatment of mucocutaneous manifestations of Behget underlying mechanisms of FMD and are not appropriate syndrome and should not be used unless the patient has preventive or long term therapy. tried and not responded to other agents. Glucocorticoids. such as prednisone (Option D). n.ray decrease the duration of attacks but also increase their fre XEY POIT{I quency. Thus, they are not appropriate for long-term or . Apremilast is a reasonable alternative to colchicine as preventive FMF therapy. a glucocorticoid-sparing agent for recurrent oral xtY P0l1lr5 ulcers in Behqet syndrome. . Familial Mediterranean fever is a systemic inflamma Bibliography tory syndrome characterized by fever, abdominal pain, Hatemi C, Christensen R, Bang D. et al. 2018 update ofthe EULAR recom rash, and arthritis, each lasting only several days. menditions fbr the management of Behqet's syndrome. Ann Rheum Dis. (Continued) 2018;77:8o8 gtA. IPMlD, 296259681

Item 1 Answer: A Item 2 Answer: B Educational Objective: Treat mucocutaneous Educational Objective: Treat familial Mediterranean fever. ulcerations in Behqet syndrome with apremilast. The most appropriate treatment is colchicine (Option B). The most appropriate treatment is apremilast (Option A). Autoinflammatory syndromes are monogenic diseases that Behqet syndrome is a systemic vasculitis characterized by result in periodic episodes of system inflammation. This recurrent oral aphthae. Other manifestations include gen, patient demonstrates multiple episodes of a systemic inflam- ital aphthae, ocular disease, skin lesions, gastrointestinal matory syndrome characterized by fever, abdominal pain, Ut (t, involvement, neurologic disease, vascular disease, and rash, and arthritis, each lasting only several days. This constel ET arthritis. The treatment of oral and genital ulcers is guided by lation is characteristic of familial Mediterranean f'ever (FMF), the severity of symptoms and the presence of other disease a disease driven by several mutations in the MEFV gene. tJ .C, manifestations. This patient's disease does not seem to be This gene encodes pyrin, a protein important to the pro responding adequately to colchicine, which is an appropriate duction and/or overproduction of interleukin 1B. Although C, vl flrst line therapy for mucocutaneous ulcerations. Hence, an the genetics continue to be studied, from a clinical point of (l, alternate or additional treatment should be tried. Apremilast view the disease is most commonly found in Jewish, Arab, Ul is an oral phosphodiesterase 4 inhibitor approved for treat and Turkish populations and follows an autosomal recessive = ment of psoriasis, psoriatic arthritis, and prevention of oral pattern. Other symptoms may include other forms of serositis, ulcers in Behget syndrome. It is a reasonable alternative to including pericarditis. During episodes, inflammatory mark colchicine as a glucocorticoid-sparing agent for patients ers are elevated; in between episodes the physical examina with recurrent oral ulcers. Apremilast must be started at a tion and laboratory results may be normal. Diagnosis is made low dose and uptitrated over a few days to achieve a main clinically and can be confirmed definitively in most patients tenance dosage of 30 mg twice daily. Clinical trial data also through genetic testing. One long term consequence of the suggest a positive impact on genital ulcers, with a trend episodic inflammation of FMF is amyloidosis, including of the toward improvement, but the studies were not powered to kidneysr this patient's low level proteinuria may be an early assess this outcome. Apremilast is usually well tolerated but manifestation. Other autoinflammatory syndrornes are rarer is associated with adverse events, such as diarrhea, nausea, and have similar but nonidentical features that allow them to and headache. It should be used cautiously in patients with be distinguished from FMF. First-line treatment oIFMF is lile depression. Systemic glucocorticoids in tapering doses can long daily prophylaxis u,'ith colchicine. which in most cases be used in patients who are refractory to colchicine and prevents attacks, prevents renal amyloidosis, and can inhibit apremilast. However, if the patient requires continued sys neutrophils and suppress interleukin 1 B generation. temic glucocorlicoid therapy, azathioprine. thalidomide, or Canakinumab (Option A) is a monoclonal antibody to tumor necrosis factor inhibitors are most appropriate. interleukin-lB that has been reported to successfully treat Ixekizumab (Option B) is an interleukin-l7a inhibitor patients with FMF, including those in whom colchicine has approved for psoriasis, psoriatic arthritis, and ankylosing spon- failed. However, canakinumab is expensive and immuno dylitis. It has not been studied for or shown to be eflective in suppressive and has not been FDA approved for FMF treat treating mucocutaneous manifestations of Behqet syndrome. ment. Given the long experience with colchicine and its There are no data on use of leflunomide (Option C) in efficacy, canakinumab should be reserved for patients with the treatment of mucocutaneous manifestations of Behget FMF in whom colchicine has failed or is not tolerated. syndrome. NSAIDs, such as indomethacin (Option C), may alle- Mycophenolate mofetil (Option D) is not effective in viate symptoms during FMF attacks but do not address the the treatment of mucocutaneous manifestations of Behget underlying mechanisms of FMD and are not appropriate syndrome and should not be used unless the patient has preventive or long term therapy. tried and not responded to other agents. Glucocorticoids. such as prednisone (Option D). n.ray decrease the duration of attacks but also increase their fre XEY POIT{I quency. Thus, they are not appropriate for long-term or . Apremilast is a reasonable alternative to colchicine as preventive FMF therapy. a glucocorticoid-sparing agent for recurrent oral xtY P0l1lr5 ulcers in Behqet syndrome. . Familial Mediterranean fever is a systemic inflamma Bibliography tory syndrome characterized by fever, abdominal pain, Hatemi C, Christensen R, Bang D. et al. 2018 update ofthe EULAR recom rash, and arthritis, each lasting only several days. menditions fbr the management of Behqet's syndrome. Ann Rheum Dis. (Continued) 2018;77:8o8 gtA. IPMlD, 296259681 123

i Answers and Critiques : ! l(EY P0lllTS (confnrcd) flndings, including malar rash, discoid rash, and alopecia. r First-line treatment of familial Mediterranean fever is This patient's presentation is not compatible with SLE. I lifelong daily prophylaxis with colchicine, which in IEY POITTS most cases prevents attacks, prevents renal amyloido- o Five clinical subtypes of psoriatic arthritis, which may ; sis, and can inhibit neutrophils and suppress overlap, are recognized: symmetric polyarthritis, : i interleukin-1 p generation. asymmetric oligoarthritis, distal interphalangeal- : predominant disease, spondyloarthritis, and arthritis !

sis, and can inhibit neutrophils and suppress overlap, are recognized: symmetric polyarthritis, : i interleukin-1 p generation. asymmetric oligoarthritis, distal interphalangeal- : predominant disease, spondyloarthritis, and arthritis ! Bibliography I mutilans. Georgin-Lavialle S, Ducharme-Benard S, Sarrabay G, et al. Systemic autoin flammatory diseases: Clinical state of the art. Best Pract Res Clin o Enthesitis, tenosynovitis, and dactylitis often occur in Rheumatol. 2020r34:101529. IPMID: 32546426] psoriatic arthritis; dactylitis is found in 40"/,' to 50% of patients and should always prompt consideration of a spondyloarthropathy. TA Item 3 Answer: B (D = Ed ucati o na I O bjective : Diagnose psoriatic arthritis. Bibliography Ritchlin CI, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl j Med. UI o, The most likely diagnosis is psoriatic arthritis (PsA) (Option 2017 ;376:957 -97O. [PMID: 28273019] doi:10.1056 NEJMral505557 CL B). Five clinical subtypes of psoriatic arthritis, which often n overlap, are recognized: symmetric polyarthritis, asym- .i llg metric oligoarthritis, distal interphalangeal-predominant Item 4 Answer: A (D disease, spondyloarthritis, and arthritis mutilans. Enthesi- ta Educational Objective: Diagnose granulomatosis with tis, tenosynovitis, and dactylitis often occur. Dactylitis is polyangiitis. found in 40'X, to 50% of patients with PsA and should always prompt consideration of a spondyloarthropathy. The most appropriate diagnostic test to perfbrnr next is kid This patient has a classic distribution for PsA. The distal ney biopsy (Option A). lhis patient's presentation is highly interphalangeal joints and an entire digit are involved (i.e., suspicious lor granulomatosis r.r,ith polyangiitis (GPA). dactylitis), with sparing of other digits. This patient has evi- The disease course began with nonspecific symptoms but dence of limited psoriasis, but the extent of psoriatic skin progressed to involve the upper and lower ainvays, eyes. involvement may not correlate with the extent of arthritis. skin. and kidneys. lhe skin rash. glomerulonephritis. In patients with PsA, affected peripheral joints sometimes and nodular lung disease are consistent with a vasculitic take on a purplish discoloration due to hypervascularit5r. process. In GPA lvith kidney involvement. kidney biopsy The Classification Criteria for Psoriatic Arthritis (CASPAR) is expected to show pathognomonic findings of pauci include evidence of psoriasis (current, past, and family imnrune crescentic necrotizing giomerulonephritis. history in first or second degree relatives), nail dystrophy, Whenever possible. it is important to confirm a diagnosis dactylitis (current or past), radiographic flndings showing of GPA r,vith tissue pathology before beginning treatment. new bone formation, and a negative rheumatoid factor given the many risks that accompanv intensive immuno result. Each of these is assigned 1 point except for current suppression; prognostic data can help guide therapy as psoriasis, which is assigned 2 points. These criteria are well. Guideline directed initial therapy fbr active. severe 91% sensitive and 98% speciflc for the diagnosis of PsA if GPA is either intravenous pulse glucocorticoids or high- 3 or more points are present. This patient's score is greater dose oral glucocorticoids plus rituximab (prelerred) or than 3. cyclophosphamide. If the diagnosis is clear and urgent This patient's symptoms are inflammatory making treatment is necessary. however, biopsy may be bl,passed osteoarthritis (Option A) unlikely despite involvement of (in this case. for example, if the ANCA panel u'ere positive the distal interphalangeal joints. In addition, osteoarthritis and the patient \ rere more acutely ill). does not cause dactylitis. Sir.rus biopsy (Option B). although less invasive than Rheumatoid arthritis can be seronegative (Option C) kidney or lung biopsy, has poor sensitiviry- and therefore in 15% to 2O"1, of patients classifled as having the disease, shoulcl not be performed ur.rless the diagnosis is in question but rheumatoid arthritis is typically a symmetric arthri- and no other tissue is alailable. tis and does not affect all of the joints in an entire digit, Althor.rgh skin biopsl, (Option C) should shon abnor- including the distal interphalangeal joint, as seen in this malities collsistent rvith a small vessel vasculitis. the find patient. ings lvould be nonspecific. Joints are affected in 90'1, of patients with systemic Thoracoscopic lung biopsy (Option D) might show vas lupus erythematosus (SLE) (Option D). The most common culitic changes consistent with GPA. but this procedure involvement is polyarthralgia, with lrank arthritis occur- has greater morbidiry than kidnel, biopsli particularly in ring in 40%. Typical distribution involves the small periph a patient u'ith tenuous respiratory status. Transbronchial eral joints. Dactylitis is not seen in SLE. Most patients with biopsy is more benign thar.r open lung biopsy but is generally SLE and arthritis also have characteristic mucocutaneous not perfbrmed. given its low sensitivity (about l0'7,).

Bibliography I mutilans. Georgin-Lavialle S, Ducharme-Benard S, Sarrabay G, et al. Systemic autoin flammatory diseases: Clinical state of the art. Best Pract Res Clin o Enthesitis, tenosynovitis, and dactylitis often occur in Rheumatol. 2020r34:101529. IPMID: 32546426] psoriatic arthritis; dactylitis is found in 40"/,' to 50% of patients and should always prompt consideration of a spondyloarthropathy. TA Item 3 Answer: B (D = Ed ucati o na I O bjective : Diagnose psoriatic arthritis. Bibliography Ritchlin CI, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl j Med. UI o, The most likely diagnosis is psoriatic arthritis (PsA) (Option 2017 ;376:957 -97O. [PMID: 28273019] doi:10.1056 NEJMral505557 CL B). Five clinical subtypes of psoriatic arthritis, which often n overlap, are recognized: symmetric polyarthritis, asym- .i llg metric oligoarthritis, distal interphalangeal-predominant Item 4 Answer: A (D disease, spondyloarthritis, and arthritis mutilans. Enthesi- ta Educational Objective: Diagnose granulomatosis with tis, tenosynovitis, and dactylitis often occur. Dactylitis is polyangiitis. found in 40'X, to 50% of patients with PsA and should always prompt consideration of a spondyloarthropathy. The most appropriate diagnostic test to perfbrnr next is kid This patient has a classic distribution for PsA. The distal ney biopsy (Option A). lhis patient's presentation is highly interphalangeal joints and an entire digit are involved (i.e., suspicious lor granulomatosis r.r,ith polyangiitis (GPA). dactylitis), with sparing of other digits. This patient has evi- The disease course began with nonspecific symptoms but dence of limited psoriasis, but the extent of psoriatic skin progressed to involve the upper and lower ainvays, eyes. involvement may not correlate with the extent of arthritis. skin. and kidneys. lhe skin rash. glomerulonephritis. In patients with PsA, affected peripheral joints sometimes and nodular lung disease are consistent with a vasculitic take on a purplish discoloration due to hypervascularit5r. process. In GPA lvith kidney involvement. kidney biopsy The Classification Criteria for Psoriatic Arthritis (CASPAR) is expected to show pathognomonic findings of pauci include evidence of psoriasis (current, past, and family imnrune crescentic necrotizing giomerulonephritis. history in first or second degree relatives), nail dystrophy, Whenever possible. it is important to confirm a diagnosis dactylitis (current or past), radiographic flndings showing of GPA r,vith tissue pathology before beginning treatment. new bone formation, and a negative rheumatoid factor given the many risks that accompanv intensive immuno result. Each of these is assigned 1 point except for current suppression; prognostic data can help guide therapy as psoriasis, which is assigned 2 points. These criteria are well. Guideline directed initial therapy fbr active. severe 91% sensitive and 98% speciflc for the diagnosis of PsA if GPA is either intravenous pulse glucocorticoids or high- 3 or more points are present. This patient's score is greater dose oral glucocorticoids plus rituximab (prelerred) or than 3. cyclophosphamide. If the diagnosis is clear and urgent This patient's symptoms are inflammatory making treatment is necessary. however, biopsy may be bl,passed osteoarthritis (Option A) unlikely despite involvement of (in this case. for example, if the ANCA panel u'ere positive the distal interphalangeal joints. In addition, osteoarthritis and the patient \ rere more acutely ill). does not cause dactylitis. Sir.rus biopsy (Option B). although less invasive than Rheumatoid arthritis can be seronegative (Option C) kidney or lung biopsy, has poor sensitiviry- and therefore in 15% to 2O"1, of patients classifled as having the disease, shoulcl not be performed ur.rless the diagnosis is in question but rheumatoid arthritis is typically a symmetric arthri- and no other tissue is alailable. tis and does not affect all of the joints in an entire digit, Althor.rgh skin biopsl, (Option C) should shon abnor- including the distal interphalangeal joint, as seen in this malities collsistent rvith a small vessel vasculitis. the find patient. ings lvould be nonspecific. Joints are affected in 90'1, of patients with systemic Thoracoscopic lung biopsy (Option D) might show vas lupus erythematosus (SLE) (Option D). The most common culitic changes consistent with GPA. but this procedure involvement is polyarthralgia, with lrank arthritis occur- has greater morbidiry than kidnel, biopsli particularly in ring in 40%. Typical distribution involves the small periph a patient u'ith tenuous respiratory status. Transbronchial eral joints. Dactylitis is not seen in SLE. Most patients with biopsy is more benign thar.r open lung biopsy but is generally SLE and arthritis also have characteristic mucocutaneous not perfbrmed. given its low sensitivity (about l0'7,). 124

Answers and Cr itiques XEY POIl{TS I(EY POITIS o It is important to confirm a diagnosis of granulomato- o A positive HLA-P.27 test result in the setting of a com- sis with polyangiitis by using tissue pathologr before pelling clinical picture confirms the diagnosis of axial beginning treatment, given the many risks that spondyloarthritis. accompany intensive i m munosuppression. . If a patient has many features of spondyloarthritis, o Standard therapy for granulomatosis with polyangiitis then a positive HLA-827 result adds little to the post- includes high-dose glucocorticoids plus rituximab test probability; ifthere are few features ofspondy- (preferred) or cyclophosphamide. loarthritis, then a positive HLA-B27 result is helpful. Bibliography Bibliography Geetha D. Jefferson JA. ANCA-associated vasculitis: core curriculum 2020. Danve A, Deodhar A. Axial spondyk)arthritis in the USA: diagnostic chal Am J Kidney Dis. 2020;75:124 137. [PMID: 3135$11] doi:10.1053/j.ajkd. lenges and missed opportunities. Clin Rheumatol. 20l9rll8:625 634 U! 2019.0,1.031 IPMID: 305885551 doi:10.1007/slO067 O18 4397 3 o ET

Bibliography Bibliography Geetha D. Jefferson JA. ANCA-associated vasculitis: core curriculum 2020. Danve A, Deodhar A. Axial spondyk)arthritis in the USA: diagnostic chal Am J Kidney Dis. 2020;75:124 137. [PMID: 3135$11] doi:10.1053/j.ajkd. lenges and missed opportunities. Clin Rheumatol. 20l9rll8:625 634 U! 2019.0,1.031 IPMID: 305885551 doi:10.1007/slO067 O18 4397 3 o ET Item 5 Answer: C Item 6 Answer: B (J E' Ed u catio n a I O biective : Evaluate for spondyloarthritis Educational Objective: Evaluate a patient by using tu with HIA-B27 testing. antinuclear antibody testing. Ut (l, The most appropriate diagnostic test to perform next is HLA The most appropriate laboratory test to perform next is anti- ta = B27 antigen testing (Option C). The test assesses for the nuclearantibody (ANA) measurement (Option B). This patient E presence ofthe HLA B27 antigen on the surface ofcells and has speciflc features of autoimmune disease, inflan.rmatory not the presence of the actual gene. This patient has inflam- polyarthritis, and photosensitive facial rash, along with fever (a matory low back pain manifesting as night pain, morning nonspecific systemic feature). ANA is directed against nuclear stiffness, and pain that improves with activity. He also has antigens and associated with systemic lupus erythematosus enthesitis of the Achilles tendon, which is seen in spon (SLE). Up to one third of the healthy population has a low dyloarthritis. A positive HLA P.27 antigen test result in the titer (1:40-1:80) for ANA, and up to 5'7, has a titer of 1:160 or setting of a compelling clinical picture conflrms the diagno higher. ANA can also be seen in other autoimmune condi sis of axial spondyloarthritis. If the HLA,-827 antigen result tions, infection, and malignancy or may be drug induced. An is negative, MRI of the pelvis to evaluate for sacroiliac joint isolated positive ANA result with nonspecific symptoms and inflammation is warranted. In a patient with inflammatory normal clinical examination does not establish the diagnosis of low back pain and a positive HLA-827 antigen result but no a connective tissue disease. In a patient with flndings strongly other features of spondyloarthritis, MRI is also indicated. In suggesting an underlying rheumatologic disease, such as this general, HLA B27 antigen testing adds probabilistic certainty patient with features of SLE, ANA testing is appropriate. ANA to the evaluation oflow back pain. Ifdiagnostic certainty is testing should be done befbre any subserolog, testing. Il the already high (i.e., the patient has many features of spon- ANA test result is positive, then specific subserologies are indi dyloarthritis), then a positive test result adds little to the cated on the basis ofthe clinical scenario. Ifthe ANA test result posttest probability; if there are few features of spondyloar is negative, then the ANA subserologic findings are typically thritis, then a positive HLA-827 antigen result is helpful. negative. Therefore, if the initial ANA result is negative, then An anteroposterior radiographic view of the pelvis is subserologr testing is not indicated. useful and is the recommended view for detecting sacro- ANA specificity or subserologr testing (i.e., testing lor iliitis. However, plain radiographs may not show evidence of antibodies to specific nuclear components, such as DNA or sacroiliitis for 1 to 2 years after symptoms develop. Thus, if centromeres) should be reserved for patients with a positive the anteroposterior radiograph is unremarkable, additional ANA result and a clinical syndrome suggesting an underly views (Option A) are not needed. ing rheumatologic disease. lf the ANA result is positive and In cases of suspected sacroiliitis, low dose CT (Option clinical flndings suggest a specific autoimmune inflamma B) is useful to clarify ambiguous changes seen on plain tory disease, then subserolos/ testing is appropriate. ln this radiographs, whereas MRI (Option D) is more sensitive and patient, if the ANA result is positive, SLE specific autoan can identiflz sacroiliac inflammation even in the absence of tibodies (anti-double stranded DNA [Option A], anti Ro/ radiographic changes. Neither imaging test is indicated at SSA and anti LalSSB antibodies [Option C], anti Smith this time, pending results of HIA B27 testing. [Option D], anti Ul ribonucleoprotein [Option E]) should Rheumatoid arthritis is an inflammatory polyarthritis be obtained to further characterize the disease. Anti double with a predilection lor the small joints of the hands and feet. stranded DNA antibodies are 95'1, specific for SLE and Rheumatoid arthritis can affect the cervical spine but not the approximately 50'7, to 60'1, sensitive. They are typically found lumbar spine or sacroiliac joints. This patient has no clinical in more severe disease, especially kidney disease. Antibody flndings that suggest rheumatoid arthritis; thus, serologic levels commonly follow disease activity and are useful to testing (Option E) is not indicated. monitor during therapy. Anti-Smith antibodies are the most

Item 5 Answer: C Item 6 Answer: B (J E' Ed u catio n a I O biective : Evaluate for spondyloarthritis Educational Objective: Evaluate a patient by using tu with HIA-B27 testing. antinuclear antibody testing. Ut (l, The most appropriate diagnostic test to perform next is HLA The most appropriate laboratory test to perform next is anti- ta = B27 antigen testing (Option C). The test assesses for the nuclearantibody (ANA) measurement (Option B). This patient E presence ofthe HLA B27 antigen on the surface ofcells and has speciflc features of autoimmune disease, inflan.rmatory not the presence of the actual gene. This patient has inflam- polyarthritis, and photosensitive facial rash, along with fever (a matory low back pain manifesting as night pain, morning nonspecific systemic feature). ANA is directed against nuclear stiffness, and pain that improves with activity. He also has antigens and associated with systemic lupus erythematosus enthesitis of the Achilles tendon, which is seen in spon (SLE). Up to one third of the healthy population has a low dyloarthritis. A positive HLA P.27 antigen test result in the titer (1:40-1:80) for ANA, and up to 5'7, has a titer of 1:160 or setting of a compelling clinical picture conflrms the diagno higher. ANA can also be seen in other autoimmune condi sis of axial spondyloarthritis. If the HLA,-827 antigen result tions, infection, and malignancy or may be drug induced. An is negative, MRI of the pelvis to evaluate for sacroiliac joint isolated positive ANA result with nonspecific symptoms and inflammation is warranted. In a patient with inflammatory normal clinical examination does not establish the diagnosis of low back pain and a positive HLA-827 antigen result but no a connective tissue disease. In a patient with flndings strongly other features of spondyloarthritis, MRI is also indicated. In suggesting an underlying rheumatologic disease, such as this general, HLA B27 antigen testing adds probabilistic certainty patient with features of SLE, ANA testing is appropriate. ANA to the evaluation oflow back pain. Ifdiagnostic certainty is testing should be done befbre any subserolog, testing. Il the already high (i.e., the patient has many features of spon- ANA test result is positive, then specific subserologies are indi dyloarthritis), then a positive test result adds little to the cated on the basis ofthe clinical scenario. Ifthe ANA test result posttest probability; if there are few features of spondyloar is negative, then the ANA subserologic findings are typically thritis, then a positive HLA-827 antigen result is helpful. negative. Therefore, if the initial ANA result is negative, then An anteroposterior radiographic view of the pelvis is subserologr testing is not indicated. useful and is the recommended view for detecting sacro- ANA specificity or subserologr testing (i.e., testing lor iliitis. However, plain radiographs may not show evidence of antibodies to specific nuclear components, such as DNA or sacroiliitis for 1 to 2 years after symptoms develop. Thus, if centromeres) should be reserved for patients with a positive the anteroposterior radiograph is unremarkable, additional ANA result and a clinical syndrome suggesting an underly views (Option A) are not needed. ing rheumatologic disease. lf the ANA result is positive and In cases of suspected sacroiliitis, low dose CT (Option clinical flndings suggest a specific autoimmune inflamma B) is useful to clarify ambiguous changes seen on plain tory disease, then subserolos/ testing is appropriate. ln this radiographs, whereas MRI (Option D) is more sensitive and patient, if the ANA result is positive, SLE specific autoan can identiflz sacroiliac inflammation even in the absence of tibodies (anti-double stranded DNA [Option A], anti Ro/ radiographic changes. Neither imaging test is indicated at SSA and anti LalSSB antibodies [Option C], anti Smith this time, pending results of HIA B27 testing. [Option D], anti Ul ribonucleoprotein [Option E]) should Rheumatoid arthritis is an inflammatory polyarthritis be obtained to further characterize the disease. Anti double with a predilection lor the small joints of the hands and feet. stranded DNA antibodies are 95'1, specific for SLE and Rheumatoid arthritis can affect the cervical spine but not the approximately 50'7, to 60'1, sensitive. They are typically found lumbar spine or sacroiliac joints. This patient has no clinical in more severe disease, especially kidney disease. Antibody flndings that suggest rheumatoid arthritis; thus, serologic levels commonly follow disease activity and are useful to testing (Option E) is not indicated. monitor during therapy. Anti-Smith antibodies are the most 125

Answers and Critiques speciflc for SLE (99%) but have low sensitivity. Antibody Medical cannabis (Option B) is increasingly available for levels do not correlate with disease activity. Anti-Ul- use in patients with chronic pain. Many states have passed ribonucleoprotein antibodies (particularly high titers) are laws legalizing the use of cannabis or allort'ing its use for sensitive for mixed connective tissue disease. Antibody levels certain medical conditions, although it is still classifled by do not correlate with disease activity. In patients with SLE, the U.S. Drug Enfbrcement Administration as a schedule I anti-Ro/SSA and anti-La/SSB antibodies are associated with agent. Current data on the effectiveness of medical cannabis photosensitive rash. In addition, offspring of mothers who for chronic pain are characterized by signiflcant heterogene are positive for anti-Ro/SSA or anti LalSSB are at increased ity in both patient populations and cannabis preparations. risk for neonatal lupus erythematosus (rash and congenital There are no high quality data on the efficacy of medical heart block). However, none of these antibodies should be cannabis speciflcally for fi bromyalgia. obtained until the ANA test result is conflrmed positive. Although tramadol may be beneficial in moderating symptoms in patients with fibromyalgia, possibly because ltY PottT D of its inhibition of serotonin and norepinephrine reuptake. (a . Antinuclear antibody (ANA) specificity or subserologz other opioids, such as oxycodone (Option C). have no evi testing (testing for antibodies to specific nuclear com- dence of efficacy. In patients with flbrom),algia. the use of = .D ponents) should be reserved for patients with a posi- IA opioids other than tramadol is more likely to result in harm o, tive ANA result and a clinical syndrome suggesting an than in beneflt. underlying connective tissue disease. Patients with flbromyalgia do not respond to anti- n inflammatory agents. Trials consisting of therapeutic doses of .st Bibliography naproxen, ibuprofen, and prednisone (Option D) have found (D Mulhearn B. Tansley SL. McHugh NJ. Autoantibodies in connecti\e tissue each to be equivalent to placebo in randomized clinical trials. disease. Best Pract Res Clin Rheumatol. 2020r3.1:101.162. IPMID, UI These agents are not indicated in patients with fibromyalgia. 318,180551 doi: t0. 1016, j.berh.2019.101.162

speciflc for SLE (99%) but have low sensitivity. Antibody Medical cannabis (Option B) is increasingly available for levels do not correlate with disease activity. Anti-Ul- use in patients with chronic pain. Many states have passed ribonucleoprotein antibodies (particularly high titers) are laws legalizing the use of cannabis or allort'ing its use for sensitive for mixed connective tissue disease. Antibody levels certain medical conditions, although it is still classifled by do not correlate with disease activity. In patients with SLE, the U.S. Drug Enfbrcement Administration as a schedule I anti-Ro/SSA and anti-La/SSB antibodies are associated with agent. Current data on the effectiveness of medical cannabis photosensitive rash. In addition, offspring of mothers who for chronic pain are characterized by signiflcant heterogene are positive for anti-Ro/SSA or anti LalSSB are at increased ity in both patient populations and cannabis preparations. risk for neonatal lupus erythematosus (rash and congenital There are no high quality data on the efficacy of medical heart block). However, none of these antibodies should be cannabis speciflcally for fi bromyalgia. obtained until the ANA test result is conflrmed positive. Although tramadol may be beneficial in moderating symptoms in patients with fibromyalgia, possibly because ltY PottT D of its inhibition of serotonin and norepinephrine reuptake. (a . Antinuclear antibody (ANA) specificity or subserologz other opioids, such as oxycodone (Option C). have no evi testing (testing for antibodies to specific nuclear com- dence of efficacy. In patients with flbrom),algia. the use of = .D ponents) should be reserved for patients with a posi- IA opioids other than tramadol is more likely to result in harm o, tive ANA result and a clinical syndrome suggesting an than in beneflt. underlying connective tissue disease. Patients with flbromyalgia do not respond to anti- n inflammatory agents. Trials consisting of therapeutic doses of .st Bibliography naproxen, ibuprofen, and prednisone (Option D) have found (D Mulhearn B. Tansley SL. McHugh NJ. Autoantibodies in connecti\e tissue each to be equivalent to placebo in randomized clinical trials. disease. Best Pract Res Clin Rheumatol. 2020r3.1:101.162. IPMID, UI These agents are not indicated in patients with fibromyalgia. 318,180551 doi: t0. 1016, j.berh.2019.101.162 xEY ?OTXTS . FDA approved medications for fibromyalgia include Item 7 Answer: E pregabalin, duloxetine, and milnacipran. Educationa I Objective: Treat fibromyalgia with o Patients with fibromyalgia do not respond to anti pregabalin. inflammatory drugs, including NSAIDs and glucocor The most appropriate additional treatment is pregabalin ticoids. and do not respond to opioids, with the (Option E). Optimal management of fibromyalgia requires a exception of tramadol. holistic approach, including education. exercise, and psycho- social support. Pharmacotherapy is often warranted, although Bibliography nonpharmacologic measures remain a cornerstone of treat- Nlacfarlane (iJ. Kronisch C. Dean L[:. et al. F-ULAR revised recommendations ment. Pregabalin, an antiepileptic drug. improves quality of fbr the management of fibromlalgia. i\nn Rheum Dis. 2017:76:318 :128. [P1\,1 I D: 27:]7781 5l doi : I 0. I I i]6 annrheumdis 2J16 2097 21 life and decreases pain. It is one of only a few medications that are FDA approved for treating flbromyalgia. The medication should be initiated at low doses at night (i.e.. 50 or 75 mg at Item 8 Answer: B bedtime) and slowly titrated as tolerated up to a maximum Educational Obiective: Diagnose diffuse idiopathic dosage of 225 mg t\,vice daily. Common adverse effects include skeletal hyperostosis. drowsiness, dizziness, and peripheral edema. Weight gain of 7% or more is seen in nearly 10'/. of patients. Off label use The most likely diagnosis is diffuse idiopathic skeletal hyperos of gabapentin. another antiepileptic drug, has demonstrated tosis (DISH) (Option B). DISH is a noninflammatory condition effectiveness in a randomized controlled trial and is frequently that occasionally is associated w,ith elevated inflammatory used for this disorder in dosages up to 600 mg twice daily. markers and causes calcification and ossification of spinal Prescribing duloxetine (Option A) would be appro ligaments (especially the anterior longitudinal ligament) and priate in a patient with flbromyalgia. particularly one with entheses (tendon and ligament attachments to bone). This depression, but not in one receiving escitalopram. Adding a leads to pain and stiffness as well as reduced range of motion serotonin-norepinephrine reuptake inhibitor atop a selec of the spine. DISH is more common in men aged 45 years and tive serotonin reuptake inhibitor would pose an unaccept older and most often involves the thoracic spine. DISH does able risk for serotonin syndrome. Duloxetine is otherwise not affect the sacroiliac joints. This patient presents u,ith clas an appropriate medication to use in Iibromyalgia, at a dos sic epidemiologic features: he is an older man. he has typical age of up to 60 mg daily; consultation with the patient's symptoms and findings of DISH consisting of back pain and psychiatrist would be essential if duloxetine needed to be stiffness without sacroiliac pain. and his radiograph shows considered. Other medications that would be appropriate the distinctive finding of flowing linear calcification and ossi for a patient not already taking a selective serotonin reuptake fication along the anterolateral aspects of the vertebral bodies inhibitor would include milnacipran and off label use of (Figure [top of next pagel). These distinctive radiographic tricyclic antidepressants (amitriptyline and nortriptyline). findings are most easily visualized on lateral images.

xEY ?OTXTS . FDA approved medications for fibromyalgia include Item 7 Answer: E pregabalin, duloxetine, and milnacipran. Educationa I Objective: Treat fibromyalgia with o Patients with fibromyalgia do not respond to anti pregabalin. inflammatory drugs, including NSAIDs and glucocor The most appropriate additional treatment is pregabalin ticoids. and do not respond to opioids, with the (Option E). Optimal management of fibromyalgia requires a exception of tramadol. holistic approach, including education. exercise, and psycho- social support. Pharmacotherapy is often warranted, although Bibliography nonpharmacologic measures remain a cornerstone of treat- Nlacfarlane (iJ. Kronisch C. Dean L[:. et al. F-ULAR revised recommendations ment. Pregabalin, an antiepileptic drug. improves quality of fbr the management of fibromlalgia. i\nn Rheum Dis. 2017:76:318 :128. [P1\,1 I D: 27:]7781 5l doi : I 0. I I i]6 annrheumdis 2J16 2097 21 life and decreases pain. It is one of only a few medications that are FDA approved for treating flbromyalgia. The medication should be initiated at low doses at night (i.e.. 50 or 75 mg at Item 8 Answer: B bedtime) and slowly titrated as tolerated up to a maximum Educational Obiective: Diagnose diffuse idiopathic dosage of 225 mg t\,vice daily. Common adverse effects include skeletal hyperostosis. drowsiness, dizziness, and peripheral edema. Weight gain of 7% or more is seen in nearly 10'/. of patients. Off label use The most likely diagnosis is diffuse idiopathic skeletal hyperos of gabapentin. another antiepileptic drug, has demonstrated tosis (DISH) (Option B). DISH is a noninflammatory condition effectiveness in a randomized controlled trial and is frequently that occasionally is associated w,ith elevated inflammatory used for this disorder in dosages up to 600 mg twice daily. markers and causes calcification and ossification of spinal Prescribing duloxetine (Option A) would be appro ligaments (especially the anterior longitudinal ligament) and priate in a patient with flbromyalgia. particularly one with entheses (tendon and ligament attachments to bone). This depression, but not in one receiving escitalopram. Adding a leads to pain and stiffness as well as reduced range of motion serotonin-norepinephrine reuptake inhibitor atop a selec of the spine. DISH is more common in men aged 45 years and tive serotonin reuptake inhibitor would pose an unaccept older and most often involves the thoracic spine. DISH does able risk for serotonin syndrome. Duloxetine is otherwise not affect the sacroiliac joints. This patient presents u,ith clas an appropriate medication to use in Iibromyalgia, at a dos sic epidemiologic features: he is an older man. he has typical age of up to 60 mg daily; consultation with the patient's symptoms and findings of DISH consisting of back pain and psychiatrist would be essential if duloxetine needed to be stiffness without sacroiliac pain. and his radiograph shows considered. Other medications that would be appropriate the distinctive finding of flowing linear calcification and ossi for a patient not already taking a selective serotonin reuptake fication along the anterolateral aspects of the vertebral bodies inhibitor would include milnacipran and off label use of (Figure [top of next pagel). These distinctive radiographic tricyclic antidepressants (amitriptyline and nortriptyline). findings are most easily visualized on lateral images. 126

I I Answers and Critiques t I Item 9 Answer: E Educational Objective: Advise smoking cessation in a I patient at risk for rheumatoid arthritis. The intervention most likely to reduce this patient's risk for : developing rheumatoid arthritis is counseling for smoking ces- sation (Option E). One of the most provocative environmental : factors for the development of rheumatoid arthritis is smoking. i A dose dependent relationship exists between smoking and I the development of seropositive rheumatoid arthritis. Smoking can lead to lung inflammation, which activates such enzymes I as peptidylarginine deiminase, which deaminates arginine to fbrm citrullinated peptides. HtA D alleles code for the shared UI epitope. The shared epitope, a five amino acid sequence, pref- o erentially binds and presents citrullinated peptide antigens. ET

as peptidylarginine deiminase, which deaminates arginine to fbrm citrullinated peptides. HtA D alleles code for the shared UI epitope. The shared epitope, a five amino acid sequence, pref- o erentially binds and presents citrullinated peptide antigens. ET This leads to the production of anti-cyclic citrullinated peptide rr, antibodies that could initiate inflammation by fixing comple- E' ment in the tissues. Patients who smoke are at increased risk for tg rheumatoid arthritis, particularly those with a tamily history of la rheumatoid arthritis, and should be counseled about smoking o Arkylosing spondylitis (AS) (Option A) is an inflamma- cessation. The risk for RA increases with an increasing number tory arthritis ofthe spine, usually presenting as chronic back ofsmoking pack years, and the risk decreases as the interval of cUt= pain and stiflness, typically before age 45 years. Radiographic smoking cessation increases. Combining behavioral counseling flndings include squaring of the vertebral bodies due to ante with pharmacotherapy is more effective than either modality rior and posterior inflammation, bone erosions, and formation alone in achieving long term smoking abstinence. of syndesmophytes, which are typically thin and vertically ori A reduced risk for rheumatoid arthritis has been ented and lead to anlrylosis. Involvement of the sacroiliac joints associated with moderate alcohol consumption in some is a hallmark of AS, and affected patients have elevated serum observational studies. There is no reason for this patient to inflammatory markers. This patient does not have the clinical, discontinue alcohol consumption (Option A) to reduce her radiographic, or laboratory findings characteristic ofAS. risk for rheumatoid arthritis. Calcium pyrophosphate deposition disease (Option C) This patient should not be counseled to discontinue her can involve the spine and has been associated with spine combined oral contraceptive pill (Option B). Observational stiffness and pain, as well as cartilage calcification and bony studies have detected either a reduced risk fbr rheumatoid an$osis. However, thick, flowing osteophytes are not typ arthritis or no impact on its development in patients taking ical ofthis disease. a combined oral contraceptive. Spondylosis defbrmans (degenerative disk disease with lncreasing physical activity (Option C) has been incon- osteophl.te formation) (Option D) is an important disorder sistently associated with a reduced risk for developing rheu to be considered in the differential diagnosis of DISH. This matoid arthritis. There are other reasons to recommend condition is usually seen in patients older than 55 years. increased physical activity to this patient, but this recom Although the spurs in the cervical and lumbar spine can mendation should not be based on the possibility of reduc resemble those seen in DISH. involvement of the anterior ing the risk for rheumatoid arthritis. longitudinal ligament in the thoracic spine characteristic of Consumption of a Mediterranean diet (Option D) is not DISH is not observed in spondylosis. specifically shown to reduce the risk for rheumatoid arthri xEY Potx?s tis. Higher intake of flsh may be associated with a lower risk . Diffuse idiopathic skeletal hyperostosis is a nonin- for rheumatoid arthritis, but studies on this association are flammatory condition that causes back pain and inconclusive, as are studies on the effect of red meat, coflee consumption, and use of' antioxidants. stiffness without sacroiliac pain, typically in men aged 45 years and older. f,tY P0lft!,. .:.:.. o Diffuse idiopathic skeletal hyperostosis is associated . Patients who smoke are at increased risk for rheuma- with a distinctive radiographic finding consisting of toid arthritis, particularly those with a family history flowing linear calcification and ossification along the of rheumatoid arthritis, and should be counseled to anterolateral aspects of the vertebral bodies. stop smoking.

This leads to the production of anti-cyclic citrullinated peptide rr, antibodies that could initiate inflammation by fixing comple- E' ment in the tissues. Patients who smoke are at increased risk for tg rheumatoid arthritis, particularly those with a tamily history of la rheumatoid arthritis, and should be counseled about smoking o Arkylosing spondylitis (AS) (Option A) is an inflamma- cessation. The risk for RA increases with an increasing number tory arthritis ofthe spine, usually presenting as chronic back ofsmoking pack years, and the risk decreases as the interval of cUt= pain and stiflness, typically before age 45 years. Radiographic smoking cessation increases. Combining behavioral counseling flndings include squaring of the vertebral bodies due to ante with pharmacotherapy is more effective than either modality rior and posterior inflammation, bone erosions, and formation alone in achieving long term smoking abstinence. of syndesmophytes, which are typically thin and vertically ori A reduced risk for rheumatoid arthritis has been ented and lead to anlrylosis. Involvement of the sacroiliac joints associated with moderate alcohol consumption in some is a hallmark of AS, and affected patients have elevated serum observational studies. There is no reason for this patient to inflammatory markers. This patient does not have the clinical, discontinue alcohol consumption (Option A) to reduce her radiographic, or laboratory findings characteristic ofAS. risk for rheumatoid arthritis. Calcium pyrophosphate deposition disease (Option C) This patient should not be counseled to discontinue her can involve the spine and has been associated with spine combined oral contraceptive pill (Option B). Observational stiffness and pain, as well as cartilage calcification and bony studies have detected either a reduced risk fbr rheumatoid an$osis. However, thick, flowing osteophytes are not typ arthritis or no impact on its development in patients taking ical ofthis disease. a combined oral contraceptive. Spondylosis defbrmans (degenerative disk disease with lncreasing physical activity (Option C) has been incon- osteophl.te formation) (Option D) is an important disorder sistently associated with a reduced risk for developing rheu to be considered in the differential diagnosis of DISH. This matoid arthritis. There are other reasons to recommend condition is usually seen in patients older than 55 years. increased physical activity to this patient, but this recom Although the spurs in the cervical and lumbar spine can mendation should not be based on the possibility of reduc resemble those seen in DISH. involvement of the anterior ing the risk for rheumatoid arthritis. longitudinal ligament in the thoracic spine characteristic of Consumption of a Mediterranean diet (Option D) is not DISH is not observed in spondylosis. specifically shown to reduce the risk for rheumatoid arthri xEY Potx?s tis. Higher intake of flsh may be associated with a lower risk . Diffuse idiopathic skeletal hyperostosis is a nonin- for rheumatoid arthritis, but studies on this association are flammatory condition that causes back pain and inconclusive, as are studies on the effect of red meat, coflee consumption, and use of' antioxidants. stiffness without sacroiliac pain, typically in men aged 45 years and older. f,tY P0lft!,. .:.:.. o Diffuse idiopathic skeletal hyperostosis is associated . Patients who smoke are at increased risk for rheuma- with a distinctive radiographic finding consisting of toid arthritis, particularly those with a family history flowing linear calcification and ossification along the of rheumatoid arthritis, and should be counseled to anterolateral aspects of the vertebral bodies. stop smoking. Bibliography . Exercise, alcohol use, and dietary factors are not Mader R, Verlaan JJ, Eshed l, et al. DifTuse idiopathic skeletal hyperostosis firmly associated with either increased or decreased (DISH): where we are now and where to go next. RMD Open. 2017;3: risk for rheumatoid arthritis. eOOO472. IPMID: 28955488] doi:10.1136/rmdopen 2017 000472

Bibliography . Exercise, alcohol use, and dietary factors are not Mader R, Verlaan JJ, Eshed l, et al. DifTuse idiopathic skeletal hyperostosis firmly associated with either increased or decreased (DISH): where we are now and where to go next. RMD Open. 2017;3: risk for rheumatoid arthritis. eOOO472. IPMID: 28955488] doi:10.1136/rmdopen 2017 000472 127

Bibliography Bibliography Salliot C. Nguyen Y Boutron Ruault MC, et al. Environment and lifestyle: DeWane ME. Waldman R, Lu J. Dermatomyositis: clinical teatures and their influence on the risk of RA. J Clin Med. 2020;9. IPMID: 32993091] pathogenesis. J Am Acad Dermatol. 2o2o;82:267 -281. IPMID: 312798081 Item 10 Answer: B Item 11 Answer: B Educational Objective: Diagnose amyopathic Educational Objective: Diagnose inflammatory bowel EI dermatomyositis. disease in a patient with an$osing spondylitis.

Item 10 Answer: B Item 11 Answer: B Educational Objective: Diagnose amyopathic Educational Objective: Diagnose inflammatory bowel EI dermatomyositis. disease in a patient with an$osing spondylitis. The most likely diagnosis is amyopathic dermatomyosi The most likely diagnosis is inflammatory bo$'el disease tis (Option B). Some patients with dermatomyositis never (lBD) (Option B). IBD occurs in up to 14'L of patients with develop muscle involvement (amyopathic dermatomyositis) ; anl<11osing spondylitis (AS), a much higher rate than the these patients can be diagnosed with skin biopsy conflrma- approximately 0.5'7, seen in the general population. Among D tion of dermatomyositis in the setting of at least 6 months patients \\.ith AS who develop IBD. Crohn disease and ulcer (a without muscle involvement. A characteristic skin rash ati\€ colitis occur with equal frequencyl IBD in AS is slightll, E .D should prompt consideration of dermatomyositis even with more common among men and occurs early in the course UI normal muscle strength and a normal serum creatine kinase ofAS. By 10 years ofAS, the risk lor IBD has returned to the o, level. This patient has a typical photosensitive distribution general population level. The bowel inflammation and gut TL rl of dermatomyositis rash on the face, including a probable dysbiosis that are common in IBD may drive the inflam early heliotrope rash over the eyelids. He also has Gottron mation in the spine, leading to AS. Clinical nranifestations 4t papules on the elbows and knees. Skin biopsy would likely of IBD in patients with combined AS and IBD are similar tir .D show characteristic interface dermatitis. Further evaluation those in patients with IBD alone. U! can include antibody and additional testing for subtle mus Celiac disease (Option A) is an immune mediated dis cle inflammation, using electromyography or MRI, but even ease that primarily affects the small intestine in response if the results are normal, this patient should be treated for to dietary gluten. It is one of the most common causes of dermatomyositis. Patients with amyopathic dermatomyo malabsorption. Celiac disease has no association u,ith AS sitis also have a high risk for interstitial lung disease and or other rheumatologic diseases. Although patients with cancer; screening for these conditions should also be part of chronic diarrhea should be evaluated lor celiac disease. IBD the initial evaluation. is a more likely diagnosis in a patient with AS. Acute cutaneous lupus erythematosus (Option A) can Irritable bowel syndrome (lBS) (Option C) is a func be difficult to distinguish clinically from dermatomyositis, tional bor,tel disorder defined by the presence of abdominal especially on the face, because it can present in the same pain in association with defe'cation and, or a change in bolr,el distribution and can have similar flndings on skin biopsy. habits. The diagnosis of IBS requires symptoms ol recurrent However, lupus is not likely to cause a heliotrope rash or abdominal pain at least I day a u,eek fbr :l months, along Gottron papules on the hands, elbows, and knees. with at least two ol the fbllou,ing three additional crite This patient's Gottron papules on the elbows and knees ria: pain related to defecation. change in stool fiequency can be difficult to distinguish from psoriasis (Option C) or change in stool consistenc'y This patient's pain is not by description or physical examination, but psoriasis is related to defecation. and her recent unintentional weight less likely to cause the photosensitive rashes seen in this loss makes IBS unlikell: patient. Small intestinal bacterial overgronth (SIBO) (Option D) Rosacea (Option D) is the most common cause of a is caused by various conditions. including impaired motility red rash in a malar distribution in an adult. Rosacea is an strictures. or blind loops. Diagnosis requires t1.'pical symp inflammatory skin condition that produces small pink pap toms and a confirmatory test (usually breath testing). SIBO ules and pustules on the central face with a variety of speciflc is associated with systemic sclerosis but l.ras not been irssoci patterns. The erythema ol the cheeks can mimic the malar ated with AS unless there is another predisposing condition. rash of systemic lupus erythematosus or dermatomyositis XEY POIf,IS but would not be expected to cause skin changes on the extremities. o Inflammatory bowel disease occurs in patients with ankylosing spondylitis at a much higher rate than in (tY P0rxTs the general population. o Some patients with dermatomyositis never develop o Patients with ankylosing spondylitis who develop muscle involvement (amyopathic dermatomyositis) abdominal pain, diarrhea, or a change in bowel habits and are diagnosed by using skin biopsy in the setting should be evaluated for inflammatory bowel disease. of at least 6 months without muscle involvement. o A characteristic skin rash should prompt considera- Bibliography tion of dermatomyositis even with normal muscle Fragoulis GE, Liava C, Daoussis D, et al. Inflammatory bowel diseases and spon strength and a normal serum creatine kinase level. dyloarthropathies: from pathogenesis to treatment. World J Gastroenterol. 2019;25:2162 2176. IPMID: 31143068] doi:10.3748/wjg.v2s.i18.2162

The most likely diagnosis is amyopathic dermatomyosi The most likely diagnosis is inflammatory bo$'el disease tis (Option B). Some patients with dermatomyositis never (lBD) (Option B). IBD occurs in up to 14'L of patients with develop muscle involvement (amyopathic dermatomyositis) ; anl<11osing spondylitis (AS), a much higher rate than the these patients can be diagnosed with skin biopsy conflrma- approximately 0.5'7, seen in the general population. Among D tion of dermatomyositis in the setting of at least 6 months patients \\.ith AS who develop IBD. Crohn disease and ulcer (a without muscle involvement. A characteristic skin rash ati\€ colitis occur with equal frequencyl IBD in AS is slightll, E .D should prompt consideration of dermatomyositis even with more common among men and occurs early in the course UI normal muscle strength and a normal serum creatine kinase ofAS. By 10 years ofAS, the risk lor IBD has returned to the o, level. This patient has a typical photosensitive distribution general population level. The bowel inflammation and gut TL rl of dermatomyositis rash on the face, including a probable dysbiosis that are common in IBD may drive the inflam early heliotrope rash over the eyelids. He also has Gottron mation in the spine, leading to AS. Clinical nranifestations 4t papules on the elbows and knees. Skin biopsy would likely of IBD in patients with combined AS and IBD are similar tir .D show characteristic interface dermatitis. Further evaluation those in patients with IBD alone. U! can include antibody and additional testing for subtle mus Celiac disease (Option A) is an immune mediated dis cle inflammation, using electromyography or MRI, but even ease that primarily affects the small intestine in response if the results are normal, this patient should be treated for to dietary gluten. It is one of the most common causes of dermatomyositis. Patients with amyopathic dermatomyo malabsorption. Celiac disease has no association u,ith AS sitis also have a high risk for interstitial lung disease and or other rheumatologic diseases. Although patients with cancer; screening for these conditions should also be part of chronic diarrhea should be evaluated lor celiac disease. IBD the initial evaluation. is a more likely diagnosis in a patient with AS. Acute cutaneous lupus erythematosus (Option A) can Irritable bowel syndrome (lBS) (Option C) is a func be difficult to distinguish clinically from dermatomyositis, tional bor,tel disorder defined by the presence of abdominal especially on the face, because it can present in the same pain in association with defe'cation and, or a change in bolr,el distribution and can have similar flndings on skin biopsy. habits. The diagnosis of IBS requires symptoms ol recurrent However, lupus is not likely to cause a heliotrope rash or abdominal pain at least I day a u,eek fbr :l months, along Gottron papules on the hands, elbows, and knees. with at least two ol the fbllou,ing three additional crite This patient's Gottron papules on the elbows and knees ria: pain related to defecation. change in stool fiequency can be difficult to distinguish from psoriasis (Option C) or change in stool consistenc'y This patient's pain is not by description or physical examination, but psoriasis is related to defecation. and her recent unintentional weight less likely to cause the photosensitive rashes seen in this loss makes IBS unlikell: patient. Small intestinal bacterial overgronth (SIBO) (Option D) Rosacea (Option D) is the most common cause of a is caused by various conditions. including impaired motility red rash in a malar distribution in an adult. Rosacea is an strictures. or blind loops. Diagnosis requires t1.'pical symp inflammatory skin condition that produces small pink pap toms and a confirmatory test (usually breath testing). SIBO ules and pustules on the central face with a variety of speciflc is associated with systemic sclerosis but l.ras not been irssoci patterns. The erythema ol the cheeks can mimic the malar ated with AS unless there is another predisposing condition. rash of systemic lupus erythematosus or dermatomyositis XEY POIf,IS but would not be expected to cause skin changes on the extremities. o Inflammatory bowel disease occurs in patients with ankylosing spondylitis at a much higher rate than in (tY P0rxTs the general population. o Some patients with dermatomyositis never develop o Patients with ankylosing spondylitis who develop muscle involvement (amyopathic dermatomyositis) abdominal pain, diarrhea, or a change in bowel habits and are diagnosed by using skin biopsy in the setting should be evaluated for inflammatory bowel disease. of at least 6 months without muscle involvement. o A characteristic skin rash should prompt considera- Bibliography tion of dermatomyositis even with normal muscle Fragoulis GE, Liava C, Daoussis D, et al. Inflammatory bowel diseases and spon strength and a normal serum creatine kinase level. dyloarthropathies: from pathogenesis to treatment. World J Gastroenterol. 2019;25:2162 2176. IPMID: 31143068] doi:10.3748/wjg.v2s.i18.2162 128

I L t Answers and Critiques L I t I L Item 12 Answer: B Educational Objective: Treat Lyme arthritis. Item 13 Answer: A Educationa I Objective: Diagnose acute calcium tr pyrophosphate crystal arthritis. t The most appropriate treatment is doxycycline (Option B). Although arthralgia and myalgia often occur at the earlier 'lhe most likely diagnosis is acute calcium pyrophosphate t (CPP) crystal arthritis (pseudogout) (Option A). Acute CPP stages of Lyme disease, Lyme arthritis is a late-stage manifes i tation. It is typically monoarticular, most commonly in the crystirl arthritis is an episoclic nrthritis that most commonly I knee. It should be suspected in patients who may have had occurs in older women. tt usually develops over several days L untreated or incompletely treated Lyme disease, although and may last fbr weeks. The knee and wrists are common not all patients will have a history compatible with previous sites. 'lhe pre'sentation is usually inflammatory with pain, Lyme disease. All patients with Lyme arthritis, however, swellir.rg. and warmth <-rf the inv'olved joint. Systernic markers I should have positive results on enzyme-linked immunosor of ir.rf lammation may be elevated. such as tl-re erythrocyte sed ; bent assay and Western blot confirmatory serologies; this is imentation rate in this patient. Plain radiographs, like the one l,t (l, the primary means of diagnosing Lyme arthritis, although a shown fbr this patient, may demonstrate cht.rndrocaicinosis. : ET I second enzyme immunoassay can be used as a confirmatory Chonclrocalcinosis is seen as a thin white Iine that tracks below test. In addition, Borrelia burgdorJ'ert DNA can be detected the surface layer ol the cartilage because it represents CPP (, by polymerase chain reaction in synovial fluid, but this test deposition within the cartilage. A definitive diagnosis n'ould -t t offers no advantage to serologic testing. Randomized con- include aspiration of the joint fluid and the clemonstration of ag trolled trials have suggested that 90'1, of patients with Lyme CPP crystals, which are weakly positively biretiingent (blue Ul arthritis are eflectively treated with a 28-day course oforal when parallel to and yellow wher.r perpendicular kr the polar o antibiotics. Doxycycline is the most widely recommended izing axis of'an optical filter) and classically rhon.rboid shaped. vt = I E first choice in antibiotic treatment of Lyme arthritis. Treat- (lout flare (Option B) is a less likely diagnosis given the ment with a 28-day course of amoxicillin is an alternative involvement of the knee without current or prior lypical flrst line therapy. For patients whose arthritis improves but joint i nvolvement (first metatarsophalangeal joi nt, ibrefeet. does not completely resolve, a second 28-day course of the ankles, ancl flngers). The ll week duration of the previ- same antibiotic can be prescribed. For pregnant and lactat ous episodes is longer than that usually seen with gout ing women, tetracyclines are generally avoided in favor of a (t-z weeks). The normal serum urate level also makes gout p Iactam antibiotic. unlikely, although serum urate levels may occasionally lall Ceftriaxone (Option A) is unnecessary in most cases into the normal range during an acute flare. Monosodiun.r of Lyme arthritis because patients generally respond to oral urate crystals are needle shaped and negatively birefrin antibiotics. Celtriaxone is not the first choice for treatment gent uncler polarized light; they appear lellow when par of Lyme arthritis unless concomitant neurologic symptoms allel ar.rd blue when perpendicular to the polarizing a.xis. are present. It may be given for moderate to severe persistent lnfectious arthritis (Option C) is unlikely because the arthritis after the failure of oral antibiotics. patient has no fever or other systemic sympt(nns afler 10 A small subset of patients may have persistent arthri days, as well as a normal complete biood count. IIer history tis that suggests a reactive arthritis, which may respond of similar episodes also argues against in{ection as the cause. to immunosuppressive therapy. For moderate to severe Nevertheless. a1l patients with acute monoiirticular arthritis persistent symptoms, treatment with hydroxychloroquine should undergo synovial fluid analysis that inclucles a Gram (Option C) or methotrexate (Option D) may be appropriate, stain anct culture to help cxclude inf'ectious arthritis. but only after failure of treatment with oral and intravenous Ill.rcumatoid arlhritis (Option D) is not a likcly diag- antibiotics. nosis because the patient has monoarticular knee afihritis, without the symmetric joint involvement of hancls. wrists, or XEY POIXTS feet typical of rheumatoid arlhritis. Finally, chonclrocalcino- . All patients with Lyme arthritis should have positive sis is not a feature of rheumatoid arthritis. results on enzyme linked immunosorbent assay and Western blot confirmatory serologies; this is the XEV POI]ITI primary means of diagnosing Lyme arthritis, although . Acute calcium pyrophosphate cr).stal arthdtis (pszudogout) a second enzyme immunoassay can be used as a is characterized by the sudden onset of pain, warmth, ten- conflrmatory test. demess, and swelling of the affected joint, usually a knee . Ninety percent of patients with Lyme arthritis are or wrist; flares are typicaUy longer than those ofgout. effectively treated with a 28-day course of oral . Definitive diagnosis of calcium pyrophosphate crystal doxycycline or amoxicillin. arthritis would include aspiration of the joint fluid and demonstration of calcium plrophosphate crystals, Bibliography which are weakly positively birefringent (blue when Arvikar SL, Steere AC. Diagnosis and treatment of Lyme arthritis. Infect Dis parallel to and yellow when perpendicular to the polar Clin North Am. 2O15;29:269-80. IPMID: 259992231 doi:10.1016/j.idc.2015. izing axis of an optical filter) and rhomboid-shaped. 02.004

L Item 12 Answer: B Educational Objective: Treat Lyme arthritis. Item 13 Answer: A Educationa I Objective: Diagnose acute calcium tr pyrophosphate crystal arthritis. t The most appropriate treatment is doxycycline (Option B). Although arthralgia and myalgia often occur at the earlier 'lhe most likely diagnosis is acute calcium pyrophosphate t (CPP) crystal arthritis (pseudogout) (Option A). Acute CPP stages of Lyme disease, Lyme arthritis is a late-stage manifes i tation. It is typically monoarticular, most commonly in the crystirl arthritis is an episoclic nrthritis that most commonly I knee. It should be suspected in patients who may have had occurs in older women. tt usually develops over several days L untreated or incompletely treated Lyme disease, although and may last fbr weeks. The knee and wrists are common not all patients will have a history compatible with previous sites. 'lhe pre'sentation is usually inflammatory with pain, Lyme disease. All patients with Lyme arthritis, however, swellir.rg. and warmth <-rf the inv'olved joint. Systernic markers I should have positive results on enzyme-linked immunosor of ir.rf lammation may be elevated. such as tl-re erythrocyte sed ; bent assay and Western blot confirmatory serologies; this is imentation rate in this patient. Plain radiographs, like the one l,t (l, the primary means of diagnosing Lyme arthritis, although a shown fbr this patient, may demonstrate cht.rndrocaicinosis. : ET I second enzyme immunoassay can be used as a confirmatory Chonclrocalcinosis is seen as a thin white Iine that tracks below test. In addition, Borrelia burgdorJ'ert DNA can be detected the surface layer ol the cartilage because it represents CPP (, by polymerase chain reaction in synovial fluid, but this test deposition within the cartilage. A definitive diagnosis n'ould -t t offers no advantage to serologic testing. Randomized con- include aspiration of the joint fluid and the clemonstration of ag trolled trials have suggested that 90'1, of patients with Lyme CPP crystals, which are weakly positively biretiingent (blue Ul arthritis are eflectively treated with a 28-day course oforal when parallel to and yellow wher.r perpendicular kr the polar o antibiotics. Doxycycline is the most widely recommended izing axis of'an optical filter) and classically rhon.rboid shaped. vt = I E first choice in antibiotic treatment of Lyme arthritis. Treat- (lout flare (Option B) is a less likely diagnosis given the ment with a 28-day course of amoxicillin is an alternative involvement of the knee without current or prior lypical flrst line therapy. For patients whose arthritis improves but joint i nvolvement (first metatarsophalangeal joi nt, ibrefeet. does not completely resolve, a second 28-day course of the ankles, ancl flngers). The ll week duration of the previ- same antibiotic can be prescribed. For pregnant and lactat ous episodes is longer than that usually seen with gout ing women, tetracyclines are generally avoided in favor of a (t-z weeks). The normal serum urate level also makes gout p Iactam antibiotic. unlikely, although serum urate levels may occasionally lall Ceftriaxone (Option A) is unnecessary in most cases into the normal range during an acute flare. Monosodiun.r of Lyme arthritis because patients generally respond to oral urate crystals are needle shaped and negatively birefrin antibiotics. Celtriaxone is not the first choice for treatment gent uncler polarized light; they appear lellow when par of Lyme arthritis unless concomitant neurologic symptoms allel ar.rd blue when perpendicular to the polarizing a.xis. are present. It may be given for moderate to severe persistent lnfectious arthritis (Option C) is unlikely because the arthritis after the failure of oral antibiotics. patient has no fever or other systemic sympt(nns afler 10 A small subset of patients may have persistent arthri days, as well as a normal complete biood count. IIer history tis that suggests a reactive arthritis, which may respond of similar episodes also argues against in{ection as the cause. to immunosuppressive therapy. For moderate to severe Nevertheless. a1l patients with acute monoiirticular arthritis persistent symptoms, treatment with hydroxychloroquine should undergo synovial fluid analysis that inclucles a Gram (Option C) or methotrexate (Option D) may be appropriate, stain anct culture to help cxclude inf'ectious arthritis. but only after failure of treatment with oral and intravenous Ill.rcumatoid arlhritis (Option D) is not a likcly diag- antibiotics. nosis because the patient has monoarticular knee afihritis, without the symmetric joint involvement of hancls. wrists, or XEY POIXTS feet typical of rheumatoid arlhritis. Finally, chonclrocalcino- . All patients with Lyme arthritis should have positive sis is not a feature of rheumatoid arthritis. results on enzyme linked immunosorbent assay and Western blot confirmatory serologies; this is the XEV POI]ITI primary means of diagnosing Lyme arthritis, although . Acute calcium pyrophosphate cr).stal arthdtis (pszudogout) a second enzyme immunoassay can be used as a is characterized by the sudden onset of pain, warmth, ten- conflrmatory test. demess, and swelling of the affected joint, usually a knee . Ninety percent of patients with Lyme arthritis are or wrist; flares are typicaUy longer than those ofgout. effectively treated with a 28-day course of oral . Definitive diagnosis of calcium pyrophosphate crystal doxycycline or amoxicillin. arthritis would include aspiration of the joint fluid and demonstration of calcium plrophosphate crystals, Bibliography which are weakly positively birefringent (blue when Arvikar SL, Steere AC. Diagnosis and treatment of Lyme arthritis. Infect Dis parallel to and yellow when perpendicular to the polar Clin North Am. 2O15;29:269-80. IPMID: 259992231 doi:10.1016/j.idc.2015. izing axis of an optical filter) and rhomboid-shaped. 02.004 129

Answers and Critiques Bibliography underll-ing sl,stemic sclerosis, which is best treated rvith Rosenthal AK. Ryan l.M. Calcium pyrophosphate deposition disease. N Engl an ACE inhibitor. Captopril in particular is usefirl in this J Med. 2016;37.1:2575 tt.1. IPMID: 27355536] doi:10.1056'NEJMral511117 situation because it has a relatively short half lif'e and can be titrated rapidly to control blood pressure. Sclero Item 14 Answer: A derma renal crisis can occur in Iimited or dilluse cutaneous systemic sclerosis but is more common in dilluse dis Ed ucati o na I O bjective : Treat ankylosing spondylitis with ease. Risk factors ir.rclude recent onset of sl'sternic sclerosis a tumor necrosis factor inhibitor. ((4 years). diffuse skin discase, presence olanti RNA pol1, The most appropriate next treatment is etanercept (Option nrerase III antibodies, and recent use of glucocorticoids. A). This patient has a clear diagnosis of ankylosing spon- 'lhe pathophl,'siology is thought to be related to endothe dylitis (AS). and first line therapy with NSAIDs has failed. lial injury leading to vascular constriction. intirnal thick The American College of Rheumatolory (ACR) recommends ening. ar-rd fibrin deposition. 'uvith endothelin I plaf ing the use of a tumor necrosis factor (TNF) inhibitor after fail an important role in tl.ris process. Also inrportant in the la ure of a trial of at least two NSAIDs for 2 tri 4 weeks each. pathophl-siology is activatior.r of the renin angiotensin (D = or if NSAIDs cannot be tolerated. TNF inhibitors. such as irldosterone s),stemr interrupting this pathual'hrs been a ke1' UI etanercept (a fusion protein), adalimumab, or infliximab to therap)'. Manifestations ol scleroderma renal crisis are q, (monoclonal antibodies), can be used. The selection may those seen in patients with hypertensive emergenc)'. such CL depend on the presence of comorbid disease, such as uve as headache, encephalopathy, retinopath)'. acute kidney n itis or inflammatory bowel disease, where the monoclonal injury'. and heart tailure. Anemia. thrombocl'topenia, and lt antibodies would be more appropriate. 'fNF inhibitors have proteinuria are comnlon laboratory features. Evidence of been shown to be disease modiffing in AS. Interleukin-l7 rnicroangiopathic hernoll'tic anemia u'ith schistoc)'tes on rD UI inhibitors, such as secukinumab, could be used in patients the peripherai blood smear is a clue to the diagnosis. ACE in whom a TNF inhibitor fails or in whom a TNF inhibitor inhibitors are disease modiff ing agents ftrr this pcltentialll' may be contraindicated. The ACR conditionally recommends Iirtal complication, regardless of the serum creatinine level. TNF inhibitors over interleukin 17 inhibitors in patients in Patients may need telnporary diirlysis. and kidney function whom NSAIDs fail or who cannot tolerate NSAIDs. may improve during therapy' fbr up to 2.1 months after Nonbiologic disease-modifying antirheumatic drugs, presentation. Prophylactic use of'ACE inhibitors does not such as methotrexate (Option B) or sulfasalazine (Option prevent scleroderma renal crisis and n.ra1' lead to poorer D), have no ellicacy in axial disease and limited efflcacy in renal outcomes. peripheral disease. Treatment with sulfasalazine is recom Immunosuppressior.r has no role in modiff ing the mended primarily fbr patients with prominent peripheral course of scleroderma renal crisis. so neither intravenous arthritis and few or no axial skeleton symptoms and in these cyclophosphamide (Option B) nor intravenous methylpred patients, it may be more eflective than methotrexate. How nisolone (Option C) is indicated. Recent use ot glucocor ever, a TNF inhibitor may be the best option fbr these patients. ticoids is a risk factor fbr scleroderma renal crisisr tl.tus. The ACR strongly recommend against treatment with glucocorticoids should be avoided. systemic glucocorticoids, such as prednisone (Option C). Intravenous rnetoprolol (Option D) does not address Glucocorticoids have numerous adverse efl'ects. which are the pathophl,siolory of scleroderma renal crisis. p Blockers more likely to occur with higher doses and longer treatment, are generally not first line therapy ftir rnost causes of' and lower doses are not as efficacious as TNF inhibitors. hl,pertensive emergencies other than episcldes associ ated with eclampsiai preeclampsia, acute coronary syn XEY POIXI drome. and aortic dissection: in these cases, labetalol or o Tumor necrosis factor inhibitors are useful in patients a short acting agent such as esmolol is typically pref'erred with ankylosing spondylitis in whom NSAIDs have to metoprolol. failed or cannot be tolerated. f,EY POIilTS Bibliography . Patients with scleroderma renal crisis may exhibit Ward MM, Deodhar A, (lensler LS, et al. 2019 update of'the American College anemia, thrombocytopenia, proteinuria, and schisto- ol Rheumatolos//Spondylitis Association ol America/Spondyloarthritis cytes on the peripheral blood smear. Research and Treatment Network Recommendations fi)r the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. o ACE inhibitors (typically captopril) can be lifesaving Arthritis Rheunlatol. 2019:71:1599-1613. IPMID: l]t+3OO:lOl doi:10.1002 irrt.41042 in patients with scleroderma renal crisis, and dosages should be titrated to control blood pressure regardless of serum creatinine level.

Bibliography underll-ing sl,stemic sclerosis, which is best treated rvith Rosenthal AK. Ryan l.M. Calcium pyrophosphate deposition disease. N Engl an ACE inhibitor. Captopril in particular is usefirl in this J Med. 2016;37.1:2575 tt.1. IPMID: 27355536] doi:10.1056'NEJMral511117 situation because it has a relatively short half lif'e and can be titrated rapidly to control blood pressure. Sclero Item 14 Answer: A derma renal crisis can occur in Iimited or dilluse cutaneous systemic sclerosis but is more common in dilluse dis Ed ucati o na I O bjective : Treat ankylosing spondylitis with ease. Risk factors ir.rclude recent onset of sl'sternic sclerosis a tumor necrosis factor inhibitor. ((4 years). diffuse skin discase, presence olanti RNA pol1, The most appropriate next treatment is etanercept (Option nrerase III antibodies, and recent use of glucocorticoids. A). This patient has a clear diagnosis of ankylosing spon- 'lhe pathophl,'siology is thought to be related to endothe dylitis (AS). and first line therapy with NSAIDs has failed. lial injury leading to vascular constriction. intirnal thick The American College of Rheumatolory (ACR) recommends ening. ar-rd fibrin deposition. 'uvith endothelin I plaf ing the use of a tumor necrosis factor (TNF) inhibitor after fail an important role in tl.ris process. Also inrportant in the la ure of a trial of at least two NSAIDs for 2 tri 4 weeks each. pathophl-siology is activatior.r of the renin angiotensin (D = or if NSAIDs cannot be tolerated. TNF inhibitors. such as irldosterone s),stemr interrupting this pathual'hrs been a ke1' UI etanercept (a fusion protein), adalimumab, or infliximab to therap)'. Manifestations ol scleroderma renal crisis are q, (monoclonal antibodies), can be used. The selection may those seen in patients with hypertensive emergenc)'. such CL depend on the presence of comorbid disease, such as uve as headache, encephalopathy, retinopath)'. acute kidney n itis or inflammatory bowel disease, where the monoclonal injury'. and heart tailure. Anemia. thrombocl'topenia, and lt antibodies would be more appropriate. 'fNF inhibitors have proteinuria are comnlon laboratory features. Evidence of been shown to be disease modiffing in AS. Interleukin-l7 rnicroangiopathic hernoll'tic anemia u'ith schistoc)'tes on rD UI inhibitors, such as secukinumab, could be used in patients the peripherai blood smear is a clue to the diagnosis. ACE in whom a TNF inhibitor fails or in whom a TNF inhibitor inhibitors are disease modiff ing agents ftrr this pcltentialll' may be contraindicated. The ACR conditionally recommends Iirtal complication, regardless of the serum creatinine level. TNF inhibitors over interleukin 17 inhibitors in patients in Patients may need telnporary diirlysis. and kidney function whom NSAIDs fail or who cannot tolerate NSAIDs. may improve during therapy' fbr up to 2.1 months after Nonbiologic disease-modifying antirheumatic drugs, presentation. Prophylactic use of'ACE inhibitors does not such as methotrexate (Option B) or sulfasalazine (Option prevent scleroderma renal crisis and n.ra1' lead to poorer D), have no ellicacy in axial disease and limited efflcacy in renal outcomes. peripheral disease. Treatment with sulfasalazine is recom Immunosuppressior.r has no role in modiff ing the mended primarily fbr patients with prominent peripheral course of scleroderma renal crisis. so neither intravenous arthritis and few or no axial skeleton symptoms and in these cyclophosphamide (Option B) nor intravenous methylpred patients, it may be more eflective than methotrexate. How nisolone (Option C) is indicated. Recent use ot glucocor ever, a TNF inhibitor may be the best option fbr these patients. ticoids is a risk factor fbr scleroderma renal crisisr tl.tus. The ACR strongly recommend against treatment with glucocorticoids should be avoided. systemic glucocorticoids, such as prednisone (Option C). Intravenous rnetoprolol (Option D) does not address Glucocorticoids have numerous adverse efl'ects. which are the pathophl,siolory of scleroderma renal crisis. p Blockers more likely to occur with higher doses and longer treatment, are generally not first line therapy ftir rnost causes of' and lower doses are not as efficacious as TNF inhibitors. hl,pertensive emergencies other than episcldes associ ated with eclampsiai preeclampsia, acute coronary syn XEY POIXI drome. and aortic dissection: in these cases, labetalol or o Tumor necrosis factor inhibitors are useful in patients a short acting agent such as esmolol is typically pref'erred with ankylosing spondylitis in whom NSAIDs have to metoprolol. failed or cannot be tolerated. f,EY POIilTS Bibliography . Patients with scleroderma renal crisis may exhibit Ward MM, Deodhar A, (lensler LS, et al. 2019 update of'the American College anemia, thrombocytopenia, proteinuria, and schisto- ol Rheumatolos//Spondylitis Association ol America/Spondyloarthritis cytes on the peripheral blood smear. Research and Treatment Network Recommendations fi)r the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. o ACE inhibitors (typically captopril) can be lifesaving Arthritis Rheunlatol. 2019:71:1599-1613. IPMID: l]t+3OO:lOl doi:10.1002 irrt.41042 in patients with scleroderma renal crisis, and dosages should be titrated to control blood pressure regardless of serum creatinine level. tr Item 15 Answer: A Educational Objective: Treat scleroderma renal crisis. Bibliography Zanatta E, Polito P, lavaro M, et al.'lherapy ofscleroderma renal crisis: state The most appropriate intravenous treatment is captopril ot the art. Autoimmun Rev 2018;17:882-889. [PMID: 30005860] doi: (Option A). This patient has hypertensive crisis due to 10. l016ii.autrev2018.03.0l2

tr Item 15 Answer: A Educational Objective: Treat scleroderma renal crisis. Bibliography Zanatta E, Polito P, lavaro M, et al.'lherapy ofscleroderma renal crisis: state The most appropriate intravenous treatment is captopril ot the art. Autoimmun Rev 2018;17:882-889. [PMID: 30005860] doi: (Option A). This patient has hypertensive crisis due to 10. l016ii.autrev2018.03.0l2 130

I L t I t Answers and Cr i!iqg9_s 1 Item 17 Answer: B tr Item 16 Answer: D Educational Objective: Treat giant cell arteritis with a Ed u cati ona I O bj ective: Diagnose interstitial lung disease glucocorticoid-sparing agent. in a patient with rheumatoid arthritis. lhe most appropriate aclditional lreatment is tocilizumab The most likely cause of this patient's exertional dyspnea is (Option D). Ciant cell arteritis (GCA) is a medical enrer interstitial lung disease (lLD) (Option B). ILD may develop ger.rcy that requires inrmediate therap1,. the risk fbr sr-rdden in 507, of patients with rheumatoid arthritis, particularly and irreversible loss of vision is imminent in the absence those who are seropositive for rheumatoid factor and anti- :

lhe most appropriate aclditional lreatment is tocilizumab The most likely cause of this patient's exertional dyspnea is (Option D). Ciant cell arteritis (GCA) is a medical enrer interstitial lung disease (lLD) (Option B). ILD may develop ger.rcy that requires inrmediate therap1,. the risk fbr sr-rdden in 507, of patients with rheumatoid arthritis, particularly and irreversible loss of vision is imminent in the absence those who are seropositive for rheumatoid factor and anti- : ol appropriate treatnlerlt. Synrptoms ancl inflamrlabry cyclic citrullinated peptide antibodies; clinically signifl nrarkers usualll,' respond rapiclll to gluc<lc'orticoids. Hort, cant disease is seen in 10'1, of patients and contributes to ever. glucocorticoids ha'n'e nrany adverse eflects, ancl this excess mortality. ILD types include bronchiolitis, organiz patient will henefit Iron.r the adclition rit a glucocorticoid- ing pneumonia, nonspeci{ic interstitial pneumonia, and sparing agcnt. Generally acceptccl indicalior.rs for a gluco- usual interstitial pneumonia. Patients may also have pul U! corticoid sparing agent include the presence of comorbid monary rheumatoid nodules. Patients with rheumatoid o ET cliseases that are negatively afiected by glucocorticoids, arthritis treated with methotrexate are also at risk for development of glucocorticoici related adverse efI'ects, and possible drug-induced parenchymal lung disease. Nonpro- prolonged neecl lbr treiltnlent. 'lhis patient nreets all indi- ductive cough and dyspnea are the most common present t, !, cations firr a glucocrlrticoid sparing ager.rt. Tocilizumab, an ing symptoms of ILD. Lung examination findings vary and tr .! interleukin 6 blocker, is highly eflective for the treatnlent may be normal. Inspiratory fine crackles suggest intersti- Ut (l, of' GCA n,hen administered during glucocurticoid tapering tial flbrosis. The evaluation of suspected ILD includes full or :rs monotherapy fbllor,r,ing discontinuation of' gluco pulmonary function testing (restrictive physiologr), chest ta = E corticoids. 'lhe 2021 American College of Rheumatologr radiography (which may be normal), and high-resolution guidelines make a conditional recomme'nclation fbr gluco CT of the chest. corticoids r,r,ith tocilizumab over oral glucocorticoids alone Heart failure (Option A) is more common in patients in patients u,ith newly diagnosccl (iCA. with rheumatoid arthritis than in the general population Cyclophosphamide (Option A) is an immunosuplrres.- and may contribute to increased mortality. The increased sive agent used to treat systelnic virsculitis, such as gran prevalence of heart failure may be due to the presence of ulomatosis poll,ar.rgiitis. Its use and ellectiveness in inflammatory mediators, antirheumatic drug therapy, amy patients with "t'ith GCA are unproven, consistir.rg m:rinly of loidosis, or ischemic heart disease. Heart failure is unlikely l f'ew uncontrollecl studies involving small nunrbers of in the absence of jugular venous distention, edema, or an Sr. patients. Patients with rheumatoid arthritis rarely develop pul- A randomized clinical trill demonstrated that inflix monary arterial hypertension (Option C); that condition is imab (Option B) dicl not reduce the proportion of patients often associated with rheumatoid vasculitis. In patients with with GCA relapses or increase the proportirtn of'paticnts long-standing ILD, secondary pulmonary hypertension can uho could taper glucocorticoid dosages. Infliximab is not develop. Pulmonary arterial hypertension is unlikely in this an eflective agent fbr thc treatmellt of GCi\ and should not patient with a normal S, and normal jugular venous pres be used. sure. The presence ofinspiratory crackles also argues against Methotrexate (Option C) is a glucocorticoid sparing pulmonary arterial hypertension. drug used in the treatment of GCA. Evidence on its eflec Pleural disease (Option D) occurs in up to 5% of patients tiveness is mixed. ancl clinical eftect seerns to be r.nodest with rheumatoid arthritis; pleural effusions are exudative irt best. and can be large. Rheumatoid arthritis pleural effusions are characterized by low glucose, pH, and complement levels, XEY POIf,IS as well as elevated levels of total protein, rheumatoid factor, . Generally accepted indications for a glucocorticoid- and Iactate dehydrogenase. A pleural effusion large enough sparing agent in patients with giant cell arteritis to cause dyspnea on exertion is most likely to be associated include the presence of comorbid diseases that are with absent breath sounds and dullness to percussion over negatively affected by glucocorticoids, development of the affected lung fleld. Inspiratory crackles would not be glucocorticoid reiated adverse effects, and prolonged expected as the only flnding. need flor glucocorticoids. . Tocilizumab, an interleukin 6 blocker, is an effective XEY POIlITS glucocorticoid sparing agent in the treatment of giant r Interstitial lung disease may develop in 50% of cell arteritis. patients with rheumatoid arthritis; clinically signifi- cant disease is seen in 10% of patients and contributes to excess mortality. Bibliography Maz M, Chung SA. Abril A. et al. 2021 American College ol Rheumatolory/ . Nonproductive cough and dyspnea are the most com- Vasculitis lbundation guideline for the management ol giant cell arteritis mon presenting symptoms of interstitial lung disease. and Takayasu arteritis. Arthritis Rheumatol. 2021. IPMID: 342358841

ol appropriate treatnlerlt. Synrptoms ancl inflamrlabry cyclic citrullinated peptide antibodies; clinically signifl nrarkers usualll,' respond rapiclll to gluc<lc'orticoids. Hort, cant disease is seen in 10'1, of patients and contributes to ever. glucocorticoids ha'n'e nrany adverse eflects, ancl this excess mortality. ILD types include bronchiolitis, organiz patient will henefit Iron.r the adclition rit a glucocorticoid- ing pneumonia, nonspeci{ic interstitial pneumonia, and sparing agcnt. Generally acceptccl indicalior.rs for a gluco- usual interstitial pneumonia. Patients may also have pul U! corticoid sparing agent include the presence of comorbid monary rheumatoid nodules. Patients with rheumatoid o ET cliseases that are negatively afiected by glucocorticoids, arthritis treated with methotrexate are also at risk for development of glucocorticoici related adverse efI'ects, and possible drug-induced parenchymal lung disease. Nonpro- prolonged neecl lbr treiltnlent. 'lhis patient nreets all indi- ductive cough and dyspnea are the most common present t, !, cations firr a glucocrlrticoid sparing ager.rt. Tocilizumab, an ing symptoms of ILD. Lung examination findings vary and tr .! interleukin 6 blocker, is highly eflective for the treatnlent may be normal. Inspiratory fine crackles suggest intersti- Ut (l, of' GCA n,hen administered during glucocurticoid tapering tial flbrosis. The evaluation of suspected ILD includes full or :rs monotherapy fbllor,r,ing discontinuation of' gluco pulmonary function testing (restrictive physiologr), chest ta = E corticoids. 'lhe 2021 American College of Rheumatologr radiography (which may be normal), and high-resolution guidelines make a conditional recomme'nclation fbr gluco CT of the chest. corticoids r,r,ith tocilizumab over oral glucocorticoids alone Heart failure (Option A) is more common in patients in patients u,ith newly diagnosccl (iCA. with rheumatoid arthritis than in the general population Cyclophosphamide (Option A) is an immunosuplrres.- and may contribute to increased mortality. The increased sive agent used to treat systelnic virsculitis, such as gran prevalence of heart failure may be due to the presence of ulomatosis poll,ar.rgiitis. Its use and ellectiveness in inflammatory mediators, antirheumatic drug therapy, amy patients with "t'ith GCA are unproven, consistir.rg m:rinly of loidosis, or ischemic heart disease. Heart failure is unlikely l f'ew uncontrollecl studies involving small nunrbers of in the absence of jugular venous distention, edema, or an Sr. patients. Patients with rheumatoid arthritis rarely develop pul- A randomized clinical trill demonstrated that inflix monary arterial hypertension (Option C); that condition is imab (Option B) dicl not reduce the proportion of patients often associated with rheumatoid vasculitis. In patients with with GCA relapses or increase the proportirtn of'paticnts long-standing ILD, secondary pulmonary hypertension can uho could taper glucocorticoid dosages. Infliximab is not develop. Pulmonary arterial hypertension is unlikely in this an eflective agent fbr thc treatmellt of GCi\ and should not patient with a normal S, and normal jugular venous pres be used. sure. The presence ofinspiratory crackles also argues against Methotrexate (Option C) is a glucocorticoid sparing pulmonary arterial hypertension. drug used in the treatment of GCA. Evidence on its eflec Pleural disease (Option D) occurs in up to 5% of patients tiveness is mixed. ancl clinical eftect seerns to be r.nodest with rheumatoid arthritis; pleural effusions are exudative irt best. and can be large. Rheumatoid arthritis pleural effusions are characterized by low glucose, pH, and complement levels, XEY POIf,IS as well as elevated levels of total protein, rheumatoid factor, . Generally accepted indications for a glucocorticoid- and Iactate dehydrogenase. A pleural effusion large enough sparing agent in patients with giant cell arteritis to cause dyspnea on exertion is most likely to be associated include the presence of comorbid diseases that are with absent breath sounds and dullness to percussion over negatively affected by glucocorticoids, development of the affected lung fleld. Inspiratory crackles would not be glucocorticoid reiated adverse effects, and prolonged expected as the only flnding. need flor glucocorticoids. . Tocilizumab, an interleukin 6 blocker, is an effective XEY POIlITS glucocorticoid sparing agent in the treatment of giant r Interstitial lung disease may develop in 50% of cell arteritis. patients with rheumatoid arthritis; clinically signifi- cant disease is seen in 10% of patients and contributes to excess mortality. Bibliography Maz M, Chung SA. Abril A. et al. 2021 American College ol Rheumatolory/ . Nonproductive cough and dyspnea are the most com- Vasculitis lbundation guideline for the management ol giant cell arteritis mon presenting symptoms of interstitial lung disease. and Takayasu arteritis. Arthritis Rheumatol. 2021. IPMID: 342358841 131

Answers and Critiques Bibliography Bibliography Spagnolo p Lee JS, Sverzellati N, et al. The lung in rheumatoid arthritis: MerolaJF, Wu S. Han J, et al. Psoriasis, psoriatic arthritis and risk ofgout focus on interstitial lung disease. Arthritis Rheumatol. 2018;70:1544 in US men and women. Ann Rheum Dis. 2015:74:1495 500. [PMID: 1554. IPMID: 29806092] doi:10.1002/art.40574 246516201 doi:10.1136/annrheumdis 2014 205212

Bibliography Bibliography Spagnolo p Lee JS, Sverzellati N, et al. The lung in rheumatoid arthritis: MerolaJF, Wu S. Han J, et al. Psoriasis, psoriatic arthritis and risk ofgout focus on interstitial lung disease. Arthritis Rheumatol. 2018;70:1544 in US men and women. Ann Rheum Dis. 2015:74:1495 500. [PMID: 1554. IPMID: 29806092] doi:10.1002/art.40574 246516201 doi:10.1136/annrheumdis 2014 205212 tr Item 18 Answer: A Educational Objective: Diagnose gouty arthritis in a Item 19 Answer: B Educational Objective: Assess a patient with systemic patient with psoriasis and psoriatic arthritis. lupus erythematosus for cardiovascular risk. 'lhe most likely diagnosis is gout!' arthritis (Option A). This The most appropriate assessment to perform is for cardio- patient has an acute painful joint in the setting ofpsoriasis vascular disease risk (Option B). Patients with systemic and psoriatic arthritis (PsA). Hyperuricemia and gout are lupus erythematosus (SLE) have a high risk for cardiovascu D comorbidities associated lvith psoriasis. It is thought that lar disease compared with the general population, including ul the rapid tllrnover of skin cells in patients r,r'ith psoriasis a greater risk for myocardial infarction and ischemic stroke, E drives protein metabolism and increases serum urate levels. .D even in younger patients. Control of the underlying SLE tt A recent study oftwo large cohorts, the Health Professionals may be the most important way to minimize this risk, but o, tbllorv up Study ancl the Nurses' Health Study: fbund that patients should also be screened for other modifiable risk EL the risk fbr gout in participar.rts with psoriasis rvas almost factors. Assessment of diet, exercise, hypertension, diabetes r.t double that of participants witl.rout psoriasis; the risk was mellitus, smoking, and potentially lipids are indicated in flve times greater in participants nith PsA than in those patients, including young patients, with SLE. .ct n,ithout either conclition. This Ope of joint preser.rtation Patientswith SLE have a higheroverall riskformalignan- rD t^ (acute swelling, severe pain. unwillingness to flex or extend cies (particularly hematologic) but not cancer-related mor joint) can have one ol three ciuses: infectious arthritis. tality; the risk for non Hodgkin lyrnphoma is at least two to hemarthrosis. or crystalline arthritis. Joint fluid analysis is three times higher than in the general population. There may necessary to rnake thc correct diagnosis. be an increased risk for cancers ofthe lulva, cervix, lung, thy- Inf'ectious arthritis (Option B) is always possible in roid, and possibly liver. Malignancy risk in SLE is tied to the a patient with acute monoarticular arthritis. particu- use of immunosuppressive agents. Breast cancer risk (Option larly r,lhen the knee is involved. Hortever. r,r'ith intectious A) does not seem to be increased, but appropriate screening arthritis, f'ever is common, synovial fluid leukocyte counts should be initiated in the future as indicated by guidelines. rrlnge f'rom 50.000 to 100.0001pL (50 100 x 10'),'L) or In patients with SLE, normocytic, normochromic higher. and the Gram stain is positive in up to 50')i, of inflammatory anemia is common; autoimmune hemoll'tic patients. In PsA. joint infection is much less common than anemia occurs in approximately 10% and correlates with gouty arthritis. SLE activity. Lymphopenia/leukopenia is also common but Patients r,l,ith osteoarthritis (Option C) usually usually mild. Thrombocltopenia occurs in 30% to 50% of describe an insidious onset of intermittent symptoms, patients with SLE, and approximately 10'7, develop severe which become more persistent and severe over time. thrombocytopenia (platelet count <50,000/pL [50 x 10e/L]) Patients with osteoarthritis generally do not have systemic in isolation or in conjunction with hemolytic anemia. Iron features. 'lhe lvpical synovial tluid analysis rtill shor,v 200 overload syndromes (Option C), such as hemochromatosis, to 2000 lcukocytes'pl. (O.Z-Z.O x l0q'L). 'lhis patient's joint are not a morbidity of SLE unless associated with increased fluid count of 40,000 leukocytesi gL (40 x 10"/l-) with 90'7,, transfusion requirements. neutrophils indicatc's that he has an inflammatory arthritis. Some patients with SLE or overlap syndromes can have not osteoarthritis. interstitial lung disease that would warrant additional test Flares ol PsA (Option D) are not typically this pain- ing with pulmonary function testing or chest CT. However, ful and usually develop more skrwly. In addition. an acute this patient is asymptomatic, and assessment for pulmonary arthritis of this magnitude is unlikely in someone \{,ith PsA disease (Option D) is not warranted. rtho is receiving methotrexate and has no other afl'ected joints. Acute monoarticular arthritis morc strongly suggests XEY POIXIS hemarthrosis. infectious arthritis, or gout. o Patients with systemic lupus erythematosus have a high risk for cardiovascular disease compared with I(EY POITIS the general population, including a greater risk for o Acute monoarticular arthritis is due to infectious myocardial infarction and ischemic stroke, even in arthritis, hemarthrosis, or acute crystalline arthritis; younger patients. joint fluid analysis is necessary to make the correct o Control of the underlying systemic lupus erythemato- diagnosis. sus may be the most important way to minimize car- . Hlperuricemia and gout are comorbidities associated diovascular risk, but patients should also be screened with psoriasis and psoriatic arthritis. for other modifiable risk factors.

tr Item 18 Answer: A Educational Objective: Diagnose gouty arthritis in a Item 19 Answer: B Educational Objective: Assess a patient with systemic patient with psoriasis and psoriatic arthritis. lupus erythematosus for cardiovascular risk. 'lhe most likely diagnosis is gout!' arthritis (Option A). This The most appropriate assessment to perform is for cardio- patient has an acute painful joint in the setting ofpsoriasis vascular disease risk (Option B). Patients with systemic and psoriatic arthritis (PsA). Hyperuricemia and gout are lupus erythematosus (SLE) have a high risk for cardiovascu D comorbidities associated lvith psoriasis. It is thought that lar disease compared with the general population, including ul the rapid tllrnover of skin cells in patients r,r'ith psoriasis a greater risk for myocardial infarction and ischemic stroke, E drives protein metabolism and increases serum urate levels. .D even in younger patients. Control of the underlying SLE tt A recent study oftwo large cohorts, the Health Professionals may be the most important way to minimize this risk, but o, tbllorv up Study ancl the Nurses' Health Study: fbund that patients should also be screened for other modifiable risk EL the risk fbr gout in participar.rts with psoriasis rvas almost factors. Assessment of diet, exercise, hypertension, diabetes r.t double that of participants witl.rout psoriasis; the risk was mellitus, smoking, and potentially lipids are indicated in flve times greater in participants nith PsA than in those patients, including young patients, with SLE. .ct n,ithout either conclition. This Ope of joint preser.rtation Patientswith SLE have a higheroverall riskformalignan- rD t^ (acute swelling, severe pain. unwillingness to flex or extend cies (particularly hematologic) but not cancer-related mor joint) can have one ol three ciuses: infectious arthritis. tality; the risk for non Hodgkin lyrnphoma is at least two to hemarthrosis. or crystalline arthritis. Joint fluid analysis is three times higher than in the general population. There may necessary to rnake thc correct diagnosis. be an increased risk for cancers ofthe lulva, cervix, lung, thy- Inf'ectious arthritis (Option B) is always possible in roid, and possibly liver. Malignancy risk in SLE is tied to the a patient with acute monoarticular arthritis. particu- use of immunosuppressive agents. Breast cancer risk (Option larly r,lhen the knee is involved. Hortever. r,r'ith intectious A) does not seem to be increased, but appropriate screening arthritis, f'ever is common, synovial fluid leukocyte counts should be initiated in the future as indicated by guidelines. rrlnge f'rom 50.000 to 100.0001pL (50 100 x 10'),'L) or In patients with SLE, normocytic, normochromic higher. and the Gram stain is positive in up to 50')i, of inflammatory anemia is common; autoimmune hemoll'tic patients. In PsA. joint infection is much less common than anemia occurs in approximately 10% and correlates with gouty arthritis. SLE activity. Lymphopenia/leukopenia is also common but Patients r,l,ith osteoarthritis (Option C) usually usually mild. Thrombocltopenia occurs in 30% to 50% of describe an insidious onset of intermittent symptoms, patients with SLE, and approximately 10'7, develop severe which become more persistent and severe over time. thrombocytopenia (platelet count <50,000/pL [50 x 10e/L]) Patients with osteoarthritis generally do not have systemic in isolation or in conjunction with hemolytic anemia. Iron features. 'lhe lvpical synovial tluid analysis rtill shor,v 200 overload syndromes (Option C), such as hemochromatosis, to 2000 lcukocytes'pl. (O.Z-Z.O x l0q'L). 'lhis patient's joint are not a morbidity of SLE unless associated with increased fluid count of 40,000 leukocytesi gL (40 x 10"/l-) with 90'7,, transfusion requirements. neutrophils indicatc's that he has an inflammatory arthritis. Some patients with SLE or overlap syndromes can have not osteoarthritis. interstitial lung disease that would warrant additional test Flares ol PsA (Option D) are not typically this pain- ing with pulmonary function testing or chest CT. However, ful and usually develop more skrwly. In addition. an acute this patient is asymptomatic, and assessment for pulmonary arthritis of this magnitude is unlikely in someone \{,ith PsA disease (Option D) is not warranted. rtho is receiving methotrexate and has no other afl'ected joints. Acute monoarticular arthritis morc strongly suggests XEY POIXIS hemarthrosis. infectious arthritis, or gout. o Patients with systemic lupus erythematosus have a high risk for cardiovascular disease compared with I(EY POITIS the general population, including a greater risk for o Acute monoarticular arthritis is due to infectious myocardial infarction and ischemic stroke, even in arthritis, hemarthrosis, or acute crystalline arthritis; younger patients. joint fluid analysis is necessary to make the correct o Control of the underlying systemic lupus erythemato- diagnosis. sus may be the most important way to minimize car- . Hlperuricemia and gout are comorbidities associated diovascular risk, but patients should also be screened with psoriasis and psoriatic arthritis. for other modifiable risk factors. 132

Answers and Critiques Bibliography t(EY POIilIS (onttnaed) Andrades C. Fuego C. Manrique Ariia S. et al. Management ofcardiovascular o Laboratory testing and imaging are usually not neces- risk in systemic lupus erythematosus: a systemxtic review. Lupus. 2017i 26:1407 7419. [PMID: 284571 97] sary to diagnose osteoarthritis but are helpful if other causes of arthritis are being considered or to help Item 20 Answer: E define the safety of potential therapies. Educational Objective: Diagnose osteoarthritis with history and physical examination. Bibliography Martel-PetletierJ, Maheu E, Pelletier JR et al. A new decision tree fbr diag No additional laboratory studies are needed (Option E). nosis of osteoarthritis in primary care: international consensus of Osteoarthritis (OA) diagnosis is based on history and physi experts. Aging Ctin Exp Res. 2019:31:19 30. IPMID, 305395'111 cal examination; radiography is conflrmatory but may not be necessary. In early OA, clinical flndings may not be accompa vt nied by radiographic changes; conversely, some patients with prominent radiographic changes may have minimal or no symptoms. Patients with OA are typically older than 50 years Item 21 Answer: C Educational Objective: Treat tophaceous gout in a tr c, ET

cal examination; radiography is conflrmatory but may not be necessary. In early OA, clinical flndings may not be accompa vt nied by radiographic changes; conversely, some patients with prominent radiographic changes may have minimal or no symptoms. Patients with OA are typically older than 50 years Item 21 Answer: C Educational Objective: Treat tophaceous gout in a tr c, ET patient with contraindications to allopurinol. of age; diagnosis at an earlier age should prompt inquiry into |., a history of previous joint damage, endocrine or metabolic 'lhe most appropriate additional trcatment is f'ebuxtlstat -,- disorders, or a genetic proclivity fbr early disease. Joints most (Option C). this patient has tophaceous gout, which is an |! tt commonly affected are the hands (first carpometacarpal inclication fbr urate lor,r,ering therap!: ll.re American Gtllege o joints, distal and proximal interphalangeal joints), feet (first of' Rheumatology (ACR) strongly recotnmencls treatntent la = metatarsophalangeal joint and mid foot), knees, hips, and with allopurinol (Option A) as the prel'erred first line agent spine, but the distribution varies. Localized OA, in which a over all other uratc lor,r,ering therapies, includitrg in patients single joint is affected, is more often a consequence of injury u,ith moderate'to severe chronic kidney clisease (CKD) or joint asymmetry and often occurs in weight-bearing joints (stage >3). \,\,ith appropriate dose adjustment. Ilort'ever. she (hip or knee). Furthermore, this patient has noninflamma ciinnot take allopurinol because of a history ol a rasl.r rt'ith tory arthritis, as evidenced by minimal morning stiffness previous use. An uncommon but scrious complication of' and no evidence of warmth, soft tissue swelling, or effusion; alkrpurinol is a hypersensitivity reaction. which may lead these lindings further support the diagnosis of OA. Addi to organ dysfunction and death. 'lherefore. allopurinol is tional tests would be helpful if other causes of arthritis were not appropriate, and therapy with fbbuxostat. a nonpurine, being considered or would aid in decisions about therapeutic noncompetitive xanthine oxidase inhibitor. is indicltecl. options. No additional tests are needed in this patient. Beciruse only 3'l'" of fbbuxostat is renally cleared, it n-ray be The cardinal signs of inflammation are pain, erythema, uscd in patients with CKD without dose adjustment if the swelling, and warmth; with the exception of pain, non estimated glomerular filtration rate is 30 to 60 ml-/mini inflammatory conditions usually lack these features. This 1.7i1 m). The starting I'ebuxostat dosage is ,10 mgrd, r'r,hich patient's history and clinical flndings do not suggest inflam nr:ry be increased to up to itO mg/d if needed on the basis of matory arthritis, in particular inflammatory autoimmune scrum urate lelel. Achieving and n-raintaining a serum urate disorders (such as systemic lupus erythematosus or rheuma target ollcss than 6.0 mg,'dl. (0.35 mmol, L) are strongly rec- toid arthritis). Evaluation for these conditions with testing ommended Ibr all patients receiving urate-lowering thcrapy. of antinuclear antibodies (Option A) or rheumatoid factor Prophyiaxis with prednisone should be continued along (Option B) is not needed. u,ith febuxostat for 3 to 6 months or until the serum urate Lyme arthritis is an infectious arthritis with an inflam level is at target. matory synovial response. It is usually monoarticular and Colchicine (Option B) is used lbr treatir.rg acute gout occasionally polyarticular. This patient has polyarticular flares and fbr long term prevention of flares while urate arthritis and does not have flndings suggestive of inflam- lowering therapy is begun. Colchicine dcles not aftect serum matory arthritis; serologic testing for Borrelia burgdorferi urite concentrations. Colchicine requires dose adjustmcnt (Option C) is unnecessary. fbr kidney disease and rthen it is takcn concurrently rt'ith Synovial fluid analysis (Option D) is helpful if effusion drugs that aflbct its n.retabolism. is present and there is concem about other causes of arthri 'Ihe ACR strongll, recommends against pegloticase tis, such as concurrent crystal arthritis, infections, or other (Option D) as a first line urale lor,vering therapy: Pegloticase inflammatory causes. This patient does not meet these criteria. is indicated in paticnts in whom allopurinol and febuxostat have failed or cannot be tolerated. It is inlravenously adtnin - t(EY PO!ltrS istered and expensive and thus should be reserved lbr an o The cardinal signs of inflammation are pain, ery- appropriilte clinical setting. Ircbuxostat has not lailed in this thema, swelling, and warmth; with the exception of piitientr thus. pegloticase is not indicated. pain, noninflammatory conditions such as osteoar- Probenccid (Option E) lolvers serum urate by bbck thritis usually lack these features. ing uric acid reabsorption in the kiclney proximal tubule. (continued) 'll-re ACR strongly recommends allopurinol or tebuxostat

patient with contraindications to allopurinol. of age; diagnosis at an earlier age should prompt inquiry into |., a history of previous joint damage, endocrine or metabolic 'lhe most appropriate additional trcatment is f'ebuxtlstat -,- disorders, or a genetic proclivity fbr early disease. Joints most (Option C). this patient has tophaceous gout, which is an |! tt commonly affected are the hands (first carpometacarpal inclication fbr urate lor,r,ering therap!: ll.re American Gtllege o joints, distal and proximal interphalangeal joints), feet (first of' Rheumatology (ACR) strongly recotnmencls treatntent la = metatarsophalangeal joint and mid foot), knees, hips, and with allopurinol (Option A) as the prel'erred first line agent spine, but the distribution varies. Localized OA, in which a over all other uratc lor,r,ering therapies, includitrg in patients single joint is affected, is more often a consequence of injury u,ith moderate'to severe chronic kidney clisease (CKD) or joint asymmetry and often occurs in weight-bearing joints (stage >3). \,\,ith appropriate dose adjustment. Ilort'ever. she (hip or knee). Furthermore, this patient has noninflamma ciinnot take allopurinol because of a history ol a rasl.r rt'ith tory arthritis, as evidenced by minimal morning stiffness previous use. An uncommon but scrious complication of' and no evidence of warmth, soft tissue swelling, or effusion; alkrpurinol is a hypersensitivity reaction. which may lead these lindings further support the diagnosis of OA. Addi to organ dysfunction and death. 'lherefore. allopurinol is tional tests would be helpful if other causes of arthritis were not appropriate, and therapy with fbbuxostat. a nonpurine, being considered or would aid in decisions about therapeutic noncompetitive xanthine oxidase inhibitor. is indicltecl. options. No additional tests are needed in this patient. Beciruse only 3'l'" of fbbuxostat is renally cleared, it n-ray be The cardinal signs of inflammation are pain, erythema, uscd in patients with CKD without dose adjustment if the swelling, and warmth; with the exception of pain, non estimated glomerular filtration rate is 30 to 60 ml-/mini inflammatory conditions usually lack these features. This 1.7i1 m). The starting I'ebuxostat dosage is ,10 mgrd, r'r,hich patient's history and clinical flndings do not suggest inflam nr:ry be increased to up to itO mg/d if needed on the basis of matory arthritis, in particular inflammatory autoimmune scrum urate lelel. Achieving and n-raintaining a serum urate disorders (such as systemic lupus erythematosus or rheuma target ollcss than 6.0 mg,'dl. (0.35 mmol, L) are strongly rec- toid arthritis). Evaluation for these conditions with testing ommended Ibr all patients receiving urate-lowering thcrapy. of antinuclear antibodies (Option A) or rheumatoid factor Prophyiaxis with prednisone should be continued along (Option B) is not needed. u,ith febuxostat for 3 to 6 months or until the serum urate Lyme arthritis is an infectious arthritis with an inflam level is at target. matory synovial response. It is usually monoarticular and Colchicine (Option B) is used lbr treatir.rg acute gout occasionally polyarticular. This patient has polyarticular flares and fbr long term prevention of flares while urate arthritis and does not have flndings suggestive of inflam- lowering therapy is begun. Colchicine dcles not aftect serum matory arthritis; serologic testing for Borrelia burgdorferi urite concentrations. Colchicine requires dose adjustmcnt (Option C) is unnecessary. fbr kidney disease and rthen it is takcn concurrently rt'ith Synovial fluid analysis (Option D) is helpful if effusion drugs that aflbct its n.retabolism. is present and there is concem about other causes of arthri 'Ihe ACR strongll, recommends against pegloticase tis, such as concurrent crystal arthritis, infections, or other (Option D) as a first line urale lor,vering therapy: Pegloticase inflammatory causes. This patient does not meet these criteria. is indicated in paticnts in whom allopurinol and febuxostat have failed or cannot be tolerated. It is inlravenously adtnin - t(EY PO!ltrS istered and expensive and thus should be reserved lbr an o The cardinal signs of inflammation are pain, ery- appropriilte clinical setting. Ircbuxostat has not lailed in this thema, swelling, and warmth; with the exception of piitientr thus. pegloticase is not indicated. pain, noninflammatory conditions such as osteoar- Probenccid (Option E) lolvers serum urate by bbck thritis usually lack these features. ing uric acid reabsorption in the kiclney proximal tubule. (continued) 'll-re ACR strongly recommends allopurinol or tebuxostat 133

Answers and Critiq_ues tr CONI over probenecid fbr urate-lowering therapy in patients rt,ith moderate to severe CKD. Probenecid is not cftective in patients with CKD (estimatecl glomerular filtration rate iirtery stenosis leading to hypertension, as r,rell as mesenteric ischemia. it affects ntedium-sized vessels and so lr,ould not : : invoive the subclavian artery. ln addition, the most common <50 mLiminr1.73 nt2) and is contraindicated in patients \\,ith n.ranifbstations of PAN are cutaneous findings (such as pal I nephrolithiasis. pable purpura) and neurologic involvernent. Roughly 7O"/,, of patients \,vith PAN have neurologic disease. most commonly \ r(lY P0rilIS . Febuxostat is recommended for patients with indica- rnanifesting as mononeuritis multiplex. Unlike in Takayasu \ arteritis, pulselessness is r.rot chlmcteristic of PAN. tions for urate-lowering therapy who have contraindi- cations to allopurinol therapy. t(EY P0ilrIS 1

: invoive the subclavian artery. ln addition, the most common <50 mLiminr1.73 nt2) and is contraindicated in patients \\,ith n.ranifbstations of PAN are cutaneous findings (such as pal I nephrolithiasis. pable purpura) and neurologic involvernent. Roughly 7O"/,, of patients \,vith PAN have neurologic disease. most commonly \ r(lY P0rilIS . Febuxostat is recommended for patients with indica- rnanifesting as mononeuritis multiplex. Unlike in Takayasu \ arteritis, pulselessness is r.rot chlmcteristic of PAN. tions for urate-lowering therapy who have contraindi- cations to allopurinol therapy. t(EY P0ilrIS 1 o Allopurinol and febuxostat are both strongly recom . Takayasu arteritis is a rare large vessel vasculitis caus i mended over probenecid as urate-lowering therapies ing inflammation and subsequent stenoses in the : D in patients with moderate-to-severe chronic kidney large arteries, including the aorta and its branches. Ut disease. o Manifestations of Takayasu arteritis can include limb E .D ischemia and associated diminished (or absent) u! Bibliography pulses, mesenteric ischemia, and hypertension due to o, FitzGerald JD. t)albeth N. Mikuls T, et al. 2020 American College of' renal artery stenosis. EL Rheunratolopgr guideline lbr the management ol gout. Arthritis Care Res rt (Hobrrken). 2O2O:72:741 760. Il,MID: 32391934] doi:10.1002iacr.24180 Bibliography .€l Keser C. Aksu K. l)iagnosis and diflerential diagnosis of large vessel vascu

o Allopurinol and febuxostat are both strongly recom . Takayasu arteritis is a rare large vessel vasculitis caus i mended over probenecid as urate-lowering therapies ing inflammation and subsequent stenoses in the : D in patients with moderate-to-severe chronic kidney large arteries, including the aorta and its branches. Ut disease. o Manifestations of Takayasu arteritis can include limb E .D ischemia and associated diminished (or absent) u! Bibliography pulses, mesenteric ischemia, and hypertension due to o, FitzGerald JD. t)albeth N. Mikuls T, et al. 2020 American College of' renal artery stenosis. EL Rheunratolopgr guideline lbr the management ol gout. Arthritis Care Res rt (Hobrrken). 2O2O:72:741 760. Il,MID: 32391934] doi:10.1002iacr.24180 Bibliography .€l Keser C. Aksu K. l)iagnosis and diflerential diagnosis of large vessel vascu .D Item 22 Answer: D litides. Rheum:ltol Int. 2019:i]9: 169 1 8.5. IPMI D: 3022]3271 doi: 10.1007r la EI Ed ucationa I Objective: Diagnose Takayasu arteritis. s00296 018 .11.57 ll

.D Item 22 Answer: D litides. Rheum:ltol Int. 2019:i]9: 169 1 8.5. IPMI D: 3022]3271 doi: 10.1007r la EI Ed ucationa I Objective: Diagnose Takayasu arteritis. s00296 018 .11.57 ll lhe most likely diagnosis is Takayasu arteritis (Option D). Item 23 Answer: A lhis rare large vessel vasculitis disproportkrnately affects Educational Objective: Treat refractory gout with young women ancl is much more conrmon in East Asia anakinra. (prev:rlence is 40imillion in Japan and up to B/million else where). Onset is usually indolent. rvith nonspecific symp The most appropriate treatment is anakinra (Option A). toms and signs presenting months to years before onset of' Anakinra is a recombinant human interleukin (lL)-1 recep frank vasculitis. The disease causes infiammation and subse tor antagonist. IL 1 cytokine activity is an important part quent stenoses in the large arterics, including the aorta and of the inflammatory process in acute gout. This patient has its branches. Manif'estations can include limb ischenria and a severe polyarticular gout flare likely provoked by diure associated diminished (or absent) pulses, mesenteric isch sis. In patients with severe refractory gout that has not emia, and hypertension due to renal aftery stenosis. Clues responded fully to other agents or in r,r'hom other agents are on exalnination include bruits over large vessels, absent contraindicated, anakinra may be used as ofllabel treat- pulses, discrepancy in blood pressure between limhs. and ment. It has a short half life and is given by subcutaneous hypertension. Laboratory findings indicate active systemic injection, 100 mg/d, usually for 3 to 5 days. The dose is inflammation but are not diagnostic. lmaging of the aorta decreased in patients with stage 4 or 5 chronic kidney dis and its branches is diagnostic: biopsy of an involvecl vessel ease (CKD). Canakinumab, a monoclonal antibody to ll-lp, is not fbasible. Thirty percent of patients can present with which blocks binding to the IL 1 receptor, is a longer-acting ocular ir-l,olvement, much olwhich is attributed to'lakayasu IL I inhibitor that may be used in refractory gout flares but retinopathy and hypertensive retir.ropathy. is more expensive than anakinra. this patient does not have the cutaneous features (pal Colchicine (Option B) is not appropriate because this pable purpura, digital ischemia, ulcers, necrosis, livedo patient has CKD and is receiving tacrolimus. Colchicine reticularis) that are the nrost conlmon symptoms ol cryo use should be avoided in patients taking concomitant cyto- globulinemic vasculitis (Option A), seen in mrtre than 90',1 chrome P450 3A and P glycoprotein inhibitors, particularly of patients. Other common manif'estations ir.rclude periph in the setting of CKD. Long term use of colchicine with tac cral ncuropathy and glomerulonephritis. rolimus or cyclosporine may result in neuromyopathy. Ciant cell arteritis (CCA) (Option B) is not present. Intra-articular, intravenous, or intramuscular gluco- Nearly all patients rvith GCA are older than 50 years. Absent corticoids (Option C) may be used to treat acute gout in pulses are typical in Takayasu arteritis but do not occur in hospitalized patients in whom both NSAIDs and colchicine GCA. In addition. GCA rarely aflbcts the descending aorla are contraindicated or those who cannot take medications and its branches: thus, renovascular hypertension tronr orally. This patient has not responded to appropriate doses renal ar1ery steltosis and nlesenteric ischemia dre not man of oral glucocorticoids, and his comorbidities (hypertension, ifbstations of GCA. hyperlipidemia, type 2 diabetes mellitus, heart failure) pres- This patient's findir.rgs do not suggest polyarteritis ent relative contraindications to additional or higher dose nodosa (PAN) (Option C). Although IAN can cause renal glucocorticoid use in any form. In addition, the polyarticular

lhe most likely diagnosis is Takayasu arteritis (Option D). Item 23 Answer: A lhis rare large vessel vasculitis disproportkrnately affects Educational Objective: Treat refractory gout with young women ancl is much more conrmon in East Asia anakinra. (prev:rlence is 40imillion in Japan and up to B/million else where). Onset is usually indolent. rvith nonspecific symp The most appropriate treatment is anakinra (Option A). toms and signs presenting months to years before onset of' Anakinra is a recombinant human interleukin (lL)-1 recep frank vasculitis. The disease causes infiammation and subse tor antagonist. IL 1 cytokine activity is an important part quent stenoses in the large arterics, including the aorta and of the inflammatory process in acute gout. This patient has its branches. Manif'estations can include limb ischenria and a severe polyarticular gout flare likely provoked by diure associated diminished (or absent) pulses, mesenteric isch sis. In patients with severe refractory gout that has not emia, and hypertension due to renal aftery stenosis. Clues responded fully to other agents or in r,r'hom other agents are on exalnination include bruits over large vessels, absent contraindicated, anakinra may be used as ofllabel treat- pulses, discrepancy in blood pressure between limhs. and ment. It has a short half life and is given by subcutaneous hypertension. Laboratory findings indicate active systemic injection, 100 mg/d, usually for 3 to 5 days. The dose is inflammation but are not diagnostic. lmaging of the aorta decreased in patients with stage 4 or 5 chronic kidney dis and its branches is diagnostic: biopsy of an involvecl vessel ease (CKD). Canakinumab, a monoclonal antibody to ll-lp, is not fbasible. Thirty percent of patients can present with which blocks binding to the IL 1 receptor, is a longer-acting ocular ir-l,olvement, much olwhich is attributed to'lakayasu IL I inhibitor that may be used in refractory gout flares but retinopathy and hypertensive retir.ropathy. is more expensive than anakinra. this patient does not have the cutaneous features (pal Colchicine (Option B) is not appropriate because this pable purpura, digital ischemia, ulcers, necrosis, livedo patient has CKD and is receiving tacrolimus. Colchicine reticularis) that are the nrost conlmon symptoms ol cryo use should be avoided in patients taking concomitant cyto- globulinemic vasculitis (Option A), seen in mrtre than 90',1 chrome P450 3A and P glycoprotein inhibitors, particularly of patients. Other common manif'estations ir.rclude periph in the setting of CKD. Long term use of colchicine with tac cral ncuropathy and glomerulonephritis. rolimus or cyclosporine may result in neuromyopathy. Ciant cell arteritis (CCA) (Option B) is not present. Intra-articular, intravenous, or intramuscular gluco- Nearly all patients rvith GCA are older than 50 years. Absent corticoids (Option C) may be used to treat acute gout in pulses are typical in Takayasu arteritis but do not occur in hospitalized patients in whom both NSAIDs and colchicine GCA. In addition. GCA rarely aflbcts the descending aorla are contraindicated or those who cannot take medications and its branches: thus, renovascular hypertension tronr orally. This patient has not responded to appropriate doses renal ar1ery steltosis and nlesenteric ischemia dre not man of oral glucocorticoids, and his comorbidities (hypertension, ifbstations of GCA. hyperlipidemia, type 2 diabetes mellitus, heart failure) pres- This patient's findir.rgs do not suggest polyarteritis ent relative contraindications to additional or higher dose nodosa (PAN) (Option C). Although IAN can cause renal glucocorticoid use in any form. In addition, the polyarticular 134

I Answers and Critiques t t I nature of his gout flare makes the use of intra articular r(EY P0tllTS glucocorticoid injection more challenging. . Topical NSAIDs are safe and effective for treatment of ! Naproxen, an NSAID (Option D), is contraindicated knee and hand osteoarthritis and should be consid in this patient because he has heart failure and is taking ered before oral NSAIDS. I Iow molecular weight heparin. NSAIDs can contribute to i worsening heart and kidney failure and increase the risk for . Oral NSAIDs are recommended for the treatment of i bleeding in patients taking anticoagulants. hand, knee, and hip osteoarthritis but should be avoided in patients with comorbidities, such as peptic TEY POIXT ulcer disease, cardiovascular disease, and chronic o In patients with severe refractory gout that has not kidney disease. responded fully to other agents or in whom other agents are contraindicated, anakinra, a recombinant Bibliography human interleukin l receptor antagonist, may be Kohsinski Sl.. Neogi 1', Hochberg MC. et lr1. 2019 An.rerican Oollege ol t,t (u used as off-label treatment. Rheumat(rogi 'Arthritis Founclation guideline fbr tlte manrgement {)l' osteoarthritis of the hand. hip, and knee. Arthritis Rheuntttol. 2020r ET 72:220 23:1. LPMID: :ll 908163 | doi:10.1 002/art.4l l.l2 Bibliography L' Fitz(ierald JD. Dalbeth N, Mikuls 1l et al. 2020 American College ot !t Rheumatology guideline fbr the management of gout. Arthritis (lare Res E I (l loboken).')O2O ;7 2:74 760. IPM ID: 3239 19:]41 doi : I 0. 1002iircr.24180 Item 25 Answer: C ag a

nature of his gout flare makes the use of intra articular r(EY P0tllTS glucocorticoid injection more challenging. . Topical NSAIDs are safe and effective for treatment of ! Naproxen, an NSAID (Option D), is contraindicated knee and hand osteoarthritis and should be consid in this patient because he has heart failure and is taking ered before oral NSAIDS. I Iow molecular weight heparin. NSAIDs can contribute to i worsening heart and kidney failure and increase the risk for . Oral NSAIDs are recommended for the treatment of i bleeding in patients taking anticoagulants. hand, knee, and hip osteoarthritis but should be avoided in patients with comorbidities, such as peptic TEY POIXT ulcer disease, cardiovascular disease, and chronic o In patients with severe refractory gout that has not kidney disease. responded fully to other agents or in whom other agents are contraindicated, anakinra, a recombinant Bibliography human interleukin l receptor antagonist, may be Kohsinski Sl.. Neogi 1', Hochberg MC. et lr1. 2019 An.rerican Oollege ol t,t (u used as off-label treatment. Rheumat(rogi 'Arthritis Founclation guideline fbr tlte manrgement {)l' osteoarthritis of the hand. hip, and knee. Arthritis Rheuntttol. 2020r ET 72:220 23:1. LPMID: :ll 908163 | doi:10.1 002/art.4l l.l2 Bibliography L' Fitz(ierald JD. Dalbeth N, Mikuls 1l et al. 2020 American College ot !t Rheumatology guideline fbr the management of gout. Arthritis (lare Res E I (l loboken).')O2O ;7 2:74 760. IPM ID: 3239 19:]41 doi : I 0. 1002iircr.24180 Item 25 Answer: C ag a Educational Objective: Diagnose cause ofjoint pain in a (I, patient with systemic lupus erythematosus. tt Item 24 Answer: D = The most appropriate management is MRI of the left hip Educational Objeaive: Treat osteoarthritis of the knees (Option C). Isolated new pain in the hip is an uncommon and hands with a topical NSAID. manifestation of a systemic lupus erythen-ratosus (SLE) flare. The most appropriate treatment is topical diclof'enac (Option A serious complication ol SLE is osteonecrosis, which most D). Topical NSAIDs, such as diclofbnac, are saf'e and ef fective commonly affects the hips but can also involve other large for treatment of knee and hand osteoarthritis (OA). For OA joints, and should be suspected when there is otherwise unex in those locations, the 2019 American College of Rheuma plained pain and/or reduced range of motion in a single joint. tolory (ACR)/Arthritis Foundation (AF) guideline suggests Long-term and high prednisone dosages (>zO mgld), severe/ that topical NSAIDs should be considered betbre oral NSAIDs active SLE. and vasculitis are all associated with increased because of f'ewer safety concerns. Topical NSAIDs are not risk. In patients with osteonecrosis, the plain radiograph can effective for hip OA and have limited eflicacy in OA of other remain normal for months after symptoms begin. MRI is the sites. modality of choice for sensitive evaluation of early disease, There is minimal benefit of opioid therapy, including with plain radiography uselul to diagnose and monitor later hydrocodone (Option A), for chronic pain control in patients stages. Small lesions can improve and resolve spontaneously, with OA. Opioids pose a high risk lor toxicity and depen but larger lesions usually lead to bony collapse and stmctural dence and should not be used to treat OA. sequelae. New hip pain in patients with a history of SLFI Oral NSAIDs, such as meloxicam (Option B). are an should prompt evaluation for osteonecrosis with N4RI. ACR/AF guideline recommended first-line treatment fbr If the patient were experiencing a more global flare hand, knee, and hip OA. However. they should be used or intolerance to her current medications, switching her cautiously in patients older than age 50 years and avoided maintenance therapy from azathioprine to mycophenolate in those with comorbidities, such as a history of peptic ulcer mof'etil (Option A) could be reasonable. However, she has disease or gastrointestinal bleeding, and in patients with no other signs of SLE activity, and so this change r.t'ould not hypertension, cardiovascular disease, or chronic kidney dis be appropriate. ease, as in this patient. This patient has a normal erythrcicyte sedimenta The ACR/AF guideline conditionally recommends topi tion rate, normal serum complement levels, and low titer cal capsaicin (Option C) for patients with knee OA and con anti double strandedDNA antibodies. Becausethispatient's ditionally recommends against topical capsaicin in patients isolated hip pain is unlikely to be caused by increased inflam with hand OA. The guideline notes limited data supporting mation. and because her disease is otherwise well controlled. the efficacy of topical capsaicin for knee OA. No direct evi increasing her prednisone dosage (Option B) would not be dence supports topical capsaicin in the treatment ol hand appropriate and could accelerate damage fiom osteonecrosis. OA, and eye contamination is possible when it is used on Physicat therapy (Option D) can be useful fbr reha the hands. bilitation of joint pain in SLE and may be helpful for this Other topical agents are available, such as lidocaine patient, but diagnosing the cause of this patient's hip pain (Option E) and methyl salicylate preparations, but they are should take priority because the diagnosis and stage of not as well studied or as eflicacious as topical NSAIDs. They osteonecrosis are important for determining the need for may be used as adjunctive measures. potential surgical intervention.

Educational Objective: Diagnose cause ofjoint pain in a (I, patient with systemic lupus erythematosus. tt Item 24 Answer: D = The most appropriate management is MRI of the left hip Educational Objeaive: Treat osteoarthritis of the knees (Option C). Isolated new pain in the hip is an uncommon and hands with a topical NSAID. manifestation of a systemic lupus erythen-ratosus (SLE) flare. The most appropriate treatment is topical diclof'enac (Option A serious complication ol SLE is osteonecrosis, which most D). Topical NSAIDs, such as diclofbnac, are saf'e and ef fective commonly affects the hips but can also involve other large for treatment of knee and hand osteoarthritis (OA). For OA joints, and should be suspected when there is otherwise unex in those locations, the 2019 American College of Rheuma plained pain and/or reduced range of motion in a single joint. tolory (ACR)/Arthritis Foundation (AF) guideline suggests Long-term and high prednisone dosages (>zO mgld), severe/ that topical NSAIDs should be considered betbre oral NSAIDs active SLE. and vasculitis are all associated with increased because of f'ewer safety concerns. Topical NSAIDs are not risk. In patients with osteonecrosis, the plain radiograph can effective for hip OA and have limited eflicacy in OA of other remain normal for months after symptoms begin. MRI is the sites. modality of choice for sensitive evaluation of early disease, There is minimal benefit of opioid therapy, including with plain radiography uselul to diagnose and monitor later hydrocodone (Option A), for chronic pain control in patients stages. Small lesions can improve and resolve spontaneously, with OA. Opioids pose a high risk lor toxicity and depen but larger lesions usually lead to bony collapse and stmctural dence and should not be used to treat OA. sequelae. New hip pain in patients with a history of SLFI Oral NSAIDs, such as meloxicam (Option B). are an should prompt evaluation for osteonecrosis with N4RI. ACR/AF guideline recommended first-line treatment fbr If the patient were experiencing a more global flare hand, knee, and hip OA. However. they should be used or intolerance to her current medications, switching her cautiously in patients older than age 50 years and avoided maintenance therapy from azathioprine to mycophenolate in those with comorbidities, such as a history of peptic ulcer mof'etil (Option A) could be reasonable. However, she has disease or gastrointestinal bleeding, and in patients with no other signs of SLE activity, and so this change r.t'ould not hypertension, cardiovascular disease, or chronic kidney dis be appropriate. ease, as in this patient. This patient has a normal erythrcicyte sedimenta The ACR/AF guideline conditionally recommends topi tion rate, normal serum complement levels, and low titer cal capsaicin (Option C) for patients with knee OA and con anti double strandedDNA antibodies. Becausethispatient's ditionally recommends against topical capsaicin in patients isolated hip pain is unlikely to be caused by increased inflam with hand OA. The guideline notes limited data supporting mation. and because her disease is otherwise well controlled. the efficacy of topical capsaicin for knee OA. No direct evi increasing her prednisone dosage (Option B) would not be dence supports topical capsaicin in the treatment ol hand appropriate and could accelerate damage fiom osteonecrosis. OA, and eye contamination is possible when it is used on Physicat therapy (Option D) can be useful fbr reha the hands. bilitation of joint pain in SLE and may be helpful for this Other topical agents are available, such as lidocaine patient, but diagnosing the cause of this patient's hip pain (Option E) and methyl salicylate preparations, but they are should take priority because the diagnosis and stage of not as well studied or as eflicacious as topical NSAIDs. They osteonecrosis are important for determining the need for may be used as adjunctive measures. potential surgical intervention. 135

: .: Answers and Critiques 1

: .: Answers and Critiques 1 TEY POITIS balanced by any benefits. Glucocorticoids are used in the ) o Patients with systemic lupus erythematosus, espe- treatment of Sjogren syndrome related systemic disease, such as interstitial lung disease, demyelinating diseases, cially those who have received high cumulative doses autoimmune hepatitis, and arthritis. It is recommended that ofglucocorticoids, are at risk for osteonecrosis, espe- glucocorticoids be used at the minimum dose and length of cially in the hip. time necessary to control active systemic disease. . MRI is the imaging modality of choice for suspected Rituximab (Option D) is not approved for the treat osteonecrosis at earlier stages of disease. ment of SjOgren syndrome and has shown no efficacy in treating oral dryness. It is appropriately prescribed to the Bibliography small subset ol patients with Sjogren syndrome who have Tse SM, Mok CC. Time trend and risk factors ofavascular bone necrosis in cryoglobulinemic vasculitis, but this patient has no signs patients with systenric lupus erythematosus. Lupus. 2017)6:715 722. of vasculitis (cutaneous ulcers, necrosis, palpable purpura, lPMtD,27831s.101 D livedo reticularis, or Raynaud phenomenon). ta € I( EY PO t TIS (D Item 26 Answer: A . Nonpharmacologic therapies are the first-line treat Ut o, Educational Obiective: Treat oral dryness of Sjdgren ment of Sjdgren syndrome-related oral dryness, a syndrome. including local moistening with water, sugar-free rl The most appropriate treatment is cevimeline (Option A). The acidic candies, lozenges, and/or mechanical stimu- patient's primary symptom is worsening oral dryness associ lants (such as sugar free chewing gum). ll E (D ated with Sjogren syndrome. There is no disease modifying o Pharmacologic stimulation of salvia with cevimeline l,I treatment to globally address manifestations of Sjogren or pilocarpine is indicated for oral dryness not relieved syndrome. and no medication alters the natural history of with nonpharmacologic therapies. chronic oral and ocular dryness. However, treatments can alleviate xerostomia and xerophthalmia. For oral dryness, Bibliography behavioral management may be enough to allay symptoms. Ramos Casals M, Brito Zenin P, Bombardieri S, et al; EULAR Sjogren This can include chewing sugarless gum or sucking on sugar Syndrome Task Force Group. EULAR recommendations for the manage ment of Sjogren's syndrome s,ith topical and systemic therapies. Ann free sour candies or lozenges to stimulate saliva, taking fre Rheum Dis. 2O2O:79:3 18. [PMID: 316727751 quent small sips of water, or using a spray bottle to moisten mucosal surfaces (to limit oral intake). Saliva substitutes are available commercially in the form of oral sprays, gels, and llem27 Answer: D rinses for more severe symptoms but are often not eflective. Educational Objective: Diagnose a secondary cause of EI Cevimeline, a cholinergic muscarinic agonist, stimulates acute calcium pyrophosphate crystal arthritis. salivation and is appropriate for moderate oral dryness that does not improve with the aforementioned interventions. The laboratory study most appropriate to perform next is Pilocarpine, another muscarinic agonist, is an equally effica- measurement of serum f'erritin (Option D). This patient's cious alternative to cevimeline. Cholinergic adverse efl'ects of recurrent acute flares of pain and srvelling in tl-re r,l'rists cevimeline and pilocarpine can include sweating, abdominal and third metacarpophalatrgeal (MCP) joint are consistent pain, nausea, flushing, and increased urination. Ocular dry with acute calcium pyrophosphate (CPP) crystal arthritis ness can be treated with over the counter remedies. such (pseudogout). 'lhe radiograph ol the MCP joints shows a as artificial tears (used during the day) and eye lubricants small hooked osteophyte of the lef t tl-rird MCP joint. Hooked (usually used betbre bedtime). Refractory or severe ocular osteophytes ol the second and third MCP joints are a charac dryness may be managed by using topical immunosuppressive teristic feature of CPP crystal arthritis. The radiograph of the containing drops, such as cyclosporine (a calcineurin inhib wrist shows calcification along the flbroarticular cartilage itor) or lifitegrast (an integrin inhibitor). collsistent u,ith chonclrocalcinosis. Synovial fluid analysis Hydroxychloroquine (Option B) does not alter the nat shows CPP crystals, nhich confirm the diagnosis. Given the ural history of Sjdgren syndrome or improve oral or ocular patient's age (<60 years), secondary causes ofCPP deposition dryness. This medication was widely favored by Sjogren (sr.rch as hyperparathyroidism. hypothyroidism, hypophos syndrome specialists until a randomized controlled trial phatasia, hypomagnesemia. and hemochromatosis) should published in2Ol4 demonstrated no efficacy for oral or ocular be sought. Iler norrnal comprehensive metabolic parlel, dryness or fatigue after 24 weeks compared with placebo. serunr magnesium level, and tlryroid stimulating hormone Hydroxychloroquine can, however, beneflt patients with level exclude all secondary causes other than henrochroma Sjogren syndrome who experience inflammatory arthritis or tosis. Measurements of serun-r f'erritin and transferrin satu subacute cutaneous lupus erythematosus. ration are appropriate screening tests for hemochromatosis. There is no indication to prescribe prednisone (Option Henrochromatosis typically presents in men age 40 years or C). Glucocorticoids will not improve oral or ocular dryness, older and in women generally after menopause because of and therefore the risks of prednisone in this patient are not slower iron accumulation in the premenopausal years.

TEY POITIS balanced by any benefits. Glucocorticoids are used in the ) o Patients with systemic lupus erythematosus, espe- treatment of Sjogren syndrome related systemic disease, such as interstitial lung disease, demyelinating diseases, cially those who have received high cumulative doses autoimmune hepatitis, and arthritis. It is recommended that ofglucocorticoids, are at risk for osteonecrosis, espe- glucocorticoids be used at the minimum dose and length of cially in the hip. time necessary to control active systemic disease. . MRI is the imaging modality of choice for suspected Rituximab (Option D) is not approved for the treat osteonecrosis at earlier stages of disease. ment of SjOgren syndrome and has shown no efficacy in treating oral dryness. It is appropriately prescribed to the Bibliography small subset ol patients with Sjogren syndrome who have Tse SM, Mok CC. Time trend and risk factors ofavascular bone necrosis in cryoglobulinemic vasculitis, but this patient has no signs patients with systenric lupus erythematosus. Lupus. 2017)6:715 722. of vasculitis (cutaneous ulcers, necrosis, palpable purpura, lPMtD,27831s.101 D livedo reticularis, or Raynaud phenomenon). ta € I( EY PO t TIS (D Item 26 Answer: A . Nonpharmacologic therapies are the first-line treat Ut o, Educational Obiective: Treat oral dryness of Sjdgren ment of Sjdgren syndrome-related oral dryness, a syndrome. including local moistening with water, sugar-free rl The most appropriate treatment is cevimeline (Option A). The acidic candies, lozenges, and/or mechanical stimu- patient's primary symptom is worsening oral dryness associ lants (such as sugar free chewing gum). ll E (D ated with Sjogren syndrome. There is no disease modifying o Pharmacologic stimulation of salvia with cevimeline l,I treatment to globally address manifestations of Sjogren or pilocarpine is indicated for oral dryness not relieved syndrome. and no medication alters the natural history of with nonpharmacologic therapies. chronic oral and ocular dryness. However, treatments can alleviate xerostomia and xerophthalmia. For oral dryness, Bibliography behavioral management may be enough to allay symptoms. Ramos Casals M, Brito Zenin P, Bombardieri S, et al; EULAR Sjogren This can include chewing sugarless gum or sucking on sugar Syndrome Task Force Group. EULAR recommendations for the manage ment of Sjogren's syndrome s,ith topical and systemic therapies. Ann free sour candies or lozenges to stimulate saliva, taking fre Rheum Dis. 2O2O:79:3 18. [PMID: 316727751 quent small sips of water, or using a spray bottle to moisten mucosal surfaces (to limit oral intake). Saliva substitutes are available commercially in the form of oral sprays, gels, and llem27 Answer: D rinses for more severe symptoms but are often not eflective. Educational Objective: Diagnose a secondary cause of EI Cevimeline, a cholinergic muscarinic agonist, stimulates acute calcium pyrophosphate crystal arthritis. salivation and is appropriate for moderate oral dryness that does not improve with the aforementioned interventions. The laboratory study most appropriate to perform next is Pilocarpine, another muscarinic agonist, is an equally effica- measurement of serum f'erritin (Option D). This patient's cious alternative to cevimeline. Cholinergic adverse efl'ects of recurrent acute flares of pain and srvelling in tl-re r,l'rists cevimeline and pilocarpine can include sweating, abdominal and third metacarpophalatrgeal (MCP) joint are consistent pain, nausea, flushing, and increased urination. Ocular dry with acute calcium pyrophosphate (CPP) crystal arthritis ness can be treated with over the counter remedies. such (pseudogout). 'lhe radiograph ol the MCP joints shows a as artificial tears (used during the day) and eye lubricants small hooked osteophyte of the lef t tl-rird MCP joint. Hooked (usually used betbre bedtime). Refractory or severe ocular osteophytes ol the second and third MCP joints are a charac dryness may be managed by using topical immunosuppressive teristic feature of CPP crystal arthritis. The radiograph of the containing drops, such as cyclosporine (a calcineurin inhib wrist shows calcification along the flbroarticular cartilage itor) or lifitegrast (an integrin inhibitor). collsistent u,ith chonclrocalcinosis. Synovial fluid analysis Hydroxychloroquine (Option B) does not alter the nat shows CPP crystals, nhich confirm the diagnosis. Given the ural history of Sjdgren syndrome or improve oral or ocular patient's age (<60 years), secondary causes ofCPP deposition dryness. This medication was widely favored by Sjogren (sr.rch as hyperparathyroidism. hypothyroidism, hypophos syndrome specialists until a randomized controlled trial phatasia, hypomagnesemia. and hemochromatosis) should published in2Ol4 demonstrated no efficacy for oral or ocular be sought. Iler norrnal comprehensive metabolic parlel, dryness or fatigue after 24 weeks compared with placebo. serunr magnesium level, and tlryroid stimulating hormone Hydroxychloroquine can, however, beneflt patients with level exclude all secondary causes other than henrochroma Sjogren syndrome who experience inflammatory arthritis or tosis. Measurements of serun-r f'erritin and transferrin satu subacute cutaneous lupus erythematosus. ration are appropriate screening tests for hemochromatosis. There is no indication to prescribe prednisone (Option Henrochromatosis typically presents in men age 40 years or C). Glucocorticoids will not improve oral or ocular dryness, older and in women generally after menopause because of and therefore the risks of prednisone in this patient are not slower iron accumulation in the premenopausal years. 136

Answers and Critiques m Testing fbr antinuclear antibodies (Option A) would be therapy or with more severe disease. There is no guidance IIJ .pptnpriate il the patient displayed characteristic signs or for optimal duration of therapy, but in the absence of flares, toNl ,ynrptoms ot sysl5'n-r1a lupus erytlrernatosus, such as malar most patients can discontinue treatment in 9 to 12 months. msh, photosensitivity, inflammakiry arthritis, weight loss, Physical therapy may help maintain muscle function and and fever. Howevel this test is not indicated because the his, should be used in all patients. tory, examination. ancl Iaboratory findings arc not consistent Hydroxychloroquine (Option A) may be helpful as with system ic lupus erythematosus. adjunct therapy for skin rashes in some patients with der Erythrocyte sedintentation rate (Option B) is a nonspe matomyositis who do not want, tolerate, or obtain adequate cific test fbr inflammation. It may be elevated in any inflam relief from topical agents and other systemic therapies. How nratory state and \"'ould not help determine the cause of this ever, antimalarial agents do not impact muscle disease and pat ient's in flummation. are not sufflcient as glucocorticoid-sparing therapy. Rheumatoid factor (Option C) is useful in the diagnosis Rituximab (Option C) is sometimes used if the disease of rheumatoid arthritis (RA). Although RA often afl'ects the does not respond adequately to glucocorticoids plus either ut (t, hands and \ /rists, it typically presents with morning stiff azathioprine or methotrexate, or ifthose agents are not tol ness and the gradual onset of pain, stiflncss, and swelling ET erated. However, this patient should receive a trial of meth in a symmctric distribution of hands and feet. Plain radio otrexate or azathioprine and intravenous immune globulin (J graphs in early RA would not show a hooked osteophlrte or before using rituximab. !t calcifi cations in the fi brocartilage. Although this patient has had a good response to pred .! nisone, symptoms are likely to recur if the glucocorticoid tt rEY POITIS o dose is tapered without glucocorticoid sparing therapy. . For patients with acute calcium pyrophosphate crystal Long-term use of moderate or high doses of glucocorticoids r^ = arthritis who are younger than age 60 years, labora- (Option D) should be avoided if possible because of cumula- tory evaluation for contributory metabolic disease tive adverse effects, including bone loss, weight gain, meta- (hyperparathyroidism, hemochromatosis, hypophos- bolic changes, and risk for cataracts and glaucoma. phatasia, hypomagnesemia) is warranted. r(EY P0ll{T5 o Hooked osteophytes of the left third metacar- pophalangeal joints and cartilage calcification are . In patients with dermatomyositis, initiation of metho- trexate or azathioprine at diagnosis or after an early radiographic findings consistent with calcium pyrophosphate crystal arthritis. initial response to glucocorticoids is the most appro- priate next step to achieve long-term disease control and to allow effective tapering ofthe prednisone dose. Bibliography Rosenthal AK, Ryan LM. Calcium pyrophosphate deposition disease. N Engl . Physical therapy may help maintain muscle function J Med. 2016;374:2575 84. IPMID: 27355536j doi:10.1056/NEJMralSlll17 and should be used in all patients with inflammatory myopathy.

m Testing fbr antinuclear antibodies (Option A) would be therapy or with more severe disease. There is no guidance IIJ .pptnpriate il the patient displayed characteristic signs or for optimal duration of therapy, but in the absence of flares, toNl ,ynrptoms ot sysl5'n-r1a lupus erytlrernatosus, such as malar most patients can discontinue treatment in 9 to 12 months. msh, photosensitivity, inflammakiry arthritis, weight loss, Physical therapy may help maintain muscle function and and fever. Howevel this test is not indicated because the his, should be used in all patients. tory, examination. ancl Iaboratory findings arc not consistent Hydroxychloroquine (Option A) may be helpful as with system ic lupus erythematosus. adjunct therapy for skin rashes in some patients with der Erythrocyte sedintentation rate (Option B) is a nonspe matomyositis who do not want, tolerate, or obtain adequate cific test fbr inflammation. It may be elevated in any inflam relief from topical agents and other systemic therapies. How nratory state and \"'ould not help determine the cause of this ever, antimalarial agents do not impact muscle disease and pat ient's in flummation. are not sufflcient as glucocorticoid-sparing therapy. Rheumatoid factor (Option C) is useful in the diagnosis Rituximab (Option C) is sometimes used if the disease of rheumatoid arthritis (RA). Although RA often afl'ects the does not respond adequately to glucocorticoids plus either ut (t, hands and \ /rists, it typically presents with morning stiff azathioprine or methotrexate, or ifthose agents are not tol ness and the gradual onset of pain, stiflncss, and swelling ET erated. However, this patient should receive a trial of meth in a symmctric distribution of hands and feet. Plain radio otrexate or azathioprine and intravenous immune globulin (J graphs in early RA would not show a hooked osteophlrte or before using rituximab. !t calcifi cations in the fi brocartilage. Although this patient has had a good response to pred .! nisone, symptoms are likely to recur if the glucocorticoid tt rEY POITIS o dose is tapered without glucocorticoid sparing therapy. . For patients with acute calcium pyrophosphate crystal Long-term use of moderate or high doses of glucocorticoids r^ = arthritis who are younger than age 60 years, labora- (Option D) should be avoided if possible because of cumula- tory evaluation for contributory metabolic disease tive adverse effects, including bone loss, weight gain, meta- (hyperparathyroidism, hemochromatosis, hypophos- bolic changes, and risk for cataracts and glaucoma. phatasia, hypomagnesemia) is warranted. r(EY P0ll{T5 o Hooked osteophytes of the left third metacar- pophalangeal joints and cartilage calcification are . In patients with dermatomyositis, initiation of metho- trexate or azathioprine at diagnosis or after an early radiographic findings consistent with calcium pyrophosphate crystal arthritis. initial response to glucocorticoids is the most appro- priate next step to achieve long-term disease control and to allow effective tapering ofthe prednisone dose. Bibliography Rosenthal AK, Ryan LM. Calcium pyrophosphate deposition disease. N Engl . Physical therapy may help maintain muscle function J Med. 2016;374:2575 84. IPMID: 27355536j doi:10.1056/NEJMralSlll17 and should be used in all patients with inflammatory myopathy. Item 28 Answer: B Bibliography Educational Objective: Treat dermatomyositis with the Oddis CV Aggarwal R. Treatment in myositis. Nat Rev Rheumatol. 2018; 14:279 289.lPMlD : 295933431 doi:10.1038/nrrheum.2018.42 addition of a glucocorticoid-sparing agent. The most appropriate treatment is to add methotrexate (Option B). This patient has classic clinical and laboratory Item 29 Answer: B leatures of dermatomyositis with myositis-associated auto- antibodies and no evidence of associated malignancy or Ed ucationa I Objective : Diagnose Felty syndrome. tr other complications. In particular, the presence of anti Mi-2 'lhe most likely diagnosis is Felty syndronre (Option B).'this antibodies predicts a good prognosis with a low risk for rare syndrcme is a complication of r.tell established rheu interstitial lung disease and cancer. Her symptoms have nratoid arthritis characterized by neutropenia and spleno completely resolved with an initial course of oral prednisone, megaly. Patients witlr t'elty syndrome are at risk for serious typically initiated at 1 mg/kg/d. Combination therapy with bacterial intbctions. lower extremity ulceration. lymphoma. glucocorticoid-sparing agents is important for maintaining a ancl r,,asculitis. Patients may present rt''ith an asympk)nlatic clinical response and for minimizing glucocorticoid adverse clecline in the neutrophil cor.rnt that is detected on routine effects in patients with dermatomyositis. Initiation of meth- laboratory testing ibr n-redication toxicity. Because a decline otrexate or azathioprine at diagnosis or after an early initial in leukocyte count can also be irn adverse ellbct of nunterous response to glucocorticoids is the most appropriate next nredications used to treat rheumatoid artl.rritis. it is import- step to achieve Iong term disease control and to allow effec ant to evaluate this possibility. llowever, medications are far tive tapering of the prednisone dose. Intravenous immune less likely kr specifically reduce only the ncutrophil count globulin can be added as flrst or second-line treatment for and are not likely to be associated with splenomegall,: Some patients with an inadequate response to initial combination patients prcsent with an infection related to neutropenia.

Item 28 Answer: B Bibliography Educational Objective: Treat dermatomyositis with the Oddis CV Aggarwal R. Treatment in myositis. Nat Rev Rheumatol. 2018; 14:279 289.lPMlD : 295933431 doi:10.1038/nrrheum.2018.42 addition of a glucocorticoid-sparing agent. The most appropriate treatment is to add methotrexate (Option B). This patient has classic clinical and laboratory Item 29 Answer: B leatures of dermatomyositis with myositis-associated auto- antibodies and no evidence of associated malignancy or Ed ucationa I Objective : Diagnose Felty syndrome. tr other complications. In particular, the presence of anti Mi-2 'lhe most likely diagnosis is Felty syndronre (Option B).'this antibodies predicts a good prognosis with a low risk for rare syndrcme is a complication of r.tell established rheu interstitial lung disease and cancer. Her symptoms have nratoid arthritis characterized by neutropenia and spleno completely resolved with an initial course of oral prednisone, megaly. Patients witlr t'elty syndrome are at risk for serious typically initiated at 1 mg/kg/d. Combination therapy with bacterial intbctions. lower extremity ulceration. lymphoma. glucocorticoid-sparing agents is important for maintaining a ancl r,,asculitis. Patients may present rt''ith an asympk)nlatic clinical response and for minimizing glucocorticoid adverse clecline in the neutrophil cor.rnt that is detected on routine effects in patients with dermatomyositis. Initiation of meth- laboratory testing ibr n-redication toxicity. Because a decline otrexate or azathioprine at diagnosis or after an early initial in leukocyte count can also be irn adverse ellbct of nunterous response to glucocorticoids is the most appropriate next nredications used to treat rheumatoid artl.rritis. it is import- step to achieve Iong term disease control and to allow effec ant to evaluate this possibility. llowever, medications are far tive tapering of the prednisone dose. Intravenous immune less likely kr specifically reduce only the ncutrophil count globulin can be added as flrst or second-line treatment for and are not likely to be associated with splenomegall,: Some patients with an inadequate response to initial combination patients prcsent with an infection related to neutropenia. 137

tr CON]. In this instance. the total leukocyte count mav be normal irt the time of presentation but fall ."r'ith treatment of the inf'ec tion. Patients rtith rhcun.ratoid arthritis can also have large the basis of history and physical examination, MRI of the pelvis may reveal erosions, edema, fatty metaplasia, and changes of inflammation (synovitis, enthesitis, or capsuli granullr lymphocyte syndrome, w'hicl.r can progress to lirrgc tis) along the sacroiliac joints. These changes are diagnos- granular lymphocytic ler-rkemia. Finclings overlap rvith Felty tic of inflammatory spondylitis. Later in the disease, plain synclrome and include ncutropenia. ancrnia. thromlloc),to radiographs of the sacroiliac joints may show narrowing, penia. splenotnegallt ancl recurrent inlections. erosions, sclerosis, or fusion. Later flndings on plain radio- AA amyloidosis (Option A) is a rare complication of' graphs of the lumbar spine may reveal early squaring of the long standing and poorly controlled rheumatoid arthritis. vertebral bodies, followed by syndesmophyte formation. In a minority of patiellts, it can leacl to splenomegaly as a Bone scanning (OptionA) is sensitive in the diagnosis of consequence of infiltration of the spleen b1, amyloid protein. inflammatory arthritis, and a negative scan excludes inflam Hovvever. AA aml,loiclosis r'r,ould not be erpected to result in mation; however, this test is rarely used in the diagnosis of D neutropenia. making it an unlikely diagr.rosis in this p:rtient. sacroiliitis or other inflammatory arthritides because it is UI Paticnts rvith rhcumatoid arthritis may develop an nonspecific. MRI is more speciflc than bone scanning in the E (D overlap syndrome characterized by features olanother auto detection of early sacroiliitis and is preferred when plain UI immune disease. such as Sj6gren s1,'ndrome (Option C) or radiography is nondiagnostic. o, s),stelnic lupus er1'themakrsus (SLU) (Option D). Hou'ever. A CT scan of the pelvis (Option B) may show bony EL the patient r'r,ould not be designated as having an overlap changes of inflammatory spondylitis, such as bony erosions. a.t syndronre in the absence ol t-vpical features of the other sclerosis, and ankylosis, but CT exposes the patient to more

tr CON]. In this instance. the total leukocyte count mav be normal irt the time of presentation but fall ."r'ith treatment of the inf'ec tion. Patients rtith rhcun.ratoid arthritis can also have large the basis of history and physical examination, MRI of the pelvis may reveal erosions, edema, fatty metaplasia, and changes of inflammation (synovitis, enthesitis, or capsuli granullr lymphocyte syndrome, w'hicl.r can progress to lirrgc tis) along the sacroiliac joints. These changes are diagnos- granular lymphocytic ler-rkemia. Finclings overlap rvith Felty tic of inflammatory spondylitis. Later in the disease, plain synclrome and include ncutropenia. ancrnia. thromlloc),to radiographs of the sacroiliac joints may show narrowing, penia. splenotnegallt ancl recurrent inlections. erosions, sclerosis, or fusion. Later flndings on plain radio- AA amyloidosis (Option A) is a rare complication of' graphs of the lumbar spine may reveal early squaring of the long standing and poorly controlled rheumatoid arthritis. vertebral bodies, followed by syndesmophyte formation. In a minority of patiellts, it can leacl to splenomegaly as a Bone scanning (OptionA) is sensitive in the diagnosis of consequence of infiltration of the spleen b1, amyloid protein. inflammatory arthritis, and a negative scan excludes inflam Hovvever. AA aml,loiclosis r'r,ould not be erpected to result in mation; however, this test is rarely used in the diagnosis of D neutropenia. making it an unlikely diagr.rosis in this p:rtient. sacroiliitis or other inflammatory arthritides because it is UI Paticnts rvith rhcumatoid arthritis may develop an nonspecific. MRI is more speciflc than bone scanning in the E (D overlap syndrome characterized by features olanother auto detection of early sacroiliitis and is preferred when plain UI immune disease. such as Sj6gren s1,'ndrome (Option C) or radiography is nondiagnostic. o, s),stelnic lupus er1'themakrsus (SLU) (Option D). Hou'ever. A CT scan of the pelvis (Option B) may show bony EL the patient r'r,ould not be designated as having an overlap changes of inflammatory spondylitis, such as bony erosions. a.t syndronre in the absence ol t-vpical features of the other sclerosis, and ankylosis, but CT exposes the patient to more 4t autoimmune disease. When SLE occurs in patients with radiation. Therefore, it is not appropriate unless the patient rheumrrtoicl arthritis, a more typical hematologic picture cannot undergo MRI. .D t^ u,oulcl include l1,mphopenia. hemolytic anemia. or throm Rheumatoid factor and anti-cyclic citrullinated peptide bocl'topenia. A positive antinuclear antibodl'test result xncl antibodies (Option D) are diagnostic tests for rheumatoid clinicirl rnanifestations secn in SLII but not in rheunratoid arthritis. Results of these tests are not typically positive in arthritis, such as kiclncy disease, might appear. Similarly. patients with ankylosing spondylitis. Rheumatoid arthritis Sjogren syndrome is diagnosed in patients with rheumatoid does not cause low back pain because it does not affect the arthritis r,r'hen sicca symptoms are prcsent. Typicallyl this lumbar spine. This patient has no peripheral inflammatory r,r,ould be accompanied by anti-Ro SSi\ antibodies anci occa joint symptoms consistent with rheumatoid arthritis, so sionally anti La SSII antibodies. these tests are not indicated. Although adults with rheu matoid arthritis may have eye involvement, it is typically KEY POIl{I5 scleritis, not uveitis as in this patient. . Felty syndrome is a complication of well-established rheumatoid arthritis characterized by neutropenia r(tY PolilT5 and splenomegaly. . When plain radiographs are normal and the clinical . Patients with Felty syndrome are at risk for serious suspicion is high, MRI of the pelvis may reveal ero- bacterial infections, lower extremity ulceration, lym- sions, ankylosis, fatty metaplasia, and inflammatory phoma, and vasculitis. changes along the sacroiliac joints that are diagnostic of inflammatory spondylitis. Bibliography . A CT scan of the pelvis may show bony changes of Gazitt T, Loughran TP Jr. Chronic rreutropenia in l.Gl. leukemia and rheuma inflammatory spondylitis, but CT exposes the patient toid arthritis. Hematololl/ Am Soc Hematol [.]cluc Program. 2017 l)ec 8; 2017(l):181 186. I PMID: Z9'l'lZ'ZS,l] doi:10.1182/asheducation 20l7.l.l8l to radiation and is reserved for patients who cannot undergo MRI.

4t autoimmune disease. When SLE occurs in patients with radiation. Therefore, it is not appropriate unless the patient rheumrrtoicl arthritis, a more typical hematologic picture cannot undergo MRI. .D t^ u,oulcl include l1,mphopenia. hemolytic anemia. or throm Rheumatoid factor and anti-cyclic citrullinated peptide bocl'topenia. A positive antinuclear antibodl'test result xncl antibodies (Option D) are diagnostic tests for rheumatoid clinicirl rnanifestations secn in SLII but not in rheunratoid arthritis. Results of these tests are not typically positive in arthritis, such as kiclncy disease, might appear. Similarly. patients with ankylosing spondylitis. Rheumatoid arthritis Sjogren syndrome is diagnosed in patients with rheumatoid does not cause low back pain because it does not affect the arthritis r,r'hen sicca symptoms are prcsent. Typicallyl this lumbar spine. This patient has no peripheral inflammatory r,r,ould be accompanied by anti-Ro SSi\ antibodies anci occa joint symptoms consistent with rheumatoid arthritis, so sionally anti La SSII antibodies. these tests are not indicated. Although adults with rheu matoid arthritis may have eye involvement, it is typically KEY POIl{I5 scleritis, not uveitis as in this patient. . Felty syndrome is a complication of well-established rheumatoid arthritis characterized by neutropenia r(tY PolilT5 and splenomegaly. . When plain radiographs are normal and the clinical . Patients with Felty syndrome are at risk for serious suspicion is high, MRI of the pelvis may reveal ero- bacterial infections, lower extremity ulceration, lym- sions, ankylosis, fatty metaplasia, and inflammatory phoma, and vasculitis. changes along the sacroiliac joints that are diagnostic of inflammatory spondylitis. Bibliography . A CT scan of the pelvis may show bony changes of Gazitt T, Loughran TP Jr. Chronic rreutropenia in l.Gl. leukemia and rheuma inflammatory spondylitis, but CT exposes the patient toid arthritis. Hematololl/ Am Soc Hematol [.]cluc Program. 2017 l)ec 8; 2017(l):181 186. I PMID: Z9'l'lZ'ZS,l] doi:10.1182/asheducation 20l7.l.l8l to radiation and is reserved for patients who cannot undergo MRI. Item 30 Answer: C Bibliography Educational Objective: Diagnose inflammatory Maksymonlch WP lmaging in axial spondyloarthritis: evalu:rtion of inflammatory and structural changes. Rheum Dis Clin North Am. 2016: sacroiliitis by using MRI. 12:645 662. IPMID; 27712019] doi:10.1016ii.rdc.2016.07.003

Item 30 Answer: C Bibliography Educational Objective: Diagnose inflammatory Maksymonlch WP lmaging in axial spondyloarthritis: evalu:rtion of inflammatory and structural changes. Rheum Dis Clin North Am. 2016: sacroiliitis by using MRI. 12:645 662. IPMID; 27712019] doi:10.1016ii.rdc.2016.07.003 The most appropriate diagnostic test to perform next is MRI of the pelvis (Option C). This patient has sympton.rs Item 31 Answer: A of inflammatory back pain with sacroiliitis consistent with ankylosing spondylitis. She has developed symptoms at a Educational Objective: Diagnose acute cutaneous lupus young age (<45 years) and has morning stiffness, nighttime erythematosus. pain, improvement of symptoms with exercise and ibupro- The most likely diagnosis is acute cutaneous lupus erythe- fen, and a history of uveitis. Her decreased range of motion matosus (ACLE) (Option A). Cutaneous lupus erythematosus of the lumbar spine in all directions is typical of this disease. can exist with or without systemic disease. There are three Early in the disease, radiographs may be normal. When plain primary patterns of lupus-speciflc skin rashes: ACLE, sub- radiographs are normal and the clinical suspicion is high on acute cutaneous lupus erythematosus, and chronic cutaneous 138

Answers and Critiques lupus erythematosus. The lupus speciflc skin diseases are not and, if MCP joints on one hand are tender and swollen, found in other conditions and have varying associations with there are usually MCP joints on the other hand (although systemic lupus erythematosus (SLE). Identifing the pattern not always the same digits on each side) that are symptom of the skin disease can be important for guiding additional atic and abnormal on physical examination as well. Other evaluation and treatment. ACLE often presents with a pho frequently involved joints are the proximal interphalangeal tosensitive malar or butterfly rash, with patchy, edematous, joints and wrists. Corresponding joints in the feet (interpha e4,.thematous areas on the cheeks and over the nose. sparing langeal joints. metatarsophalangeal joints. and ankles) are the nasolabial folds. Similar rashes can occur on other sun also often affected. exposed skin, including the neck, upper chest, and arms. Ankylosing spondylitis (Option A) is a chronic inflam Nearly all patients with ACLE have SLE, and as such tend to matory disease affecting the axial skeleton, entheses, and have systemic symptoms and positive serologic results (typi peripheral joints. [n contrast to other forms of spondyloar cally antinuclear, anti Ro/SSA, and anti-La/SSB antibodies). thritis, sacroiliac joint involvement is considered an essential Lupus pernio (Option B) is a skin manifestation seen in feature of ankylosing spondylitis. About one third ofpatients UI (, some patients with sarcoidosis. Skin lesions can occur on the develop hip joint involvement, and about one third develop ET face, including the cheeks, nose, lips, forehead, or ears, and peripheral arthritis elsewhere, often in the shoulders but not are firm and purple. These skin lesions are not photosensi the N4CP joints. L' tive and do not appear on the chest or arms. Erosive (inflammatory) osteoarthritis (OA) (Option E' Rosacea (Option C) is the most common cause of an B) is a subset of primary hand OA. Clinically, erosive OA .E erythematous rash in the malar distribution. Rosacea is mostly afl'ects the distal interphalangeal and less commonly Ul

lupus erythematosus. The lupus speciflc skin diseases are not and, if MCP joints on one hand are tender and swollen, found in other conditions and have varying associations with there are usually MCP joints on the other hand (although systemic lupus erythematosus (SLE). Identifing the pattern not always the same digits on each side) that are symptom of the skin disease can be important for guiding additional atic and abnormal on physical examination as well. Other evaluation and treatment. ACLE often presents with a pho frequently involved joints are the proximal interphalangeal tosensitive malar or butterfly rash, with patchy, edematous, joints and wrists. Corresponding joints in the feet (interpha e4,.thematous areas on the cheeks and over the nose. sparing langeal joints. metatarsophalangeal joints. and ankles) are the nasolabial folds. Similar rashes can occur on other sun also often affected. exposed skin, including the neck, upper chest, and arms. Ankylosing spondylitis (Option A) is a chronic inflam Nearly all patients with ACLE have SLE, and as such tend to matory disease affecting the axial skeleton, entheses, and have systemic symptoms and positive serologic results (typi peripheral joints. [n contrast to other forms of spondyloar cally antinuclear, anti Ro/SSA, and anti-La/SSB antibodies). thritis, sacroiliac joint involvement is considered an essential Lupus pernio (Option B) is a skin manifestation seen in feature of ankylosing spondylitis. About one third ofpatients UI (, some patients with sarcoidosis. Skin lesions can occur on the develop hip joint involvement, and about one third develop ET face, including the cheeks, nose, lips, forehead, or ears, and peripheral arthritis elsewhere, often in the shoulders but not are firm and purple. These skin lesions are not photosensi the N4CP joints. L' tive and do not appear on the chest or arms. Erosive (inflammatory) osteoarthritis (OA) (Option E' Rosacea (Option C) is the most common cause of an B) is a subset of primary hand OA. Clinically, erosive OA .E erythematous rash in the malar distribution. Rosacea is mostly afl'ects the distal interphalangeal and less commonly Ul more likely to include pustular lesions and visible telangiec affects the proximal interphalangeal joints. Erosive OA is o tasias and does not spare the nasolabial fold. more inflammatory and painlul than typical hand OA and is ta = Subacute cutaneous lupus erythematosus (SCLE) more common in women. Erosive OA is not associated with (Option D) appears as one of two variants: annular and generalized OA and usually spares the thumb bases. Erosive polycyclic photosensitive plaques on the back. chest, and arthritis does not involve the MCP joints. extremities, or psoriasiform scaly plaques in a similar distri Reactive arthritis (Option C) is a rare cause of inflamma bution. SCLE does not scar but may resolve with temporary tory arthritis that can occur following speciflc genitourinary pigmentary changes. Fewer than one in f,our patients with and gastrointestinal infections. Arthritis is asymmetric and may SCLE have SLE, and as many as one in three cases are drug be monoarticular or oligoarticular; joints commonly affected induced. The latter may resolve with withdrawal of the caus include the knee, ankle, and wrist. Enthesitis is especially com ative agent. This patient's rash does not match the typical mon; Achilles tendinitis and plantar fasciitis occur in up to 90'X, presentation ofSCLE. of cases. l)actylitis can also occur. The spine and sacroiliac joints are less commonly involved. Symmetric involvement of the l(EY POl]tT5 MCP joints is not characteristic of reactive arthritis. o Acute cutaneous lupus erythematosus often presents with the classic photosensitive malar or butterfly rash, t(EY P0ilaIS with patchy, edematous, erythematous areas on the . In rheumatoid arthritis, both hands are usually cheeks and over the nose, sparing the nasolabial folds; involved, most commonly manifesting as symmetric similar rashes can occur on other sun exposed skin, involvement of the MCP joints. including the neck, upper chest, and arms. o In rheumatoid arthritis, the interphalangeal joints, . Nearly all patients with acute cutaneous lupus erythe metatarsophalangeal joints, and ankles are often also matosus have systemic lupus erythematosus and as symmetrically affected. such tend to have systemic symptoms and positive serologies. Bibliography Sparks JA. Rheumatoid arthritis. Ann Intern Med. 2019r170:lTC1 ITCl6. IPMID: 110.5968791 doi: 10.71126 rAITC2OI90l010 Bibliography \t'enzel J. Cutaneous h-lpus erythematosus: new insights into pathogenesis Item 33 and therilpeutic strNtcflies. Nat Rev Rheumatol. 201911.5:519 532. [PMID: 31 39971 1 I Answer: D Educational Objective: Treat newly diagnosed tr ANCA associated vasculitis. Item 32 Answer: D The most appropriate treatnlent is high dose glucocorticoids Educational Objective: Diagnose rheumatoid arthritis and rituximab (Option D). This patient has granulomatosis by the pattern ofjoint involvement. n,ith polyangiitis (CIA). ANCA-associated vasculitis is sug- The most likely cause of this patient's joint pain is rheuma gestecl lry the scvere ancl inflammatory multisystemic il]ness. toid arthritis (Option D), given joint involvement that is poly Clues that this is GPA specifically include sinus, kidney. and articular and includes the metacarpophalangeal (MCP) joints. h-rng involvcnrent; the skin flndings (palpable purpura is not In rheumatoid arthritis. both hands are usuallv involved, specilic fbr GPA but strongly sugqests a small vessel vasculitis);

more likely to include pustular lesions and visible telangiec affects the proximal interphalangeal joints. Erosive OA is o tasias and does not spare the nasolabial fold. more inflammatory and painlul than typical hand OA and is ta = Subacute cutaneous lupus erythematosus (SCLE) more common in women. Erosive OA is not associated with (Option D) appears as one of two variants: annular and generalized OA and usually spares the thumb bases. Erosive polycyclic photosensitive plaques on the back. chest, and arthritis does not involve the MCP joints. extremities, or psoriasiform scaly plaques in a similar distri Reactive arthritis (Option C) is a rare cause of inflamma bution. SCLE does not scar but may resolve with temporary tory arthritis that can occur following speciflc genitourinary pigmentary changes. Fewer than one in f,our patients with and gastrointestinal infections. Arthritis is asymmetric and may SCLE have SLE, and as many as one in three cases are drug be monoarticular or oligoarticular; joints commonly affected induced. The latter may resolve with withdrawal of the caus include the knee, ankle, and wrist. Enthesitis is especially com ative agent. This patient's rash does not match the typical mon; Achilles tendinitis and plantar fasciitis occur in up to 90'X, presentation ofSCLE. of cases. l)actylitis can also occur. The spine and sacroiliac joints are less commonly involved. Symmetric involvement of the l(EY POl]tT5 MCP joints is not characteristic of reactive arthritis. o Acute cutaneous lupus erythematosus often presents with the classic photosensitive malar or butterfly rash, t(EY P0ilaIS with patchy, edematous, erythematous areas on the . In rheumatoid arthritis, both hands are usually cheeks and over the nose, sparing the nasolabial folds; involved, most commonly manifesting as symmetric similar rashes can occur on other sun exposed skin, involvement of the MCP joints. including the neck, upper chest, and arms. o In rheumatoid arthritis, the interphalangeal joints, . Nearly all patients with acute cutaneous lupus erythe metatarsophalangeal joints, and ankles are often also matosus have systemic lupus erythematosus and as symmetrically affected. such tend to have systemic symptoms and positive serologies. Bibliography Sparks JA. Rheumatoid arthritis. Ann Intern Med. 2019r170:lTC1 ITCl6. IPMID: 110.5968791 doi: 10.71126 rAITC2OI90l010 Bibliography \t'enzel J. Cutaneous h-lpus erythematosus: new insights into pathogenesis Item 33 and therilpeutic strNtcflies. Nat Rev Rheumatol. 201911.5:519 532. [PMID: 31 39971 1 I Answer: D Educational Objective: Treat newly diagnosed tr ANCA associated vasculitis. Item 32 Answer: D The most appropriate treatnlent is high dose glucocorticoids Educational Objective: Diagnose rheumatoid arthritis and rituximab (Option D). This patient has granulomatosis by the pattern ofjoint involvement. n,ith polyangiitis (CIA). ANCA-associated vasculitis is sug- The most likely cause of this patient's joint pain is rheuma gestecl lry the scvere ancl inflammatory multisystemic il]ness. toid arthritis (Option D), given joint involvement that is poly Clues that this is GPA specifically include sinus, kidney. and articular and includes the metacarpophalangeal (MCP) joints. h-rng involvcnrent; the skin flndings (palpable purpura is not In rheumatoid arthritis. both hands are usuallv involved, specilic fbr GPA but strongly sugqests a small vessel vasculitis); 139

Answers and Critiques tr CONT, peripheral nervous svsteln inr,olvement (left foot senson, bss): and the presence of antiproteinase 3 antibodies. To conflrn.r the diagnosis irnd guide management, tissue biopsl' (in this for the management of OA includes educational. behav- ioral, psychosocial, and physical interventions. as r.tell as pharmacologic therapy. In some patients, physical. psycho case. kidnel') rnay be done i{'possible. High dose glucocorti social, mind-body interventions may be adequate to con- coids plus either rituximab (preferred) or c),clophosphamide trol symptoms; others may need sequential or combination is the appropriate treirtment for induction of remission in approaches. For a motivated patient like this one, mind body selere orgarl threatening or lif'e threatening GPA. Selecteci interventions, such as tai chi, are appropriate to consider patients nray benefit frorn plasma erchange. Once rernission as an adjunct option. Tai chi is a traditional Chinese mind is achieved, patients should receive maintenance therapl.con body practice that combines meditation with slon. gentle, sisting of rituxinrirb, methotrexate. or azathioprine: rituximab graceful movements; deep diaphragmatic breathing: and appears to be most effective for prer,,enting relapse and is relaxation. Tai chi has been shown in a randomized trial to guideline pret.erred. On their olr,n. high dose glucocorticoids be as beneficial as physical therapy for knee and hip OA pain are not suf ficient fbr induction and maintenance treatment ol and is strongly recommended by the American College of tt ANCA associated vasculitis. Mortality rates in patients receiv- Rheumatologz (ACR)/Arthritis Foundation (AF) guideline (D ing only glucocorlicoids are high. Observational studies from for the management of knee and/or hip osteoarthritis. = gt the 1970s ar.rd l9U0s demonstrated that glucocorlicoids plus Strong evidence supports the use of exercise in the o, cyclophosphamide was associated r,r,ith a significant improve treatment of knee and hip OA. Most studies that assessed the CL ment in sunival. fivc times that of historical controls. and a role ol aerobic exercise in the management of OA evaluated n lou,er frequency ol relapse. walking and found it to be beneficial. However, high-impact lt Clucocorticoicls plus azathioprine (Option A) is not exercises (Option A) are not tolerated by patients with knee adequate ftrr inducing remission of GPA. Azathioprine has OA and may be harmful. Thus, they are not appropriate for .D vl been usecl to maintain remission once achiel.ed (although this patient. rituximab is superior firr maintenance o{'remission). but this Patients frequently use transcutaneous electrical nerve combination has never been shou'n tcl induce remission in stimulation (TENS) (Option C) to help relieve the pain asso- active ANCA associated vasculitis. ciated with knee and/or hip OA. Holr,'ever, studies have Although glucocorticoids plus methotrexate (Option B) demonstrated a lack of benefit. and TENS should not be are pref'erred for active. nonsevere GPA. this patient has recommended to the patient. se\ere slistemic CPA ancl tl.rerefore requires high-dose glu Weight loss is associated with a meaningful improve cocorlicoids plus rituxin.rab. ment in knee, hip, and hand OA symptoms that is propor Althougl.r glucocorlicoids plus mlcophenolate moletil tional to the loss of weight. The efficacy of weight loss for OA (Option C) can induce remission in ANCA associated \ascu symptom management is enhanced by use of a concomitant litis, patients treated u,ith this therap-v" ha'"e a higher rate of exercise program. Beyond that, speciflc diets, such as a vegan relapse than those treated with glucocorticoids plus rituximab. diet (Option D), have not been shown to decrease OA related Because ANCA associated vasculitis is a chrcnic condition. the symptoms and should not be recommended. treatment least associated with relapse is the most preferable. XEY POI lITS XEY POIilIt . A comprehensive plan for the management of osteoar- o High-dose glucocorticoids alone are not sufficient for thritis includes educational, behavioral, psychosocial, induction and maintenance treatment of ANCA- and physical interventions, as well as pharmacologic associated vasculitis. therapy. . High-dose glucocorticoids plus rituximab are the pre- o Tai chi is as beneficial as physical therapy for patients ferred treatment for induction of remission in severe with osteoarthritis of the knee and/or hip. organ-threatening or life-threatening granulomatosis with polyangiitis. Bibliography Kolasinski SL, Neogi T, Hochberg MC. et al. 2019 American College of Rheumatologl/Arthritis Foundation guideline for the management of Bibliography osteoarthritis of the hand. hip. and knee. Arthritis Rheumatol. 2020: Chung SA, Langford CA, Maz M, et al. 2021 American College of 72:220 - 233. IPMID: 319081 63] doi:10. 1002 art.41142 Rheumatolos//Vasculitis Foundation Guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 2021. IPMl D: 34235894] Item 35

tr CONT, peripheral nervous svsteln inr,olvement (left foot senson, bss): and the presence of antiproteinase 3 antibodies. To conflrn.r the diagnosis irnd guide management, tissue biopsl' (in this for the management of OA includes educational. behav- ioral, psychosocial, and physical interventions. as r.tell as pharmacologic therapy. In some patients, physical. psycho case. kidnel') rnay be done i{'possible. High dose glucocorti social, mind-body interventions may be adequate to con- coids plus either rituximab (preferred) or c),clophosphamide trol symptoms; others may need sequential or combination is the appropriate treirtment for induction of remission in approaches. For a motivated patient like this one, mind body selere orgarl threatening or lif'e threatening GPA. Selecteci interventions, such as tai chi, are appropriate to consider patients nray benefit frorn plasma erchange. Once rernission as an adjunct option. Tai chi is a traditional Chinese mind is achieved, patients should receive maintenance therapl.con body practice that combines meditation with slon. gentle, sisting of rituxinrirb, methotrexate. or azathioprine: rituximab graceful movements; deep diaphragmatic breathing: and appears to be most effective for prer,,enting relapse and is relaxation. Tai chi has been shown in a randomized trial to guideline pret.erred. On their olr,n. high dose glucocorticoids be as beneficial as physical therapy for knee and hip OA pain are not suf ficient fbr induction and maintenance treatment ol and is strongly recommended by the American College of tt ANCA associated vasculitis. Mortality rates in patients receiv- Rheumatologz (ACR)/Arthritis Foundation (AF) guideline (D ing only glucocorlicoids are high. Observational studies from for the management of knee and/or hip osteoarthritis. = gt the 1970s ar.rd l9U0s demonstrated that glucocorlicoids plus Strong evidence supports the use of exercise in the o, cyclophosphamide was associated r,r,ith a significant improve treatment of knee and hip OA. Most studies that assessed the CL ment in sunival. fivc times that of historical controls. and a role ol aerobic exercise in the management of OA evaluated n lou,er frequency ol relapse. walking and found it to be beneficial. However, high-impact lt Clucocorticoicls plus azathioprine (Option A) is not exercises (Option A) are not tolerated by patients with knee adequate ftrr inducing remission of GPA. Azathioprine has OA and may be harmful. Thus, they are not appropriate for .D vl been usecl to maintain remission once achiel.ed (although this patient. rituximab is superior firr maintenance o{'remission). but this Patients frequently use transcutaneous electrical nerve combination has never been shou'n tcl induce remission in stimulation (TENS) (Option C) to help relieve the pain asso- active ANCA associated vasculitis. ciated with knee and/or hip OA. Holr,'ever, studies have Although glucocorticoids plus methotrexate (Option B) demonstrated a lack of benefit. and TENS should not be are pref'erred for active. nonsevere GPA. this patient has recommended to the patient. se\ere slistemic CPA ancl tl.rerefore requires high-dose glu Weight loss is associated with a meaningful improve cocorlicoids plus rituxin.rab. ment in knee, hip, and hand OA symptoms that is propor Althougl.r glucocorlicoids plus mlcophenolate moletil tional to the loss of weight. The efficacy of weight loss for OA (Option C) can induce remission in ANCA associated \ascu symptom management is enhanced by use of a concomitant litis, patients treated u,ith this therap-v" ha'"e a higher rate of exercise program. Beyond that, speciflc diets, such as a vegan relapse than those treated with glucocorticoids plus rituximab. diet (Option D), have not been shown to decrease OA related Because ANCA associated vasculitis is a chrcnic condition. the symptoms and should not be recommended. treatment least associated with relapse is the most preferable. XEY POI lITS XEY POIilIt . A comprehensive plan for the management of osteoar- o High-dose glucocorticoids alone are not sufficient for thritis includes educational, behavioral, psychosocial, induction and maintenance treatment of ANCA- and physical interventions, as well as pharmacologic associated vasculitis. therapy. . High-dose glucocorticoids plus rituximab are the pre- o Tai chi is as beneficial as physical therapy for patients ferred treatment for induction of remission in severe with osteoarthritis of the knee and/or hip. organ-threatening or life-threatening granulomatosis with polyangiitis. Bibliography Kolasinski SL, Neogi T, Hochberg MC. et al. 2019 American College of Rheumatologl/Arthritis Foundation guideline for the management of Bibliography osteoarthritis of the hand. hip. and knee. Arthritis Rheumatol. 2020: Chung SA, Langford CA, Maz M, et al. 2021 American College of 72:220 - 233. IPMID: 319081 63] doi:10. 1002 art.41142 Rheumatolos//Vasculitis Foundation Guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 2021. IPMl D: 34235894] Item 35 Item 34 Answer: B Answer: B Ed ucational Objective: Diagnose basic calcium tr phosphate-associated arthritis. Educational Objective: Manage osteoarthritis of the knee The most likely diagnosis is basic calcium phosphate asso with tai chi. ciated arthritis (Option B). Deposition of basic calcium The most appropriate treatment is tai chi (Option B). This pl.rosphate crystals (hydroxyappatite) occurs in older per patient has knee osteoarthritis (OA). A comprehensive plan sons and targcts pcriarticular tendons and ligaments. In

Item 34 Answer: B Answer: B Ed ucational Objective: Diagnose basic calcium tr phosphate-associated arthritis. Educational Objective: Manage osteoarthritis of the knee The most likely diagnosis is basic calcium phosphate asso with tai chi. ciated arthritis (Option B). Deposition of basic calcium The most appropriate treatment is tai chi (Option B). This pl.rosphate crystals (hydroxyappatite) occurs in older per patient has knee osteoarthritis (OA). A comprehensive plan sons and targcts pcriarticular tendons and ligaments. In 140 q

Answers and Critiques fi rare instances, basic calcium phosphate crystal deposition Rheumatoid arthritis (Option D) rarely presents in the E is associated with inflammatory arthritis and periarthritis. shoulder in older patients. It is associated with in{lamma GONI most classically manifesting in older women as "Milwau tory joint fluid (leukocyte count, 2000 20.000/pl. [2.0 20 x kee shoulder." '[his inflammatory state causes progressive fOe/L]) and is not associated with periarticular calcifications destruction of the glenohumeral joint. and destruction of on plain radiographs. Monoarticular presentations of rheu the rotator cuff as shown in the radiograph below. The red matoid arthritis are uncommon. arrow pointing to the humeral head, illustrates aggressive KTY POIXTS bone destruction at the glenohumeral junction. The blue arrow illustrates distended subacromial/subdeltoid bursa o Deposition of basic calcium phosphate crystals with fluid and calcific debris. Basic calcium phosphate crys- (hydroxyappatite) occurs in older persons and targets tals are not seen on routine synovial fluid analysis because periarticular tendons and ligaments. visualization requires special stains and/or electron micros- . In rare instances, basic calcium phosphate crystal copy. Unlike in other crystal induced diseases. pain onset is deposition is associated with inflammatory arthritis vt (u gradual. and periarthritis, most classically manifesting in older ET women as "Milwaukee shoulder," an inflammatory state that causes progressive destruction of the rotator rJ cuff and glenohumeral joint. !, .E ul BibHography (l, McCarthy GM, Dunne A. Calcium crystal deposition diseases beyond gout. t= Nat Rev Rheumatol. 2018;14:592-602. IPMID: 30190520] doi:10.1038/ s41584 018 0078-5

fi rare instances, basic calcium phosphate crystal deposition Rheumatoid arthritis (Option D) rarely presents in the E is associated with inflammatory arthritis and periarthritis. shoulder in older patients. It is associated with in{lamma GONI most classically manifesting in older women as "Milwau tory joint fluid (leukocyte count, 2000 20.000/pl. [2.0 20 x kee shoulder." '[his inflammatory state causes progressive fOe/L]) and is not associated with periarticular calcifications destruction of the glenohumeral joint. and destruction of on plain radiographs. Monoarticular presentations of rheu the rotator cuff as shown in the radiograph below. The red matoid arthritis are uncommon. arrow pointing to the humeral head, illustrates aggressive KTY POIXTS bone destruction at the glenohumeral junction. The blue arrow illustrates distended subacromial/subdeltoid bursa o Deposition of basic calcium phosphate crystals with fluid and calcific debris. Basic calcium phosphate crys- (hydroxyappatite) occurs in older persons and targets tals are not seen on routine synovial fluid analysis because periarticular tendons and ligaments. visualization requires special stains and/or electron micros- . In rare instances, basic calcium phosphate crystal copy. Unlike in other crystal induced diseases. pain onset is deposition is associated with inflammatory arthritis vt (u gradual. and periarthritis, most classically manifesting in older ET women as "Milwaukee shoulder," an inflammatory state that causes progressive destruction of the rotator rJ cuff and glenohumeral joint. !, .E ul BibHography (l, McCarthy GM, Dunne A. Calcium crystal deposition diseases beyond gout. t= Nat Rev Rheumatol. 2018;14:592-602. IPMID: 30190520] doi:10.1038/ s41584 018 0078-5 Item 35 Answer: B Educational Objective: Treat rheumatoid arthritis with the most appropriate biologic therapy.

fi rare instances, basic calcium phosphate crystal deposition Rheumatoid arthritis (Option D) rarely presents in the E is associated with inflammatory arthritis and periarthritis. shoulder in older patients. It is associated with in{lamma GONI most classically manifesting in older women as "Milwau tory joint fluid (leukocyte count, 2000 20.000/pl. [2.0 20 x kee shoulder." '[his inflammatory state causes progressive fOe/L]) and is not associated with periarticular calcifications destruction of the glenohumeral joint. and destruction of on plain radiographs. Monoarticular presentations of rheu the rotator cuff as shown in the radiograph below. The red matoid arthritis are uncommon. arrow pointing to the humeral head, illustrates aggressive KTY POIXTS bone destruction at the glenohumeral junction. The blue arrow illustrates distended subacromial/subdeltoid bursa o Deposition of basic calcium phosphate crystals with fluid and calcific debris. Basic calcium phosphate crys- (hydroxyappatite) occurs in older persons and targets tals are not seen on routine synovial fluid analysis because periarticular tendons and ligaments. visualization requires special stains and/or electron micros- . In rare instances, basic calcium phosphate crystal copy. Unlike in other crystal induced diseases. pain onset is deposition is associated with inflammatory arthritis vt (u gradual. and periarthritis, most classically manifesting in older ET women as "Milwaukee shoulder," an inflammatory state that causes progressive destruction of the rotator rJ cuff and glenohumeral joint. !, .E ul BibHography (l, McCarthy GM, Dunne A. Calcium crystal deposition diseases beyond gout. t= Nat Rev Rheumatol. 2018;14:592-602. IPMID: 30190520] doi:10.1038/ s41584 018 0078-5 Item 35 Answer: B Educational Objective: Treat rheumatoid arthritis with the most appropriate biologic therapy. The most appropriate treatment is adalimumab (Option B). Rheumatoid arthritis treatment is aimed at controlling clin- ical disease and joint damage. Patients whose condition is Adhesive capsulitis (frozen shoulder) (Option A) usually unresponsive to initial treatment with methotrexate, with occurs in patients aged 40 to 70 years. The cause appears to or without another nonbiologic disease modifying anti- involve glenohumeral joint capsular thickening and fibrosis. rheumatic drug, could receive triple therapy (methotrexate, Patients describe shoulder pain that is often constant but sulfasalazine, and hydroxychloroquine) or a biologic agent. is worse at night and in cold weather: shoulder stiffness The choice of a drug regimen in such patients depends on is common. Adhesive capsulitis can be idiopathic but is many factors, including disease activity, comorbid condi- also associated with prolonged immobilization, anteced tions, patient preferences for route of administration and ent shoulder surgery or injury. diabetes mellitus, hypo frequency ofdosing, adverse prognostic features, and regu- thyroidism, and autoimmune disorders. On examination. latory and cost barriers to drug access. This patient has active patients have limited passive and active range of motion in clinical disease and radiographic evidence ofworsening joint all directions. Plain radiographs are of limited diagnostic use damage despite combination treatment with sulfasalazine in patients with adhesive capsulitis: most often the radio and methotrexate. Escalation to additional therapy with a graphs are normal, except for osteopenia in some cases. This tumor necrosis factor (TNF) inhibitor, such as adalimumab, patient's abnormal shoulder radiograph is not consistent is an appropriate choice. Despite multiple comorbidities, this with adhesive capsulitis. patient has no contraindications to treatment with a biologic Calcium pyrophosphate deposition (CPPD) disease (such as active infection or heart failure). All TNF inhibitors (Option C) is an unlikely diagnosis. Although it may involve provide similarbeneflt and maybe used in this patient based the shoulder joint, it is typically associated with osteoar- on the factors outlined above. These regimens may have a thritis, not severe erosive joint destruction. Calcium pyro- faster onset of action than triple therapy with nonbiologic phosphate crystals, which are weakly positively birefringent disease-modi$zing antirheumatic drugs. (blue when parallel to and yellow when perpendicular to Reasonable alternatives to a TNF inhibitor include sev the polarizing axis ol'an optical filter) and classically rhom' eral other parenterally administered agents, including aba boid shaped, are usually identified in the joint fluid. Chon. tacept (Option A), the anti-interleukin-6 receptor antibody drocalcinosis, visible as a thin white line that tracks below tocilizumab (Option D), and the oral targeted synthetic the surface layer of the cartilage within the joint. may be Janus kinase inhibitor tofacitinib (Option E). However, visible on plain radiograph. Flxtensive soft tissue calcifica these agents are usually used after failure or intolerance of tion such as seen in this radiograph is not typical of CPPD. a TNF inhibitor. Furthermore, this patient has signiflcant

The most appropriate treatment is adalimumab (Option B). Rheumatoid arthritis treatment is aimed at controlling clin- ical disease and joint damage. Patients whose condition is Adhesive capsulitis (frozen shoulder) (Option A) usually unresponsive to initial treatment with methotrexate, with occurs in patients aged 40 to 70 years. The cause appears to or without another nonbiologic disease modifying anti- involve glenohumeral joint capsular thickening and fibrosis. rheumatic drug, could receive triple therapy (methotrexate, Patients describe shoulder pain that is often constant but sulfasalazine, and hydroxychloroquine) or a biologic agent. is worse at night and in cold weather: shoulder stiffness The choice of a drug regimen in such patients depends on is common. Adhesive capsulitis can be idiopathic but is many factors, including disease activity, comorbid condi- also associated with prolonged immobilization, anteced tions, patient preferences for route of administration and ent shoulder surgery or injury. diabetes mellitus, hypo frequency ofdosing, adverse prognostic features, and regu- thyroidism, and autoimmune disorders. On examination. latory and cost barriers to drug access. This patient has active patients have limited passive and active range of motion in clinical disease and radiographic evidence ofworsening joint all directions. Plain radiographs are of limited diagnostic use damage despite combination treatment with sulfasalazine in patients with adhesive capsulitis: most often the radio and methotrexate. Escalation to additional therapy with a graphs are normal, except for osteopenia in some cases. This tumor necrosis factor (TNF) inhibitor, such as adalimumab, patient's abnormal shoulder radiograph is not consistent is an appropriate choice. Despite multiple comorbidities, this with adhesive capsulitis. patient has no contraindications to treatment with a biologic Calcium pyrophosphate deposition (CPPD) disease (such as active infection or heart failure). All TNF inhibitors (Option C) is an unlikely diagnosis. Although it may involve provide similarbeneflt and maybe used in this patient based the shoulder joint, it is typically associated with osteoar- on the factors outlined above. These regimens may have a thritis, not severe erosive joint destruction. Calcium pyro- faster onset of action than triple therapy with nonbiologic phosphate crystals, which are weakly positively birefringent disease-modi$zing antirheumatic drugs. (blue when parallel to and yellow when perpendicular to Reasonable alternatives to a TNF inhibitor include sev the polarizing axis ol'an optical filter) and classically rhom' eral other parenterally administered agents, including aba boid shaped, are usually identified in the joint fluid. Chon. tacept (Option A), the anti-interleukin-6 receptor antibody drocalcinosis, visible as a thin white line that tracks below tocilizumab (Option D), and the oral targeted synthetic the surface layer of the cartilage within the joint. may be Janus kinase inhibitor tofacitinib (Option E). However, visible on plain radiograph. Flxtensive soft tissue calcifica these agents are usually used after failure or intolerance of tion such as seen in this radiograph is not typical of CPPD. a TNF inhibitor. Furthermore, this patient has signiflcant 141

Answers and Critiques comorbidities that should prompt caution with consid Arthritis is common in patients with systemic lupus eration of these therapies. Abatacept has been associated ery,thematosus (SLE) (Option D). SLE arthritis can have an with exacerbations of COPD in clinical trials but not in acute or subacute onseti can be mono . oligo . or poll,artic real world practice. However. it must be given cautiously ular; frequently affects small joints of the hands. elbon's. and in patients with COPD. Tocilizumab increases the risk for knees: and can lead to malalignment deformities similar to bowel perforation in patients with a history of diverticuli- rheumatoid arthritis. However. SLE arthritis does not lead tis, and tofacitinib poses an increased risk for thrombotic to underlying bony erosions as seen in rheumatoid arthritis. events. The number of joints involved is usually fbrt'er than seen in Anakinra (Option C) is an interleukin-1 blocker rheumatoid arthritis. Characteristic mucocutaneous flnd approved for rheumatoid arthritis. but it is less efficacious ings of SLE accompany arthritis onset. including malar rash. than other biologics and rarely used for this indication. discoid rash, and alopecia. Systemic involvement (e.g.. leu kopenia. thrombocytopenia, nephritis) may also be present. TEY POIXI D Almost all patients with SLE will be positive for antinuclear vt o Patients with rheumatoid arthritis not responding to antibodies. Because this patient lacks any additional features € .D methotrexate, with or without another nonbiologic of SLE. and because positivity for anti cyclic citrullinated UI disease modiffing antirheumatic drug, could receive peptide antibodies is not a feature of SLE arthritis. a diagno o, triple therapy (methotrexate, sulfasalazine, and sis of SLE is unlikely. EL hydroxychloroquine) or a biologic agent. n f,EY POITIS

comorbidities that should prompt caution with consid Arthritis is common in patients with systemic lupus eration of these therapies. Abatacept has been associated ery,thematosus (SLE) (Option D). SLE arthritis can have an with exacerbations of COPD in clinical trials but not in acute or subacute onseti can be mono . oligo . or poll,artic real world practice. However. it must be given cautiously ular; frequently affects small joints of the hands. elbon's. and in patients with COPD. Tocilizumab increases the risk for knees: and can lead to malalignment deformities similar to bowel perforation in patients with a history of diverticuli- rheumatoid arthritis. However. SLE arthritis does not lead tis, and tofacitinib poses an increased risk for thrombotic to underlying bony erosions as seen in rheumatoid arthritis. events. The number of joints involved is usually fbrt'er than seen in Anakinra (Option C) is an interleukin-1 blocker rheumatoid arthritis. Characteristic mucocutaneous flnd approved for rheumatoid arthritis. but it is less efficacious ings of SLE accompany arthritis onset. including malar rash. than other biologics and rarely used for this indication. discoid rash, and alopecia. Systemic involvement (e.g.. leu kopenia. thrombocytopenia, nephritis) may also be present. TEY POIXI D Almost all patients with SLE will be positive for antinuclear vt o Patients with rheumatoid arthritis not responding to antibodies. Because this patient lacks any additional features € .D methotrexate, with or without another nonbiologic of SLE. and because positivity for anti cyclic citrullinated UI disease modiffing antirheumatic drug, could receive peptide antibodies is not a feature of SLE arthritis. a diagno o, triple therapy (methotrexate, sulfasalazine, and sis of SLE is unlikely. EL hydroxychloroquine) or a biologic agent. n f,EY POITIS Bibliography o Rheumatoid arthritis is characterized by the subacute lr onset of pain and swelling in multiple small joints of Smolen JS, Landewd RBM, Bijlsnla lWJ. d al. EULAR recommendations fbr .D the management of rheun'latoid rrthritis with synthetic and biological ut the hands and feet, associated with prolonged morn- disease-modifying antirheumatic drugs, 2019 update. Ann Rheum Dis. 2O2O:79 :685 699. IPMl D: 319693281 ing stiffness and physical examination evidence of polyarticu lar synoviti s. . Laboratory studies supporting the diagnosis of rheu Item 37 Answer: C matoid arthritis include rheumatoid factor, anti-cyclic Educational Objective: Diagnose rheumatoid arthritis. citrullinated peptide antibodies, and elevated inflam- matory markers. The most likely diagnosis is rheumatoid arthritis (Option C). Rheumatoid arthritis is characterized by the subacute Bibliography onset of pain and swelling in multiple joints, including the Sparks JA. Rheumatoid arthritis. Ann lntern l\{ed. 2019:170:lTCl ITCl6. proximal interphalangeal joints of the hands and feet, meta IPMID: 305968791 doi: 10.7326 AITC2OI90l0l0 carpophalangeal and metatarsophalangeal joints, wrists, knees, and ankles. Prolonged morning stiffness is common; physical examination reveals polyarticular synovitis. Joint Item 38 Answer: B involvement is characteristically symmetric. Distal interpha- Educational Objective: Screen for cancer in a patient langeal joints are rarely. ilever, involved. Laboratory studies with dermatomyositis. supporting the diagnosis include rheumatoid factor (present in 7O"/,, of patients. but of limited specificity), anti-cyclic The most appropriate test to perform next is a colonos citrullinated peptide antibodies (present in 70'l,, of patients copy (Option B). This patient has dermatomyositis. A mus- and 9511, specific), and elevated inflammatory markers. cle biopsy is not necessary to diagnose dermatoml,ositis in Arthritis due to chikungunya virus (Option A) may patients with characteristic clinical and laboratory findings, mimic rheumatoid arthritis with polyarticular involvement including proximal muscle weakness. strikingly elevated of small and large joints. Onset is typically more rapid than serum creatine kinase levels. and skin manifestations that in rheumatoid arthritis; follows travel to endemic areas: and are unique to dermatomyositis. The most typical feature is is preceded by fever, headaches, and rash. Autoantibodies the Gottron rash (Gottron papules and Gottron sign), which would not be expected to be positive, although inflamma is characterized by erythematous to violaceous areas over the tory markers may be elevated. metacarpophalangeal and proximal interphalangeal joints. Parvovirus B19 infection (Option B) causes a symmet There is an association between risk for malignancy and ric inflammatory arthritis involving the hands that mimics dermatomyositis (3- to 12-fold higher in patients with new rheumatoid arthritis. Although polyarticular synovitis may dermatomyositis than in age-matched populations) and, to a be present initially, joint swelling resolves in days to weeks lesser extent, polymyositis. The risk for malignancy is great in most cases. Onset typically occurs after exposure to a par est in the 3 years following the diagnosis of dermatomyositis vovirus-infected child, such as in a daycare setting. Adults or polymyositis. Common associated cancers are ovarian. with parvovirus B19 arthritis usually do not display the char lung, pancreas, stomach, and colon cancer and lymphoma. acteristic "slapped cheek" rash seen in children. Anti cyclic The most important initial step is symptom-directed test- citrullinated antibodies are typically absent. ing and age and sex-appropriate cancer screening because

Bibliography o Rheumatoid arthritis is characterized by the subacute lr onset of pain and swelling in multiple small joints of Smolen JS, Landewd RBM, Bijlsnla lWJ. d al. EULAR recommendations fbr .D the management of rheun'latoid rrthritis with synthetic and biological ut the hands and feet, associated with prolonged morn- disease-modifying antirheumatic drugs, 2019 update. Ann Rheum Dis. 2O2O:79 :685 699. IPMl D: 319693281 ing stiffness and physical examination evidence of polyarticu lar synoviti s. . Laboratory studies supporting the diagnosis of rheu Item 37 Answer: C matoid arthritis include rheumatoid factor, anti-cyclic Educational Objective: Diagnose rheumatoid arthritis. citrullinated peptide antibodies, and elevated inflam- matory markers. The most likely diagnosis is rheumatoid arthritis (Option C). Rheumatoid arthritis is characterized by the subacute Bibliography onset of pain and swelling in multiple joints, including the Sparks JA. Rheumatoid arthritis. Ann lntern l\{ed. 2019:170:lTCl ITCl6. proximal interphalangeal joints of the hands and feet, meta IPMID: 305968791 doi: 10.7326 AITC2OI90l0l0 carpophalangeal and metatarsophalangeal joints, wrists, knees, and ankles. Prolonged morning stiffness is common; physical examination reveals polyarticular synovitis. Joint Item 38 Answer: B involvement is characteristically symmetric. Distal interpha- Educational Objective: Screen for cancer in a patient langeal joints are rarely. ilever, involved. Laboratory studies with dermatomyositis. supporting the diagnosis include rheumatoid factor (present in 7O"/,, of patients. but of limited specificity), anti-cyclic The most appropriate test to perform next is a colonos citrullinated peptide antibodies (present in 70'l,, of patients copy (Option B). This patient has dermatomyositis. A mus- and 9511, specific), and elevated inflammatory markers. cle biopsy is not necessary to diagnose dermatoml,ositis in Arthritis due to chikungunya virus (Option A) may patients with characteristic clinical and laboratory findings, mimic rheumatoid arthritis with polyarticular involvement including proximal muscle weakness. strikingly elevated of small and large joints. Onset is typically more rapid than serum creatine kinase levels. and skin manifestations that in rheumatoid arthritis; follows travel to endemic areas: and are unique to dermatomyositis. The most typical feature is is preceded by fever, headaches, and rash. Autoantibodies the Gottron rash (Gottron papules and Gottron sign), which would not be expected to be positive, although inflamma is characterized by erythematous to violaceous areas over the tory markers may be elevated. metacarpophalangeal and proximal interphalangeal joints. Parvovirus B19 infection (Option B) causes a symmet There is an association between risk for malignancy and ric inflammatory arthritis involving the hands that mimics dermatomyositis (3- to 12-fold higher in patients with new rheumatoid arthritis. Although polyarticular synovitis may dermatomyositis than in age-matched populations) and, to a be present initially, joint swelling resolves in days to weeks lesser extent, polymyositis. The risk for malignancy is great in most cases. Onset typically occurs after exposure to a par est in the 3 years following the diagnosis of dermatomyositis vovirus-infected child, such as in a daycare setting. Adults or polymyositis. Common associated cancers are ovarian. with parvovirus B19 arthritis usually do not display the char lung, pancreas, stomach, and colon cancer and lymphoma. acteristic "slapped cheek" rash seen in children. Anti cyclic The most important initial step is symptom-directed test- citrullinated antibodies are typically absent. ing and age and sex-appropriate cancer screening because 142

Answers and Critiques patients with active malignancy associated with dermato- anakinra and canakinumab, has been successful. Anti inter- myositis need prompt. appropriate treatment fbr both can leukin 6 therapies have shown promise. cer and the autoimmune disease. lf an initial directed cancer Like AOSD, familial Mediterranean f'ever (FMF) (Option screen is normal, many experts will order CT of the chest, B) is a disease of systemic inflammation; it is also associated abdomen, and pelvis. Because this patient has unintentional with fever, joint pain, abdominal pain, and rash in the set weight loss and anemia, the flrst test should be a colonos- ting of high inflammatory markers. However, patients with copy to assess for colorectal cancer. FMF typically experience lifelong recurrent intermittent Results of antinuclear antibody testing (Option A) are episodes of inflammatory disease, typically lasting several positive in about 50'X, of patients with dermatomyositis, but days and occurring approximately monthly, rather than the a positive result would not meaningfully add to the diagnos persistent inflammatory state experienced by this patient. tic or prognostic evaluation. Patients with infectious endocarditis (Option C) expe Muscle biopsy (Option C) would likely confirm the rience fevers, petechial rashes, and arthritis/arthralgia. diagnosis and can be useful to improve understanding Although infectious endocarditis should always be consid UI o of prognosis. However, this test is not necessary to diag- ered in patients with fever ol unknown origin, the pattern ET nose dermatomyositis when the clinical features are this of daily evening fevers accompanied by salmon pink rash is typical. not characteristic, and the lack of a cardiac murmur argues (J Pulmonary function testing (Option D) and other against the diagnosis. -t evaluation for lung disease may also be warranted in most Patients with systemic lupus erythematosus (SLE) tg patients with dermatomyositis. especially those with symp (Option D) may experience a wide constellation of symp- UI (l, toms or findings, antisynthetase antibodies, or factors pos toms, including rash, arthritis, and serositis. Fever in SLE ing high risk for interstitial lung disease. In a patient without UI may be present but is not typically as high as seen here, and = E active pulmonary symptoms, however, this testing is less it does not cycle daily. Moreover, the salmon pink rash seen urgent than is an evaluation for cancer. here, directly associated with fever, is not characteristic of SLE. SLE is much less common in men, n.raking it less likely I(EY POITTS in this patient. . A muscle biopsy is not necessary to diagnose dermat omyositis in patients with characteristic clinical and f,EY POII{T laboratory findings, including proximal muscle weak- . Adult onset Still disease, a condition of unknown ness, strikingly elevated serum creatine kinase levels, cause, is characterized by daily evening fevers; and skin manifestations that are unique to dermato- salmon pink rash; inflammatory arthritis; sore throatl myositis. serositis; and Iaboratory findings of high inflamma- o The risk for malignancy is 3- to 12 fold higher in tory markers, elevated ferritin level, and leukocytosis. patients with new dermatomyositis than in age matched populations; symptom-driven testing Bibliography Giacomelli R. Ruscitti P, Shoenfbld \'. A comprehensi\.e review on ,dult and age- and sex appropriate cancer screening are onset Still's disease. J Autoimmun. 2018193:2.1 36. IPMID: 300771'251 indicated.

patients with active malignancy associated with dermato- anakinra and canakinumab, has been successful. Anti inter- myositis need prompt. appropriate treatment fbr both can leukin 6 therapies have shown promise. cer and the autoimmune disease. lf an initial directed cancer Like AOSD, familial Mediterranean f'ever (FMF) (Option screen is normal, many experts will order CT of the chest, B) is a disease of systemic inflammation; it is also associated abdomen, and pelvis. Because this patient has unintentional with fever, joint pain, abdominal pain, and rash in the set weight loss and anemia, the flrst test should be a colonos- ting of high inflammatory markers. However, patients with copy to assess for colorectal cancer. FMF typically experience lifelong recurrent intermittent Results of antinuclear antibody testing (Option A) are episodes of inflammatory disease, typically lasting several positive in about 50'X, of patients with dermatomyositis, but days and occurring approximately monthly, rather than the a positive result would not meaningfully add to the diagnos persistent inflammatory state experienced by this patient. tic or prognostic evaluation. Patients with infectious endocarditis (Option C) expe Muscle biopsy (Option C) would likely confirm the rience fevers, petechial rashes, and arthritis/arthralgia. diagnosis and can be useful to improve understanding Although infectious endocarditis should always be consid UI o of prognosis. However, this test is not necessary to diag- ered in patients with fever ol unknown origin, the pattern ET nose dermatomyositis when the clinical features are this of daily evening fevers accompanied by salmon pink rash is typical. not characteristic, and the lack of a cardiac murmur argues (J Pulmonary function testing (Option D) and other against the diagnosis. -t evaluation for lung disease may also be warranted in most Patients with systemic lupus erythematosus (SLE) tg patients with dermatomyositis. especially those with symp (Option D) may experience a wide constellation of symp- UI (l, toms or findings, antisynthetase antibodies, or factors pos toms, including rash, arthritis, and serositis. Fever in SLE ing high risk for interstitial lung disease. In a patient without UI may be present but is not typically as high as seen here, and = E active pulmonary symptoms, however, this testing is less it does not cycle daily. Moreover, the salmon pink rash seen urgent than is an evaluation for cancer. here, directly associated with fever, is not characteristic of SLE. SLE is much less common in men, n.raking it less likely I(EY POITTS in this patient. . A muscle biopsy is not necessary to diagnose dermat omyositis in patients with characteristic clinical and f,EY POII{T laboratory findings, including proximal muscle weak- . Adult onset Still disease, a condition of unknown ness, strikingly elevated serum creatine kinase levels, cause, is characterized by daily evening fevers; and skin manifestations that are unique to dermato- salmon pink rash; inflammatory arthritis; sore throatl myositis. serositis; and Iaboratory findings of high inflamma- o The risk for malignancy is 3- to 12 fold higher in tory markers, elevated ferritin level, and leukocytosis. patients with new dermatomyositis than in age matched populations; symptom-driven testing Bibliography Giacomelli R. Ruscitti P, Shoenfbld \'. A comprehensi\.e review on ,dult and age- and sex appropriate cancer screening are onset Still's disease. J Autoimmun. 2018193:2.1 36. IPMID: 300771'251 indicated. Bibliography Item 40 Answer: C Qiang JK. Kim WB. Biribergenova A. et tl. Risk of maligniinc) in dermato Educational Objective: Treat fibromyalgia in a patient myositis and polymyositis. J Cutan Med Surg. 2017;21:l3l 136. [PMID: 'lts:tltzgl with depression and anxiety. The most appropriate treatment is duloxetine (Option C). Item 39 Answer: A ln addition to discussing the diagnosis at length and pro Ed u cati o n a I Obj ective : Diagnose adult-onset Still disease. viding education regarding nonpharmacologic recommen dations, such as low impact aerobic exercise, a medication The most Iikely diagnosis is adult onset Still disease (AOSD) is warranted. Choice of pharmacologic therapy is based (Option A). This patient's symptoms (daily evening fevers on symptom proflle, patient comorbidities, and medication accompanied by salmon-pink rash, inflammatory arthritis, adverse effects because few trials have directly compared sore throat, and serositis) and laboratory evidence ol high the efflcacy of medications. Of the available choices, duloxe inflammatory markers and leukocytosis are most consistent tine (a serotonin norepinephrine reuptake inhibitor) is most with AOSD, a condition of unknown cause. His high serum appropriate tbr a patient with fibromyalgia and comorbid ferritin level, although not specific, is fairly characteristic of depression and anxiety because it is FDA approved for these AOSD. Because no speciflc test exists fbr AOSD, it remains a indications as well. Duloxetine should be started at 30 mgrd diagnosis of exclusion, and other causes should be consid and titrated to 60 mg/d after a week or so to mitigate nausea, ered. Past treatment options for AOSD, including glucocor a frequent early adverse effect that usually dissipates over ticoids and methotrexate, were frequently inadequate. The time. If the drug is stopped, a slow taper should be used use of interleukin-p directed biologic therapies, including because withdrawal symptoms often occur with sudden

Bibliography Item 40 Answer: C Qiang JK. Kim WB. Biribergenova A. et tl. Risk of maligniinc) in dermato Educational Objective: Treat fibromyalgia in a patient myositis and polymyositis. J Cutan Med Surg. 2017;21:l3l 136. [PMID: 'lts:tltzgl with depression and anxiety. The most appropriate treatment is duloxetine (Option C). Item 39 Answer: A ln addition to discussing the diagnosis at length and pro Ed u cati o n a I Obj ective : Diagnose adult-onset Still disease. viding education regarding nonpharmacologic recommen dations, such as low impact aerobic exercise, a medication The most Iikely diagnosis is adult onset Still disease (AOSD) is warranted. Choice of pharmacologic therapy is based (Option A). This patient's symptoms (daily evening fevers on symptom proflle, patient comorbidities, and medication accompanied by salmon-pink rash, inflammatory arthritis, adverse effects because few trials have directly compared sore throat, and serositis) and laboratory evidence ol high the efflcacy of medications. Of the available choices, duloxe inflammatory markers and leukocytosis are most consistent tine (a serotonin norepinephrine reuptake inhibitor) is most with AOSD, a condition of unknown cause. His high serum appropriate tbr a patient with fibromyalgia and comorbid ferritin level, although not specific, is fairly characteristic of depression and anxiety because it is FDA approved for these AOSD. Because no speciflc test exists fbr AOSD, it remains a indications as well. Duloxetine should be started at 30 mgrd diagnosis of exclusion, and other causes should be consid and titrated to 60 mg/d after a week or so to mitigate nausea, ered. Past treatment options for AOSD, including glucocor a frequent early adverse effect that usually dissipates over ticoids and methotrexate, were frequently inadequate. The time. If the drug is stopped, a slow taper should be used use of interleukin-p directed biologic therapies, including because withdrawal symptoms often occur with sudden 143

Answers and Critiques discontinuation. Patients should be made aware that ben- major osteoporosis-related fracture). Thus, treatment for efits of the medication will not be seen for several weeks. glucocorticoid-induced osteoporosis is appropriate. This To measure interval improvement, the Fibromyalgia Impact approach also applies to patients at moderate or interme Questionnaire (a validated clinical tool) or other validated diate risk for fracture (FRAX risk score for the hip ofl?, to clinical tool should be completed before and an appropriate 3%); those with a score of 10% to 19'1, overall would also be time after an intervention to assess change in clinical status. a candidate for preventive treatment. Oral bisphosphonates, Although amitriptyline (Option A) is an acceptable such as alendronate, are flrst-line therapy because of their off label therapy for flbromyalgia, it is sedating and not efficacy, cost, availability, and ease of administration. They appropriate for someone with a job such as truck driving. are preferred in guidelines not only because ofcost, safety, Amitriptyline is not an effective antidepressant at the low and e{ficacy but also because ofa lack ofsuperiority ofother doses recommended for flbromyalgia. osteoporosis medications. Clinical trial data show that both Diclofenac (Option B) is an NSAID. Anti-inflammatory alendronate and risedronate have elficacy in glucocorticoid D medications, including NSAIDs and glucocorticoids, are not induced osteoporosis. For patients who cannot tolerate oral Ut more effective than placebo in treating flbromyalgia. bisphosphonates or have other circumstances precluding € .D Pregabalin (Option D), although an FDA-approved med their use, intravenous zoledronic acid may be used. ar. ication for flbromyalgia, is not the best option fbr someone Calcitonin (Option B) is not typically used to treat or o, with a physically hazardous occupation because both seda prevent glucocorticoid induced osteoporosis because effi EL tion and dizziness are frequent adverse effects. Pregabalin cacy data are lacking and other, more effective drugs are n would also not address this patient's depression or anxiety. available. It Although tramadol (Option E) is helpful fbr treating Romosozumab (Option C) is a dual anabolic and anti E fibromyalgia in the short term, prescribing an opioid is inap- resorptive agent that works by inhibiting sclerostin. No data .D UI propriate in a patient with a history of opioid use disorder or yet support the use of romosozumab for preventing or treat someone with a job that requires a constant state of alertness. ing glucocorticoid-induced osteoporosis. Other options are teriparatide (a parathyroid hormone I(EY POI]ITS analogue) (Option D) and denosumab (a receptor activator r Choice of pharmacologic therapy for fibromyalgia is of nuclear factor rB [RANK] ligand inhibitor). Teriparatide based on symptom profile, patient comorbidities, and is the next best option for patients who cannot tolerate medication adverse effects. bisphosphonates or who continue to sustain fractures while o Duloxetine is appropriate for a patient with fibromy taking bisphosphonates. However, it is not the preferred first algia and comorbid depression and anxiety because it choice for this patient. Denosumab is used as a backup to is approved for these indications as well. bisphosphonates and teriparatide, primarily because of the increased risk for vertebral fracture after discontinuation.

discontinuation. Patients should be made aware that ben- major osteoporosis-related fracture). Thus, treatment for efits of the medication will not be seen for several weeks. glucocorticoid-induced osteoporosis is appropriate. This To measure interval improvement, the Fibromyalgia Impact approach also applies to patients at moderate or interme Questionnaire (a validated clinical tool) or other validated diate risk for fracture (FRAX risk score for the hip ofl?, to clinical tool should be completed before and an appropriate 3%); those with a score of 10% to 19'1, overall would also be time after an intervention to assess change in clinical status. a candidate for preventive treatment. Oral bisphosphonates, Although amitriptyline (Option A) is an acceptable such as alendronate, are flrst-line therapy because of their off label therapy for flbromyalgia, it is sedating and not efficacy, cost, availability, and ease of administration. They appropriate for someone with a job such as truck driving. are preferred in guidelines not only because ofcost, safety, Amitriptyline is not an effective antidepressant at the low and e{ficacy but also because ofa lack ofsuperiority ofother doses recommended for flbromyalgia. osteoporosis medications. Clinical trial data show that both Diclofenac (Option B) is an NSAID. Anti-inflammatory alendronate and risedronate have elficacy in glucocorticoid D medications, including NSAIDs and glucocorticoids, are not induced osteoporosis. For patients who cannot tolerate oral Ut more effective than placebo in treating flbromyalgia. bisphosphonates or have other circumstances precluding € .D Pregabalin (Option D), although an FDA-approved med their use, intravenous zoledronic acid may be used. ar. ication for flbromyalgia, is not the best option fbr someone Calcitonin (Option B) is not typically used to treat or o, with a physically hazardous occupation because both seda prevent glucocorticoid induced osteoporosis because effi EL tion and dizziness are frequent adverse effects. Pregabalin cacy data are lacking and other, more effective drugs are n would also not address this patient's depression or anxiety. available. It Although tramadol (Option E) is helpful fbr treating Romosozumab (Option C) is a dual anabolic and anti E fibromyalgia in the short term, prescribing an opioid is inap- resorptive agent that works by inhibiting sclerostin. No data .D UI propriate in a patient with a history of opioid use disorder or yet support the use of romosozumab for preventing or treat someone with a job that requires a constant state of alertness. ing glucocorticoid-induced osteoporosis. Other options are teriparatide (a parathyroid hormone I(EY POI]ITS analogue) (Option D) and denosumab (a receptor activator r Choice of pharmacologic therapy for fibromyalgia is of nuclear factor rB [RANK] ligand inhibitor). Teriparatide based on symptom profile, patient comorbidities, and is the next best option for patients who cannot tolerate medication adverse effects. bisphosphonates or who continue to sustain fractures while o Duloxetine is appropriate for a patient with fibromy taking bisphosphonates. However, it is not the preferred first algia and comorbid depression and anxiety because it choice for this patient. Denosumab is used as a backup to is approved for these indications as well. bisphosphonates and teriparatide, primarily because of the increased risk for vertebral fracture after discontinuation. Bibliography t(EY POll{TS Mactarlane GJ. Kronisch C. Dean LE. et al. I:ULAR revised recommendations Ibr the management ol fibromyalgia. Ann Rheum Dis. 2017;76:318-328. o Glucocorticoid therapy is a major risk factor for bone IPMID, 27377815) doi:10.11 36/annrheumdis 2016 209724 loss and increased fracture risk. . Patients receiving long-term glucocorticoids should Item 41 Answer: A be assessed for bone loss and fracture risk and treated on the basis of the assessment. Educational Objective: Treat glucocorticoid-induced osteoporosis with an oral bisphosphonate. Bibliography The most appropriate treatment is alendronate (Option A). Buckley L, Cuyatt G, Fink HA, et al. 2017 American College ofRheumatologr Glucocorticoid therapy is a major risk factor for bone loss guideline fbr the prevention and treatment of glucocorticoid induced osteoporosis. Arthritis Rheumatol. 2017 ;69:1521 1537. IPMID: 28585373] and increased fracture risk. In addition, fractures occur at higher bone mineral density values than in patients with postmenopausal osteoporosis. The risk increases with dos Item 42 Answer: D age and duration, but even low dosages of5 to 7.5 mg/d are Educational Objective: Diagnose a mechanical associated with increased risk for fracture. Thus, patients soft-tissue injury. receiving long term glucocorticoids should be assessed for bone loss and fracture risk and treated on the basis of the This patient has a mechanical soft tissue injury (Option D), assessment. Both bone density measurement and gluco likely lateral epicondylitis. Common nonarticular sources corticoid-corrected (addition of 15'2, to the risk), Fracture of musculoskeletal symptoms are the soft tissues (tendons, Risk Assessment Tool (FRAX)-calculated, 10 year proba ligaments, and bursae) around or away from the joints. bility can be helpful in this assessment. This patient has Isolated tendon and/or ligament involvement usually sug- a corrected FRAX score for the hip of 3.5'1,, placing her at gests noninflammatory disorders, such as mechanical a high risk for fracture and above the treatment thresh- injury/irritation, overuse, or degeneration (e.g., rotator cuff old to prevent hip fracture (>s'2, at the hip or >20% for disorders or tennis elbow).

Bibliography t(EY POll{TS Mactarlane GJ. Kronisch C. Dean LE. et al. I:ULAR revised recommendations Ibr the management ol fibromyalgia. Ann Rheum Dis. 2017;76:318-328. o Glucocorticoid therapy is a major risk factor for bone IPMID, 27377815) doi:10.11 36/annrheumdis 2016 209724 loss and increased fracture risk. . Patients receiving long-term glucocorticoids should Item 41 Answer: A be assessed for bone loss and fracture risk and treated on the basis of the assessment. Educational Objective: Treat glucocorticoid-induced osteoporosis with an oral bisphosphonate. Bibliography The most appropriate treatment is alendronate (Option A). Buckley L, Cuyatt G, Fink HA, et al. 2017 American College ofRheumatologr Glucocorticoid therapy is a major risk factor for bone loss guideline fbr the prevention and treatment of glucocorticoid induced osteoporosis. Arthritis Rheumatol. 2017 ;69:1521 1537. IPMID: 28585373] and increased fracture risk. In addition, fractures occur at higher bone mineral density values than in patients with postmenopausal osteoporosis. The risk increases with dos Item 42 Answer: D age and duration, but even low dosages of5 to 7.5 mg/d are Educational Objective: Diagnose a mechanical associated with increased risk for fracture. Thus, patients soft-tissue injury. receiving long term glucocorticoids should be assessed for bone loss and fracture risk and treated on the basis of the This patient has a mechanical soft tissue injury (Option D), assessment. Both bone density measurement and gluco likely lateral epicondylitis. Common nonarticular sources corticoid-corrected (addition of 15'2, to the risk), Fracture of musculoskeletal symptoms are the soft tissues (tendons, Risk Assessment Tool (FRAX)-calculated, 10 year proba ligaments, and bursae) around or away from the joints. bility can be helpful in this assessment. This patient has Isolated tendon and/or ligament involvement usually sug- a corrected FRAX score for the hip of 3.5'1,, placing her at gests noninflammatory disorders, such as mechanical a high risk for fracture and above the treatment thresh- injury/irritation, overuse, or degeneration (e.g., rotator cuff old to prevent hip fracture (>s'2, at the hip or >20% for disorders or tennis elbow). 144

Answers and Critiques The elbow is a very unlikely location for a degenera- with vaccinations 2 to 4 weeks before initiating immu- tive joint disease (Option A), such as osteoarthritis. Localized nomodulatory agents, but this is not easy to accomplish. osteoarlhritis, in which a single joint is affected, is more often a Evidence suggests attenuation of response to vaccines in consequence of injury or joint asymmetry and often occurs in patients receiving biologic agents. Patients receiving tra weight bearing joints (hip or knee), not the elbows or shoul ditional immunomodulatory agents (disease modifying ders. Because this patient has no history of injury and has full antirheumatic drugs) in doses that cause only low grade range of elbow motion, localized osteoarthritis is unlikely. immunosuppression can receive any immunizations, killed Disorders of central pain processing (Option B), such or live, without any problems. Low-grade immunosuppres as fibromyalgia, have hyperresponsive pain centers in the sion is deflned as short term prednisone use of less than brain and spinal cord. Patients characteristically note allody- 20 mgld, methotrexate dosage of less than 0.4 mg/kg/wk, nia (a heightened sensitivity to stimuli that are not normally and azathioprine dosage of less than 3.0 mg/kg/d. Patients painful) and hyperalgesia (an increased response to painful who are receiving these immunosuppressive agents at higher stimuli). An additional characteristic feature is "wind up" dosages should not receive live vaccines. Similarly, patients t o or temporal summation. When repeatedly exposed to a receiving biologic or small-molecule therapies should not ET mildly uncomfortable stimulus, patients with flbromyalgia receive live vaccines, such as measles, mumps, and rubella, experience progressively additive pain, indicating that the or live attenuated vaccines, such as influenza and herpes (, pain stimuli are both persistent and inadequately damped. zoster, because ofrisk for infection by the vaccine agent. In -tE Finally, patients fypically have difluse rather than localized this patient, methotrexate at a low dosage (0.2 mg/kg/wk) ag pain. This patient has no features characteristic of a central would not constitute a contraindication to administration vt L pain processing disorder. The local nature of her pain also !, of any vaccination. However, she is also is being treated argues against flbromyalgia. which is a disease of wide with tofacitinib, and vaccination with measles, mumps, and vt = E spread pain. rubella is therefore contraindicated. The differentiation between inflammatory and non- The hepatitis B virus (Option A), quadrivalent influenza inflammatory signs and symptoms is central to the evalu (Option C), tetanus toxoid, reduced diphtheria toxoid, and ation of patients with musculoskeletal pain. Autoimmune acellular pertussis (Option D), and 13 valent pneumococcal conditions typically present with inflammation, whereas conjugate (Option E) are killed vaccines and are not contra mechanical or degenerative disorders are characteristically indicated in this patient. noninflammatory. The cardinal signs of inflammation are f,EY POII{T pain, erythema, swelling, and warmth; with the excep, tion of pain, noninflammatory conditions usually lack these . Patients receiving biologic or small-molecule thera- features. These features are absent in this patient, making pies should not receive live vaccines (such as measles, inflammatory arthritis (Option C) an unlikely diagnosis. mumps, and rubella) or live attenuated vaccines (such as influenza and herpes zoster) because of risk for I(EY POITTS infection by the vaccine agent. . Isolated tendon and/or ligament involvement usually suggests noninflammatory disorders, such as mechan- Bibliography ical injury/irritation, overuse, or degeneration. Furer V, Rondaan C, Heijstek MW, et al. 2019 update of EULAR recommen . The cardinal signs of inflammation are pain, ery- dations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020;79:39 52. IPMID: et+tgOOSl thema, swelling, and warmth; with the exception of pain, noninflammatory conditions usually lack these features. Item 44 Answer: B Educational Objective: Confirm the diagnosis of Bibliography rheumatoid arthritis with autoantibody testing. Ilatten R. Coady D. The rheumatological examination. Medicine. 2018;46:161 165. doi.orgi 10. l0161j.mpmed.2O17.12.OO2 The combination of anti-cyclic citrullinated peptide (CCP) antibodies and rheumatoid lactor (Option B) will be most helpful in establishing the diagnosis. Among some Item 43 Answer: B 100 genetic loci currently recognized as associated with Educational Objedive: Avoid live vaccines in a patient rheumatoid arthritis (RA) risk, the most important is the receiving biologic therapy. class II HLA group, especially HLA D alleles. These alleles code for the shared epitope, a five-amino acid sequence that The measles, mumps, and rubella vaccine (Option B) is binds and presents citrullinated peptide antigens important contraindicated in this patient. Patients with autoimmune in the pathophysiologz of RA. Because citrulline is an amino rheumatologic diseases, such as rheumatoid arthritis, are acid that does not normally occur in humans, citrullinated at increased risk for infections because of multiple factors, proteins are immunogenic, especially in people who also and infection prevention and vaccination are crucial. Ide- have the shared epitope. Citrulline is formed by the action of ally, patients with autoimmune diseases should be updated the enzyme peptidylarginine deiminase, which is found at

The elbow is a very unlikely location for a degenera- with vaccinations 2 to 4 weeks before initiating immu- tive joint disease (Option A), such as osteoarthritis. Localized nomodulatory agents, but this is not easy to accomplish. osteoarlhritis, in which a single joint is affected, is more often a Evidence suggests attenuation of response to vaccines in consequence of injury or joint asymmetry and often occurs in patients receiving biologic agents. Patients receiving tra weight bearing joints (hip or knee), not the elbows or shoul ditional immunomodulatory agents (disease modifying ders. Because this patient has no history of injury and has full antirheumatic drugs) in doses that cause only low grade range of elbow motion, localized osteoarthritis is unlikely. immunosuppression can receive any immunizations, killed Disorders of central pain processing (Option B), such or live, without any problems. Low-grade immunosuppres as fibromyalgia, have hyperresponsive pain centers in the sion is deflned as short term prednisone use of less than brain and spinal cord. Patients characteristically note allody- 20 mgld, methotrexate dosage of less than 0.4 mg/kg/wk, nia (a heightened sensitivity to stimuli that are not normally and azathioprine dosage of less than 3.0 mg/kg/d. Patients painful) and hyperalgesia (an increased response to painful who are receiving these immunosuppressive agents at higher stimuli). An additional characteristic feature is "wind up" dosages should not receive live vaccines. Similarly, patients t o or temporal summation. When repeatedly exposed to a receiving biologic or small-molecule therapies should not ET mildly uncomfortable stimulus, patients with flbromyalgia receive live vaccines, such as measles, mumps, and rubella, experience progressively additive pain, indicating that the or live attenuated vaccines, such as influenza and herpes (, pain stimuli are both persistent and inadequately damped. zoster, because ofrisk for infection by the vaccine agent. In -tE Finally, patients fypically have difluse rather than localized this patient, methotrexate at a low dosage (0.2 mg/kg/wk) ag pain. This patient has no features characteristic of a central would not constitute a contraindication to administration vt L pain processing disorder. The local nature of her pain also !, of any vaccination. However, she is also is being treated argues against flbromyalgia. which is a disease of wide with tofacitinib, and vaccination with measles, mumps, and vt = E spread pain. rubella is therefore contraindicated. The differentiation between inflammatory and non- The hepatitis B virus (Option A), quadrivalent influenza inflammatory signs and symptoms is central to the evalu (Option C), tetanus toxoid, reduced diphtheria toxoid, and ation of patients with musculoskeletal pain. Autoimmune acellular pertussis (Option D), and 13 valent pneumococcal conditions typically present with inflammation, whereas conjugate (Option E) are killed vaccines and are not contra mechanical or degenerative disorders are characteristically indicated in this patient. noninflammatory. The cardinal signs of inflammation are f,EY POII{T pain, erythema, swelling, and warmth; with the excep, tion of pain, noninflammatory conditions usually lack these . Patients receiving biologic or small-molecule thera- features. These features are absent in this patient, making pies should not receive live vaccines (such as measles, inflammatory arthritis (Option C) an unlikely diagnosis. mumps, and rubella) or live attenuated vaccines (such as influenza and herpes zoster) because of risk for I(EY POITTS infection by the vaccine agent. . Isolated tendon and/or ligament involvement usually suggests noninflammatory disorders, such as mechan- Bibliography ical injury/irritation, overuse, or degeneration. Furer V, Rondaan C, Heijstek MW, et al. 2019 update of EULAR recommen . The cardinal signs of inflammation are pain, ery- dations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020;79:39 52. IPMID: et+tgOOSl thema, swelling, and warmth; with the exception of pain, noninflammatory conditions usually lack these features. Item 44 Answer: B Educational Objective: Confirm the diagnosis of Bibliography rheumatoid arthritis with autoantibody testing. Ilatten R. Coady D. The rheumatological examination. Medicine. 2018;46:161 165. doi.orgi 10. l0161j.mpmed.2O17.12.OO2 The combination of anti-cyclic citrullinated peptide (CCP) antibodies and rheumatoid lactor (Option B) will be most helpful in establishing the diagnosis. Among some Item 43 Answer: B 100 genetic loci currently recognized as associated with Educational Objedive: Avoid live vaccines in a patient rheumatoid arthritis (RA) risk, the most important is the receiving biologic therapy. class II HLA group, especially HLA D alleles. These alleles code for the shared epitope, a five-amino acid sequence that The measles, mumps, and rubella vaccine (Option B) is binds and presents citrullinated peptide antigens important contraindicated in this patient. Patients with autoimmune in the pathophysiologz of RA. Because citrulline is an amino rheumatologic diseases, such as rheumatoid arthritis, are acid that does not normally occur in humans, citrullinated at increased risk for infections because of multiple factors, proteins are immunogenic, especially in people who also and infection prevention and vaccination are crucial. Ide- have the shared epitope. Citrulline is formed by the action of ally, patients with autoimmune diseases should be updated the enzyme peptidylarginine deiminase, which is found at 145

Answers and Critiques sites ol inflammation and deiminates arginine to form citrul patients with inclusion body myositis have cricopharyngeal Iinated peptides. Anti-CCP antibodies are closely associated muscle involvement, leading to dysphagia and increased risk with the pathogenesis of RA and are highly speciflc (9S'1,). fbr aspiration. Patients with inclusion body myositis can have In addition, anti-CCP antibodies may be positive in patients elevated serum creatine kinase levels. but elevations are usu with RA who are negative for rheumatoid factor. Rheumatoid ally more modest, less than 10 times the upper limit of normal, factor is less speciflc tbr RA, is present in only about 70'l. of as compared with other forms of idiopathic inflammatory patients with RA, and may be seen in other diseases (such as myopathies in which serum creatine kinase levels are gener hepatitis C virus infection, endocarditis, and systemic lupus ally higher. A muscle biopsy can help to conflrm the diagnosis erythematosus). However, a f'ew patients, particularly early but is not needed when clinical fbatures are characteristic. in the course of the disease, may be negative for anti CCP Polymyositis (Option B) can also present with prcigres antibodies but positive for rheumatoid factor; thus, both anti sive muscle weakness. However, it generally progresses more CCP antibodies and rheumatoid factor, rather than either rapidly over weeks or months and involves only the proximal D alone (Options A, D), should be measured to increase the muscles. Activities such as arising from a chaiq climbing UI diagnostic speciflcity and sensitivity of testing. When they stairs, and lifting objects above shoulder height are typically E are present together, their specificity is further increased. afl'ected. Onset over several years with a more modest degree .D - U) tsoth antibodies are included in the diagnostic criteria for RA. of weakness, as seen in this patient, would be unusual in poly q, The complement system is an essential part ol the myositis. In addition, polymyositis would not be expected to CL immune response, promoting vasodilation, attracting leu cause weakness of the hands or the distal arm muscles. a.l kocytes, and assisting in the lysis of opsonized bacteria Statins are generally safe and well tolerated. 'lhey can ll during humoral immunity. Complement components, such cause asymptomatic. dose related elevations in aminotrans E as C3 and C4 (Option C), are acute phase reactants that t'erase levels in approximately 1'l, of patients, but liver injury .D l^ are synthesized in the liver and rise in many inflammatory occurs in less than 0.001'X, ofpatients. The incidence ofstatin states. However, in response to diseases that lead to immune associated muscle symptoms is no greater than 1u1,, and the complex formation (systemic lupus erythematosus; cryo incidence of myopathy (Option C) and rhabdomyolysis is globulinemic and urticarial vasculitis) and other states, such less than 0.1'ln. However, some patients can have muscle as inlections (bacterial endocarditis, sepsis, viremia) and symptoms from statin therapy without an elevation in serum glomerulonephritis, complement cascades are activated, and creatine kinase levels. and it can then be difficult to be cer serum C3 and C4 levels fall because of excessive consump tain whether muscle symptoms are due to statin therapy. tion. Although serum C3 and C,1 levels may be elevated in '[he patient's prolonged course, minor serum creatine kinase patients with RA, this nonspecific finding will not be helpful elevation. and muscie weakness distribution are more char in establishing the diagnosis. acteristic of inclusion body myositis than statin myopathy. Other autoimmune disorders, such as systemic lupus rEY POIIITS erythematosus (Option D), can cause myositis. However, r Anti cyclic citrullinated peptide antibodies are a diag- they generally have other characteristic features, such as nostic marker of rheumatoid arthritis and have a high arthralgia and skin rashes, that are not seen in this patient. specificity (95%) but may be absent in early disease I(EY POII{T when rheumatoid factor is positive. o lnclusion body myositis can be distinguished from . The presence of both anti-cyclic citrullinated peptide other forms of idiopathic inflammatory myopathy by an antibodies and rheumatoid factor increases the diag insidious onset, slower progression, and involvement of nostic likelihood of rheumatoid arthritis. distal muscle groups as well as proximal muscles.

sites ol inflammation and deiminates arginine to form citrul patients with inclusion body myositis have cricopharyngeal Iinated peptides. Anti-CCP antibodies are closely associated muscle involvement, leading to dysphagia and increased risk with the pathogenesis of RA and are highly speciflc (9S'1,). fbr aspiration. Patients with inclusion body myositis can have In addition, anti-CCP antibodies may be positive in patients elevated serum creatine kinase levels. but elevations are usu with RA who are negative for rheumatoid factor. Rheumatoid ally more modest, less than 10 times the upper limit of normal, factor is less speciflc tbr RA, is present in only about 70'l. of as compared with other forms of idiopathic inflammatory patients with RA, and may be seen in other diseases (such as myopathies in which serum creatine kinase levels are gener hepatitis C virus infection, endocarditis, and systemic lupus ally higher. A muscle biopsy can help to conflrm the diagnosis erythematosus). However, a f'ew patients, particularly early but is not needed when clinical fbatures are characteristic. in the course of the disease, may be negative for anti CCP Polymyositis (Option B) can also present with prcigres antibodies but positive for rheumatoid factor; thus, both anti sive muscle weakness. However, it generally progresses more CCP antibodies and rheumatoid factor, rather than either rapidly over weeks or months and involves only the proximal D alone (Options A, D), should be measured to increase the muscles. Activities such as arising from a chaiq climbing UI diagnostic speciflcity and sensitivity of testing. When they stairs, and lifting objects above shoulder height are typically E are present together, their specificity is further increased. afl'ected. Onset over several years with a more modest degree .D - U) tsoth antibodies are included in the diagnostic criteria for RA. of weakness, as seen in this patient, would be unusual in poly q, The complement system is an essential part ol the myositis. In addition, polymyositis would not be expected to CL immune response, promoting vasodilation, attracting leu cause weakness of the hands or the distal arm muscles. a.l kocytes, and assisting in the lysis of opsonized bacteria Statins are generally safe and well tolerated. 'lhey can ll during humoral immunity. Complement components, such cause asymptomatic. dose related elevations in aminotrans E as C3 and C4 (Option C), are acute phase reactants that t'erase levels in approximately 1'l, of patients, but liver injury .D l^ are synthesized in the liver and rise in many inflammatory occurs in less than 0.001'X, ofpatients. The incidence ofstatin states. However, in response to diseases that lead to immune associated muscle symptoms is no greater than 1u1,, and the complex formation (systemic lupus erythematosus; cryo incidence of myopathy (Option C) and rhabdomyolysis is globulinemic and urticarial vasculitis) and other states, such less than 0.1'ln. However, some patients can have muscle as inlections (bacterial endocarditis, sepsis, viremia) and symptoms from statin therapy without an elevation in serum glomerulonephritis, complement cascades are activated, and creatine kinase levels. and it can then be difficult to be cer serum C3 and C4 levels fall because of excessive consump tain whether muscle symptoms are due to statin therapy. tion. Although serum C3 and C,1 levels may be elevated in '[he patient's prolonged course, minor serum creatine kinase patients with RA, this nonspecific finding will not be helpful elevation. and muscie weakness distribution are more char in establishing the diagnosis. acteristic of inclusion body myositis than statin myopathy. Other autoimmune disorders, such as systemic lupus rEY POIIITS erythematosus (Option D), can cause myositis. However, r Anti cyclic citrullinated peptide antibodies are a diag- they generally have other characteristic features, such as nostic marker of rheumatoid arthritis and have a high arthralgia and skin rashes, that are not seen in this patient. specificity (95%) but may be absent in early disease I(EY POII{T when rheumatoid factor is positive. o lnclusion body myositis can be distinguished from . The presence of both anti-cyclic citrullinated peptide other forms of idiopathic inflammatory myopathy by an antibodies and rheumatoid factor increases the diag insidious onset, slower progression, and involvement of nostic likelihood of rheumatoid arthritis. distal muscle groups as well as proximal muscles. Bibliography Bibliography \Vlrburtor.r L, Hider St.. Mallen CD. et al. Suspected very early inflammatory rheumatic diseases in prinrirry cart. Best Pract Res CIin Rheumatol. l.undberg lE, de \risser M. Werth Vll Chssilication ol m),-ositis. Nat Rev 2019:33:101,119. IPMID: 318105501 doi: 10. lOl6r'j.berh.2019.06.001 Rheunratol. 2O18:14i269 278. lPMll): 2965112i1 doi:l0.1038inrrheunr. 201rJ.4l

Bibliography Bibliography \Vlrburtor.r L, Hider St.. Mallen CD. et al. Suspected very early inflammatory rheumatic diseases in prinrirry cart. Best Pract Res CIin Rheumatol. l.undberg lE, de \risser M. Werth Vll Chssilication ol m),-ositis. Nat Rev 2019:33:101,119. IPMID: 318105501 doi: 10. lOl6r'j.berh.2019.06.001 Rheunratol. 2O18:14i269 278. lPMll): 2965112i1 doi:l0.1038inrrheunr. 201rJ.4l Item 45 Answer: A Ed u cati o na I O bj ective : Diagnose inclusion body myositis. 'lhe most likely diagnosis is inclusion body myositis (Option ttem 46 Answer: C Educational Objective: Treat systemic lupus tr erythematosus with nephritis. A). h.rclusion body myositis is an uncommon cause of weak 'lhe most appropriate treatlrent is prednisone plus hldrory ness generally seen in older adults, characterized by a slow insidious onset. It can be distinguished clinically from poly chlorocluine and mycophenolirte mofetil (Option C)' this myositis by the involvement of distal muscle groups in addition prtient has new onset s1'sten-ric lupus erythematosus (SI.F.) to proximal muscle groups. Weakness in flnger flexors and r,r,ith nephritis. t.upr.rs nephritis can present with rrlini atrophy of tbrearm muscles are characteristic features. Muscle r.r.ral laboratory abnorntalities (non nephrotic proteinuria. distribution is usually but not always symmetric. Up to half of hcmaturia), fiank neph ril is ( hypertensiort, lower extreln i ty 146

Answers and Critiques tr CONT. edema, active urine sediment, and elevated serum creati nine level), and/or nephrosis (nephrotic range proteinuria. dependent edema, and thrombosis). Anti double-stranded and mouth breathing are among the most common causes of dry mouth. Her symptoms do not suggest a speciflc rheuma- tologic disorder. In particular, she is unlikely to have Sjogren DNA antibody titers are a marker for risk, and complement syndrome (Option C). Oral dryness is a common symp consumption is a common phenomenon during active kid tom, whereas Sjdgren syndrome is relatively rare. She has ney disease. Untreated active disease may progress to kidney no ocular dryness; has a serologic proflle that does not com tailure. He has f'ew other symptoms ot'SLE, but laboratory port with a diagnosis of Sj0gren syndrome (absence of high findings and clinicai presentation strongly suggest this diag titers of antinuclear antibodies and/or rheumatoid factor, nosis. Although kidney biopsy is indicated to determine anti Ro/SSA, and anti LalSSB autoantibodies); and has no histologic subtlpe and chronicity, treatment should not be other symptoms, physical examination flndings, or labora delayed. I{igh dose or "pulse" glucocorticoicls are indicated tory results to suggest the disease. Although it is not impos- fbr new or recurrent active nephritis and should be fblloued sible that she has Sj6gren syndrome, the oral dryness is more by a glucocorticoid taper. Ilydroxychloroquine is indicated likely the result of another cause. Several medications (such ur (u in almost all patients rn'ith newly diagnosed SLE. In addition, as antidepressants and antihistamines) frequently cause oral ET fbr moderate or severe disease that is organ threatening, dryness. The patient takes three such medications (amitripty i additional immunosuppressive therapy is indicated to con- line, cetirizine, and citalopram). It is important that patients (J trol disease and to allow {br tapering of glucocorticoid ther like this are not misdiagnosed with rheumatologic disease !t apy. For most patients with new nephritis, induction with and treated inappropriately with immunosuppressive agents. rE mycophenolate mof'etil is the preferred agent. lntravenous Hypothyroidism in adults (Option A) is often associated U!

tr CONT. edema, active urine sediment, and elevated serum creati nine level), and/or nephrosis (nephrotic range proteinuria. dependent edema, and thrombosis). Anti double-stranded and mouth breathing are among the most common causes of dry mouth. Her symptoms do not suggest a speciflc rheuma- tologic disorder. In particular, she is unlikely to have Sjogren DNA antibody titers are a marker for risk, and complement syndrome (Option C). Oral dryness is a common symp consumption is a common phenomenon during active kid tom, whereas Sjdgren syndrome is relatively rare. She has ney disease. Untreated active disease may progress to kidney no ocular dryness; has a serologic proflle that does not com tailure. He has f'ew other symptoms ot'SLE, but laboratory port with a diagnosis of Sj0gren syndrome (absence of high findings and clinicai presentation strongly suggest this diag titers of antinuclear antibodies and/or rheumatoid factor, nosis. Although kidney biopsy is indicated to determine anti Ro/SSA, and anti LalSSB autoantibodies); and has no histologic subtlpe and chronicity, treatment should not be other symptoms, physical examination flndings, or labora delayed. I{igh dose or "pulse" glucocorticoicls are indicated tory results to suggest the disease. Although it is not impos- fbr new or recurrent active nephritis and should be fblloued sible that she has Sj6gren syndrome, the oral dryness is more by a glucocorticoid taper. Ilydroxychloroquine is indicated likely the result of another cause. Several medications (such ur (u in almost all patients rn'ith newly diagnosed SLE. In addition, as antidepressants and antihistamines) frequently cause oral ET fbr moderate or severe disease that is organ threatening, dryness. The patient takes three such medications (amitripty i additional immunosuppressive therapy is indicated to con- line, cetirizine, and citalopram). It is important that patients (J trol disease and to allow {br tapering of glucocorticoid ther like this are not misdiagnosed with rheumatologic disease !t apy. For most patients with new nephritis, induction with and treated inappropriately with immunosuppressive agents. rE mycophenolate mof'etil is the preferred agent. lntravenous Hypothyroidism in adults (Option A) is often associated U! cyclophosphamide can also be used if patients have severe with a buming sensation of the mouth, but oral dryness is o disease or are intolerant to mycophenolate. not a commonly reported symptom. This patient has appro- = a

cyclophosphamide can also be used if patients have severe with a buming sensation of the mouth, but oral dryness is o disease or are intolerant to mycophenolate. not a commonly reported symptom. This patient has appro- = a Prednisone plus azathioprine (Option A) could be used priately treated hypothyroidism, with a normal thyroid- as maintenance therapy; typically along with hydroxychlor stimulating hormone level, making this diagnosis unlikely. oquine. but azathioprine is not first-line therapy fbr ner.r, This patient's history review of systems, and physical onset lupus nephritis. examination do not suggest systemic lupus ery.thematosus Prednisone plus hydroxychloroquine (Option B) (Option D). Prominently absent from this patient's history is appropriate initial therapy for mild SLE. However, in are indications ofskin disease, serositis, and kidney disease; a patient with organ threatening disease, such as lupus other than dry mouth, the physical examination is normal. nephritis, combination immunosuppressant tl-rerapy that The normal ery.throcyte sedimentation rate argues against a includes mycophenolate mofetil or cyclophosphamide is system inflammatory or autoimmune condition. An antinu rreeded to control the disease. clear antibody titer of 1:80 is nonspecific and unremarkable Prednisone alone (Option D) will help control immedi and may be seen in up to 50% of persons tested. Even at much ate symptoms, but nithout additional immunosuppressive higher titers, a positive antinuclear antibody result alone does agents, return of disease activity is likely as the prednisone not imply the presence of systemic lupus erythematosus. dosage is tapered. Prolonged use ofmoderate or high-dose t(EY PO$tT5 glucocorticoids is associated r.tith a r,ariety of adl.erse out comes and should be avoided. o ]\{edications, such as antidepressants and antihista- mines, and mouth breathing are common causes of (EY POITT' drymouth. . For systemic lupus erythematosus that is organ- . In the absence of additional suggestive symptoms, threatening, combination immunosuppressive physical findings, and supporting laboratory data, oral therapy is indicated to control disease. dryness should not be attributed to a rheumatologic o For most patients with newly diagnosed lupus nephri- condition. tis, induction with glucocorticoids and mycophenolate mofetil is the preferred immunosuppressive treatment. Bibliography Shiboski CH, Shiboski SC, Seror R, et al; International Sjogren's Syndrome Bibliography Criteria 'Working Group. 2016 American College of Rheumatolos// European League Against Rheumatism classification criteria fbr primary Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR Sjdgren's syndrome: a consensus and data driven methodolos/ involving recommendations for the management of systemic lupus erythematosus. three international patient cohorts. Ann Rheum Dis. 2ol7;76:9 16. Ann Rheum Dis.2019;78:736 745. [PMID: 30926722] IPMID : 27 7 a9 4661 doi : 1 0. 113 6 /annrheumdis 201 6 21057 7

Prednisone plus azathioprine (Option A) could be used priately treated hypothyroidism, with a normal thyroid- as maintenance therapy; typically along with hydroxychlor stimulating hormone level, making this diagnosis unlikely. oquine. but azathioprine is not first-line therapy fbr ner.r, This patient's history review of systems, and physical onset lupus nephritis. examination do not suggest systemic lupus ery.thematosus Prednisone plus hydroxychloroquine (Option B) (Option D). Prominently absent from this patient's history is appropriate initial therapy for mild SLE. However, in are indications ofskin disease, serositis, and kidney disease; a patient with organ threatening disease, such as lupus other than dry mouth, the physical examination is normal. nephritis, combination immunosuppressant tl-rerapy that The normal ery.throcyte sedimentation rate argues against a includes mycophenolate mofetil or cyclophosphamide is system inflammatory or autoimmune condition. An antinu rreeded to control the disease. clear antibody titer of 1:80 is nonspecific and unremarkable Prednisone alone (Option D) will help control immedi and may be seen in up to 50% of persons tested. Even at much ate symptoms, but nithout additional immunosuppressive higher titers, a positive antinuclear antibody result alone does agents, return of disease activity is likely as the prednisone not imply the presence of systemic lupus erythematosus. dosage is tapered. Prolonged use ofmoderate or high-dose t(EY PO$tT5 glucocorticoids is associated r.tith a r,ariety of adl.erse out comes and should be avoided. o ]\{edications, such as antidepressants and antihista- mines, and mouth breathing are common causes of (EY POITT' drymouth. . For systemic lupus erythematosus that is organ- . In the absence of additional suggestive symptoms, threatening, combination immunosuppressive physical findings, and supporting laboratory data, oral therapy is indicated to control disease. dryness should not be attributed to a rheumatologic o For most patients with newly diagnosed lupus nephri- condition. tis, induction with glucocorticoids and mycophenolate mofetil is the preferred immunosuppressive treatment. Bibliography Shiboski CH, Shiboski SC, Seror R, et al; International Sjogren's Syndrome Bibliography Criteria 'Working Group. 2016 American College of Rheumatolos// European League Against Rheumatism classification criteria fbr primary Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR Sjdgren's syndrome: a consensus and data driven methodolos/ involving recommendations for the management of systemic lupus erythematosus. three international patient cohorts. Ann Rheum Dis. 2ol7;76:9 16. Ann Rheum Dis.2019;78:736 745. [PMID: 30926722] IPMID : 27 7 a9 4661 doi : 1 0. 113 6 /annrheumdis 201 6 21057 7 Item 47 Answer: B Item 48 Answer: B Educational Objective: Diagnose medication-induced Ed u cati o na I O bj ective : Diagnose hypersensitivity xerostomia. vasculitis.

Item 47 Answer: B Item 48 Answer: B Educational Objective: Diagnose medication-induced Ed u cati o na I O bj ective : Diagnose hypersensitivity xerostomia. vasculitis. The most likely cause of this patient's oral dryness is medi- The most likely diagnosis is hypersensitivity vasculitis cation adverse effects (Option B). Medication adverse effects (Option B), a limited cutaneous small vessel vasculitis. 147

Answers and Critiques This patient has a vasculitic rash, with a large crop of pete- Bibliography chiae and palpable purpura. The appearance of the rash Frumholtz I-. I-aurent Roussei S, Lipsker D, et al. Cutaneous vasculitis: suggests small-vessel rather than medium vessel involve- reviei( on diagnosis and clinicopathologic correlations. CIin Rev Allerg' Immunol.2020. [PMID:32378145] doi:10.1007 s12016 020 08788 l ment (for example, there are no subcutaneous nodules or necrosis). Several types ofsmall vessel vasculitis can affect the skin. The first step in the evaluation of a cutaneous Answer: E Item 49 vasculitis is to determine whether systemic symptoms or flndings are present. In this case, no flndings suggest a sys- Educational Objective: Screen for Hl-{-B's8:Ol allele temic illness. The physical examination is unremarkable before starting allopurinol therapy. aside from the rash, and results of laboratory testing are The most appropriate management is HIA 8'58:01 allele test similarly unrevealing. This strongly suggests that the diag ing (Option E). Presence of this allele has been associated with nosis is hypersensitivity vasculitis. This condition is often a higher incidence of allopurinol hlpersensitivity Testing for triggered by medications (thiazide diuretics are among this allele is conditionally recommended by the American Col- Ut the most lrequent culprits) or infections, although about lege of Rheumatologr (ACR) in high-risk populations (includ € (D 50'1, of patients have no known precipitant. Drug-induced ing persons ofKorean, Han Chinese, Thai, and African descent, ut hypersensitivity vasculitis most often occurs 7 to 10 days in whom HLA-B'58:01 is more common) before initiation of o, after the introduction of a new medication, and recovery allopurinol given the potential severity of a hypersensitivity EL is likely with discontinuation of the drug. If symptoms reaction. This reaction is heralded by a rash that may progress n persist or recur, anti-inflammatory agents, topical or low to DRESS (drug reaction with eosinophilia and systemic rymp dose systemic glucocorticoids, colchicine, or dapsone may toms) syndrome (DRESS is also increasingly being referred ,tr E be helpful. to as drug induced hypersensitivity syndrome [DIHS] and .D .,t This presentation is not congruent with eosinophilic drug hypersensitivity syndrome [DHS]). Hypersensitivity to granulomatosis with polyangiitis (Option A). This systemic allopurinol may also include Stevens Johnson syndrome and small vessel vasculitis invariably involves the lungs (usually toxic epidermal necrolysis. This patient has risk factors for with a prodromal phase of rhinitis and asthma and other allopurinol hypersensitivity, including Han Chinese descent. pulmonary manifestations with disease progression) and and should undergo HLA-B'58:01 allele testing. Additional often affects the peripheral nervous system and skin. Lab risk factors for severe cutaneous reactions include female sex, oratory testing reveals the presence of ANCA antibodies history of rash with allopurinol, and concurrent use of thia- (myeloperoxidase subtype) about half the time, and periph- zide or loop diuretics. Drug hypersensitivity can still occur in eral eosinophilia is expected. patients negative for the HLA 8'58:01 allele, and patients must Polyarteritis nodosa (Option C) is unlikely. Although be counseled to stop the drug immediately if a rash occurs. it can present with palpable purpura, as in small-vessel If the allele is present, allopurinol (Option A) should vasculitis, other skin flndings indicating medium-vessel be avoided and a different urate-lowering agent, such as involvement would be present (e.g., livedo reticularis, sub febuxostat (Option C), should be used. However, allopurinol cutaneous nodules, painful deep ulcers, or skin necrosis). remains the urate lowering drug of choice, and caution This patient has no other features of polyarteritis nodosa, should be used when prescribing febuxostat to patients with such as constitutional and musculoskeletal symptoms, a history of cardiovascular disease. Allele testing remains peripheral nervous system involvement, or gastrointestinal the best choice for this patient. Allopurinol desensitization disease. is conditionally recommended for patients with a previ- Rheumatoid vasculitis (Option D) is rare. It develops ous allergic response to allopurinol who cannot be treated in patients with long-standing and severe rheumatoid with other oral urate-lowering agents, such as febuxostat or arthritis and is almost nonexistent in properly treated probenecid. patients. It most often affects the skin but is a medium- Low-dose aspirin can raise the serum urate level vessel vasculitis. This patient does not have rheuma through renal uric acid retention. However, the ACR con- toid arthropathy; thus, rheumatoid vasculitis is not a ditionally recommends against stopping aspirin (Option B) possibility. in patients with gout who are taking it for appropriate indi cations. This patient should continue his low dose aspirin as secondary prevention of coronary artery disease events. XEY POIilTS Abacavir is a nucleoside analog used in the treatment ol o The first step in the evaluation of a cutaneous vasculi HIV infection. Abacavir is associated with a severe hypersen tis is to determine whether systemic symptoms or sitivity reaction in individuals identifled by the HLA-B-57:01 findings are present. allele (Option D). Patients who are prescribed abacavir must . Hypersensitivity vasculitis, a limited cutaneous small- flrst undergo testing to show they are HLA 8'57:01 negati've vessel vasculitis, is often triggered by medications or in order to reduce the risk for a hypersensitivity reaction. As with allopurinol, absence of the allele does not protect infections, although about 50% ofpatients have no patients from hypersensitivity reactions, and appropriate known precipitant. counseling should be provided.

This patient has a vasculitic rash, with a large crop of pete- Bibliography chiae and palpable purpura. The appearance of the rash Frumholtz I-. I-aurent Roussei S, Lipsker D, et al. Cutaneous vasculitis: suggests small-vessel rather than medium vessel involve- reviei( on diagnosis and clinicopathologic correlations. CIin Rev Allerg' Immunol.2020. [PMID:32378145] doi:10.1007 s12016 020 08788 l ment (for example, there are no subcutaneous nodules or necrosis). Several types ofsmall vessel vasculitis can affect the skin. The first step in the evaluation of a cutaneous Answer: E Item 49 vasculitis is to determine whether systemic symptoms or flndings are present. In this case, no flndings suggest a sys- Educational Objective: Screen for Hl-{-B's8:Ol allele temic illness. The physical examination is unremarkable before starting allopurinol therapy. aside from the rash, and results of laboratory testing are The most appropriate management is HIA 8'58:01 allele test similarly unrevealing. This strongly suggests that the diag ing (Option E). Presence of this allele has been associated with nosis is hypersensitivity vasculitis. This condition is often a higher incidence of allopurinol hlpersensitivity Testing for triggered by medications (thiazide diuretics are among this allele is conditionally recommended by the American Col- Ut the most lrequent culprits) or infections, although about lege of Rheumatologr (ACR) in high-risk populations (includ € (D 50'1, of patients have no known precipitant. Drug-induced ing persons ofKorean, Han Chinese, Thai, and African descent, ut hypersensitivity vasculitis most often occurs 7 to 10 days in whom HLA-B'58:01 is more common) before initiation of o, after the introduction of a new medication, and recovery allopurinol given the potential severity of a hypersensitivity EL is likely with discontinuation of the drug. If symptoms reaction. This reaction is heralded by a rash that may progress n persist or recur, anti-inflammatory agents, topical or low to DRESS (drug reaction with eosinophilia and systemic rymp dose systemic glucocorticoids, colchicine, or dapsone may toms) syndrome (DRESS is also increasingly being referred ,tr E be helpful. to as drug induced hypersensitivity syndrome [DIHS] and .D .,t This presentation is not congruent with eosinophilic drug hypersensitivity syndrome [DHS]). Hypersensitivity to granulomatosis with polyangiitis (Option A). This systemic allopurinol may also include Stevens Johnson syndrome and small vessel vasculitis invariably involves the lungs (usually toxic epidermal necrolysis. This patient has risk factors for with a prodromal phase of rhinitis and asthma and other allopurinol hypersensitivity, including Han Chinese descent. pulmonary manifestations with disease progression) and and should undergo HLA-B'58:01 allele testing. Additional often affects the peripheral nervous system and skin. Lab risk factors for severe cutaneous reactions include female sex, oratory testing reveals the presence of ANCA antibodies history of rash with allopurinol, and concurrent use of thia- (myeloperoxidase subtype) about half the time, and periph- zide or loop diuretics. Drug hypersensitivity can still occur in eral eosinophilia is expected. patients negative for the HLA 8'58:01 allele, and patients must Polyarteritis nodosa (Option C) is unlikely. Although be counseled to stop the drug immediately if a rash occurs. it can present with palpable purpura, as in small-vessel If the allele is present, allopurinol (Option A) should vasculitis, other skin flndings indicating medium-vessel be avoided and a different urate-lowering agent, such as involvement would be present (e.g., livedo reticularis, sub febuxostat (Option C), should be used. However, allopurinol cutaneous nodules, painful deep ulcers, or skin necrosis). remains the urate lowering drug of choice, and caution This patient has no other features of polyarteritis nodosa, should be used when prescribing febuxostat to patients with such as constitutional and musculoskeletal symptoms, a history of cardiovascular disease. Allele testing remains peripheral nervous system involvement, or gastrointestinal the best choice for this patient. Allopurinol desensitization disease. is conditionally recommended for patients with a previ- Rheumatoid vasculitis (Option D) is rare. It develops ous allergic response to allopurinol who cannot be treated in patients with long-standing and severe rheumatoid with other oral urate-lowering agents, such as febuxostat or arthritis and is almost nonexistent in properly treated probenecid. patients. It most often affects the skin but is a medium- Low-dose aspirin can raise the serum urate level vessel vasculitis. This patient does not have rheuma through renal uric acid retention. However, the ACR con- toid arthropathy; thus, rheumatoid vasculitis is not a ditionally recommends against stopping aspirin (Option B) possibility. in patients with gout who are taking it for appropriate indi cations. This patient should continue his low dose aspirin as secondary prevention of coronary artery disease events. XEY POIilTS Abacavir is a nucleoside analog used in the treatment ol o The first step in the evaluation of a cutaneous vasculi HIV infection. Abacavir is associated with a severe hypersen tis is to determine whether systemic symptoms or sitivity reaction in individuals identifled by the HLA-B-57:01 findings are present. allele (Option D). Patients who are prescribed abacavir must . Hypersensitivity vasculitis, a limited cutaneous small- flrst undergo testing to show they are HLA 8'57:01 negati've vessel vasculitis, is often triggered by medications or in order to reduce the risk for a hypersensitivity reaction. As with allopurinol, absence of the allele does not protect infections, although about 50% ofpatients have no patients from hypersensitivity reactions, and appropriate known precipitant. counseling should be provided. 148

Answers and Criti ques rEY POI IIIS t(EY POlt{IS o Presence ofthe HLA-B.58:01 allele has been associ- . Total joint replacement is a curative option for patients ated with a higher incidence of allopurinol hypersen- with osteoarthritis in whom conservative therapy has sitivity and is more prevalent in persons of Korean, failed; it relieves pain and improves function. Han Chinese, Thai, and African descent. . The American College of Rheumatologr/Arthritis o Testing for the HLA-B.58:01 allele is recommended in Foundation recommends against the use of chondroi- high-risk populations before initiation of allopurinol tin sulfate (with or without glucosamine), biologics, given the potential severity of a hypersensitivity intra-articular hyaluronic acid, platelet-rich plasma, reaction. stem cells. or botulinum toxin in the treatment of knee osteoarthritis. Bibliography FitzGerald JD, Dalbeth N, Mikuls 1l et al. 2020 American College of Bibliography 9t Rheumatolos/ guideline for the management ol gout. Arthritis Care Res c, (Hoboken). 2020;72:744 760. [PMID: 323919341 doi:10.1002/acr.24180 Kolasinski SL. Neogi 1. llochberg M(1, et al.2019 American (irllege ol' RheumatololyiArthritis I,bundation guideline tbr the management of E osteoarthritis ol the hand. hip. ancl knee. Arthritis Rheumatol. 2020: L 7 2:220 233. I PM I D: 3 I 9081 63 I doi : I 0. l002irrt..4 I 1.'12 rr, Item 50 Answer: E =, .! Educational Objective: Treat advanced, symptomatic ah osteoarthritis with joint replacement surgery. Item 51 Answer: D o Educational Objective: Diagnose polyarteritis nodosa. ut The most appropriate treatment is total knee replacement = (Option E). This patient has osteoarthritis (OA) that has Magr.retic resonilnce angiographv ol the abtiomen (Option not responded to nonpharmacologic and pharmacologic D) is nrost liliely to establish the diagnosis. lhe nrost lil<cly approaches and is limiting function. Total joint replace cliagnosis is polyarteritis r.rodosir (PAN), a nredium vessel ment is a curative option for patients in whom conservative r,asculitis. The patient hls an inllarnrnatory disease n,ith therapy has failedl it relieves pain and improves function. neu, onset kidney disease but rtrithout evidence of glonrcru Overall, outcomes are excellent, with small risk for hardware lar involvernent. Unlike small vessel '"'asculitis, r,r'l-riclr causes loosening and Iate infection. Osteotomy is an alternative for glomerulonephritis, t']AN afiects the renal virsculirturcr there younger patients with varus or valgus knee and predomi fbre. it does not generallv cause rn active urinary secli nantiy unicompartmental disease. rnenl but can crusc rcnal insufficiencl- rnd hypertension. Multiple high quality studies have shown that 'lhe nodular skin lesions sLlggest r-neclium vessel virsculitis. arthroscopic surgery for knee OA (Option A) provides no The postprlr.tdial abdominal pain points to nrcscnteric iscl.r advantage over conservative management unless joint buck emia. 'lhc patient has a left fbot drop. sr-rggesting periphcral ling, instabili0r, or locking is present. This patient does not nenropathl,. Mononeuritis multiplex. which c:rn be seen in have these indications. small or medium vessel disease. is cornmon in PAN. Whcn Because of lack of efhcacy, the 2019 American College a patient suspectecl ot having PAN has abdominal sympbrns. of Rheumatologz (ACR)/Arthritis Foundation (AF) guideline inraging of the mesenteric vasculature c:rn be diagnostic. In strongly recommends against the use of chondroitin sulfate this casc. rxignctic resonrnce angiography lr,ould clenron in patients with knee and/or hip OA, as well as combination stratc characteristic findings of tAN allecting the gut: lnulti products that include glucosamine and chondroitin sulfate plc iureurysms and lnminul irregularities (stenosis) in bigger (Option B). irrteries. r,t ith occlusive lesions in smaller ones. The ACR/AF guideline recommends against the use of The clinical scenario cloes not suggest any ol the hyaluronic acid injections (Option C). The guideline recog- ANCi\ rssociated vasculitides. AN(lA associirtcd vasculiti nizes the limited evidence for the benefit of this treatment. des involve small vessels, and paticnts may havc sympk)rns particularly when other alternatives have failed to provide relatecl kr the upper and loner airw:iys, kidneys (glon.rerr-rlo beneflt. Debate about the role of these injections contin- rrephritis). and eyes, ears. iu'rcl skin (pllpablc'purpura): cor.r ues because of conflicting efhcacy data across trials and stitutional s],'nlptonrs arc also comrnon. Therefbre, testing fbr meta-analyses, as well as their high cost. However, they are ANCi\ (Option A) is unlikcly to be helpful. frequently used in practice for knee OA. llepatitis A virus testing (Option B) nould not aicl in Intra-articular platelet-rich plasma (Option D) is not diagr.rosis. llepatitis IJ vims (llBV) and tllV. Ibr r,vhich the efflcacious in the treatment of knee OA. The ACR/AF guide paticnt is ncgativc. cau cilLlse PAN (and. rnure rarelyl so car-r I line strongly recommends against it; the lack of standardiza- hepatitis C virus). Heprtitis A vims docs not. Llecause IlllV tion in availabie preparations of platelet-rich plasma makes prevalence has declir.rccl since tl.re advent of the I IBV r,accir.re it difficult to identifiz exactly what is being injected. The ancl antiviral treatmcnt, the proportion ot' paticnts with guideline also recommends against other similar therapies, HBV associated PAN hls dcclitred fiom :16'2, to less than such as intra-articular injection of stem cells, biologics, or 5')1, of all IAN cascs; most contemporxry cascs are tlterefbre botulinum toxin. considerccl to irc prirnarily autoimnrunc.

rEY POI IIIS t(EY POlt{IS o Presence ofthe HLA-B.58:01 allele has been associ- . Total joint replacement is a curative option for patients ated with a higher incidence of allopurinol hypersen- with osteoarthritis in whom conservative therapy has sitivity and is more prevalent in persons of Korean, failed; it relieves pain and improves function. Han Chinese, Thai, and African descent. . The American College of Rheumatologr/Arthritis o Testing for the HLA-B.58:01 allele is recommended in Foundation recommends against the use of chondroi- high-risk populations before initiation of allopurinol tin sulfate (with or without glucosamine), biologics, given the potential severity of a hypersensitivity intra-articular hyaluronic acid, platelet-rich plasma, reaction. stem cells. or botulinum toxin in the treatment of knee osteoarthritis. Bibliography FitzGerald JD, Dalbeth N, Mikuls 1l et al. 2020 American College of Bibliography 9t Rheumatolos/ guideline for the management ol gout. Arthritis Care Res c, (Hoboken). 2020;72:744 760. [PMID: 323919341 doi:10.1002/acr.24180 Kolasinski SL. Neogi 1. llochberg M(1, et al.2019 American (irllege ol' RheumatololyiArthritis I,bundation guideline tbr the management of E osteoarthritis ol the hand. hip. ancl knee. Arthritis Rheumatol. 2020: L 7 2:220 233. I PM I D: 3 I 9081 63 I doi : I 0. l002irrt..4 I 1.'12 rr, Item 50 Answer: E =, .! Educational Objective: Treat advanced, symptomatic ah osteoarthritis with joint replacement surgery. Item 51 Answer: D o Educational Objective: Diagnose polyarteritis nodosa. ut The most appropriate treatment is total knee replacement = (Option E). This patient has osteoarthritis (OA) that has Magr.retic resonilnce angiographv ol the abtiomen (Option not responded to nonpharmacologic and pharmacologic D) is nrost liliely to establish the diagnosis. lhe nrost lil<cly approaches and is limiting function. Total joint replace cliagnosis is polyarteritis r.rodosir (PAN), a nredium vessel ment is a curative option for patients in whom conservative r,asculitis. The patient hls an inllarnrnatory disease n,ith therapy has failedl it relieves pain and improves function. neu, onset kidney disease but rtrithout evidence of glonrcru Overall, outcomes are excellent, with small risk for hardware lar involvernent. Unlike small vessel '"'asculitis, r,r'l-riclr causes loosening and Iate infection. Osteotomy is an alternative for glomerulonephritis, t']AN afiects the renal virsculirturcr there younger patients with varus or valgus knee and predomi fbre. it does not generallv cause rn active urinary secli nantiy unicompartmental disease. rnenl but can crusc rcnal insufficiencl- rnd hypertension. Multiple high quality studies have shown that 'lhe nodular skin lesions sLlggest r-neclium vessel virsculitis. arthroscopic surgery for knee OA (Option A) provides no The postprlr.tdial abdominal pain points to nrcscnteric iscl.r advantage over conservative management unless joint buck emia. 'lhc patient has a left fbot drop. sr-rggesting periphcral ling, instabili0r, or locking is present. This patient does not nenropathl,. Mononeuritis multiplex. which c:rn be seen in have these indications. small or medium vessel disease. is cornmon in PAN. Whcn Because of lack of efhcacy, the 2019 American College a patient suspectecl ot having PAN has abdominal sympbrns. of Rheumatologz (ACR)/Arthritis Foundation (AF) guideline inraging of the mesenteric vasculature c:rn be diagnostic. In strongly recommends against the use of chondroitin sulfate this casc. rxignctic resonrnce angiography lr,ould clenron in patients with knee and/or hip OA, as well as combination stratc characteristic findings of tAN allecting the gut: lnulti products that include glucosamine and chondroitin sulfate plc iureurysms and lnminul irregularities (stenosis) in bigger (Option B). irrteries. r,t ith occlusive lesions in smaller ones. The ACR/AF guideline recommends against the use of The clinical scenario cloes not suggest any ol the hyaluronic acid injections (Option C). The guideline recog- ANCi\ rssociated vasculitides. AN(lA associirtcd vasculiti nizes the limited evidence for the benefit of this treatment. des involve small vessels, and paticnts may havc sympk)rns particularly when other alternatives have failed to provide relatecl kr the upper and loner airw:iys, kidneys (glon.rerr-rlo beneflt. Debate about the role of these injections contin- rrephritis). and eyes, ears. iu'rcl skin (pllpablc'purpura): cor.r ues because of conflicting efhcacy data across trials and stitutional s],'nlptonrs arc also comrnon. Therefbre, testing fbr meta-analyses, as well as their high cost. However, they are ANCi\ (Option A) is unlikcly to be helpful. frequently used in practice for knee OA. llepatitis A virus testing (Option B) nould not aicl in Intra-articular platelet-rich plasma (Option D) is not diagr.rosis. llepatitis IJ vims (llBV) and tllV. Ibr r,vhich the efflcacious in the treatment of knee OA. The ACR/AF guide paticnt is ncgativc. cau cilLlse PAN (and. rnure rarelyl so car-r I line strongly recommends against it; the lack of standardiza- hepatitis C virus). Heprtitis A vims docs not. Llecause IlllV tion in availabie preparations of platelet-rich plasma makes prevalence has declir.rccl since tl.re advent of the I IBV r,accir.re it difficult to identifiz exactly what is being injected. The ancl antiviral treatmcnt, the proportion ot' paticnts with guideline also recommends against other similar therapies, HBV associated PAN hls dcclitred fiom :16'2, to less than such as intra-articular injection of stem cells, biologics, or 5')1, of all IAN cascs; most contemporxry cascs are tlterefbre botulinum toxin. considerccl to irc prirnarily autoimnrunc. 149

Answers and Critiques m PAN spares the glomerulus but can affect the larger Like allopurinol, f'ebuxostat (Option C) is a urate 1or,r. IIJ 1qns1 vessels, leading to hypertension and renal insuffi- ering agent that inhibits xanthine oxidase. It is indicated in coNT cien.y. A biopsy of the kidney (Option C) would therefore be patients in n,hom allopurinol has failed or lvho cannot toler nondiagnostic (unless medium vessels were included in the ate allopurinol. This patient has ner,er receired urate lowering biopsy, which would result in bleeding). therapy; therefore, febuxostat is not indicated. Probenecid (Option D) is not a preferred medication {EY POIIIIS for this patient. Allopurinol is strongly recommended as the . Polyarteritis nodosa is a medium-vessel vasculitis that preferred urate lowering agent. In addition. probenecid is affects the renal vasculature and causes nodular skin contraindicated in patients with nephrolithiasis. lesions, abdominal pain, and mononeuritis multiplex. TEY POtl{T5 . In a patient who has polyarteritis nodosa with abdominal symptoms, magnetic resonance angiogra- . Urate lowering therapy is strongly recommended for D patients with gout and any of the following indica- phy can be diagnostic. UI tions: one or more subcutaneous tophi; evidence of (D radiographic damage (any modality) attributable to = Bibliography l^ gout; or frequent gout flares, with "frequent" being De Virgilio A. Greco A. Magliulo G. et al. Polyarteritis nodosa: a contempo- q, rary overvie$,. Autoimmun Rev 2016;15:56.1 70. [PMID: 2688.1100] defined as tvvo or more episodes annually. doi:10.1016/j.autrev2016.02.015 CL rl . Allopurinol is strongly recommended as the preferred urate lowering agent, over all other agents, including l! (D art tr Item 52 Answer: A Educational Objective: Treat chronic recurrent gout with in patients with moderate to severe chronic kidney disease (stage >3). urate-lowering therapy. Bibliography The most appropriate treatment to add is aliopurinol (Option Fitzcerald JD. Dalbeth N, Mikuls T. et al. 2020 American College of A). this patient has a recent history ol gouty bursitis as well Rheumatolos/ guideline lbr the management of gout. Arthritis Care Res (Hoboken). 2O2O:72:714 760. LPMID: 32391%41 doi:10.1002racr.24180 as a history ofrecurrent episodes ofgouty arthritis. tophi. and elevated serum urate. The American College of Rheumatologr (ACR) strongly recommends initiating urate-lowering therapy Item 53 Answer: A for patients with gout and any of the following indications: Educational Objective: Treat parvovirus B19 arthropathy one or more subcutaneous tophi; evidence of radiographic damage (any modalifi) attributable to gout; or frequent gout The most appropriate treatment is an NSAID, such as flares, with "frequent" being deflned as tvvo or more annuaily diclofenac (Option A). The patient has an acute onset of This patient has two indications for urate-iowering therapy: polyarticular arthralgia with minimal flndings of inflam t'wo or more recurrent episodes per year and tophi. Allopu- matory synovitis on physical examination. The history of rinol, a xanthine oxidase inhibitor, is strongly recommended a recent febrile illness with the subsequent appearance of by the ACR as first-line urate-lowering therapy in all patients, a facial rash in the patient's child suggests parvovirus B19 including those with moderate to severe chronic kidney dis- infection (Iifth disease). Up to 60% of adults with parvovirus ease, with appropriate dose adjustments. In patients tak- B19 infection experience arthritis. It often presents acutely, ing aliopurinol, the HLA-B.58:01 allele is associated lvith a is symmetric and polyarticular, and typically involves the markedly elevated risk for acute hypersensitiviS reaction, proximal small joints of the hands. Parvovirus B19 arthri- also known as DRESS (drug reaction with eosinophilia and tis should be suspected when appropriate clinical features systemic symptoms) syndrome. Testing for the HLA-B-58:01 are present in someone who has exposure to children. allele before starting allopurinol is conditionally recom- Acute parvovirus B19 inlection is diagnosed by detecting mended for patients of southeast Asian (e.g., Han Chinese. anti parvovirus IgM antibodies in the serum. The patient's Korean, Thai) or African descent. It is appropriate to continue symptoms could also suggest rheumatoid arthritis or pso naproxen as prophylactic therapy for 3 to 6 months along with riatic arthritis, but the brief duration of symptoms does not the initiation of urate lowering therapy to prevent flares whiie permit diagnosis of either of these entities at this time. It is the serum urate level is lowered. appropriate to relieve symptoms with an NSAID but not to Colchicine (Option B) may be used for treatment of start immunosuppressive therapy now. acute gouty arthritis or for long term prevention of flares Etanercept (Option B) is a tumor necrosis factor inhib while urate-lowering therapy is initiated. If it is used to itor that can be chosen as flrst line therapy for rheumatoid prevent flares during urate lowering therapy, it should be arthritis. The diagnosis of rheumatoid arthritis would need continued for 3 to 6 months or until serum urate is at target to be conflrmed by a longer duration of symptoms and level. This patient has responded to naproxen and therefore additional laboratory testing (such as complete blood count. does not need additional acute treatment ofhis gout or addi- erythrocy.te sedimentation rate, C-reactive protein, rheuma- tional medication for prevention. Colchicine does not affect toid factor, and anti cyclic citrullinated peptide antibodies) the serum urate level. and radiographic studies.

m PAN spares the glomerulus but can affect the larger Like allopurinol, f'ebuxostat (Option C) is a urate 1or,r. IIJ 1qns1 vessels, leading to hypertension and renal insuffi- ering agent that inhibits xanthine oxidase. It is indicated in coNT cien.y. A biopsy of the kidney (Option C) would therefore be patients in n,hom allopurinol has failed or lvho cannot toler nondiagnostic (unless medium vessels were included in the ate allopurinol. This patient has ner,er receired urate lowering biopsy, which would result in bleeding). therapy; therefore, febuxostat is not indicated. Probenecid (Option D) is not a preferred medication {EY POIIIIS for this patient. Allopurinol is strongly recommended as the . Polyarteritis nodosa is a medium-vessel vasculitis that preferred urate lowering agent. In addition. probenecid is affects the renal vasculature and causes nodular skin contraindicated in patients with nephrolithiasis. lesions, abdominal pain, and mononeuritis multiplex. TEY POtl{T5 . In a patient who has polyarteritis nodosa with abdominal symptoms, magnetic resonance angiogra- . Urate lowering therapy is strongly recommended for D patients with gout and any of the following indica- phy can be diagnostic. UI tions: one or more subcutaneous tophi; evidence of (D radiographic damage (any modality) attributable to = Bibliography l^ gout; or frequent gout flares, with "frequent" being De Virgilio A. Greco A. Magliulo G. et al. Polyarteritis nodosa: a contempo- q, rary overvie$,. Autoimmun Rev 2016;15:56.1 70. [PMID: 2688.1100] defined as tvvo or more episodes annually. doi:10.1016/j.autrev2016.02.015 CL rl . Allopurinol is strongly recommended as the preferred urate lowering agent, over all other agents, including l! (D art tr Item 52 Answer: A Educational Objective: Treat chronic recurrent gout with in patients with moderate to severe chronic kidney disease (stage >3). urate-lowering therapy. Bibliography The most appropriate treatment to add is aliopurinol (Option Fitzcerald JD. Dalbeth N, Mikuls T. et al. 2020 American College of A). this patient has a recent history ol gouty bursitis as well Rheumatolos/ guideline lbr the management of gout. Arthritis Care Res (Hoboken). 2O2O:72:714 760. LPMID: 32391%41 doi:10.1002racr.24180 as a history ofrecurrent episodes ofgouty arthritis. tophi. and elevated serum urate. The American College of Rheumatologr (ACR) strongly recommends initiating urate-lowering therapy Item 53 Answer: A for patients with gout and any of the following indications: Educational Objective: Treat parvovirus B19 arthropathy one or more subcutaneous tophi; evidence of radiographic damage (any modalifi) attributable to gout; or frequent gout The most appropriate treatment is an NSAID, such as flares, with "frequent" being deflned as tvvo or more annuaily diclofenac (Option A). The patient has an acute onset of This patient has two indications for urate-iowering therapy: polyarticular arthralgia with minimal flndings of inflam t'wo or more recurrent episodes per year and tophi. Allopu- matory synovitis on physical examination. The history of rinol, a xanthine oxidase inhibitor, is strongly recommended a recent febrile illness with the subsequent appearance of by the ACR as first-line urate-lowering therapy in all patients, a facial rash in the patient's child suggests parvovirus B19 including those with moderate to severe chronic kidney dis- infection (Iifth disease). Up to 60% of adults with parvovirus ease, with appropriate dose adjustments. In patients tak- B19 infection experience arthritis. It often presents acutely, ing aliopurinol, the HLA-B.58:01 allele is associated lvith a is symmetric and polyarticular, and typically involves the markedly elevated risk for acute hypersensitiviS reaction, proximal small joints of the hands. Parvovirus B19 arthri- also known as DRESS (drug reaction with eosinophilia and tis should be suspected when appropriate clinical features systemic symptoms) syndrome. Testing for the HLA-B-58:01 are present in someone who has exposure to children. allele before starting allopurinol is conditionally recom- Acute parvovirus B19 inlection is diagnosed by detecting mended for patients of southeast Asian (e.g., Han Chinese. anti parvovirus IgM antibodies in the serum. The patient's Korean, Thai) or African descent. It is appropriate to continue symptoms could also suggest rheumatoid arthritis or pso naproxen as prophylactic therapy for 3 to 6 months along with riatic arthritis, but the brief duration of symptoms does not the initiation of urate lowering therapy to prevent flares whiie permit diagnosis of either of these entities at this time. It is the serum urate level is lowered. appropriate to relieve symptoms with an NSAID but not to Colchicine (Option B) may be used for treatment of start immunosuppressive therapy now. acute gouty arthritis or for long term prevention of flares Etanercept (Option B) is a tumor necrosis factor inhib while urate-lowering therapy is initiated. If it is used to itor that can be chosen as flrst line therapy for rheumatoid prevent flares during urate lowering therapy, it should be arthritis. The diagnosis of rheumatoid arthritis would need continued for 3 to 6 months or until serum urate is at target to be conflrmed by a longer duration of symptoms and level. This patient has responded to naproxen and therefore additional laboratory testing (such as complete blood count. does not need additional acute treatment ofhis gout or addi- erythrocy.te sedimentation rate, C-reactive protein, rheuma- tional medication for prevention. Colchicine does not affect toid factor, and anti cyclic citrullinated peptide antibodies) the serum urate level. and radiographic studies. 150

Answers and Critiques Hydroxychloroquine (Option C) is indicated for the Systematic reviews and meta-analyses suggest that acet treatment of signs and symptoms of systemic lupus erythe aminophen (Option A) provides no beneflt for hip or knee matosus, dermatoml,ositis, and rheumatoid arthritis. In the OA. Acetaminophen may be considered as add on therapy absence of a diagnosis of one of these conditions, hydroxy for short term and episodic use but is not appropriate as chloroquine is not appropriate empiric treatment fbr an initial therapy for this patient. acute polyarthritis. Duloxetine (Option B), a serotonin-norepinephrine lVlethotrexate (Option D) is appropriate flrst line ther reuptake inhibitor with central neryous system activity, has apy for rheumatoid arthritis and psoriatic arthritis. How shorn,n efllcacy for OA pain and would also be reasonable ever, before initiation of an immunosuppressive therapy. the for this patient. However, it should be used only if NSAIDs diagnosis of rheumatoid arthritis or psoriatic arthritis must are inadequate and is not the best choice for initial therapy. be confirmed. When symptoms are present for only a few Gabapentin (Option C) and pregabalin are more effec days, causes ofjoint pain and swelling, such as viral inf'ection tive than placebo in the treatment of neuropathic pain and drug reactions, are in the diftbrential diagnosis. When conditions, such as postherpetic neuralgia and diabetic t (u symptoms are present for at least 6 weeks, these diagnostic neuropathy. There is no evidence of their eflectiveness for ET possibilities become less likely and higher suspicion for chronic OA pain. Furthermore, they may be associated with rheumatologic diseases will emerge. On the basis of the time dose dependent dizziness and sedation. Thus, gabapentin is U frame over which this patient reports symptoms, initiation not appropriate for this patient. of methotrexate is not appropriate. Opioid therapy provides limited benefit fbr chronic =, IE pain control in patients with OA and poses a high risk for la I(EY POIIITS (t, toxicity and dependence. Opioid use should be avoided for o Parvovirus B19 arthropathy often presents acutely, is OA treatment. Tramadol (Option E), a partial opioid with UI = symmetric and polyarticular, and typically involves fewer adverse effects and less addictive potential than pure the proximal small joints of the hands. opioids, may be considered in some patients, but it should o Parvovirus B19 arthropathy should be suspected when be used only in limited circumstances, and never as an initial appropriate clinical features are present in someone therapy. who has exposure to children and is diagnosed by KEY POI]IIS detecting anti parvovirus IgM antibodies in the serum. . NSAIDs are often the initial treatment of choice for osteoarthritis if used judiciously in low risk patients, Bibliography with minimizing and monitoring of adverse effects. Mauermann M. Ilochiluf Stange K. Klelntrrnn A, et al. Paru^,irus inli,ction in early arthritis. Clin Exp Rheumirkrl. 2016 Mar Apr:3.1:207 13. It,l\'llI): o Acetaminophen provides no benefit for hip or knee oste 268866871 oarthritis; it may be considered as add on therapy for short term and episodic use but not as initial therapy. Item 54 Answer: D Educational Objective: Use NSAIDs for initial Bibliography osteoarthritis treatment. Kolasinski SI-. Neogi T. Hochberg MC. et al. 2019 Americilr.r College of Rheumrtololl/ Arthritis Foundirtion guideline for the mi:lncgement of ostcorrthritis of the hand. hip. and knee. Arthritis Rhcr"lnliltol. 2020i The most appropriate initial treatment for this patient with 72:220 233. IPMID: 31908163] doi:10.1002,'art.411,12 osteoarthritis (OA) is an NSAID, such as piroxicam (Option D). NSAIDs inhibit cyclooxygenase enzymes, blocking gen eration of the lipid prostaglandin E,,,. NSAIDs are efhca Item 55 Answer: B cious in OA and are strongly recommended by the 2019 Educational Objective: Treat polymyalgia rheumatica. American College of Rheumatology/Arthritis Foundation for hand, hip, and knee OA. However, their adverse efl'ect The most appropriate management is prednisone, l5 mg/d proflles make sustained use problematic, especially in older (Option B). This patient has polymyalgia rheumatica (PMR) persons and patients with comorbidities. Topical NSAIDs are characterized by symmetric proximal myalgia and stiflhess, effective and because of their saf'ety profile are preferred to accompanied by constitutional symptoms and an elevated oral NSAIDs. However, topical NSAIDs are ineffective in the C reactive protein level. Symptoms are most pronounced treatment of hip OA. For this patient with hand, knee, and in the morning and improve after several hours. Although hip OA, oral NSAIDs are the initial treatment of choice. This some patients also have peripheral arthritis (usually of the patient has no risk factors for common contraindications knees and wrists), most do not. Physical flndings are usu- and adverse effects, such as peptic ulcer disease or kidney ally limited to difficulty moving the affected areas (shoul disease. Hence, piroxicam would be a reasonable choice as ders and hips). There is no diagnostic test specific fbr PMR. initial treatment and may adequately relieve her symptoms. With a reasonable degree ol suspicion for PMR, an empiric It would also be prudent lbr the patient to take piroxicam glucocorticoid trial is appropriate. Initiating prednisone at regularly for a limited time and consider taking it as needed 12.5 to 20 mg/d is appropriate for this generally self limited in the future. illness. Symptoms usually improve dramatically within

Hydroxychloroquine (Option C) is indicated for the Systematic reviews and meta-analyses suggest that acet treatment of signs and symptoms of systemic lupus erythe aminophen (Option A) provides no beneflt for hip or knee matosus, dermatoml,ositis, and rheumatoid arthritis. In the OA. Acetaminophen may be considered as add on therapy absence of a diagnosis of one of these conditions, hydroxy for short term and episodic use but is not appropriate as chloroquine is not appropriate empiric treatment fbr an initial therapy for this patient. acute polyarthritis. Duloxetine (Option B), a serotonin-norepinephrine lVlethotrexate (Option D) is appropriate flrst line ther reuptake inhibitor with central neryous system activity, has apy for rheumatoid arthritis and psoriatic arthritis. How shorn,n efllcacy for OA pain and would also be reasonable ever, before initiation of an immunosuppressive therapy. the for this patient. However, it should be used only if NSAIDs diagnosis of rheumatoid arthritis or psoriatic arthritis must are inadequate and is not the best choice for initial therapy. be confirmed. When symptoms are present for only a few Gabapentin (Option C) and pregabalin are more effec days, causes ofjoint pain and swelling, such as viral inf'ection tive than placebo in the treatment of neuropathic pain and drug reactions, are in the diftbrential diagnosis. When conditions, such as postherpetic neuralgia and diabetic t (u symptoms are present for at least 6 weeks, these diagnostic neuropathy. There is no evidence of their eflectiveness for ET possibilities become less likely and higher suspicion for chronic OA pain. Furthermore, they may be associated with rheumatologic diseases will emerge. On the basis of the time dose dependent dizziness and sedation. Thus, gabapentin is U frame over which this patient reports symptoms, initiation not appropriate for this patient. of methotrexate is not appropriate. Opioid therapy provides limited benefit fbr chronic =, IE pain control in patients with OA and poses a high risk for la I(EY POIIITS (t, toxicity and dependence. Opioid use should be avoided for o Parvovirus B19 arthropathy often presents acutely, is OA treatment. Tramadol (Option E), a partial opioid with UI = symmetric and polyarticular, and typically involves fewer adverse effects and less addictive potential than pure the proximal small joints of the hands. opioids, may be considered in some patients, but it should o Parvovirus B19 arthropathy should be suspected when be used only in limited circumstances, and never as an initial appropriate clinical features are present in someone therapy. who has exposure to children and is diagnosed by KEY POI]IIS detecting anti parvovirus IgM antibodies in the serum. . NSAIDs are often the initial treatment of choice for osteoarthritis if used judiciously in low risk patients, Bibliography with minimizing and monitoring of adverse effects. Mauermann M. Ilochiluf Stange K. Klelntrrnn A, et al. Paru^,irus inli,ction in early arthritis. Clin Exp Rheumirkrl. 2016 Mar Apr:3.1:207 13. It,l\'llI): o Acetaminophen provides no benefit for hip or knee oste 268866871 oarthritis; it may be considered as add on therapy for short term and episodic use but not as initial therapy. Item 54 Answer: D Educational Objective: Use NSAIDs for initial Bibliography osteoarthritis treatment. Kolasinski SI-. Neogi T. Hochberg MC. et al. 2019 Americilr.r College of Rheumrtololl/ Arthritis Foundirtion guideline for the mi:lncgement of ostcorrthritis of the hand. hip. and knee. Arthritis Rhcr"lnliltol. 2020i The most appropriate initial treatment for this patient with 72:220 233. IPMID: 31908163] doi:10.1002,'art.411,12 osteoarthritis (OA) is an NSAID, such as piroxicam (Option D). NSAIDs inhibit cyclooxygenase enzymes, blocking gen eration of the lipid prostaglandin E,,,. NSAIDs are efhca Item 55 Answer: B cious in OA and are strongly recommended by the 2019 Educational Objective: Treat polymyalgia rheumatica. American College of Rheumatology/Arthritis Foundation for hand, hip, and knee OA. However, their adverse efl'ect The most appropriate management is prednisone, l5 mg/d proflles make sustained use problematic, especially in older (Option B). This patient has polymyalgia rheumatica (PMR) persons and patients with comorbidities. Topical NSAIDs are characterized by symmetric proximal myalgia and stiflhess, effective and because of their saf'ety profile are preferred to accompanied by constitutional symptoms and an elevated oral NSAIDs. However, topical NSAIDs are ineffective in the C reactive protein level. Symptoms are most pronounced treatment of hip OA. For this patient with hand, knee, and in the morning and improve after several hours. Although hip OA, oral NSAIDs are the initial treatment of choice. This some patients also have peripheral arthritis (usually of the patient has no risk factors for common contraindications knees and wrists), most do not. Physical flndings are usu- and adverse effects, such as peptic ulcer disease or kidney ally limited to difficulty moving the affected areas (shoul disease. Hence, piroxicam would be a reasonable choice as ders and hips). There is no diagnostic test specific fbr PMR. initial treatment and may adequately relieve her symptoms. With a reasonable degree ol suspicion for PMR, an empiric It would also be prudent lbr the patient to take piroxicam glucocorticoid trial is appropriate. Initiating prednisone at regularly for a limited time and consider taking it as needed 12.5 to 20 mg/d is appropriate for this generally self limited in the future. illness. Symptoms usually improve dramatically within 151

Answers and Critiques 48 hours (diagnostically helpful), and tapering may begin IgG. Type III is usually associated with autoimmune disease after 2 weeks. and is characterized by polyclonal IgG and polyclonal IgM. This patient has a clear diagnosis of PMR, and there is This patient has severe cryoglobulinemia, r,r'ith ne\\' onset no need to seek an alternative diagnosis that is not suggested kidney failure, palpable purpura, and peripheral neuropathy by the clinical presentation. Testing for rheumatoid factor, affecting the left radial nerve. Cutaneous involvement (pal- antinuclear antibodies, and ANCA (Option A) is unnecessary pable purpura, digital ischemia, ulcers, necrosis. and livedo because this patient shows no evidence of diseases such as reticularis) occurs in about 90'7, of patients. Other common rheumatoid arthritis, systemic lupus erythematosus (SLE), manifestations include glomerulonephritis (usually mem or granulomatosis with polyangiitis. Rheumatoid arthritis branoproliferative) and arthralgia without arthritis. Pulmo is characterized by a chronic inflammatory polyarthritis nary and or gastrointestinal involvement is rare. In addition affecting large and small joints, with a predilection for the to detection of cryoglobulins, laboratory abnormalities fre small joints of the hands and feet. SLE is a multisystem auto quently include depressed C4 complement and low CHro, immune disease affecting mainly women (90"1,), and skin as well as a positive rheumatoid factor result; this patient's gt rash and joint symptoms aflect 90'1, of patients. Granuloma undetectable C4 level in conjunction with a high rheumatoid € (} tosis with polyangiitis aflects the upper and lower airways, factor level therefore strongly support a cryoglobulinemia vt kidneys, eyes, and ears. diagnosis. Most cases of mixed cryoglobulinemia result from q, A prednisone dosage of 60 mg/d (Option C) is much too another underlying condition, the most common of which EL high and unnecessary for PMR. This dosage is used to treat is hepatitis C virus infection (suggested by elevated amino ('! giant cell arteritis. transferase levels). Patients with cryoglobulinemia should Although the patient's primary concern is "pain every undergo hepatitis C virus testing and be treated ifthe result ,tr (} where," further questioning reveals that the patient has pain is positive. Severe cryoglobulinemia requires urgent treat gl in distinct areas. It is crucial to pinpoint areas of discomfort ment r,r,ith high-dose glucocorticoids plus rituximab. via history because different disease processes result in dis Hypersensitivity vasculitis (Option B) can appear as tinct patterns of pain. Patients with chronic widespread pain showers of purpura on the extremities but does not lead to syndromes, such as flbromyalgia, may indeed have difluse systemic disease (glomerulonephritis, hypocomplemente- pain. However, patients with other, more localized issues mia, neuropathy, and nephropathy). often report "pain every.where," and in the absence ofa good Polyarteritis nodosa (Option C), a medium vessel history premature closure may lead to an incorrect diagno- vasculitis, most commonly aflects the skin (tender erythem sis. In this case, diagnosing fibromyalgia and prescribing atous nodules akin to erythema nodosum, palpable pur pregabalin (Option D) would be incorrect. pura, livedo reticularis, ulcers), peripheral nervous system (mononeuritis multiplex), and gut. However, polyarteritis IEY POITIS nodosa does not cause glomerulonephritis, hypocomple . Polymyalgia rheumatica is characterized by symmet- mentemia. or an elevated rheumatoid factor. It can cause ric proximal myalgia and stiffness, accompanied by purpuric lesions, but not to the degree seen in cryoglobu constitutional symptoms and elevated infl ammatory linemia. markers. Rheumatoid vasculitis (Option D) is seen in patients . For polymyalgia rheumatica, initiating prednisone at with long-standing and severe rheumatoid arthritis. This 12.5 to 20 mg/d is appropriate treatment. patient has no history of arthropathy, and, despite his arthralgia, does not have fiank arthritis. The rheumatoid fac Bibliography tor level is elevated, but this test is not speciflc (results can be Matteson El-, I)ejaco C. Polymyalgia rheumatica. Ann lntern Med. 2017: elevated in chronic bacterial or certain viral infections and 166:l'IC65 ll'(180. [PMID: 284603951 doi: 10.71]26 AITC2Ol7O5O2O Sjdgren syndrome, for example). Anti-cyclic citrullinated peptide antibodies, which are more speciflc for rheumatoid arthritis. are not present. Finally, kidney involvement is pres Item 55 ent in this case but rare in rheumatoid vasculitis. Ansyyer: A Educational Objective: Diagnose cryoglobulinemic XEY POITTS vasculitis. r Clinical manifestations of cryoglobulinemia include The most likely diagnosis is cryoglobulinemic vasculitis cutaneous involvement (palpable purpura, digital (Option A). Cryoglobulinemic vasculitis results from cryo- ischemia, ulcers, necrosis, and livedo reticularis), globulin containing immune complexes depositing in small- peripheral neuropathy, arthralgia, and glomerulone- and medium-sized arteries, leading to an inflammatory phritis (usually membranoproliferative). response. Of the three types of cryoglobulinemia, only types o In addition to detection of cryoglobulins, cryoglobu- II and III (mixed cryoglobulinemia) cause vasculitis. Type II, Iinemia-associated laboratory abnormalities fre which usually results from certain viral infections and auto quently include depressed C4 complement and low immune disease, is typifled by a monoclonal IgM with activ CHro, as well as a positive rheumatoid factor result. ity against IgG (i.e., a rheumatoid factor) as well as polyclonal

48 hours (diagnostically helpful), and tapering may begin IgG. Type III is usually associated with autoimmune disease after 2 weeks. and is characterized by polyclonal IgG and polyclonal IgM. This patient has a clear diagnosis of PMR, and there is This patient has severe cryoglobulinemia, r,r'ith ne\\' onset no need to seek an alternative diagnosis that is not suggested kidney failure, palpable purpura, and peripheral neuropathy by the clinical presentation. Testing for rheumatoid factor, affecting the left radial nerve. Cutaneous involvement (pal- antinuclear antibodies, and ANCA (Option A) is unnecessary pable purpura, digital ischemia, ulcers, necrosis. and livedo because this patient shows no evidence of diseases such as reticularis) occurs in about 90'7, of patients. Other common rheumatoid arthritis, systemic lupus erythematosus (SLE), manifestations include glomerulonephritis (usually mem or granulomatosis with polyangiitis. Rheumatoid arthritis branoproliferative) and arthralgia without arthritis. Pulmo is characterized by a chronic inflammatory polyarthritis nary and or gastrointestinal involvement is rare. In addition affecting large and small joints, with a predilection for the to detection of cryoglobulins, laboratory abnormalities fre small joints of the hands and feet. SLE is a multisystem auto quently include depressed C4 complement and low CHro, immune disease affecting mainly women (90"1,), and skin as well as a positive rheumatoid factor result; this patient's gt rash and joint symptoms aflect 90'1, of patients. Granuloma undetectable C4 level in conjunction with a high rheumatoid € (} tosis with polyangiitis aflects the upper and lower airways, factor level therefore strongly support a cryoglobulinemia vt kidneys, eyes, and ears. diagnosis. Most cases of mixed cryoglobulinemia result from q, A prednisone dosage of 60 mg/d (Option C) is much too another underlying condition, the most common of which EL high and unnecessary for PMR. This dosage is used to treat is hepatitis C virus infection (suggested by elevated amino ('! giant cell arteritis. transferase levels). Patients with cryoglobulinemia should Although the patient's primary concern is "pain every undergo hepatitis C virus testing and be treated ifthe result ,tr (} where," further questioning reveals that the patient has pain is positive. Severe cryoglobulinemia requires urgent treat gl in distinct areas. It is crucial to pinpoint areas of discomfort ment r,r,ith high-dose glucocorticoids plus rituximab. via history because different disease processes result in dis Hypersensitivity vasculitis (Option B) can appear as tinct patterns of pain. Patients with chronic widespread pain showers of purpura on the extremities but does not lead to syndromes, such as flbromyalgia, may indeed have difluse systemic disease (glomerulonephritis, hypocomplemente- pain. However, patients with other, more localized issues mia, neuropathy, and nephropathy). often report "pain every.where," and in the absence ofa good Polyarteritis nodosa (Option C), a medium vessel history premature closure may lead to an incorrect diagno- vasculitis, most commonly aflects the skin (tender erythem sis. In this case, diagnosing fibromyalgia and prescribing atous nodules akin to erythema nodosum, palpable pur pregabalin (Option D) would be incorrect. pura, livedo reticularis, ulcers), peripheral nervous system (mononeuritis multiplex), and gut. However, polyarteritis IEY POITIS nodosa does not cause glomerulonephritis, hypocomple . Polymyalgia rheumatica is characterized by symmet- mentemia. or an elevated rheumatoid factor. It can cause ric proximal myalgia and stiffness, accompanied by purpuric lesions, but not to the degree seen in cryoglobu constitutional symptoms and elevated infl ammatory linemia. markers. Rheumatoid vasculitis (Option D) is seen in patients . For polymyalgia rheumatica, initiating prednisone at with long-standing and severe rheumatoid arthritis. This 12.5 to 20 mg/d is appropriate treatment. patient has no history of arthropathy, and, despite his arthralgia, does not have fiank arthritis. The rheumatoid fac Bibliography tor level is elevated, but this test is not speciflc (results can be Matteson El-, I)ejaco C. Polymyalgia rheumatica. Ann lntern Med. 2017: elevated in chronic bacterial or certain viral infections and 166:l'IC65 ll'(180. [PMID: 284603951 doi: 10.71]26 AITC2Ol7O5O2O Sjdgren syndrome, for example). Anti-cyclic citrullinated peptide antibodies, which are more speciflc for rheumatoid arthritis. are not present. Finally, kidney involvement is pres Item 55 ent in this case but rare in rheumatoid vasculitis. Ansyyer: A Educational Objective: Diagnose cryoglobulinemic XEY POITTS vasculitis. r Clinical manifestations of cryoglobulinemia include The most likely diagnosis is cryoglobulinemic vasculitis cutaneous involvement (palpable purpura, digital (Option A). Cryoglobulinemic vasculitis results from cryo- ischemia, ulcers, necrosis, and livedo reticularis), globulin containing immune complexes depositing in small- peripheral neuropathy, arthralgia, and glomerulone- and medium-sized arteries, leading to an inflammatory phritis (usually membranoproliferative). response. Of the three types of cryoglobulinemia, only types o In addition to detection of cryoglobulins, cryoglobu- II and III (mixed cryoglobulinemia) cause vasculitis. Type II, Iinemia-associated laboratory abnormalities fre which usually results from certain viral infections and auto quently include depressed C4 complement and low immune disease, is typifled by a monoclonal IgM with activ CHro, as well as a positive rheumatoid factor result. ity against IgG (i.e., a rheumatoid factor) as well as polyclonal 152

Answers and Critiques Bibliography Bibliography Fuentes A, Mardones C, Burgos PI. Understanding the cryoglobulinemias. Curr Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College Rheumatol Rep. 2019;21:60. [PMID: 317,11077] doi:10.1007/sll926 019 of Rheumatologr guideline fbr the management of reproductive health 0859 0 in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020r 72:529 556. [PMtD, 32090480]

Bibliography Bibliography Fuentes A, Mardones C, Burgos PI. Understanding the cryoglobulinemias. Curr Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College Rheumatol Rep. 2019;21:60. [PMID: 317,11077] doi:10.1007/sll926 019 of Rheumatologr guideline fbr the management of reproductive health 0859 0 in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020r 72:529 556. [PMtD, 32090480] Item 57 Answer: D Ed ucationa I Objective : Treat rheumatoid arthritis Item 58 Answer: B during pregnancy. Educational Objective: Diaglose the cause ofjoint pain The most appropriate preconception management is discontin- in a patient with psoriasis. uation of leflunomide (Option D). Leflunomide is highly tera- The most likely diagnosis is osteoarthritis (OA) (Option B). togenic and absolutely contraindicated with pregnancy. During Psoriatic arthritis (PsA) is one of the few forms of inflam the preconception phase, leflunornide should be discontinued. matory arthritis that affects the distal interphalangeal joints. Ut The active metabolite of leflunomide (teriflunomide) under o This Iocation is also commonly aflected by OA. This patient goes enterohepatic circulation and has a half life of nearly ET has a classic history for OA, with minimal morning stiffness, 3 weeks. Because 5 half-lives are required for a metabolite to pain with increasing use, and a classic distribution in the (, be significantly cleared, leflunomide levels have been detected hands (distal interphalangeal and proximal interphalangeal in the serum months following discontinuation of the drug. joints). Her radiographs are also typical for OA and show no =t E tu Demonstration of undetectabie blood levels is needed befbre r,l erosions. The literature conllrms thal 47n/,' of patients with q, conception. An ll day cholestyramine washout must be used psoriasis who were thought to have PsA had another cause to remo\e teriflunomide and should be followed up with mea of joint pain, most commonly OA. vl = g surement of leflunomide and its metabolite levels to ensure Hyperuricemia is reported to have a high prevalence removal of drug. Management of rheumatoid arthritis (RA) in patients with psoriasis. This metabolic derangement can during pregnancy is complicated. be associated with gout development. In chronic recur Discontinuation of medications used to treat RA rent gout (Option A), patients experience increasingly fre- (Option A) may be feasible in some patients whose disease quent and severe, and often polyarticular, arthritic attacks. is well controlled, but most patients need to continue ther These attacks may eventually evolve into a persistent chronic apy during pregnancy especially if de escalation of therapy arthritis. The characteristic radiographic changes of estab- reactivates disease, as in this patient. She is likely to require lished disease include punched-out lesions with overhang- continued therapy during pregnancy. ing edges ofcortical bone. This patient's clinical history and Patients with active disease who are receiving tumor radiographic flndings are not consistent with chronic gout. necrosis factor inhibitors can continue these medications Patients with PsA (Option C) have an inflammatory through conception; the duration of use during pregnancy form of arthritis that manif'ests with prolonged morning depends on the speciflc agent. Certolizumab (Option B) stiffness (>30 minutes) and symptoms that improve with may be continued throughout pregnancy because it crosses activity. PsA affects up to 25'X, of people with psoriasis, and the placenta in low to undetectable amounts. Other tumor the associated joint disease develops after the appearance necrosis factor inhibitors, such as etanercept, adalimumab, of skin changes in 85% of patients. The joint manifestation infliximab, and golimumab, may be continued safely until can be pauciarticular or polyarticular and can be accompa- the start of the third trimester. nied by axial involvement. Enthesitis (inflammation where Hydroxychloroquine (Option C) crosses the placenta. tendons/ligaments insert into bone) is seen in almost half However, the dose typically used to treat systemic lupus ery- of patients with PsA, and dactylitis is equally common. Nail thematosus or other rheumatologic diseases does not pose changes are common and are associated with distal inter- a risk for letal toxicity. It is safe to continue hydroxychloro phalangeal arthritis and enthesitis. These flndings are not quine in this patient. present in this patient, making PsA unlikely at this time. Because leflunomide is absolutely contraindicated Rheumatoid arthritis (Option D) characteristically affects during any stage of pregnancy, continuation of all three the metacarpophalangeal joints, metatarsophalangeal joints, medications is inappropriate (Option E). and proximal interphalangeal joints of the hands and feet but spares the distal interphalangeal joints ofboth the upper and l(EY por{Ts lower extremities. This patient's pattern of joint involvement o Leflunomide is highly teratogenic and absolutely con- is most compatible with OA, not rheumatoid arthritis. traindicated during any stage of pregnancy; during the preconception phase, leflunomide should be dis- rEY POIl{II continued and cholestyramine used to remove its o Psoriatic arthritis is one of the few forms of inflamma- metabolite. tory arthritis that affects the distal interphalangeal joints. . Hydroxychloroquine can be continued throughout . The most common missed diagnosis in patients with pregnancy. psoriasis and arthritis is osteoarthritis.

Item 57 Answer: D Ed ucationa I Objective : Treat rheumatoid arthritis Item 58 Answer: B during pregnancy. Educational Objective: Diaglose the cause ofjoint pain The most appropriate preconception management is discontin- in a patient with psoriasis. uation of leflunomide (Option D). Leflunomide is highly tera- The most likely diagnosis is osteoarthritis (OA) (Option B). togenic and absolutely contraindicated with pregnancy. During Psoriatic arthritis (PsA) is one of the few forms of inflam the preconception phase, leflunornide should be discontinued. matory arthritis that affects the distal interphalangeal joints. Ut The active metabolite of leflunomide (teriflunomide) under o This Iocation is also commonly aflected by OA. This patient goes enterohepatic circulation and has a half life of nearly ET has a classic history for OA, with minimal morning stiffness, 3 weeks. Because 5 half-lives are required for a metabolite to pain with increasing use, and a classic distribution in the (, be significantly cleared, leflunomide levels have been detected hands (distal interphalangeal and proximal interphalangeal in the serum months following discontinuation of the drug. joints). Her radiographs are also typical for OA and show no =t E tu Demonstration of undetectabie blood levels is needed befbre r,l erosions. The literature conllrms thal 47n/,' of patients with q, conception. An ll day cholestyramine washout must be used psoriasis who were thought to have PsA had another cause to remo\e teriflunomide and should be followed up with mea of joint pain, most commonly OA. vl = g surement of leflunomide and its metabolite levels to ensure Hyperuricemia is reported to have a high prevalence removal of drug. Management of rheumatoid arthritis (RA) in patients with psoriasis. This metabolic derangement can during pregnancy is complicated. be associated with gout development. In chronic recur Discontinuation of medications used to treat RA rent gout (Option A), patients experience increasingly fre- (Option A) may be feasible in some patients whose disease quent and severe, and often polyarticular, arthritic attacks. is well controlled, but most patients need to continue ther These attacks may eventually evolve into a persistent chronic apy during pregnancy especially if de escalation of therapy arthritis. The characteristic radiographic changes of estab- reactivates disease, as in this patient. She is likely to require lished disease include punched-out lesions with overhang- continued therapy during pregnancy. ing edges ofcortical bone. This patient's clinical history and Patients with active disease who are receiving tumor radiographic flndings are not consistent with chronic gout. necrosis factor inhibitors can continue these medications Patients with PsA (Option C) have an inflammatory through conception; the duration of use during pregnancy form of arthritis that manif'ests with prolonged morning depends on the speciflc agent. Certolizumab (Option B) stiffness (>30 minutes) and symptoms that improve with may be continued throughout pregnancy because it crosses activity. PsA affects up to 25'X, of people with psoriasis, and the placenta in low to undetectable amounts. Other tumor the associated joint disease develops after the appearance necrosis factor inhibitors, such as etanercept, adalimumab, of skin changes in 85% of patients. The joint manifestation infliximab, and golimumab, may be continued safely until can be pauciarticular or polyarticular and can be accompa- the start of the third trimester. nied by axial involvement. Enthesitis (inflammation where Hydroxychloroquine (Option C) crosses the placenta. tendons/ligaments insert into bone) is seen in almost half However, the dose typically used to treat systemic lupus ery- of patients with PsA, and dactylitis is equally common. Nail thematosus or other rheumatologic diseases does not pose changes are common and are associated with distal inter- a risk for letal toxicity. It is safe to continue hydroxychloro phalangeal arthritis and enthesitis. These flndings are not quine in this patient. present in this patient, making PsA unlikely at this time. Because leflunomide is absolutely contraindicated Rheumatoid arthritis (Option D) characteristically affects during any stage of pregnancy, continuation of all three the metacarpophalangeal joints, metatarsophalangeal joints, medications is inappropriate (Option E). and proximal interphalangeal joints of the hands and feet but spares the distal interphalangeal joints ofboth the upper and l(EY por{Ts lower extremities. This patient's pattern of joint involvement o Leflunomide is highly teratogenic and absolutely con- is most compatible with OA, not rheumatoid arthritis. traindicated during any stage of pregnancy; during the preconception phase, leflunomide should be dis- rEY POIl{II continued and cholestyramine used to remove its o Psoriatic arthritis is one of the few forms of inflamma- metabolite. tory arthritis that affects the distal interphalangeal joints. . Hydroxychloroquine can be continued throughout . The most common missed diagnosis in patients with pregnancy. psoriasis and arthritis is osteoarthritis. 153

Answers and Critiques Bibliography (EY P0IXTS (orilinued) Cladman DD. Clinical features and diagnostic considerations in psoriatic arthritis. Rheum Dis Clin North Am. 2015:41:569 79. [PMID: 26.1762191 o Anti-Scl 70 antibodies are generally associated with doi: I 0.1016/j.rdc.20l 5.07.003 diffuse cutaneous systemic sclerosis, with a prevalence approaching 30'7,, and these antibodies are associated Item 59 Answer: C with a higher risk for interstitial lung disease. Ed ucational Objective: Diagnose limited cutaneous systemic sclerosis. Bibliography Stochmal -\. Czuu'ara J, 'lrojanor,r,ska M. et al. Antinuclear antibodies in The most likely diagrosis is limited cutaneous systemic scle s)stemic sclerosis: an update. CIin Rev Allerg, Immunol. 2o20:58:-10 51. rosis (LcSSc) (Option C). Anticentromere antibodies (titer of lP\llD:306077491 doi:10.1007 s12016 018 8718 8 1:80 or higher) are rare in healthy people. The finding ofanti- centromere antibodies (ACAs) in the setting of Ralnaud phe D nomenon is 60'X, sensitive and 98'7, speciflc for LcSSc, which Item 60 Answer: C t was previously knov,n as the CREST slmdrome. Patients with E Ed ucationa I Objective: Diagnose Sjogren syndrome. (D LcSSc have manifbstations that can include calcinosis, Ray ta naud phenomenon, esophageal dysmotility, sclerodactyly, and The most appropriate diagnostic test to perform next is A' 3 telangiectasia (CREST); all flve conditions may not be present. anti Ro/SSA antibodies (Option C). This patient has flnd EL The presence of anticentromere antibodies increases the risk ings highly suggestive of Sjogren syndrome, oral and ocular n for pulmonary hypertension, which occurs in 20"1, of these dryness and enlarged parotid glands. She also has other non tt patients. Patients who have only Raynaud phenomenon and specific symptoms (achiness, fatigue. and Raynaud phenom (D ACA must be followed for development of LcSSc. This patient enon) that are common in patients with Sjdgren syndrome. t^ with recent onset of Ra,,naud phenomenon is showing features Anti Ro/SSA antibodies are the most speciflc diagnostic test. ofLcSSc. Although gastroesophageal reflux disease is common The patient also has an elevated rheumatoid factor lerel. in the general population, the recent onset oftelangiectasias and a flnding seen often in patients with Sj6gren syndrome. sclerodactyly suggests LcSSc. The telangiectasias seen in LcSSc Although rheumatoid factor is more common in Sj6gren are matted; these clusters of dilated vessels appear as small pink syndrome than in rheumatoid arthritis, it is not speciflc to or red macules that blanch on light pressure. They are most either disease. commonly seen on the face, mucous membrane, and hands. ANCA testing (Option A) would not be informative for Patients with diffuse cutaneous systemic sclerosis (DcSSc) this case because the patient's presentation does not suggest (Option A) have skin involvement that is more extensive than systemic vasculitis. Clinical manifestations of vasculitis are that found in LcSSc and additionally includes the arms, trunk, the result of tissue ischemia associated with the involved and lower extremities. Anti Scl 70 antibodies are generally vessels. ANCA associated vasculitides involve small vessels. associated with DcSSc, with a prevalence approaching 30'1,, and patients may have symptoms related to the upper and and these antibodies are associated with a higher risk for inter Iower airways, kidneys, eyes, ears, and skin; constitutional stitial lung disease. ACAs are uncommon in DcSSc. symptoms are also common. Eosinophilic fasciitis (Option B) is associated with Anti cyclic citrullinated peptide (CCP) antibodies orange peel induration (peau d'orange) ofproximal extrem (Option B) are more speciflc than rheumatoid factor for ities, with sparing of hands and face, and the presence of diagnosing rheumatoid arthritis. Ho'nrever, in a patient who peripheral eosinophilia. The presence of Raynaud phenom seems likely to have Sjdgren syndrome, anti CCP antibody enon and the positive ACA result make eosinophilic fasciitis testing is not helpful. Only a small proportion of people an unlikely diagnosis. presenting with joint discomfort have rheumatoid arthritis. Mixed connective tissue disease (Option D) is a speciflc The normal joint examination provides another clue that overlap syndrome that includes clinical manif'estations of at rheumatoid arthritis is unlikely. least two of the following: systemic lupus erythematosus, Cryoglobulinemia can be caused by Sjdgren syndrome, polymyositis, and systemic sclerosis. Positive results for anti- but there is no reason to suspect cryoglobulinemia in this Ul-ribonucleoprotein antibodies are the primary laboratory patient. Cryoglobulinemic ischemia is fixed rather than feature in many patients. The absence of flndings associated reversible (digital tips often appear gangrenous). Cryoglob with another connective tissue disease and a positive ACA ulins (Option D) cause small and medium vessel vasculitis titer support the diagnosis of LcSSc rather than mixed con by depositing in vessel walls and inciting an inflammatory nective tissue disease. response. Cryoglobulinemia almost always causes a rash (e.g.. leukocytoclastic vasculitis manifesting as palpable purpura) XEY POIf,IS and often causes mononeuritis multiplex and arthralgia. . The finding of anticentromere antibodies in the set Kidney disease, usually membranoproliferative glomerulo ting of Raynaud phenomenon is 60% sensitive and nephritis, is also frequently seen. Rheumatoid factor and an 98% specific for the development of limited cutaneous elevated erythrocyte sedimentation rate are expected in cryo systemic sclerosis. globulinemia, but the rest of this patient's clinical picture (Continued) does not support the diagnosis of cryoglobulinemia.

Bibliography (EY P0IXTS (orilinued) Cladman DD. Clinical features and diagnostic considerations in psoriatic arthritis. Rheum Dis Clin North Am. 2015:41:569 79. [PMID: 26.1762191 o Anti-Scl 70 antibodies are generally associated with doi: I 0.1016/j.rdc.20l 5.07.003 diffuse cutaneous systemic sclerosis, with a prevalence approaching 30'7,, and these antibodies are associated Item 59 Answer: C with a higher risk for interstitial lung disease. Ed ucational Objective: Diagnose limited cutaneous systemic sclerosis. Bibliography Stochmal -\. Czuu'ara J, 'lrojanor,r,ska M. et al. Antinuclear antibodies in The most likely diagrosis is limited cutaneous systemic scle s)stemic sclerosis: an update. CIin Rev Allerg, Immunol. 2o20:58:-10 51. rosis (LcSSc) (Option C). Anticentromere antibodies (titer of lP\llD:306077491 doi:10.1007 s12016 018 8718 8 1:80 or higher) are rare in healthy people. The finding ofanti- centromere antibodies (ACAs) in the setting of Ralnaud phe D nomenon is 60'X, sensitive and 98'7, speciflc for LcSSc, which Item 60 Answer: C t was previously knov,n as the CREST slmdrome. Patients with E Ed ucationa I Objective: Diagnose Sjogren syndrome. (D LcSSc have manifbstations that can include calcinosis, Ray ta naud phenomenon, esophageal dysmotility, sclerodactyly, and The most appropriate diagnostic test to perform next is A' 3 telangiectasia (CREST); all flve conditions may not be present. anti Ro/SSA antibodies (Option C). This patient has flnd EL The presence of anticentromere antibodies increases the risk ings highly suggestive of Sjogren syndrome, oral and ocular n for pulmonary hypertension, which occurs in 20"1, of these dryness and enlarged parotid glands. She also has other non tt patients. Patients who have only Raynaud phenomenon and specific symptoms (achiness, fatigue. and Raynaud phenom (D ACA must be followed for development of LcSSc. This patient enon) that are common in patients with Sjdgren syndrome. t^ with recent onset of Ra,,naud phenomenon is showing features Anti Ro/SSA antibodies are the most speciflc diagnostic test. ofLcSSc. Although gastroesophageal reflux disease is common The patient also has an elevated rheumatoid factor lerel. in the general population, the recent onset oftelangiectasias and a flnding seen often in patients with Sj6gren syndrome. sclerodactyly suggests LcSSc. The telangiectasias seen in LcSSc Although rheumatoid factor is more common in Sj6gren are matted; these clusters of dilated vessels appear as small pink syndrome than in rheumatoid arthritis, it is not speciflc to or red macules that blanch on light pressure. They are most either disease. commonly seen on the face, mucous membrane, and hands. ANCA testing (Option A) would not be informative for Patients with diffuse cutaneous systemic sclerosis (DcSSc) this case because the patient's presentation does not suggest (Option A) have skin involvement that is more extensive than systemic vasculitis. Clinical manifestations of vasculitis are that found in LcSSc and additionally includes the arms, trunk, the result of tissue ischemia associated with the involved and lower extremities. Anti Scl 70 antibodies are generally vessels. ANCA associated vasculitides involve small vessels. associated with DcSSc, with a prevalence approaching 30'1,, and patients may have symptoms related to the upper and and these antibodies are associated with a higher risk for inter Iower airways, kidneys, eyes, ears, and skin; constitutional stitial lung disease. ACAs are uncommon in DcSSc. symptoms are also common. Eosinophilic fasciitis (Option B) is associated with Anti cyclic citrullinated peptide (CCP) antibodies orange peel induration (peau d'orange) ofproximal extrem (Option B) are more speciflc than rheumatoid factor for ities, with sparing of hands and face, and the presence of diagnosing rheumatoid arthritis. Ho'nrever, in a patient who peripheral eosinophilia. The presence of Raynaud phenom seems likely to have Sjdgren syndrome, anti CCP antibody enon and the positive ACA result make eosinophilic fasciitis testing is not helpful. Only a small proportion of people an unlikely diagnosis. presenting with joint discomfort have rheumatoid arthritis. Mixed connective tissue disease (Option D) is a speciflc The normal joint examination provides another clue that overlap syndrome that includes clinical manif'estations of at rheumatoid arthritis is unlikely. least two of the following: systemic lupus erythematosus, Cryoglobulinemia can be caused by Sjdgren syndrome, polymyositis, and systemic sclerosis. Positive results for anti- but there is no reason to suspect cryoglobulinemia in this Ul-ribonucleoprotein antibodies are the primary laboratory patient. Cryoglobulinemic ischemia is fixed rather than feature in many patients. The absence of flndings associated reversible (digital tips often appear gangrenous). Cryoglob with another connective tissue disease and a positive ACA ulins (Option D) cause small and medium vessel vasculitis titer support the diagnosis of LcSSc rather than mixed con by depositing in vessel walls and inciting an inflammatory nective tissue disease. response. Cryoglobulinemia almost always causes a rash (e.g.. leukocytoclastic vasculitis manifesting as palpable purpura) XEY POIf,IS and often causes mononeuritis multiplex and arthralgia. . The finding of anticentromere antibodies in the set Kidney disease, usually membranoproliferative glomerulo ting of Raynaud phenomenon is 60% sensitive and nephritis, is also frequently seen. Rheumatoid factor and an 98% specific for the development of limited cutaneous elevated erythrocyte sedimentation rate are expected in cryo systemic sclerosis. globulinemia, but the rest of this patient's clinical picture (Continued) does not support the diagnosis of cryoglobulinemia. 154

Answers and Critiques XEY POITIS narrowi ng. Thus, adding hydroxychloroquine to febu xostat e Anti Ro/SSA antibodies are the most specific labora- would not be appropriate. Probenecid (Option B), a uricosuric drug, is not eflec I tory test for diagnosis of Sj6gren syndrome. tive as a urate-lowering agent in patients with chronic kid . Although rheumatoid factor is more common in ney disease (estimated glomerular llltration rate <50 mL/ Sjdgren syndrome than in rheumatoid arthritis, it is min/1.73 m2) and should not be added to febuxostat in this not specific to either disease. patient. Continuing febuxostat alone (Option D) wiil not further Bibliography lower serum urate levels; the patient has been receiving this Shiboski (lFI, Shiboski SC, Seror R, et ali lnternrtional Sjdgren's Syndrome therapy for 1 year and has steady state levels, and therefore Criteria Working Group. 2016 American College of Rheumatolos// she will not likely benefit further from it. European l-eague Against Rheumatism classification criteria for primary Sjogren's syndromei a consensus and data driven methodolos/ involving three international patient cohorts. Ann Rheum Dis. 2017;76:9 16- I(EY POIilI ta q, IPMID : 277 89 1661 doi : I 0. 1 I 36 /a nnrheumdis 2O1 6 21 O 57 1 . Switching to pegloticase rather than continuing cur rent urate-lowering therapy is strongly recommended ET .P for patients with gout for whom allopurinol, febux Item 61 Answer: C U Ed u cati ona I Objective : Treat refractory tophaceous ostat, or uricosurics have failed to achieve the serum E urate target and who continue to have frequent gout tli' gout with pegloticase. UI flares (two or more flares per year) or who have non- The most appropriate treatment is to stop febuxostat and resolving subcutaneous tophi. o (,t start pegloticase (Option C). This patient has chronic topha = E ceous gout with a persistently elevated urate level above Bibliography target (<6.0 mg/dl [O.ss mmol/L]) despite maximum dose Fitzcerald lD. Dalbeth N. Mikuls T. et al. 2020 American College of Rheumatologr guideline fbr the management of gout. Arthritis Cirre Res febuxostat. Switching to pegloticase rather than continuing (Hoboken). 2020;72:714 760. IPMID: 3239193.11 doi:l0.lOO2/acr24luo current urate lowering therapy is strongly recommended for patients with gout for whom allopurinol, febuxostat, or uricosurics have failed to achieve the serum urate target Item 62 Answer: C and who continue to have frequent gout flares (two or more Educational Objective: Treat interstitial lung disease in flares per year) or who have subcutaneous tophi. Because systemic sclerosis. this patient is allergic to allopurinol and febuxostat has failed, pegloticase is indicated. Pegloticase is recombinant The most appropriate treatment is mycophenolate mofetil pegrlated uricase administered intravenously every 2 weeks. (Option C). This patient with systemic sclerosis has classic All patients should be screened for glucose 6 phosphate manif.estations of interstitial lung disease (lLD), which occurs dehydrogenase (G6PD) activity before administration of in 50'2, of patients with difluse cutaneous systemic sclerosis. pegloticase; low activity of G6PD poses a risk for hemo The prevalence is even higher in those who have anti Scl lytic anemia and methemoglobinemia, and pegloticase is 70 antibodies (857,). This patient has dyspnea on exertion, contraindicated in that setting. Pegloticase rapidly lowers cough, a reduction in FVC and DIco, and a high resolution the serum urate level, and prophylactic therapy (colchicine, CT scan th:rt is typical for nonspecific interstitial pneumo NSAIDs, or glucocorticoids) must be administered concur nitis. Patients may also have usual interstitial pneumoni- rently with treatment. Formation of antibody to pegloticase tis. A usual interstitial pneumonitis pattern demonstrates may occur (30% 50% of patients) and cause severe infusion honeycombing on high resolution CT and is less responsive reactions. Serum urate level must be checked before each to therapy than nonspeciflc interstitial pneumonitis. The infusion. After the initial dose, a serum urate level greater 6-minute r,r,alk test provides a functional assessment; if oxy than 6.0 mg/dl (0.35 mmol/L) on t\,vo consecutive assess- gen desaturation of 88'2, or below occurs while the patient is ments indicates loss of efficacy due to antibody formation. walking, the patient is a candidate for home oxygen therapy. necessitating discontinuation of pegloticase. Pegloticase Some studies suggest that aggressive treatment of gastro should not be given with any other urate lowering therapy intestinal reflux disease may have a positive effect on ILD so that interpretation of the serum urate level before each progression. Mycophenolate mofetil is a mainstay of therapy infusion is clear. Therefore. this patient should discontinue for ILD in systemic sclerosis. Data from open-label trials sug febuxostat. gest that mycophenolate mofetil can stabilize and, in some Hydroxychloroquine (Option A) is used in the treat- cases, improve lung function. The Scleroderma Lung Study ll ment of rheumatoid arthritis. This patient does not have a compared oral cyclophosphamide for 1 year to mycopheno history of rheumatoid arthritis. The erosions seen on her Iate mofletil for 2 years. Both agents were equally eflicacious radiographs are typical of gout with sclerotic borders and in improving and stabilizing FVC; however, mycophenolate overhanging edges. Typical rheumatoid arthritis radio mofetil was better tolerated and can be used for many years. graphic changes include periarticular osteopenia, mar whereas cyclophosphamide has a time limited utility due to ginal erosions without overhanging edges, and joint space toxicity. Expert opinion places mycophenolate mofetil flrst

XEY POITIS narrowi ng. Thus, adding hydroxychloroquine to febu xostat e Anti Ro/SSA antibodies are the most specific labora- would not be appropriate. Probenecid (Option B), a uricosuric drug, is not eflec I tory test for diagnosis of Sj6gren syndrome. tive as a urate-lowering agent in patients with chronic kid . Although rheumatoid factor is more common in ney disease (estimated glomerular llltration rate <50 mL/ Sjdgren syndrome than in rheumatoid arthritis, it is min/1.73 m2) and should not be added to febuxostat in this not specific to either disease. patient. Continuing febuxostat alone (Option D) wiil not further Bibliography lower serum urate levels; the patient has been receiving this Shiboski (lFI, Shiboski SC, Seror R, et ali lnternrtional Sjdgren's Syndrome therapy for 1 year and has steady state levels, and therefore Criteria Working Group. 2016 American College of Rheumatolos// she will not likely benefit further from it. European l-eague Against Rheumatism classification criteria for primary Sjogren's syndromei a consensus and data driven methodolos/ involving three international patient cohorts. Ann Rheum Dis. 2017;76:9 16- I(EY POIilI ta q, IPMID : 277 89 1661 doi : I 0. 1 I 36 /a nnrheumdis 2O1 6 21 O 57 1 . Switching to pegloticase rather than continuing cur rent urate-lowering therapy is strongly recommended ET .P for patients with gout for whom allopurinol, febux Item 61 Answer: C U Ed u cati ona I Objective : Treat refractory tophaceous ostat, or uricosurics have failed to achieve the serum E urate target and who continue to have frequent gout tli' gout with pegloticase. UI flares (two or more flares per year) or who have non- The most appropriate treatment is to stop febuxostat and resolving subcutaneous tophi. o (,t start pegloticase (Option C). This patient has chronic topha = E ceous gout with a persistently elevated urate level above Bibliography target (<6.0 mg/dl [O.ss mmol/L]) despite maximum dose Fitzcerald lD. Dalbeth N. Mikuls T. et al. 2020 American College of Rheumatologr guideline fbr the management of gout. Arthritis Cirre Res febuxostat. Switching to pegloticase rather than continuing (Hoboken). 2020;72:714 760. IPMID: 3239193.11 doi:l0.lOO2/acr24luo current urate lowering therapy is strongly recommended for patients with gout for whom allopurinol, febuxostat, or uricosurics have failed to achieve the serum urate target Item 62 Answer: C and who continue to have frequent gout flares (two or more Educational Objective: Treat interstitial lung disease in flares per year) or who have subcutaneous tophi. Because systemic sclerosis. this patient is allergic to allopurinol and febuxostat has failed, pegloticase is indicated. Pegloticase is recombinant The most appropriate treatment is mycophenolate mofetil pegrlated uricase administered intravenously every 2 weeks. (Option C). This patient with systemic sclerosis has classic All patients should be screened for glucose 6 phosphate manif.estations of interstitial lung disease (lLD), which occurs dehydrogenase (G6PD) activity before administration of in 50'2, of patients with difluse cutaneous systemic sclerosis. pegloticase; low activity of G6PD poses a risk for hemo The prevalence is even higher in those who have anti Scl lytic anemia and methemoglobinemia, and pegloticase is 70 antibodies (857,). This patient has dyspnea on exertion, contraindicated in that setting. Pegloticase rapidly lowers cough, a reduction in FVC and DIco, and a high resolution the serum urate level, and prophylactic therapy (colchicine, CT scan th:rt is typical for nonspecific interstitial pneumo NSAIDs, or glucocorticoids) must be administered concur nitis. Patients may also have usual interstitial pneumoni- rently with treatment. Formation of antibody to pegloticase tis. A usual interstitial pneumonitis pattern demonstrates may occur (30% 50% of patients) and cause severe infusion honeycombing on high resolution CT and is less responsive reactions. Serum urate level must be checked before each to therapy than nonspeciflc interstitial pneumonitis. The infusion. After the initial dose, a serum urate level greater 6-minute r,r,alk test provides a functional assessment; if oxy than 6.0 mg/dl (0.35 mmol/L) on t\,vo consecutive assess- gen desaturation of 88'2, or below occurs while the patient is ments indicates loss of efficacy due to antibody formation. walking, the patient is a candidate for home oxygen therapy. necessitating discontinuation of pegloticase. Pegloticase Some studies suggest that aggressive treatment of gastro should not be given with any other urate lowering therapy intestinal reflux disease may have a positive effect on ILD so that interpretation of the serum urate level before each progression. Mycophenolate mofetil is a mainstay of therapy infusion is clear. Therefore. this patient should discontinue for ILD in systemic sclerosis. Data from open-label trials sug febuxostat. gest that mycophenolate mofetil can stabilize and, in some Hydroxychloroquine (Option A) is used in the treat- cases, improve lung function. The Scleroderma Lung Study ll ment of rheumatoid arthritis. This patient does not have a compared oral cyclophosphamide for 1 year to mycopheno history of rheumatoid arthritis. The erosions seen on her Iate mofletil for 2 years. Both agents were equally eflicacious radiographs are typical of gout with sclerotic borders and in improving and stabilizing FVC; however, mycophenolate overhanging edges. Typical rheumatoid arthritis radio mofetil was better tolerated and can be used for many years. graphic changes include periarticular osteopenia, mar whereas cyclophosphamide has a time limited utility due to ginal erosions without overhanging edges, and joint space toxicity. Expert opinion places mycophenolate mofetil flrst 155

An swe-11 -1 1 d 9.!!'q.! :t for both induction and maintenance therapy in patients with inflammatory lower extremity arthritis, reactive arthritis. systemic sclerosis and ILD. and psoriatic arthritis. Upper extrenriry findings make lllV Hydroxychloroquine (Option A) may be useful for infbction less likely. this patient's skin finding is typical of' arthritis in systemic sclerosis but does not play a role in other dissen.rinated gonococcirl infection rather than I I I\r associated manifestations of the disease, including ILD. arthritis, nrhich may have no skin nrani{estations or may be Methotrexate (Option B) has utility in skin disease and associated with kerakrderma blenorrhagicum, cir-cinate bal arthritis of systemic sclerosis, but no data suggest it is useful anitis. ancl psoriasis. for ILD. Arlhritis due to lyrne disease (Option D) tends to have Nintedanib (Option D), a tyrosine kinase inhibitor, slows a subacute onset and nronoarticulirr presentation. typically the progression of idiopathic pulmonary flbrosis and ILD in causing a swollen but not exquisitely painful knee. Patients the setting of systemic sclerosis. However, the patients who will sometinres note accompanying firtigue but not constitutional beneflt the most, when to initiate therapy, and optimal duration symptoms. No skin nranifestations are associated Lyme "vith D of therapy are unclear. Most experts reserve nintedanib for irrthritis because it is a late n.ranifestation of Borrelia burgdor UI patients who cannot take mycophenolate mofetil or cyclophos lbri inl'ection and is not associated with erythema nrigratrs. E phamide or who progress while receiving these treatments. The cliflerential cliagnosis of nerv onset oligoarticular .D ul inflanrmatory arthritis in a 1'oung \r'oman should include o, XEY POIXIS systemic lupus ery4hematosus (SLE) (Option E). Arthralgia and CL . Interstitial lung disease occurs in 50'/. of patients with arthritis are presellt in up to 95',1, ot patients with SLE at some f.l diffuse cutaneous systemic sclerosis; the prevalence is point in their disease. l]ouever, the abrupt onset of symptonrs 85% in the presence ofanti-Scl 70 antibodies. in this case and the absence of skin n.ranifbstations lvpical of It (D . Mycophenolate mofetil is a mainstay of therapy for SLE (alopecia. discoid lesions. malar rash) make Sl.E less likely tn interstitial lung disease in systemic sclerosis. X EY PO Il{IS o Gonococcal arthritis may present as an acute inflam Bibliography matory monoarthritis. Volkmann ER. Tashkin Dq Li N. et al. Mycophenolate mofetil versus placebo tt)r systemic sclerosis related interstitial lung disease: an lnttlysis of o An arthritis-dermatitis syndrome characterized by Scleroderma l.ung Studies I and ll. Arthritis Rheumatol. 2ol7t69:1451 1.160. IPMID: 28376288] doi:10.1002/art.,1011,1 acutely painful tenosynovitis, migratory arthralgia, and pustular or vesiculopustular skin lesions is the most common manifestation of gonococcal arthritis.

An swe-11 -1 1 d 9.!!'q.! :t for both induction and maintenance therapy in patients with inflammatory lower extremity arthritis, reactive arthritis. systemic sclerosis and ILD. and psoriatic arthritis. Upper extrenriry findings make lllV Hydroxychloroquine (Option A) may be useful for infbction less likely. this patient's skin finding is typical of' arthritis in systemic sclerosis but does not play a role in other dissen.rinated gonococcirl infection rather than I I I\r associated manifestations of the disease, including ILD. arthritis, nrhich may have no skin nrani{estations or may be Methotrexate (Option B) has utility in skin disease and associated with kerakrderma blenorrhagicum, cir-cinate bal arthritis of systemic sclerosis, but no data suggest it is useful anitis. ancl psoriasis. for ILD. Arlhritis due to lyrne disease (Option D) tends to have Nintedanib (Option D), a tyrosine kinase inhibitor, slows a subacute onset and nronoarticulirr presentation. typically the progression of idiopathic pulmonary flbrosis and ILD in causing a swollen but not exquisitely painful knee. Patients the setting of systemic sclerosis. However, the patients who will sometinres note accompanying firtigue but not constitutional beneflt the most, when to initiate therapy, and optimal duration symptoms. No skin nranifestations are associated Lyme "vith D of therapy are unclear. Most experts reserve nintedanib for irrthritis because it is a late n.ranifestation of Borrelia burgdor UI patients who cannot take mycophenolate mofetil or cyclophos lbri inl'ection and is not associated with erythema nrigratrs. E phamide or who progress while receiving these treatments. The cliflerential cliagnosis of nerv onset oligoarticular .D ul inflanrmatory arthritis in a 1'oung \r'oman should include o, XEY POIXIS systemic lupus ery4hematosus (SLE) (Option E). Arthralgia and CL . Interstitial lung disease occurs in 50'/. of patients with arthritis are presellt in up to 95',1, ot patients with SLE at some f.l diffuse cutaneous systemic sclerosis; the prevalence is point in their disease. l]ouever, the abrupt onset of symptonrs 85% in the presence ofanti-Scl 70 antibodies. in this case and the absence of skin n.ranifbstations lvpical of It (D . Mycophenolate mofetil is a mainstay of therapy for SLE (alopecia. discoid lesions. malar rash) make Sl.E less likely tn interstitial lung disease in systemic sclerosis. X EY PO Il{IS o Gonococcal arthritis may present as an acute inflam Bibliography matory monoarthritis. Volkmann ER. Tashkin Dq Li N. et al. Mycophenolate mofetil versus placebo tt)r systemic sclerosis related interstitial lung disease: an lnttlysis of o An arthritis-dermatitis syndrome characterized by Scleroderma l.ung Studies I and ll. Arthritis Rheumatol. 2ol7t69:1451 1.160. IPMID: 28376288] doi:10.1002/art.,1011,1 acutely painful tenosynovitis, migratory arthralgia, and pustular or vesiculopustular skin lesions is the most common manifestation of gonococcal arthritis. tr Item 63 Answer: A Ed ucationa I Objective : Diagnose disseminated Bibliography Ross JJ. Septic arthritis of native ioints. lnfect Dis Clin North Am. 2017; gonococcal infection. 31:2O3 218. IPMID: 28366221] '[he most likely diagnosis is disseminatecl gonococca] infec tion (Option A). Although gor.rococcal arthritis may present as an acute inflammatory monoarthritis, the most typical Item 64 Answer: A llresentation is an arthritis dermatitis syndrome charac Educational Objective: Diagnose mixed connective terized by fbver, chills, malaise, acutely painful tenosynovi tissue disease. tis, migratory arlhralgia. and pustular or vesiculopustular skin lesions. More rarely, hemorrhagic nracules or papules The most appropriate diagnosis is mixed connective tissue dis rnay be seen. Most patients have 2 to 10 skin lesions, most ease (MCTD) (Option A). MCTD is an overlap syndrome that commonly on the distal extremities. Women nlay present includes clinical features of systemic sclerosis, systemic lupus cluring or immediately after menstrual periods. However. erythematosus, andior inflammatory myositis. It is associated genital s1'mptoms are often absent. Disserninated gonococcal with anti-Ul ribonucleoprotein (RNP) antibodies. Clinical infbction should be part of the difl'erential diagnosis fbr any features may present sequentially over time, as in this patient sexually active patient presenting'nvith possible inf'ectious presenting with proximal muscle weakness consistent with arthritis or inf'ectious tenosynovitis, rcgardless of age. inflammatory myositis. Ralmaud phenomenon is common Acute l.repatitis B virr.rs (HBV) inf'ection (Option B) is in patients with MCTD. Gastroesophageal reflux may be due included in the difl'erential cliagnosis of'disseminated gono to esophageal dysmotility, a systemic sclerosis-like condition; coccal infection. Patients with acute IIUV infection can also the presence of diffusely puffi fingers is also a common find develop fever, chills, polyar-thritis, tenosynovitis. and rash. ing in early systemic sclerosis. Treatment of MCTD is based on Hortever, the arthritis of ircute HBV inf'ection is usually the speciflc organ system involved. The presence ofnew myo- polyarticular and symmetric. In addition. the rash may be sitis requires treatment with immunosuppressive medication. urticarial. lichenoid, or palpable purpura, but not pustular. Rheumatoid arthritis (Option B) causes an inflamma- tllV infection (Option C) has been associatecl with a tory arthritis, typically involving the metacarpophalangeal variety of musculoskeletal presentations, including a short joints and wrists, and may be associated with Raynaud phe lived (<24 hour) painful :rrticular syndrome. oligoarticular nomenon. However, it is not associated with anti UI-RNP

tr Item 63 Answer: A Ed ucationa I Objective : Diagnose disseminated Bibliography Ross JJ. Septic arthritis of native ioints. lnfect Dis Clin North Am. 2017; gonococcal infection. 31:2O3 218. IPMID: 28366221] '[he most likely diagnosis is disseminatecl gonococca] infec tion (Option A). Although gor.rococcal arthritis may present as an acute inflammatory monoarthritis, the most typical Item 64 Answer: A llresentation is an arthritis dermatitis syndrome charac Educational Objective: Diagnose mixed connective terized by fbver, chills, malaise, acutely painful tenosynovi tissue disease. tis, migratory arlhralgia. and pustular or vesiculopustular skin lesions. More rarely, hemorrhagic nracules or papules The most appropriate diagnosis is mixed connective tissue dis rnay be seen. Most patients have 2 to 10 skin lesions, most ease (MCTD) (Option A). MCTD is an overlap syndrome that commonly on the distal extremities. Women nlay present includes clinical features of systemic sclerosis, systemic lupus cluring or immediately after menstrual periods. However. erythematosus, andior inflammatory myositis. It is associated genital s1'mptoms are often absent. Disserninated gonococcal with anti-Ul ribonucleoprotein (RNP) antibodies. Clinical infbction should be part of the difl'erential diagnosis fbr any features may present sequentially over time, as in this patient sexually active patient presenting'nvith possible inf'ectious presenting with proximal muscle weakness consistent with arthritis or inf'ectious tenosynovitis, rcgardless of age. inflammatory myositis. Ralmaud phenomenon is common Acute l.repatitis B virr.rs (HBV) inf'ection (Option B) is in patients with MCTD. Gastroesophageal reflux may be due included in the difl'erential cliagnosis of'disseminated gono to esophageal dysmotility, a systemic sclerosis-like condition; coccal infection. Patients with acute IIUV infection can also the presence of diffusely puffi fingers is also a common find develop fever, chills, polyar-thritis, tenosynovitis. and rash. ing in early systemic sclerosis. Treatment of MCTD is based on Hortever, the arthritis of ircute HBV inf'ection is usually the speciflc organ system involved. The presence ofnew myo- polyarticular and symmetric. In addition. the rash may be sitis requires treatment with immunosuppressive medication. urticarial. lichenoid, or palpable purpura, but not pustular. Rheumatoid arthritis (Option B) causes an inflamma- tllV infection (Option C) has been associatecl with a tory arthritis, typically involving the metacarpophalangeal variety of musculoskeletal presentations, including a short joints and wrists, and may be associated with Raynaud phe lived (<24 hour) painful :rrticular syndrome. oligoarticular nomenon. However, it is not associated with anti UI-RNP 156

t Answers and antibodies or myositis and thus is an unlikely diagnosis in Cyclophosphamide (Option A) can be considered as sal I

t Answers and antibodies or myositis and thus is an unlikely diagnosis in Cyclophosphamide (Option A) can be considered as sal I this patient. vage therapy for patients with severe inflammatory myositis Systemic lupus ery.thematosus (SLE) (Option C) is asso refractory to other therapies but is not considered flrst or ciated with such clinical features as photosensitive rash, sero- second Iine treatment. The potential for harm outweighs the : sitis, kidney disease, cytopenias, and hypocomplementemia. expected benefit in patients with inclusion body myositis, Myositis may be a feature of SLE, but the lack of other features and cyclophosphamide should not be initiated. of SLE in this patient, coupled with the features of systemic Intravenous immune globulin (Option B) can be used sclerosis (puffu fingers and gastroesophageal reflux), makes in patients with polymyositis or dermatomyositis who have this a less likely diagnosis. The presence ofantinuclear anti- an inadequate response to initial combination therapy with bodies helps establish a diagnosis of SLE but is not speciflc glucocorticoids and traditional immunosuppressive agents, for SLE, and antinuclear antibodies are commonly fbund in such as methotrexate or azathioprine. However, it would other rheumatologic diseases, including MCTD. not be likely to add beneflt in patients with inclusion body Undifferentiated connective tissue disease (Option D) is myositis without a glucocorticoid response. a^ o associated with milder symptoms of arthritis and Raynaud For patients with most forms of idiopathic inflamma- ET phenomenon. It is not associated with myositis or systemic tory myopathies, adding methotrexate (Option C) to gluco sclerosis features. Although patients are positive for antinu- corticoids for combination therapy is a good initial practice IJ clear antibodies, they are usually negative for the specific that can reduce the total amount and duration ofglucocor t, extractable nuclear antigen subsets (e.g., anti-double-stranded ticoid use. Ilowever, there is little evidence for methotrexate .E DNA, anti Ro/SSA, anti LalSSB, anti UI-RNP antibodies, or other glucocorticoid sparing therapy in patients with UI

this patient. vage therapy for patients with severe inflammatory myositis Systemic lupus ery.thematosus (SLE) (Option C) is asso refractory to other therapies but is not considered flrst or ciated with such clinical features as photosensitive rash, sero- second Iine treatment. The potential for harm outweighs the : sitis, kidney disease, cytopenias, and hypocomplementemia. expected benefit in patients with inclusion body myositis, Myositis may be a feature of SLE, but the lack of other features and cyclophosphamide should not be initiated. of SLE in this patient, coupled with the features of systemic Intravenous immune globulin (Option B) can be used sclerosis (puffu fingers and gastroesophageal reflux), makes in patients with polymyositis or dermatomyositis who have this a less likely diagnosis. The presence ofantinuclear anti- an inadequate response to initial combination therapy with bodies helps establish a diagnosis of SLE but is not speciflc glucocorticoids and traditional immunosuppressive agents, for SLE, and antinuclear antibodies are commonly fbund in such as methotrexate or azathioprine. However, it would other rheumatologic diseases, including MCTD. not be likely to add beneflt in patients with inclusion body Undifferentiated connective tissue disease (Option D) is myositis without a glucocorticoid response. a^ o associated with milder symptoms of arthritis and Raynaud For patients with most forms of idiopathic inflamma- ET phenomenon. It is not associated with myositis or systemic tory myopathies, adding methotrexate (Option C) to gluco sclerosis features. Although patients are positive for antinu- corticoids for combination therapy is a good initial practice IJ clear antibodies, they are usually negative for the specific that can reduce the total amount and duration ofglucocor t, extractable nuclear antigen subsets (e.g., anti-double-stranded ticoid use. Ilowever, there is little evidence for methotrexate .E DNA, anti Ro/SSA, anti LalSSB, anti UI-RNP antibodies, or other glucocorticoid sparing therapy in patients with UI and anti smooth muscle antibodies). inclusion body myositis, especially if they have no meaning o ful clinical response to high-dose glucocorticoids. vt = xtY PotilIs Restarting prednisone (Option E) in this case is unlikely r Mixed connective tissue disease is an overlap syndrome to benefit the patient because he had little to no meaningful that includes clinical features of systemic sclerosis, sys response to prednisone when initially instituted. Adverse temic lupus erythematosus, and/or inflammatory elfects associated with long-term glucocorticoid use, includ myositis; it is associated with Raynaud phenomenon ing glucocorticoid myopathy, could exacerbate his reduced and anti-Ul ribonucleoprotein antibodies. muscle function. . Treatment of mixed connective tissue disease is based t(EY POtl{TS on the specific organ system involved. I . Patients with inclusion body myositis often have little improvement while receiving immunosuppressive Bibliography therapies; these therapies should be discontinued ifthey Cunnarsson R, tletlevik SO, Lilleby V et al. N,lixed connective tissue disease. Best Pract Res Clin Rheumabl. 2016;30:9.5 lll. [PMID: 27121219) doi:t}. are not effective. l0l 6ij.berh.2016.03.002 o Physical therapy may help patients with inclusion body myositis to maintain muscle function for activities of Item 65 Answer: D daily living. Educational Objective: Treat inclusion body myositis. Bibliography The most appropriate treatment is to initiate physical ther Creenberg SA. Inclusion body myositis: clinical features rrnd pathogenesis. apy (Option D). Inclusion body myositis is an insidious con Nat Rev Rheumatol. 2019 May;15(5):257 272. I PMID: 308377081 doi: 10.10i18/s41584-Ol9-O186 x dition affecting older adults. It is distinguishable from other forms of myositis by its slow progression and different pat tern of muscle involvement. Both proximal and distal muscle Item 66 involvement occur; finger and forearm flexor involvement is nearly pathognomonic. Up to half of patients with inclu Answer: A Ed ucationa I Objective : Diagnose Chikungunya arthritis. tr sion body myositis have cricopharyngeal muscle involve- Inf'ection with chikungunya virus (Option A) is the most ment, leading to dysphagia and increased risk for aspiration. likely diagnosis. Chikungunya is an arbovirus spread by Serum creatine kinase levels are elevated to a lesser extent nrosquitocs. Acute infbction is heralded by the abrupt onsct than seen in other forms of idiopathic inflammatory myopa- of serere. polyarticuhr arthralgiir artcl fever, an exanthen-r:r thies. Autoantibodies are less often present, but anti NTSc1A lhat may bc fbcal or difluse, ancl conjunctivitis. 'lhe distri autoantibodies are found in up to half of patients and rarely bution o{ the arthritis is often bilaterally syrnmetric and in healthy persons. Patients with inclusion body myositis, usually involves 10 or nrore joints. Ihe temperature is olten unlike those with other forms of idiopathic myositis, often greater than 119.0 "C (102.2 "F). ancl fel.er persists fbr 3 to have little improvement while receiving immunosuppressive 5 days. l,aburatory testing may rcvcal leukopcnia, lymph therapies. Therapeutic trials should not be continued if they openia, thrombocytopenia. ancl elevated scrunr arninr.r are not effective. Physical therapy may help patients to main translerase and creatinine levels. Chikungunya virus can be tain muscle function for activities of daily living. detected b1, polymerase chain reaction for 1 u,eek after onset

and anti smooth muscle antibodies). inclusion body myositis, especially if they have no meaning o ful clinical response to high-dose glucocorticoids. vt = xtY PotilIs Restarting prednisone (Option E) in this case is unlikely r Mixed connective tissue disease is an overlap syndrome to benefit the patient because he had little to no meaningful that includes clinical features of systemic sclerosis, sys response to prednisone when initially instituted. Adverse temic lupus erythematosus, and/or inflammatory elfects associated with long-term glucocorticoid use, includ myositis; it is associated with Raynaud phenomenon ing glucocorticoid myopathy, could exacerbate his reduced and anti-Ul ribonucleoprotein antibodies. muscle function. . Treatment of mixed connective tissue disease is based t(EY POtl{TS on the specific organ system involved. I . Patients with inclusion body myositis often have little improvement while receiving immunosuppressive Bibliography therapies; these therapies should be discontinued ifthey Cunnarsson R, tletlevik SO, Lilleby V et al. N,lixed connective tissue disease. Best Pract Res Clin Rheumabl. 2016;30:9.5 lll. [PMID: 27121219) doi:t}. are not effective. l0l 6ij.berh.2016.03.002 o Physical therapy may help patients with inclusion body myositis to maintain muscle function for activities of Item 65 Answer: D daily living. Educational Objective: Treat inclusion body myositis. Bibliography The most appropriate treatment is to initiate physical ther Creenberg SA. Inclusion body myositis: clinical features rrnd pathogenesis. apy (Option D). Inclusion body myositis is an insidious con Nat Rev Rheumatol. 2019 May;15(5):257 272. I PMID: 308377081 doi: 10.10i18/s41584-Ol9-O186 x dition affecting older adults. It is distinguishable from other forms of myositis by its slow progression and different pat tern of muscle involvement. Both proximal and distal muscle Item 66 involvement occur; finger and forearm flexor involvement is nearly pathognomonic. Up to half of patients with inclu Answer: A Ed ucationa I Objective : Diagnose Chikungunya arthritis. tr sion body myositis have cricopharyngeal muscle involve- Inf'ection with chikungunya virus (Option A) is the most ment, leading to dysphagia and increased risk for aspiration. likely diagnosis. Chikungunya is an arbovirus spread by Serum creatine kinase levels are elevated to a lesser extent nrosquitocs. Acute infbction is heralded by the abrupt onsct than seen in other forms of idiopathic inflammatory myopa- of serere. polyarticuhr arthralgiir artcl fever, an exanthen-r:r thies. Autoantibodies are less often present, but anti NTSc1A lhat may bc fbcal or difluse, ancl conjunctivitis. 'lhe distri autoantibodies are found in up to half of patients and rarely bution o{ the arthritis is often bilaterally syrnmetric and in healthy persons. Patients with inclusion body myositis, usually involves 10 or nrore joints. Ihe temperature is olten unlike those with other forms of idiopathic myositis, often greater than 119.0 "C (102.2 "F). ancl fel.er persists fbr 3 to have little improvement while receiving immunosuppressive 5 days. l,aburatory testing may rcvcal leukopcnia, lymph therapies. Therapeutic trials should not be continued if they openia, thrombocytopenia. ancl elevated scrunr arninr.r are not effective. Physical therapy may help patients to main translerase and creatinine levels. Chikungunya virus can be tain muscle function for activities of daily living. detected b1, polymerase chain reaction for 1 u,eek after onset 157

Answers and Critiques ot syll.lptoms. after lt,hich testing becrtmes unreliable. Spe to 3 weeks after an enteric infection or a bout of nongono EX cific lgM antibody is detectable ill 5 to 10 da1,'s afler symp coccal urethritis or cervicitis. loint inflammation can be CONT. tolr onset and remains positivc fbr up kt 2 to 3 rnonths. This intense, with high leukocyte counts in the synovial fluid. patient's intensity of pain, lnrgc trunrber of joints involvcd, The sacroiliac joints and spine may be involved. Enthesitis higl.r temperature. and residence in an endemic area make usually affects the heel (plantar fasciitis or Achilles ten- chikungunya the most likely diagn<tsis. dinitis) or may present as dactylitis of the flngers or toes. Acute hepatitis B virus infection (Option B) ma1' be Extra articular features can include nonpainful oral ulcers: lccompanied by an abmpt. severe onset olpoly'articular joint ocular inflammation (conjunctivitis, keratitis, episcleritis. pain that antedates and ternrinates r,r'ith the onset of jaunclicc. or anterior uveitis)r and a psoriasiform rash (keratoderma Hort'eler. it is not associatecl r'r'ith irn ircr-rte f'ebrile onset or blennorrhagicum), typically on the hands and feet. Some 'uvidespread maculopapular rash: other skin findings. such as patients also develop circinate balanitis on the glans penis urticaria, small vessel vasculitis. and ery.tl.rema multifbrme, or erythema nodosum on the lower extremities. Reactive D have been associated with acute hepatitis B virus infection. arthritis is treated with NSAIDs at anti inflammatory doses la I lepatitis C virus inf'ection (Option C) is largely asynrp tbr at least 2 weeks. If relief is incomplete, intra-articular E bmatic but occasionally is acctimpanied by polyarthritis. glucocorticoid injections and oral glucocorticoids can be lD aa llowever, it is not associated with an acute febrile onset or used. If symptoms persist beyond 3 to 6 months, the use of o, nracukrpapular rash. When hepatilis C virus inlection is disease modifliing antirheumatic drugs. such as sulfasala CL associated with cryoglclbulinenria. arthralgia ma1' be seen zine, methotrexate, or tumor necrosis factor inhibitors. may rl but the r:rsh is purpuric. Other skin mar.ritestations of hep be necessary for symptom control and to prevent joint ero lt atitis C virus infection nrav inclutle livedo reticularis. ery sion. Therapy is discontinued 3 to 6 months follor,r'ing dis- (D thema multiforme. and lichcn ltlanus. ease remission. Most cases of reactive arthritis last 6 weeks Ut HIV infbction (Option D) is associirted u,ith sereral mus to 6 months; only 25'X, of patients have persistent disease. culoskeletal syndromes. Although the painful articular syn [.ong term complications can include erosive arthritis, usu clrome is characterized by an abrupt onset of arthralgia and ally of the metatarsophalangeal joints; aortitis with aortic nryalgia, it is not associatecl witl.r fl'ver, is oligoarticular and valve insufficiency; atrioventricular heart block; and uveitis. asymnretdc, most lrequently involves the joints of the lower Antibiotics, such as azithromycin (Option A), generally cxtrcmities, and typically resolves r,r'ithin a day HlV associated are not indicated in reactive arthritis because they do not arthritis, leactive afillritis. and psoriatic arthritis are some affect illness outcomes. Antibiotics may be used for per times seen in patients u,ith tllV infbctior.r but do not hare ln sistent enteritis and for patients with symptoms of acute ure- acute onset and are not associated \\'ith fe\,er and rash. thritis or persistent Chlomydio associated reactive arthritis. This patient has no indication for antibiotic therapy I(EY POITIS Between 50% and B0'7, of patients with reactive arthritis . Acute infection with chikungunya virus is heralded by are HLA B27 positive. but testing for HLA B27 (Option B) is the abrupt onset of severe, polyarticular arthralgia, useful only if the diagnosis is uncertain. In this patient. the high temperature, rash, and conjunctivitis and often diagnosis is not in question and HLA B27 results would not with bilaterally symmetric polyarticular arthritis. change treatment. . Chikungunya virus can be detected polymerase chain Stool cultures (Option D) would be useful only if the reaction for 1 week after onset of symptoms; specific diarrhea persisted. This patient had short-lived enteritis, so IgM antibody is detectable in 5 to 10 days after symp- stool studies are not indicated. tom onset and remains positive for up to 2 to 3 months. I(EY POITTS . Reactive arthritis typically entails arthritisienthesitis Bibliography in the lower extremities 2 to 3 weeks after an enteric Pathak H. Mohan MC, Ravindran V Chikungunya arthritis. Clin Med (Lond). 2019;19:381 385. [PMID: 31530685] doi:1o.7861 clinmed.2019-0035 infection or a bout of nongonococcal urethritis or cervicitis. . Reactive arthritis is treated with NSAIDs at anti- Item 67 Answer: C inflammatory doses for at least 2 weeks. Ed ucationa I Objective : Treat reactive arthritis. Bibliography The most appropriate management is an NSAID, such as Schmitt SK. Reacti\€ arthritis. Intl,ct [)is Clin North Am. 2017:31:265 277 piroxicam (Option C). The patient has post enteric infection lPl\'llD: 282925.101 doi:10.1016 i.idc.20l7.ol.002 reactive arthritis, with asymmetric pauci arthritis involv ing the lower extremities, enthesitis involving the Achilles Item 68 Answer: C tendon, and dactylitis of the right fourth toe and left third and fourth toes. Reactive arthritis is the least common form Educational Obiective: Treat lgG4-related disease. of spondyloarthritis (2'l,, of cases). Reactive arthritis typi 'llre rnost irppropriate trealnrent is rituximab (Option C). The cally entails arthritis/enthesitis in the lower extremities 2 ir.rfiltrative involvement of'the parotid and lacrimal glands,

ot syll.lptoms. after lt,hich testing becrtmes unreliable. Spe to 3 weeks after an enteric infection or a bout of nongono EX cific lgM antibody is detectable ill 5 to 10 da1,'s afler symp coccal urethritis or cervicitis. loint inflammation can be CONT. tolr onset and remains positivc fbr up kt 2 to 3 rnonths. This intense, with high leukocyte counts in the synovial fluid. patient's intensity of pain, lnrgc trunrber of joints involvcd, The sacroiliac joints and spine may be involved. Enthesitis higl.r temperature. and residence in an endemic area make usually affects the heel (plantar fasciitis or Achilles ten- chikungunya the most likely diagn<tsis. dinitis) or may present as dactylitis of the flngers or toes. Acute hepatitis B virus infection (Option B) ma1' be Extra articular features can include nonpainful oral ulcers: lccompanied by an abmpt. severe onset olpoly'articular joint ocular inflammation (conjunctivitis, keratitis, episcleritis. pain that antedates and ternrinates r,r'ith the onset of jaunclicc. or anterior uveitis)r and a psoriasiform rash (keratoderma Hort'eler. it is not associatecl r'r'ith irn ircr-rte f'ebrile onset or blennorrhagicum), typically on the hands and feet. Some 'uvidespread maculopapular rash: other skin findings. such as patients also develop circinate balanitis on the glans penis urticaria, small vessel vasculitis. and ery.tl.rema multifbrme, or erythema nodosum on the lower extremities. Reactive D have been associated with acute hepatitis B virus infection. arthritis is treated with NSAIDs at anti inflammatory doses la I lepatitis C virus inf'ection (Option C) is largely asynrp tbr at least 2 weeks. If relief is incomplete, intra-articular E bmatic but occasionally is acctimpanied by polyarthritis. glucocorticoid injections and oral glucocorticoids can be lD aa llowever, it is not associated with an acute febrile onset or used. If symptoms persist beyond 3 to 6 months, the use of o, nracukrpapular rash. When hepatilis C virus inlection is disease modifliing antirheumatic drugs. such as sulfasala CL associated with cryoglclbulinenria. arthralgia ma1' be seen zine, methotrexate, or tumor necrosis factor inhibitors. may rl but the r:rsh is purpuric. Other skin mar.ritestations of hep be necessary for symptom control and to prevent joint ero lt atitis C virus infection nrav inclutle livedo reticularis. ery sion. Therapy is discontinued 3 to 6 months follor,r'ing dis- (D thema multiforme. and lichcn ltlanus. ease remission. Most cases of reactive arthritis last 6 weeks Ut HIV infbction (Option D) is associirted u,ith sereral mus to 6 months; only 25'X, of patients have persistent disease. culoskeletal syndromes. Although the painful articular syn [.ong term complications can include erosive arthritis, usu clrome is characterized by an abrupt onset of arthralgia and ally of the metatarsophalangeal joints; aortitis with aortic nryalgia, it is not associatecl witl.r fl'ver, is oligoarticular and valve insufficiency; atrioventricular heart block; and uveitis. asymnretdc, most lrequently involves the joints of the lower Antibiotics, such as azithromycin (Option A), generally cxtrcmities, and typically resolves r,r'ithin a day HlV associated are not indicated in reactive arthritis because they do not arthritis, leactive afillritis. and psoriatic arthritis are some affect illness outcomes. Antibiotics may be used for per times seen in patients u,ith tllV infbctior.r but do not hare ln sistent enteritis and for patients with symptoms of acute ure- acute onset and are not associated \\'ith fe\,er and rash. thritis or persistent Chlomydio associated reactive arthritis. This patient has no indication for antibiotic therapy I(EY POITIS Between 50% and B0'7, of patients with reactive arthritis . Acute infection with chikungunya virus is heralded by are HLA B27 positive. but testing for HLA B27 (Option B) is the abrupt onset of severe, polyarticular arthralgia, useful only if the diagnosis is uncertain. In this patient. the high temperature, rash, and conjunctivitis and often diagnosis is not in question and HLA B27 results would not with bilaterally symmetric polyarticular arthritis. change treatment. . Chikungunya virus can be detected polymerase chain Stool cultures (Option D) would be useful only if the reaction for 1 week after onset of symptoms; specific diarrhea persisted. This patient had short-lived enteritis, so IgM antibody is detectable in 5 to 10 days after symp- stool studies are not indicated. tom onset and remains positive for up to 2 to 3 months. I(EY POITTS . Reactive arthritis typically entails arthritisienthesitis Bibliography in the lower extremities 2 to 3 weeks after an enteric Pathak H. Mohan MC, Ravindran V Chikungunya arthritis. Clin Med (Lond). 2019;19:381 385. [PMID: 31530685] doi:1o.7861 clinmed.2019-0035 infection or a bout of nongonococcal urethritis or cervicitis. . Reactive arthritis is treated with NSAIDs at anti- Item 67 Answer: C inflammatory doses for at least 2 weeks. Ed ucationa I Objective : Treat reactive arthritis. Bibliography The most appropriate management is an NSAID, such as Schmitt SK. Reacti\€ arthritis. Intl,ct [)is Clin North Am. 2017:31:265 277 piroxicam (Option C). The patient has post enteric infection lPl\'llD: 282925.101 doi:10.1016 i.idc.20l7.ol.002 reactive arthritis, with asymmetric pauci arthritis involv ing the lower extremities, enthesitis involving the Achilles Item 68 Answer: C tendon, and dactylitis of the right fourth toe and left third and fourth toes. Reactive arthritis is the least common form Educational Obiective: Treat lgG4-related disease. of spondyloarthritis (2'l,, of cases). Reactive arthritis typi 'llre rnost irppropriate trealnrent is rituximab (Option C). The cally entails arthritis/enthesitis in the lower extremities 2 ir.rfiltrative involvement of'the parotid and lacrimal glands, 158

Answers and Critiques tr CONT together \,ith retroperitonell fibrosis and periaortitis. is nrost consistent \\rith [gG.1 relatecl disease. IgG.l positive plasnrablasts on biopsy con[irnt thc dirrgnosis. The patient's Pulmonary arlerial hypertension (PAH) occurs in roughly 10'7, of patients with systemic sclerosis and is more prevalent in the limited form (in this patient, evidenced by distal only clevated alkaline phosphatasc lcvcl suggests associated bil skin involvement). PAH is a major cause of morbidity and iary involvement. 'lhe absencc of elevated serum IgG4 anti mortality. Risk factors include anticentromere antibodies, boclies is not exclusior-rary because serum antibodies are antibodies to U1 ribonucleoprotein, antiphospholipid anti often not present. Treatment of lgG4 related disease r.nost bodies, disease duration greater than 6 years, and telangi often consists of initial high dose glucclcorticoids lbllo"vecl ectasias. TTE provides an estimation of pulmonary arterial bv a slort, taper. Beciruse the cliserrse often recurs ciuring systolic pressure and assessment of both right and left tape'r. nr-rd because glucocorticoirls bear significtrnt toxic heart size and function. Current recommendations based itr': co:rdministration ol rituxinrab (irn anti CD20 antibody on expert opinion vary. but PAH screening with pulmo that indirectly depletes plasnrablirsts) is olten initiated to nary function tests and TTE at baseline and at the time of' pernlit accelerated glucocorticoid taper. l{or,r,ever. ritux development of any new signs or symptoms is reasonable. ta o inrab nronotherapy is also eltec'tive and can be used alonc ln addition, most experts obtain pulmonary function tests ET in pltients with absolute or relative contraindications tcl and TTE annually. PAH is typically associated with a Dt.c<r glucocorticoid theraplr that is less than 60'X, of predicted and is disproportionately (J Cevimeline (Option A) is rr lrarirsympathetic musca low compared with the decrease in lung volumes (FVC/ .E, rinic agonist used to trcrt sicca in patients with Sjogrerr Dr.co ratio >1.6) or a decrease in Dt.co ctf 2O''1, or greater in .E syndrune. Because this paticnt has parotid enlargement. 1 year. In this patient, an elevated FVC/Dr-co ratio (1.66) tl (, shc n.rigl.tt hare sicca and rnight bcnefit fiom cevimeline. suggests the possibility of PAH and mandates the need fbr Ilou,e."'er. cevimeline h:rs not becn stuclied in the context of 'l"l'E. Because TTE may be more sensitive than specific. fur vt = E IgG.1 parotitis, and tlre patient hls r.rot reported dry nrouth. ther testing is required il the results indicate possible PAH. Methotrexate (Option B) is a clisease r.r-rodify-ir-rg anti Cardiac magnetic resonance imaging (Option A) can rheumatic drug used as x glucocorticoici sparing agent fbr measure right ventricular mass, and right ventricular hyper nrrrly diseases, including ANCA vlsculitis. Methotrexate hrs trophy can be a clue to the presence of PAH. However, this llso been used extensively lbr icliopathic retroperitoneal test is expensive and cannot estimate pulmonary artery li brosi s. I Ioweveq limited evidence supports methotrL'xxtc pressure. TTE, on the other hand, can be used fbr that to xssist in glucocorlicoid trpering or as a single agent in purpose. Ig(i1 rclated disc'ase. [t rryor-rlcl therefbre not be the first High resolution CT o1' the chest (Option B) is most choicc in this instance. useful to Iook for underlying interstitial lung disease (which Surgical debridement of the retroperitoneal mrrss is more prevalent in dilluse than in limited cutaneous sys- (Option D) may'be necessary if the mlss threatens to erode temic sclerosis). However, the normal pulmonary examina into thc aorta. but thirt is not the cirse in this patient.'lhe tion, normal FVC, and significantly diminished DLco more rnass is \ryrapped around both uretersl however, there is nt-r strongly suggest PAH and the need fbr TTE. hydnrnephrosis or deterioration ot'kidney function to sug Right hearl catheterization (Option C) is the gold stan gest obstructive nephropathy, which would require ureteral dard fbr conflrming PAH, but it is invasive and is typically stcnt plrcement. At this ciisease stage, medicai treatnlent is done after noninvasive tests suggest PAH. Right heart cath nlore appropriate. eterization should be performed in most patients with an abnormal TTE result to confirm the diagnosis of PAH and tcl s I( EY POI TI guide therapy. . Treatment of IgG4-related disease most often consists of initial high-dose glucocorticoids and rituximab; t( EY P0 t ilI3 rituximab can be used alone in patients with absolute o In systemic sclerosis, pulmonary arterial hypertension or relative contraindications to glucocorticoid therapy. is tlpically associated with a Dlco less than 60% of predicted and is disproportionately low compared Bibliography with the decrease in lung volumes (FVC/Drco I)erugino CA, Stone lFI. IgG4 relxted disease: rn Lrpdate on pathophysiologl ratio >1.6) and inrplications for clinicll clre. Nrt Rcv Rheumatol. 2020;76:702-714. lPMll):1129390601 r In patients with systemic sclerosis, transthoracic echocardiography can estimate pulmonary arterial systolic pressure and assess both right and left heart Item 69 Answer: D size and function.

tr CONT together \,ith retroperitonell fibrosis and periaortitis. is nrost consistent \\rith [gG.1 relatecl disease. IgG.l positive plasnrablasts on biopsy con[irnt thc dirrgnosis. The patient's Pulmonary arlerial hypertension (PAH) occurs in roughly 10'7, of patients with systemic sclerosis and is more prevalent in the limited form (in this patient, evidenced by distal only clevated alkaline phosphatasc lcvcl suggests associated bil skin involvement). PAH is a major cause of morbidity and iary involvement. 'lhe absencc of elevated serum IgG4 anti mortality. Risk factors include anticentromere antibodies, boclies is not exclusior-rary because serum antibodies are antibodies to U1 ribonucleoprotein, antiphospholipid anti often not present. Treatment of lgG4 related disease r.nost bodies, disease duration greater than 6 years, and telangi often consists of initial high dose glucclcorticoids lbllo"vecl ectasias. TTE provides an estimation of pulmonary arterial bv a slort, taper. Beciruse the cliserrse often recurs ciuring systolic pressure and assessment of both right and left tape'r. nr-rd because glucocorticoirls bear significtrnt toxic heart size and function. Current recommendations based itr': co:rdministration ol rituxinrab (irn anti CD20 antibody on expert opinion vary. but PAH screening with pulmo that indirectly depletes plasnrablirsts) is olten initiated to nary function tests and TTE at baseline and at the time of' pernlit accelerated glucocorticoid taper. l{or,r,ever. ritux development of any new signs or symptoms is reasonable. ta o inrab nronotherapy is also eltec'tive and can be used alonc ln addition, most experts obtain pulmonary function tests ET in pltients with absolute or relative contraindications tcl and TTE annually. PAH is typically associated with a Dt.c<r glucocorticoid theraplr that is less than 60'X, of predicted and is disproportionately (J Cevimeline (Option A) is rr lrarirsympathetic musca low compared with the decrease in lung volumes (FVC/ .E, rinic agonist used to trcrt sicca in patients with Sjogrerr Dr.co ratio >1.6) or a decrease in Dt.co ctf 2O''1, or greater in .E syndrune. Because this paticnt has parotid enlargement. 1 year. In this patient, an elevated FVC/Dr-co ratio (1.66) tl (, shc n.rigl.tt hare sicca and rnight bcnefit fiom cevimeline. suggests the possibility of PAH and mandates the need fbr Ilou,e."'er. cevimeline h:rs not becn stuclied in the context of 'l"l'E. Because TTE may be more sensitive than specific. fur vt = E IgG.1 parotitis, and tlre patient hls r.rot reported dry nrouth. ther testing is required il the results indicate possible PAH. Methotrexate (Option B) is a clisease r.r-rodify-ir-rg anti Cardiac magnetic resonance imaging (Option A) can rheumatic drug used as x glucocorticoici sparing agent fbr measure right ventricular mass, and right ventricular hyper nrrrly diseases, including ANCA vlsculitis. Methotrexate hrs trophy can be a clue to the presence of PAH. However, this llso been used extensively lbr icliopathic retroperitoneal test is expensive and cannot estimate pulmonary artery li brosi s. I Ioweveq limited evidence supports methotrL'xxtc pressure. TTE, on the other hand, can be used fbr that to xssist in glucocorlicoid trpering or as a single agent in purpose. Ig(i1 rclated disc'ase. [t rryor-rlcl therefbre not be the first High resolution CT o1' the chest (Option B) is most choicc in this instance. useful to Iook for underlying interstitial lung disease (which Surgical debridement of the retroperitoneal mrrss is more prevalent in dilluse than in limited cutaneous sys- (Option D) may'be necessary if the mlss threatens to erode temic sclerosis). However, the normal pulmonary examina into thc aorta. but thirt is not the cirse in this patient.'lhe tion, normal FVC, and significantly diminished DLco more rnass is \ryrapped around both uretersl however, there is nt-r strongly suggest PAH and the need fbr TTE. hydnrnephrosis or deterioration ot'kidney function to sug Right hearl catheterization (Option C) is the gold stan gest obstructive nephropathy, which would require ureteral dard fbr conflrming PAH, but it is invasive and is typically stcnt plrcement. At this ciisease stage, medicai treatnlent is done after noninvasive tests suggest PAH. Right heart cath nlore appropriate. eterization should be performed in most patients with an abnormal TTE result to confirm the diagnosis of PAH and tcl s I( EY POI TI guide therapy. . Treatment of IgG4-related disease most often consists of initial high-dose glucocorticoids and rituximab; t( EY P0 t ilI3 rituximab can be used alone in patients with absolute o In systemic sclerosis, pulmonary arterial hypertension or relative contraindications to glucocorticoid therapy. is tlpically associated with a Dlco less than 60% of predicted and is disproportionately low compared Bibliography with the decrease in lung volumes (FVC/Drco I)erugino CA, Stone lFI. IgG4 relxted disease: rn Lrpdate on pathophysiologl ratio >1.6) and inrplications for clinicll clre. Nrt Rcv Rheumatol. 2020;76:702-714. lPMll):1129390601 r In patients with systemic sclerosis, transthoracic echocardiography can estimate pulmonary arterial systolic pressure and assess both right and left heart Item 69 Answer: D size and function. Educational Objective: Diagnose pulmonary arterial hypertension in a patient with limited cutaneous systemic Bibliography sclerosis. Sundaram SM, Chung L. An update on systentic sclerosis associated pulmo nJry arterial hypertension: a review ol the current literature. (lurr The most appropriate diagnostic test to perform next Rhcumatol Rep. 2018;20:10. I PMlt): 29,1880161 doi:10.1007is11926 ol8 is transthoracic echocardiography (TTE) (Option D). o7o9 5

Educational Objective: Diagnose pulmonary arterial hypertension in a patient with limited cutaneous systemic Bibliography sclerosis. Sundaram SM, Chung L. An update on systentic sclerosis associated pulmo nJry arterial hypertension: a review ol the current literature. (lurr The most appropriate diagnostic test to perform next Rhcumatol Rep. 2018;20:10. I PMlt): 29,1880161 doi:10.1007is11926 ol8 is transthoracic echocardiography (TTE) (Option D). o7o9 5 159

Answers and Critiques Item 70 Answer: C Bibliography Martinez Prat L. Nissen MJ, Lamacchia C, et al. Comparison of serological Ed u catio n a I O bj ective: Evaluate for rheumatoid biomarkers in rheumatoid arthritis and their combination to impro\€ arthritis using laboratory testing. diagnostic performance. Front tmmunol. 2018:9:1113. lPlvllD: 29928272] doi:10.3389 fimmu.2018.01113 The most helpful diagnostic studies will be rheumatoid factor (RF) and anti cyclic citrullinated peptide (CCP) antibodies (Option C). Rheumatoid arthritis presents Item 71 Answer: D with symmetric, polyarticular inflammatory synovitis and Educational Objective: Diagnose sarcoidosis. EX prominently involves the small joints of the hands and feet. These include the proximal interphalangeal, metacar- The most appropriate diagnostic test to perform next is pophalangeal, and interphalangeal joints of the toes and skin biopsy (Option D). The combination of inflltrative and metatarsophalangeal joints. RF is found in approximately destructive bone lesions. skin lesions. parotid and lacrimal 70% of patients with rheumatoid arthritis and may be enlargement. l-rilar lymphadenopath)', and hepatic nodules present at the time of disease onset; however, it has limited strongly sllggests sarcoidosis, an inflammatory disease tl-rat ta E speciflcity. Anti CCP antibodies are also present inTO% of is characterized by formation of noncaseating granulomas .D patients with rheumatoid arthritis but have a speciflcity that can infiltrate almost any organ. Sarcoidosis is best diag UI o, of 95%. Positivity for both tests increases the likelihood of nosed b-r- histologic assessment of a biopsl' specimen o{' EL rheumatoid arthritis and may assist in early diagnosis. afl'ected tissue. In this case. skin is the most accessible tissue rl C reactive protein and ery.throcyte sedimentation rate and is clinically involved; granulomatous skin inrolrement (Option A) are inflammatory markers that can be elevated is common in sarcoidosis and aflects approximatell' 25'li, of .tt patients. in a host of infectious conditions, as well as reflect systemic (D I nfi ltratir,e involvement ol bone suggests the possibilig' ta inflammation in diseases such as rheumatoid arthritis. How- ever, they have no diagnostic specificity for any particular of a malignant condition. potentialll' a lymphoma. Such a disease and do not distinguish among forms of inflamma diagnosis could be supported by the hilar l1'mphadenopa- tory arthritis. thy or-r chest radiograph, as rvell as by the parotid (but not Enzyme linked immunosorbent assay and Western blot commonly lacrimal) enlargement. Horverer. the patient has serologies (Option B) can be useful in the diagnosis of Lyme no other li,mphadenopathli her complete blood cour-rt is disease, including Lyme arthritis. However, this testing is nomal. and the nodular ir.rvolvement of the liver and skin not appropriate in this patient. The patient has po$articular r,r,oulcl be atypical. Moreover. sympton.l duration ot 2 vears symmetric inflammatory arthritis, which is not a pattern is r-rot cor-rsister-rt lvith 11,'n.rphoma. Bone biopsy (Option A) of presentation of Lyme disease. The Spical presentation of and bronchoscopic biopsl ol'a hilar t; mph node (Option B) Lyme arthritis is a subacute onset of monoarticular inflam coulcl distinguish lymphoma f'rom sarcoidosis. bnt both tests matory arthritis of the knee. are irlasive and are not needed if a skin biopsv confirms Viral infections, such as rubella and parvovirus B19, sarcoidosis. are associated with an acute polyarthritis syndrome that Parotid and lacrimal enlargement couid be consistent may mimic rheumatoid arthritis. These viral syndromes u,ith Sjogren syndrome, an infiltrative disease of exocrine lzpically last only a few days to several weeks, usually less glands. Sj6gren s_v-.ndrome can affect the skin and joints; than 6 weeks. Serologic testing (Option D) can help identify honever. in the skin it q,pically produces a non nodular viral syndromes in some individuals with early disease. rash, and in the joints it produces a nonerosi'ue arthritis Anti-CCP antibodies are usually negative in patients with rather than iin infiltratire disease of bone. Nodular liver viral syndromes causing po\zarthritis. Early identiflcation of involvement would not be expected. Diagnosis of Sj6gren rheumatoid arthritis is important for initiation of effective syndrorne could involve obtaining a lip biopsy (Option C). therapy to prevent joint damage. Initial measurement of RF along r,vith anti Ro/SSA rtr anti LaTSSB antibodl testing: and anti CPP antibodies is the best diagnostic test option in houever. sarcoidosis is more likely and a skin biopsy u'ould this patient with a 7 week history of symmetric, polyartic be definitive. ular inflammatory synovitis that prominently involves the l(tY Porlrls small joints of the hands. o Sarcoidosis is an inflammatory disease that is charac I(lY POlttrs terized by formation of noncaseating gtanulomas and can infiltrate almost any organ, including bone. . The most useful laboratory studies to aid in the diag nosis of rheumatoid arthritis are rheumatoid factor o Sarcoidosis is best diagnosed by histologic assessment and anti-cyclic citrullinated peptide antibodies. of a biopsy specimen of affected tissue; when skin is o Rheumatoid factor and anti cyclic citrullinated pep- involved, biopsy is simple and can be definitive.

Item 70 Answer: C Bibliography Martinez Prat L. Nissen MJ, Lamacchia C, et al. Comparison of serological Ed u catio n a I O bj ective: Evaluate for rheumatoid biomarkers in rheumatoid arthritis and their combination to impro\€ arthritis using laboratory testing. diagnostic performance. Front tmmunol. 2018:9:1113. lPlvllD: 29928272] doi:10.3389 fimmu.2018.01113 The most helpful diagnostic studies will be rheumatoid factor (RF) and anti cyclic citrullinated peptide (CCP) antibodies (Option C). Rheumatoid arthritis presents Item 71 Answer: D with symmetric, polyarticular inflammatory synovitis and Educational Objective: Diagnose sarcoidosis. EX prominently involves the small joints of the hands and feet. These include the proximal interphalangeal, metacar- The most appropriate diagnostic test to perform next is pophalangeal, and interphalangeal joints of the toes and skin biopsy (Option D). The combination of inflltrative and metatarsophalangeal joints. RF is found in approximately destructive bone lesions. skin lesions. parotid and lacrimal 70% of patients with rheumatoid arthritis and may be enlargement. l-rilar lymphadenopath)', and hepatic nodules present at the time of disease onset; however, it has limited strongly sllggests sarcoidosis, an inflammatory disease tl-rat ta E speciflcity. Anti CCP antibodies are also present inTO% of is characterized by formation of noncaseating granulomas .D patients with rheumatoid arthritis but have a speciflcity that can infiltrate almost any organ. Sarcoidosis is best diag UI o, of 95%. Positivity for both tests increases the likelihood of nosed b-r- histologic assessment of a biopsl' specimen o{' EL rheumatoid arthritis and may assist in early diagnosis. afl'ected tissue. In this case. skin is the most accessible tissue rl C reactive protein and ery.throcyte sedimentation rate and is clinically involved; granulomatous skin inrolrement (Option A) are inflammatory markers that can be elevated is common in sarcoidosis and aflects approximatell' 25'li, of .tt patients. in a host of infectious conditions, as well as reflect systemic (D I nfi ltratir,e involvement ol bone suggests the possibilig' ta inflammation in diseases such as rheumatoid arthritis. How- ever, they have no diagnostic specificity for any particular of a malignant condition. potentialll' a lymphoma. Such a disease and do not distinguish among forms of inflamma diagnosis could be supported by the hilar l1'mphadenopa- tory arthritis. thy or-r chest radiograph, as rvell as by the parotid (but not Enzyme linked immunosorbent assay and Western blot commonly lacrimal) enlargement. Horverer. the patient has serologies (Option B) can be useful in the diagnosis of Lyme no other li,mphadenopathli her complete blood cour-rt is disease, including Lyme arthritis. However, this testing is nomal. and the nodular ir.rvolvement of the liver and skin not appropriate in this patient. The patient has po$articular r,r,oulcl be atypical. Moreover. sympton.l duration ot 2 vears symmetric inflammatory arthritis, which is not a pattern is r-rot cor-rsister-rt lvith 11,'n.rphoma. Bone biopsy (Option A) of presentation of Lyme disease. The Spical presentation of and bronchoscopic biopsl ol'a hilar t; mph node (Option B) Lyme arthritis is a subacute onset of monoarticular inflam coulcl distinguish lymphoma f'rom sarcoidosis. bnt both tests matory arthritis of the knee. are irlasive and are not needed if a skin biopsv confirms Viral infections, such as rubella and parvovirus B19, sarcoidosis. are associated with an acute polyarthritis syndrome that Parotid and lacrimal enlargement couid be consistent may mimic rheumatoid arthritis. These viral syndromes u,ith Sjogren syndrome, an infiltrative disease of exocrine lzpically last only a few days to several weeks, usually less glands. Sj6gren s_v-.ndrome can affect the skin and joints; than 6 weeks. Serologic testing (Option D) can help identify honever. in the skin it q,pically produces a non nodular viral syndromes in some individuals with early disease. rash, and in the joints it produces a nonerosi'ue arthritis Anti-CCP antibodies are usually negative in patients with rather than iin infiltratire disease of bone. Nodular liver viral syndromes causing po\zarthritis. Early identiflcation of involvement would not be expected. Diagnosis of Sj6gren rheumatoid arthritis is important for initiation of effective syndrorne could involve obtaining a lip biopsy (Option C). therapy to prevent joint damage. Initial measurement of RF along r,vith anti Ro/SSA rtr anti LaTSSB antibodl testing: and anti CPP antibodies is the best diagnostic test option in houever. sarcoidosis is more likely and a skin biopsy u'ould this patient with a 7 week history of symmetric, polyartic be definitive. ular inflammatory synovitis that prominently involves the l(tY Porlrls small joints of the hands. o Sarcoidosis is an inflammatory disease that is charac I(lY POlttrs terized by formation of noncaseating gtanulomas and can infiltrate almost any organ, including bone. . The most useful laboratory studies to aid in the diag nosis of rheumatoid arthritis are rheumatoid factor o Sarcoidosis is best diagnosed by histologic assessment and anti-cyclic citrullinated peptide antibodies. of a biopsy specimen of affected tissue; when skin is o Rheumatoid factor and anti cyclic citrullinated pep- involved, biopsy is simple and can be definitive. tide (CCP) antibodies are approximately 70% sensitive in the diagnosis of rheumatoid arthritis, but anti-CCP Bibliography antibodies are 95"L specific. Kuchaz EJ. Osseous manifestations of sarcoidosis. Reumatologia. 2020; 58:93 100. IPMID: 324766821

tide (CCP) antibodies are approximately 70% sensitive in the diagnosis of rheumatoid arthritis, but anti-CCP Bibliography antibodies are 95"L specific. Kuchaz EJ. Osseous manifestations of sarcoidosis. Reumatologia. 2020; 58:93 100. IPMID: 324766821 160

Answers and Critiques Item72 Answer: D Bibliography Educational Objective: Diagnose renal amyloidosis Mercieca C, van der Horst Bruinsm, IE, Borg AA. Pulmonary, renal irnd neurological comorbidities in patients with ankylosing spondylitis; associated with poorly controlled anlgdosing spondylitis. implications fbr clinical practice. Curr Rheumatol Rep. 2O14;16:434. IPMID: 249255891 doi:10.1007/sll926 o14 O4:r4 7 The most likely diagnosis is renal amyloidosis (Option D). Patients with long-standing, poorly controlled inflammatory diseases, such as ankylosing spondylitis (AS) or rheumatoid Item 73 Answer: B arthritis, can develop renal amyloidosis (AA amyloidosis). Educational Objective: Treat rheumatoid arthritis with The prevalence of kidney disease in AS is 2',/, to 13'l.; in the disease modiffing antirheumatic drugs. past, AA amyloidosis was the leading cause of kidney disease (and remains a major cause) in patients with uncontrolled AS. The most appropriate treatment is methotrexate (Option B). With the advent of biologic therapy and subsequent control The patient has rheumatoid arthritis, and methotrexate is ot inflammation in AS, the prevalence of AA amyloidosis has considered the flrst line treatment ol a patient with a new I,l diagnosis of rheumatoid arthritis. Methotrexate can be used o, declined. AA amyloidosis most commonly aflects the kid neys, manifesting as proteinuria and eventually end stage alone for rheumatoid arthritis, and the dose can be titrated ET kidney disease. It less commonly affbcts the gastrointesti up over a period of weeks, with periodic assessment of .E the clinical response and laboratory measures of systemic (J nal tract, heart, and peripheral nerves. In AS, AA amyloi dosis is most often seen in men, patients with peripheral inflammation (erythrocyte sedimentation rate, C reactive =, E .! joint disease, and patients with a history of uveitis. Affected protein) and monitoring fbr medication toxicity. Contra' vt patients will usually manilest high levels of inflammatory ceptive use in women of child bearing age is recommended q, markers, such as erythrocyte sedimentation rate and C because methotrexate can be associated with pregnancy loss U! = E reactive protein, indicating insufficient control of disease and fetal abnormalities. Il methotrexate alone is inadequate related inflammation. Treatment with efl'ective medications. after a trial for an appropriate length of time, it can also such as tumor necrosis factor inhibitors, may stabilize or be used in combination with additional disease modifying improve the kidney manif'estations of AA amyloidosis in agents, including tumor necrosis factor inhibitors, abata patients with AS. When AA amyloidosis is suspected, Congo cept, tofacitinib, and rituximab. red staining of biopsy specimens from the kidney, rectum, or NSAIDs, such as diclofenac (Option A), are not indicated abdominal subcutaneous fat will reveal amyloid deposition. fbr the treatment of rheumatoid arthritis and should not be a Analgesic nephropathy (Option A) may develop after substitute for initiating treatment with a disease modifying years of NSAID use and typically presents with abnormali ergent. NSAIDs may be used in patients with rheumatoid ties on routine urinalysis, including pyuria, proteinuria, and irrthritis and other fbrms of inflammatory arthritis to relieve hematuria. Chronic kidney disease and end stage kidney symptoms. However, they would not be expected to alter the disease can develop in some patients. This patient's urine natural history of the disease or prevent permanent deformi findings are not compatible with analgesic nephropathy. ties or radiographic damage. NSAID use with glucocorticoids lgA nephropathy (Option B) is seen in patients with should be avoided. and caution should be exercised with AS but typically manifests as hematuria and proteinuria, concomitant methotrexate. not isolated proteinuria. lgA nephropathy in patients with IVlycophenolate mof'etil (Option C) is an immunosup AS tends to be milder, with less renal insufficiency, than pressive drug that reversibly inhibits inosine monophos in those with idiopathic IgA nephropathy. More aggressive phate dehydrogenase and aflects lymphocyte stimulation treatment of AS does not seem to afl'ect the clinical course of and proliferation. It is important in the treatment of systemic the AS-related IgA nephropathy. lupus erythematosus and in transplant recipients but has no Interstitial nephritis (Option C) can be caused by a role in the management of rheumatoid arthritis. variety of medications, including NSAlDs. antibiotics, and Rituximab (Option D) is indicated for the treatment ol proton pump inhibitors. Symptoms may include fever, rash, rheumatoid arthritis. However, it is not an appropriate choice ancl eosinophilia/eosinophiluria. All patients will have a rise fbr initial therapy in this patient. Rituximab is indicated fbr in serum creatinine levels as well as pyuria, hematuria, and treatment of patients who have had an inadequate response proteinuria. Leukocyte casts are typically seen on urinalysis. to methotrexate alone or in whom multiple other agents have This patient lacks these laboratory findings. firiled. Rituximab is given via intravenous administration ot' two doses 2 weeks apart every 6 months. Thus, the time KEY POI l{TS liame over which it would be expected to work in rheumatoid arthritis would be inappropriate for a patient with new onset o Patients with long-standing, poorly controlled anky- disease who has not yet been treated with methotrexate. losing spondylitis can develop renal (AA) amyloidosis, the major cause of kidney disease in these patients. I(EY POITTS r AA amyloidosis most commonly affects the kidneys, o Methotrexate is the first-line treatment of a patient manifesting as proteinuria and, eventually, renal with a new diagnosis of rheumatoid arthritis. insufficiency. (Continued)

Item72 Answer: D Bibliography Educational Objective: Diagnose renal amyloidosis Mercieca C, van der Horst Bruinsm, IE, Borg AA. Pulmonary, renal irnd neurological comorbidities in patients with ankylosing spondylitis; associated with poorly controlled anlgdosing spondylitis. implications fbr clinical practice. Curr Rheumatol Rep. 2O14;16:434. IPMID: 249255891 doi:10.1007/sll926 o14 O4:r4 7 The most likely diagnosis is renal amyloidosis (Option D). Patients with long-standing, poorly controlled inflammatory diseases, such as ankylosing spondylitis (AS) or rheumatoid Item 73 Answer: B arthritis, can develop renal amyloidosis (AA amyloidosis). Educational Objective: Treat rheumatoid arthritis with The prevalence of kidney disease in AS is 2',/, to 13'l.; in the disease modiffing antirheumatic drugs. past, AA amyloidosis was the leading cause of kidney disease (and remains a major cause) in patients with uncontrolled AS. The most appropriate treatment is methotrexate (Option B). With the advent of biologic therapy and subsequent control The patient has rheumatoid arthritis, and methotrexate is ot inflammation in AS, the prevalence of AA amyloidosis has considered the flrst line treatment ol a patient with a new I,l diagnosis of rheumatoid arthritis. Methotrexate can be used o, declined. AA amyloidosis most commonly aflects the kid neys, manifesting as proteinuria and eventually end stage alone for rheumatoid arthritis, and the dose can be titrated ET kidney disease. It less commonly affbcts the gastrointesti up over a period of weeks, with periodic assessment of .E the clinical response and laboratory measures of systemic (J nal tract, heart, and peripheral nerves. In AS, AA amyloi dosis is most often seen in men, patients with peripheral inflammation (erythrocyte sedimentation rate, C reactive =, E .! joint disease, and patients with a history of uveitis. Affected protein) and monitoring fbr medication toxicity. Contra' vt patients will usually manilest high levels of inflammatory ceptive use in women of child bearing age is recommended q, markers, such as erythrocyte sedimentation rate and C because methotrexate can be associated with pregnancy loss U! = E reactive protein, indicating insufficient control of disease and fetal abnormalities. Il methotrexate alone is inadequate related inflammation. Treatment with efl'ective medications. after a trial for an appropriate length of time, it can also such as tumor necrosis factor inhibitors, may stabilize or be used in combination with additional disease modifying improve the kidney manif'estations of AA amyloidosis in agents, including tumor necrosis factor inhibitors, abata patients with AS. When AA amyloidosis is suspected, Congo cept, tofacitinib, and rituximab. red staining of biopsy specimens from the kidney, rectum, or NSAIDs, such as diclofenac (Option A), are not indicated abdominal subcutaneous fat will reveal amyloid deposition. fbr the treatment of rheumatoid arthritis and should not be a Analgesic nephropathy (Option A) may develop after substitute for initiating treatment with a disease modifying years of NSAID use and typically presents with abnormali ergent. NSAIDs may be used in patients with rheumatoid ties on routine urinalysis, including pyuria, proteinuria, and irrthritis and other fbrms of inflammatory arthritis to relieve hematuria. Chronic kidney disease and end stage kidney symptoms. However, they would not be expected to alter the disease can develop in some patients. This patient's urine natural history of the disease or prevent permanent deformi findings are not compatible with analgesic nephropathy. ties or radiographic damage. NSAID use with glucocorticoids lgA nephropathy (Option B) is seen in patients with should be avoided. and caution should be exercised with AS but typically manifests as hematuria and proteinuria, concomitant methotrexate. not isolated proteinuria. lgA nephropathy in patients with IVlycophenolate mof'etil (Option C) is an immunosup AS tends to be milder, with less renal insufficiency, than pressive drug that reversibly inhibits inosine monophos in those with idiopathic IgA nephropathy. More aggressive phate dehydrogenase and aflects lymphocyte stimulation treatment of AS does not seem to afl'ect the clinical course of and proliferation. It is important in the treatment of systemic the AS-related IgA nephropathy. lupus erythematosus and in transplant recipients but has no Interstitial nephritis (Option C) can be caused by a role in the management of rheumatoid arthritis. variety of medications, including NSAlDs. antibiotics, and Rituximab (Option D) is indicated for the treatment ol proton pump inhibitors. Symptoms may include fever, rash, rheumatoid arthritis. However, it is not an appropriate choice ancl eosinophilia/eosinophiluria. All patients will have a rise fbr initial therapy in this patient. Rituximab is indicated fbr in serum creatinine levels as well as pyuria, hematuria, and treatment of patients who have had an inadequate response proteinuria. Leukocyte casts are typically seen on urinalysis. to methotrexate alone or in whom multiple other agents have This patient lacks these laboratory findings. firiled. Rituximab is given via intravenous administration ot' two doses 2 weeks apart every 6 months. Thus, the time KEY POI l{TS liame over which it would be expected to work in rheumatoid arthritis would be inappropriate for a patient with new onset o Patients with long-standing, poorly controlled anky- disease who has not yet been treated with methotrexate. losing spondylitis can develop renal (AA) amyloidosis, the major cause of kidney disease in these patients. I(EY POITTS r AA amyloidosis most commonly affects the kidneys, o Methotrexate is the first-line treatment of a patient manifesting as proteinuria and, eventually, renal with a new diagnosis of rheumatoid arthritis. insufficiency. (Continued) 161

Answers and Critiques XEY POlllTS (otldiawd) Streptococci (Option D) are less commonll intpli cated in prosthetic joint in{'cctittrts than are staph}lococci. . If methotrexate alone is inadequate, it can be used in accollnting tbr about i0')1, of positive sy'noYial fluid culturcs combination with additional disease-modifying from infbcted prosthetic joiltts. agents, including tumor necrosis factor inhibitors, abatacept, tofacitinib, and rituximab. XEY POIXTS r Early onset (<3 months) and late-onset (>12 months) Bibliography prosthetic joint infections are most commonly due to Singh JA. Saag KG. Bridges St- Jr. et ill. 2015 American College of Staphylococcus oureus; delayed onset (3 to 12 months) Rheumatologl guideline lbr the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016:68:l 26. IPNIID: 265.159.10] doi:10.1002 infection is most often due to coagulase-negative art.39.180 staphylococcus. o Delayed-onset (3 to 12 months) prosthetic joint infec- D Item 74 UI E (D tr Answer: C Ed ucational Objective: Diagnose prosthetic joint tion is characterized by an insidious onset and subtle physical examination findings (absence of fever, local pain only, slight warmth, mild effusion). infection with coagulase-negative staphylococcus. vt o, Irrfection \ ,ith Stoph.Ulococ'cris epirlermidis. a coagulasc Bibliography a- negative staphylococcus. is nlosl likel1, (Option C). Earll n onset (<:l nlonths after surgerv) prosthetic joint infectior.rs Beanr E. Osmon D. Prosthetic joint infection update. Infect Dis Clin North Anr. 2018:32:843 859. [PMID: 3o2-ll7 17 | doi:10.1016 i.idc.2018.06.005

XEY POlllTS (otldiawd) Streptococci (Option D) are less commonll intpli cated in prosthetic joint in{'cctittrts than are staph}lococci. . If methotrexate alone is inadequate, it can be used in accollnting tbr about i0')1, of positive sy'noYial fluid culturcs combination with additional disease-modifying from infbcted prosthetic joiltts. agents, including tumor necrosis factor inhibitors, abatacept, tofacitinib, and rituximab. XEY POIXTS r Early onset (<3 months) and late-onset (>12 months) Bibliography prosthetic joint infections are most commonly due to Singh JA. Saag KG. Bridges St- Jr. et ill. 2015 American College of Staphylococcus oureus; delayed onset (3 to 12 months) Rheumatologl guideline lbr the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016:68:l 26. IPNIID: 265.159.10] doi:10.1002 infection is most often due to coagulase-negative art.39.180 staphylococcus. o Delayed-onset (3 to 12 months) prosthetic joint infec- D Item 74 UI E (D tr Answer: C Ed ucational Objective: Diagnose prosthetic joint tion is characterized by an insidious onset and subtle physical examination findings (absence of fever, local pain only, slight warmth, mild effusion). infection with coagulase-negative staphylococcus. vt o, Irrfection \ ,ith Stoph.Ulococ'cris epirlermidis. a coagulasc Bibliography a- negative staphylococcus. is nlosl likel1, (Option C). Earll n onset (<:l nlonths after surgerv) prosthetic joint infectior.rs Beanr E. Osmon D. Prosthetic joint infection update. Infect Dis Clin North Anr. 2018:32:843 859. [PMID: 3o2-ll7 17 | doi:10.1016 i.idc.2018.06.005 lt are often due to Stciph.qkrc'oc'clls olu?Lls. gram negirtivc (D bacilli. anaerobes. or pollmicrobial infection. Delalecl UI onset (3 to 12 months after surgery) infections are ofter.r Item 75 Answer: B dtrc to coagulase-negative staphylococci. Cutibocteriunt Educational Obiective: Treat mild systemic lupus species, or enterococci. [.:rte onset infections (>12 rnonths) erythematosus. irre often due to S. crurzu.s, gram negative bacilli. clr p hcnrolytic streptococci. '[ris patient de'veloped ne\\r symp The most appropriate treatment is prednisone and hydroxy toms in a prosthetic knec about 6 nronths after tot:rl joint chloroquine (Option B). This patient has clear flndings of arthroplasty: His history is t-v-pical of delayed prosthetic new but relatively mild systemic lupus erythematosus (SLE). joint infection, with an insidious rather than abrupt olrset She has skin and joint involvement and thrombocytope of initially mild but then persistr.rlt s) mptoms. The phl,sical nia without evidence of other organ involvement. First line e\ilmination Iindings are subtle: an absence of fever. krcal therapy for mild SLE includes hydroxychloroquine. often pain onl1,. slight r'r,armth. and mild efiirsion. The orglnisrn with glucocorticoids if a more rapid response is needed. most commonly irnplicatecl in prosthetic joint ir.rfection Many patients will need additional immunomodulatory in this setting with subacutc onsct. subtle findings :l to 12 therapy at some point in their disease. Hydroxychloroquine months trfter surgery is coirgulirse negative staphylococ is a mainstay of treatment in SLE because it reduces disease cus. Because of the fiequency of staphylococcal infectior.rs, associated damage, prevents disease flares, and improves kid it is ah^,ays appropriate to initiate ernpiric treatment ibr ney and overall survival. In addition, hydroxychloroquine infcction r.r,hile awaitirrg culturc rcsults: r,ancomlcin is au may reduce the risk for thrombosis, liver disease, and myo appropriate first choice. Whcn aspiratior-r ol a prosthetic cardial infarction and improve lipid profiles. Glucocorticoids joint is required. the procedure shoulcl be perfbrn.recl b1'an are also used in most patients with SLE. particularly in acute orthopedic surgeon. disease. After disease stabilizes, glucocorticoids are tapered Prosthetic joint infection uith Neisseria gonorrhoeae to the lowest effective dosage. pref'erably to no more than (Option A) almost never occurs. Ihe arthritis associated \\'it11 7.5 mgrd within 4 to 6 months. and should be discontinued gonorrheal infection is generirlly abrupt in onset and oftell entirely if possible. Glucocorticoid exposure. especially at acconrpanied by exquisitely p:iinful tenos)inovitis, fever. ancl high doses, should be limited because of associated risk for skir.r lesions. The lesions rangc fiont single pustules to a le."l, organ damage, infection, and premature mortality. Azathio lesions that might be papular. pustular. ur hemorrhagic lnd prine or methotrexate is recommended if patients with mild ltre nrost fiequently firund on the distal extremities. Thesc disease have refractory symptoms. All patients with SLE findings are not seen in this patient. should be counseled on sun protection, vaccinations. and I)seirdomonos oeruginoso (Option B) is occ:rsionall_r' lifestyle modiflcations to optimize cardiovascular health. implicated in prosthetic joint infcctions but is considerablv Prednisone alone (Option A) is likely to help with her less common than grarn positivc organisms. often repre current symptoms but is unlikely to provide Iasting benefits sented in iess than 10'.1, of positive cultures. A l.ristory o1 after it is tapered or discontinued. gastrointestinal or genitourinlr_"- infecti<-rn or immunosup For patients with more severe SLE manifestations. pression puts patients at higher risk fbr prosthetic joint including nephritis, central nervous system disease, or infcction with Pseudornoncrs sltecies. 'll.ris patient does not other more severe manifestations, additional therapy is war have a hisbry compatiblc with suclr infection. ranted. Induction with mycophenolate or cyclophosphamide

lt are often due to Stciph.qkrc'oc'clls olu?Lls. gram negirtivc (D bacilli. anaerobes. or pollmicrobial infection. Delalecl UI onset (3 to 12 months after surgery) infections are ofter.r Item 75 Answer: B dtrc to coagulase-negative staphylococci. Cutibocteriunt Educational Obiective: Treat mild systemic lupus species, or enterococci. [.:rte onset infections (>12 rnonths) erythematosus. irre often due to S. crurzu.s, gram negative bacilli. clr p hcnrolytic streptococci. '[ris patient de'veloped ne\\r symp The most appropriate treatment is prednisone and hydroxy toms in a prosthetic knec about 6 nronths after tot:rl joint chloroquine (Option B). This patient has clear flndings of arthroplasty: His history is t-v-pical of delayed prosthetic new but relatively mild systemic lupus erythematosus (SLE). joint infection, with an insidious rather than abrupt olrset She has skin and joint involvement and thrombocytope of initially mild but then persistr.rlt s) mptoms. The phl,sical nia without evidence of other organ involvement. First line e\ilmination Iindings are subtle: an absence of fever. krcal therapy for mild SLE includes hydroxychloroquine. often pain onl1,. slight r'r,armth. and mild efiirsion. The orglnisrn with glucocorticoids if a more rapid response is needed. most commonly irnplicatecl in prosthetic joint ir.rfection Many patients will need additional immunomodulatory in this setting with subacutc onsct. subtle findings :l to 12 therapy at some point in their disease. Hydroxychloroquine months trfter surgery is coirgulirse negative staphylococ is a mainstay of treatment in SLE because it reduces disease cus. Because of the fiequency of staphylococcal infectior.rs, associated damage, prevents disease flares, and improves kid it is ah^,ays appropriate to initiate ernpiric treatment ibr ney and overall survival. In addition, hydroxychloroquine infcction r.r,hile awaitirrg culturc rcsults: r,ancomlcin is au may reduce the risk for thrombosis, liver disease, and myo appropriate first choice. Whcn aspiratior-r ol a prosthetic cardial infarction and improve lipid profiles. Glucocorticoids joint is required. the procedure shoulcl be perfbrn.recl b1'an are also used in most patients with SLE. particularly in acute orthopedic surgeon. disease. After disease stabilizes, glucocorticoids are tapered Prosthetic joint infection uith Neisseria gonorrhoeae to the lowest effective dosage. pref'erably to no more than (Option A) almost never occurs. Ihe arthritis associated \\'it11 7.5 mgrd within 4 to 6 months. and should be discontinued gonorrheal infection is generirlly abrupt in onset and oftell entirely if possible. Glucocorticoid exposure. especially at acconrpanied by exquisitely p:iinful tenos)inovitis, fever. ancl high doses, should be limited because of associated risk for skir.r lesions. The lesions rangc fiont single pustules to a le."l, organ damage, infection, and premature mortality. Azathio lesions that might be papular. pustular. ur hemorrhagic lnd prine or methotrexate is recommended if patients with mild ltre nrost fiequently firund on the distal extremities. Thesc disease have refractory symptoms. All patients with SLE findings are not seen in this patient. should be counseled on sun protection, vaccinations. and I)seirdomonos oeruginoso (Option B) is occ:rsionall_r' lifestyle modiflcations to optimize cardiovascular health. implicated in prosthetic joint infcctions but is considerablv Prednisone alone (Option A) is likely to help with her less common than grarn positivc organisms. often repre current symptoms but is unlikely to provide Iasting benefits sented in iess than 10'.1, of positive cultures. A l.ristory o1 after it is tapered or discontinued. gastrointestinal or genitourinlr_"- infecti<-rn or immunosup For patients with more severe SLE manifestations. pression puts patients at higher risk fbr prosthetic joint including nephritis, central nervous system disease, or infcction with Pseudornoncrs sltecies. 'll.ris patient does not other more severe manifestations, additional therapy is war have a hisbry compatiblc with suclr infection. ranted. Induction with mycophenolate or cyclophosphamide 152

Answers and Critiques (Option C) would be reasonable, in addition to glucocorti- ll1 acute flare, ntainly to improve {irtr-ire adherence' but coids and hydroxychloroquine, in that setting. This patient only il tl-re patient is also treing adequately treated ftlr the does not require this degree of pharmacotherapy unless her acute flare. Allopurinr-rl i,vill not 1.reat the acute flare and' disease progresses. if adrninisterecl alone. may' actr-rally prolong the f lare dura Alt patients with a new diagnosis of SLE probably tion. When initiating allopr-rrinol, paticnts shoulcl cotrtinue I require some immunomodulatory therapy, such as hydroxy tiking anti inflantnratory f lare prophylaxis ft)r irt least 3 to i chloroquine. Those with cutaneous symptoms alone can also 6 months because urate lowcring transiently raiscs the fre : quency of flare occurrence. be treated with topical agents, such as hydrocortisone cream t (Option D), and monitored carefully, but this patient has NSAIDs. such as indontcthacin (Option C). given fbr 5 t<r I joint inflammation and hematologic Iindings that warrant 7 clays are also ef lective in treating acute gout. NSAIDs have t intervention with additional systen.ric theraplt an antiplatclet ef I'cct atrd are associated r,r'ith risk ftrr gastro t I intestinal ulcer:rtion and bleeding. This patient is receiving (EY POIilIS UI I anticoagulation: thus. NSAIDs arc contraindicated. (l, t o First-line therapy for most patients with systemic Prednisone (Option )) may be an eflective trcatment ol ET lupus erythematosus includes hydroxychloroquine acute gout. l-lowcver, it raiscs the blood glucose Ievel and is t with glucocorticoids. not tl'rc best choicc in a patient rvith type 2 diabetes mellitus. I (J I . Hydroxychloroquine is a mainstay of treatment in t(EY POfi{Tt g =, systemic lupus erythematosus because it reduces IE i . In the absence ofchronic kidney disease, colchicine, tt I disease-associated damage, prevents disease flares, 1.2 mg, lollowed by a single 0.6 mg dose in t hour, is o t and improves kidney and overall survival. an effective treatment of acute gout within the first yt = E i 24 hours. Bibliography :

(Option C) would be reasonable, in addition to glucocorti- ll1 acute flare, ntainly to improve {irtr-ire adherence' but coids and hydroxychloroquine, in that setting. This patient only il tl-re patient is also treing adequately treated ftlr the does not require this degree of pharmacotherapy unless her acute flare. Allopurinr-rl i,vill not 1.reat the acute flare and' disease progresses. if adrninisterecl alone. may' actr-rally prolong the f lare dura Alt patients with a new diagnosis of SLE probably tion. When initiating allopr-rrinol, paticnts shoulcl cotrtinue I require some immunomodulatory therapy, such as hydroxy tiking anti inflantnratory f lare prophylaxis ft)r irt least 3 to i chloroquine. Those with cutaneous symptoms alone can also 6 months because urate lowcring transiently raiscs the fre : quency of flare occurrence. be treated with topical agents, such as hydrocortisone cream t (Option D), and monitored carefully, but this patient has NSAIDs. such as indontcthacin (Option C). given fbr 5 t<r I joint inflammation and hematologic Iindings that warrant 7 clays are also ef lective in treating acute gout. NSAIDs have t intervention with additional systen.ric theraplt an antiplatclet ef I'cct atrd are associated r,r'ith risk ftrr gastro t I intestinal ulcer:rtion and bleeding. This patient is receiving (EY POIilIS UI I anticoagulation: thus. NSAIDs arc contraindicated. (l, t o First-line therapy for most patients with systemic Prednisone (Option )) may be an eflective trcatment ol ET lupus erythematosus includes hydroxychloroquine acute gout. l-lowcver, it raiscs the blood glucose Ievel and is t with glucocorticoids. not tl'rc best choicc in a patient rvith type 2 diabetes mellitus. I (J I . Hydroxychloroquine is a mainstay of treatment in t(EY POfi{Tt g =, systemic lupus erythematosus because it reduces IE i . In the absence ofchronic kidney disease, colchicine, tt I disease-associated damage, prevents disease flares, 1.2 mg, lollowed by a single 0.6 mg dose in t hour, is o t and improves kidney and overall survival. an effective treatment of acute gout within the first yt = E i 24 hours. Bibliography : r Fanouriakis A. Kostopoulou M. Alunno A, et al. 2019 update of the EULAR o Administering urate-lowering therapy, such as allopu- ; recommendations fbr the management of systemic lupus erythematosus. rinol, in the absence of anti-inflammatory therapy may Ann Rheum Dis. 2019;78:736-745. IPMI D: 309267221 result in recurrent flares of acute gout. :

r Fanouriakis A. Kostopoulou M. Alunno A, et al. 2019 update of the EULAR o Administering urate-lowering therapy, such as allopu- ; recommendations fbr the management of systemic lupus erythematosus. rinol, in the absence of anti-inflammatory therapy may Ann Rheum Dis. 2019;78:736-745. IPMI D: 309267221 result in recurrent flares of acute gout. : Item 76 Answer: B Bibliography ; t EX Educational Objective: Treat acute gout with colchicine. tritzcerald JD, Dalbcth N. l\,tikuls T, et al. 2020 American College ol' Rheumatolos/ guideline fbr the management of gout. Arthritis Care Res i 'lhe nrost appropriate treatnrent is colchicine (Option B). (Hoboken). 2o2o..l 2:741 760. [PMID: 323919341 doi:10.1002/acr.24180

t EX Educational Objective: Treat acute gout with colchicine. tritzcerald JD, Dalbcth N. l\,tikuls T, et al. 2020 American College ol' Rheumatolos/ guideline fbr the management of gout. Arthritis Care Res i 'lhe nrost appropriate treatnrent is colchicine (Option B). (Hoboken). 2o2o..l 2:741 760. [PMID: 323919341 doi:10.1002/acr.24180 'lhis patient's presentrtion is consistent lvith an ircute flare of classic podagra (gor-rt ol the great toc) lvitl.r pain. swelling, Item 77 Answer: D and reclness ol the first r.netatarsophalangeal joir.rt. His r-:rdio- Educational Objective: Diagnose lupus nephritis with a gruph shou's changes consistent u'itl.r chronic gout),arthritis kidney biopsy. in the rnetatarsophalangeal joint, with soft tissue swelling. tophus. trnd r'rell defined erosions that havc sclerotic bor- 'lhe most appropriate diagr.rostic test to perfbrm ncxt is dcrs and ovcrhanging margins. (lolcl'ricine is an eft'ective kidncy biopsy (Option D). This patierlt has acute systemic trcatlxenl of acute grut u,ithin the first 24 hours of the h"tpus crythernatosus (St.E) with proteinuriir ancl hematuria eirisoclc. [n the iibsence of chronic kidrrclr discase. the initial conccnring fbr kidne-y involvement. Iler positive results lor dose is 1.2 mg, lbllowed by a singlc 0.6 mg close t hour later antinuclear and anti double-strandecl DNA antibodies ancl ancl then 0.6 mg dail1, therealter if' r.reedcd. Colchicine. dcpressed serum complement values support this cliagnosis. 0.(r mg dail1,, 6ny be continued ancl ttsed as prophyhxis Additional evaluation in patients suspected ol having lupus u'hile urate lowering therap), is initiirted. Oolchitine rnal' nephritis should include 2.1 hour urine measLrrcment fbr result in gastrointestinal toxicity, ancl ckrsing may be limited quantitation of lrroteinuria ancl a kidney biopsy. Patients b)'gastrointestinal tolerance. 'lbpical icc l.relps reduce clura lvith SLE with any sign of kidney involvement ilre can tion of the flrrre and ma1, be r-rsed as adjunctive theraplr didates for kidney biops1,. Indications include proteinuria the Americar.r College <tf Rhcumatology (ACR) strongly grcater than 500 mg.24 h, urine pnltein creatinine ratio rccomnrencls initiating urate lornerir.rg therapy tbr patients greater than 500 mg,'g (especialll, in thc setling ol hematuria with gout and any of thc fbllor,l,ing inclications: onc or more andior cellular casts), tir unexplained decrease in estirnatecl subcntlneous tophi; e\riclencc of rldiographic darnage (any glomcrrrlar filtriition rate. Biops), results are important for moclality) attributable to gout: or lreqnent gout flares. with choosing incluction thcrapy and cletermining prognosis. "frequent" being clefined as two or more annually 'lhe ACR S[.E can cause nellropsl,chiatric rnanif'estations (cerebri rccommends treating to a maxinrum serum uratt: levcl of tis). including seizure. delirium, psychosis, or stroke, which lcss thirn 6.o nrg,dL (0.:15 mrnol,L). Allopurinol (Option A) can be importanl to iclentify rvhen choosirlg management is indicirted ir-r tl'ris patient lbr long term trclltnrcnt girren strategies. Ilrair.r MRI (Option A) is sensitive tbr cletection of' the racliographic changes ol gouty arthritis. Current ACR abnormalitics associated r,vith cerebritis buI can be difficu]t guidelines support initiating nratc lor,r'cring therapy during to inlerpret. This paticnt has no symptr)ms to sugigest central

'lhis patient's presentrtion is consistent lvith an ircute flare of classic podagra (gor-rt ol the great toc) lvitl.r pain. swelling, Item 77 Answer: D and reclness ol the first r.netatarsophalangeal joir.rt. His r-:rdio- Educational Objective: Diagnose lupus nephritis with a gruph shou's changes consistent u'itl.r chronic gout),arthritis kidney biopsy. in the rnetatarsophalangeal joint, with soft tissue swelling. tophus. trnd r'rell defined erosions that havc sclerotic bor- 'lhe most appropriate diagr.rostic test to perfbrm ncxt is dcrs and ovcrhanging margins. (lolcl'ricine is an eft'ective kidncy biopsy (Option D). This patierlt has acute systemic trcatlxenl of acute grut u,ithin the first 24 hours of the h"tpus crythernatosus (St.E) with proteinuriir ancl hematuria eirisoclc. [n the iibsence of chronic kidrrclr discase. the initial conccnring fbr kidne-y involvement. Iler positive results lor dose is 1.2 mg, lbllowed by a singlc 0.6 mg close t hour later antinuclear and anti double-strandecl DNA antibodies ancl ancl then 0.6 mg dail1, therealter if' r.reedcd. Colchicine. dcpressed serum complement values support this cliagnosis. 0.(r mg dail1,, 6ny be continued ancl ttsed as prophyhxis Additional evaluation in patients suspected ol having lupus u'hile urate lowering therap), is initiirted. Oolchitine rnal' nephritis should include 2.1 hour urine measLrrcment fbr result in gastrointestinal toxicity, ancl ckrsing may be limited quantitation of lrroteinuria ancl a kidney biopsy. Patients b)'gastrointestinal tolerance. 'lbpical icc l.relps reduce clura lvith SLE with any sign of kidney involvement ilre can tion of the flrrre and ma1, be r-rsed as adjunctive theraplr didates for kidney biops1,. Indications include proteinuria the Americar.r College <tf Rhcumatology (ACR) strongly grcater than 500 mg.24 h, urine pnltein creatinine ratio rccomnrencls initiating urate lornerir.rg therapy tbr patients greater than 500 mg,'g (especialll, in thc setling ol hematuria with gout and any of thc fbllor,l,ing inclications: onc or more andior cellular casts), tir unexplained decrease in estirnatecl subcntlneous tophi; e\riclencc of rldiographic darnage (any glomcrrrlar filtriition rate. Biops), results are important for moclality) attributable to gout: or lreqnent gout flares. with choosing incluction thcrapy and cletermining prognosis. "frequent" being clefined as two or more annually 'lhe ACR S[.E can cause nellropsl,chiatric rnanif'estations (cerebri rccommends treating to a maxinrum serum uratt: levcl of tis). including seizure. delirium, psychosis, or stroke, which lcss thirn 6.o nrg,dL (0.:15 mrnol,L). Allopurinol (Option A) can be importanl to iclentify rvhen choosirlg management is indicirted ir-r tl'ris patient lbr long term trclltnrcnt girren strategies. Ilrair.r MRI (Option A) is sensitive tbr cletection of' the racliographic changes ol gouty arthritis. Current ACR abnormalitics associated r,vith cerebritis buI can be difficu]t guidelines support initiating nratc lor,r'cring therapy during to inlerpret. This paticnt has no symptr)ms to sugigest central 153

l11we_1s and Critiqtes tr CONT. nervous syslent discase. so a brain MRI is less likelr,to Lle useful in this case. Chest CT (Option B) can be useful lbr identificalion of maintaining range of motion, and reducing disability: transi tion to an ongoing daily exercise program is optimal. If NSAIDs fail or the patient cannot tolerate NSAIDs, serositis, interstitial lung disease. or pulmona4, cmbolisru. a tumor necrosis factor (TNF) inhibitor. such as etaner u'hich can all be associated."r ith Sl.E, but this patient has no cept (Option A), is recommended as second line disease- cLlrrent cardiopuintonary s!mptonls or exanlination abn<tr modi$ring therapy. The eflicacy of TNF inhibitors in patients malities. CT with contrast poses a risk fbr contrxst-induced with active AS has been demonstrated in numerous ran- nephropathf in this patient \\'ith an increased serum creat domized controlled trials, which showed improvements in inine level. clinical. radiographic, and MRI outcomes. Patients in whom S[-E is associatecl n,ith pcricarditis. pericarclill or pleu a TNF inhibitor fails should receive an interleukin 17 inhib- ral eflusions. and other nranifestations ofserositis. Echocar itor, such as secukinumab or ixekizumab. diography (Option C) can be useful to assess fbr the presencc Nonbiologic agents, such as methotrexate (Option B) or and severity of pericarditis lnd effusions. as uell as the sulfasalazine (Option D), do not play a role in axial disease UI possibility of valvular clisease. In a patient u'ith a norntal but could be used as additional therapy as needed for signif € cardiopulrnonlrry examination ancl no cardiac s!'mptoms. icant peripheral joint disease. Sulfasalazine is the preferred o Ut echocardiographf is less uselul fbr guiding management agent. This patient has no evidence of peripheral joint dis- o, than is a kidney biopsy. ease. and these nonbiologic agents are not indicated. =L E n t(tY P0tilTt XEY POIIITI =. o Recognized indications for kidney biopsy in patients . Physical therapy and NSAIDs are the recommended =. ,EI tr with systemic lupus ery.thematosus include glomeru- first-line therapies for ankylosing spondylitis. (D ta lar hematuria and/or cellular casts, spot urine . If NSAIDs fail or the patient cannot tolerate NSAIDs, a protein-creatinine ratio greater than 500 mg/g, or tumor necrosis factor inhibitor is second line therapy unexplained decrease in estimated glomerular for ankylosing spondylitis. filtration rate. . In patients with lupus nephritis, kidney biopsy results Bibliography are important for choosing induction therapy and Ward MM. Deodhar A, Gensler I-S, et al. 2019 Update of the American College of RheumatoloEl//Spondylitis Association ol Americar determining prognosis. Spondyloarthritis Research and Treatment Net$ork Recommendations for the Treatnlent ofAnkylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2019:71:1599 1613. IPMID: Bibliography 314360361 Fanouriakis A. Kostopoulou M. Cheema K, et al. 2019 Update ofthe Joint Eur()pean League Against Rheumatism and European Renal Association European Dialysis and Transplant Association (EULAR/ERA ED'IA) rec ommendations for the management of lupus nephritis. Ann Rheum Dis. Item 79 Answer: C 2020:79:713 723. [PMID: 322208341 Educational Objective: Identi$ probable lymphoma in a patient with Sjdgren gmdrome.

tr CONT. nervous syslent discase. so a brain MRI is less likelr,to Lle useful in this case. Chest CT (Option B) can be useful lbr identificalion of maintaining range of motion, and reducing disability: transi tion to an ongoing daily exercise program is optimal. If NSAIDs fail or the patient cannot tolerate NSAIDs, serositis, interstitial lung disease. or pulmona4, cmbolisru. a tumor necrosis factor (TNF) inhibitor. such as etaner u'hich can all be associated."r ith Sl.E, but this patient has no cept (Option A), is recommended as second line disease- cLlrrent cardiopuintonary s!mptonls or exanlination abn<tr modi$ring therapy. The eflicacy of TNF inhibitors in patients malities. CT with contrast poses a risk fbr contrxst-induced with active AS has been demonstrated in numerous ran- nephropathf in this patient \\'ith an increased serum creat domized controlled trials, which showed improvements in inine level. clinical. radiographic, and MRI outcomes. Patients in whom S[-E is associatecl n,ith pcricarditis. pericarclill or pleu a TNF inhibitor fails should receive an interleukin 17 inhib- ral eflusions. and other nranifestations ofserositis. Echocar itor, such as secukinumab or ixekizumab. diography (Option C) can be useful to assess fbr the presencc Nonbiologic agents, such as methotrexate (Option B) or and severity of pericarditis lnd effusions. as uell as the sulfasalazine (Option D), do not play a role in axial disease UI possibility of valvular clisease. In a patient u'ith a norntal but could be used as additional therapy as needed for signif € cardiopulrnonlrry examination ancl no cardiac s!'mptoms. icant peripheral joint disease. Sulfasalazine is the preferred o Ut echocardiographf is less uselul fbr guiding management agent. This patient has no evidence of peripheral joint dis- o, than is a kidney biopsy. ease. and these nonbiologic agents are not indicated. =L E n t(tY P0tilTt XEY POIIITI =. o Recognized indications for kidney biopsy in patients . Physical therapy and NSAIDs are the recommended =. ,EI tr with systemic lupus ery.thematosus include glomeru- first-line therapies for ankylosing spondylitis. (D ta lar hematuria and/or cellular casts, spot urine . If NSAIDs fail or the patient cannot tolerate NSAIDs, a protein-creatinine ratio greater than 500 mg/g, or tumor necrosis factor inhibitor is second line therapy unexplained decrease in estimated glomerular for ankylosing spondylitis. filtration rate. . In patients with lupus nephritis, kidney biopsy results Bibliography are important for choosing induction therapy and Ward MM. Deodhar A, Gensler I-S, et al. 2019 Update of the American College of RheumatoloEl//Spondylitis Association ol Americar determining prognosis. Spondyloarthritis Research and Treatment Net$ork Recommendations for the Treatnlent ofAnkylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2019:71:1599 1613. IPMID: Bibliography 314360361 Fanouriakis A. Kostopoulou M. Cheema K, et al. 2019 Update ofthe Joint Eur()pean League Against Rheumatism and European Renal Association European Dialysis and Transplant Association (EULAR/ERA ED'IA) rec ommendations for the management of lupus nephritis. Ann Rheum Dis. Item 79 Answer: C 2020:79:713 723. [PMID: 322208341 Educational Objective: Identi$ probable lymphoma in a patient with Sjdgren gmdrome. Item 78 Answer: C Lymphoma (Option C) is most likely responsible for this patient's recent symptoms. Patients with Sjogren syndrome Educational Objective: Treat an$losing spondylitis are at high risk for lymphoma (5'7, lifetime risk); 60'2, of with NSAIDs. these cases are mucosa associated lymphoid tissue lym The most appropriate treatment is naproxen (Option C). This phomas. Risk factors include parotid gland enlargement. patient has classic ankylosing spondylitis (AS), as suggested depressed C4 complement level, elevated rheumatoid fac- by inflammatory Iow back pain with signs of sacroiliac joint tor level, elevated anti Ro/SSA and/or anti La/SSB antibody irritation, limitation of lumbar spine motion, and changes of levels, monoclonal gammopathy, and cryoglobulinemic vas sacroiliitis on radiograph. NSAIDs are recommended flrst- culitis. ln addition to having several of these risk factors, line therapy for AS. In general, an NSAID must be dosed this patient has systemic "B symptoms" associated with toward the higher end of the dosing range to modif,z new lymphoma: fever, weight loss, and drenching night sweats. bone formation and have a significant impact on inflamma Light-chain (AL) amyloidosis (Option A) is a clonal tion. If an NSAID is started early in the course of AS (<3 years), plasma cell dyscrasia characterized by production of amy 35%, of patients will enter remission compared with only loidogenic )" or r free light chains. These light chains can 12'1, to 15"/,, of those starting it later. Unlike with other rheu- deposit in various organs, resulting in varying clinical pre matologic diseases, evidence suggests that NSAID use in AS sentations of the disease, most commonly the nephrotic has a disease modi$zing effect. Patients should be aware of syndrome, restrictive cardiomyopathy, peripheral neuropa and monitored for NSAID toxicity, such as hypertension, gas thy, and hepatomegaly. AL amyloidosis can be a rare com- trointestinal bleeding, and kidney disease. Physical therapy plication of IgM associated monoclonal gammopathy and is the most important nonpharmacologic intervention in AS. can rarely inflltrate the parotid glands. This patient's pre- The goals of therapy include improving pain and stiffness, sentation, however, is most consistent with classic Sjogren

Item 78 Answer: C Lymphoma (Option C) is most likely responsible for this patient's recent symptoms. Patients with Sjogren syndrome Educational Objective: Treat an$losing spondylitis are at high risk for lymphoma (5'7, lifetime risk); 60'2, of with NSAIDs. these cases are mucosa associated lymphoid tissue lym The most appropriate treatment is naproxen (Option C). This phomas. Risk factors include parotid gland enlargement. patient has classic ankylosing spondylitis (AS), as suggested depressed C4 complement level, elevated rheumatoid fac- by inflammatory Iow back pain with signs of sacroiliac joint tor level, elevated anti Ro/SSA and/or anti La/SSB antibody irritation, limitation of lumbar spine motion, and changes of levels, monoclonal gammopathy, and cryoglobulinemic vas sacroiliitis on radiograph. NSAIDs are recommended flrst- culitis. ln addition to having several of these risk factors, line therapy for AS. In general, an NSAID must be dosed this patient has systemic "B symptoms" associated with toward the higher end of the dosing range to modif,z new lymphoma: fever, weight loss, and drenching night sweats. bone formation and have a significant impact on inflamma Light-chain (AL) amyloidosis (Option A) is a clonal tion. If an NSAID is started early in the course of AS (<3 years), plasma cell dyscrasia characterized by production of amy 35%, of patients will enter remission compared with only loidogenic )" or r free light chains. These light chains can 12'1, to 15"/,, of those starting it later. Unlike with other rheu- deposit in various organs, resulting in varying clinical pre matologic diseases, evidence suggests that NSAID use in AS sentations of the disease, most commonly the nephrotic has a disease modi$zing effect. Patients should be aware of syndrome, restrictive cardiomyopathy, peripheral neuropa and monitored for NSAID toxicity, such as hypertension, gas thy, and hepatomegaly. AL amyloidosis can be a rare com- trointestinal bleeding, and kidney disease. Physical therapy plication of IgM associated monoclonal gammopathy and is the most important nonpharmacologic intervention in AS. can rarely inflltrate the parotid glands. This patient's pre- The goals of therapy include improving pain and stiffness, sentation, however, is most consistent with classic Sjogren 164

Answers and Critiques syndrome, with exocrinopathy afl'ecting salivary and lacri presc'nt and are not specific. Otl'rer antibr-rdies. including ANCA mal glands, laboratory test results consistent with Sjdgren (especially p ANCA) and F-actin, can bc seen with min(,1)'. syndrome, and recent onset of systemic disease symptoms clinc use. Most patier.rts with dmg-induced lupus sympk)n-Is suggesting lymphoma. r"iII improve lr,ith discontinuation of the rnedicirtiort e:tusing Prominent symptoms of' hypothyroidism (Option B) the qrmpton,s, bLlt solre may r.reed synrpkrmatic treatmcnt. include fatigue, weight gain, myalgia, and arthralgia. Lab Granulonrrtosis w'ith polyangiitis (Option B) is a oratory iindings may include anemia, elevated LDL choles small vessel vasculitis associated with ANCA that ry'picrlll terol, and hyponatremia. Hypothyroidism cannot explain causes constitutional symptoms, upper and krwer lint'ay the patient's weight loss, low C4 complement level, or disease. and glomerulonephritis. this pirtient has an ANCA, monoclonal gammopathy. In addition, the patient's thyroid which can be seen in a variety of aut<.rimnrune:rncl infectious stimulating hormone level is normal, excluding hypothy states, but her clinical presentation is not suggestive of an roidism as a cause of the patient's recent symptoms. AN(.A associ:rted rast'ulitis. Primary Sjogren syndrome occurs in isolation; second Rheumatoid arthritis (RA) (Option C) cirn also cause la (l, ary Sjogren syndrome occurs in the setting of other rheu joint findings in the distribution describecl. lncl lacli of 3 ET matologic diseases, most commonly rheumatoid arthritis rheunratoicl factor ar.rd anti cy,clic citrullinatcci pcpticle .= (Option D) and systemic Iupus erythematosus. Patients with antiboclies does not rule out ItA. This cliagnosis coulcl llso L' rheumatoid arthritis and Sj0gren syndrome may have lab be considere<l if'synovitis persists aftcr discontinuation ol E' oratory findings similar to those found in this patient, but mir.rocycline. E .E this patient has Sj0gren syndrome antibodies and negative SLE (Option D) is also in the diflerer.rlirrl diagnosis. ra (I, results fbr anti cyclic citrullinated peptide antibodies. In although it is lcss likely than clrug induced lupus erytl.re addition, examination does not suggest synovitis (the patient lr:ltoslls in x patient t:rking urirrocl,clir.rc. [t shou]d be c<ln- = Ut

syndrome, with exocrinopathy afl'ecting salivary and lacri presc'nt and are not specific. Otl'rer antibr-rdies. including ANCA mal glands, laboratory test results consistent with Sjdgren (especially p ANCA) and F-actin, can bc seen with min(,1)'. syndrome, and recent onset of systemic disease symptoms clinc use. Most patier.rts with dmg-induced lupus sympk)n-Is suggesting lymphoma. r"iII improve lr,ith discontinuation of the rnedicirtiort e:tusing Prominent symptoms of' hypothyroidism (Option B) the qrmpton,s, bLlt solre may r.reed synrpkrmatic treatmcnt. include fatigue, weight gain, myalgia, and arthralgia. Lab Granulonrrtosis w'ith polyangiitis (Option B) is a oratory iindings may include anemia, elevated LDL choles small vessel vasculitis associated with ANCA that ry'picrlll terol, and hyponatremia. Hypothyroidism cannot explain causes constitutional symptoms, upper and krwer lint'ay the patient's weight loss, low C4 complement level, or disease. and glomerulonephritis. this pirtient has an ANCA, monoclonal gammopathy. In addition, the patient's thyroid which can be seen in a variety of aut<.rimnrune:rncl infectious stimulating hormone level is normal, excluding hypothy states, but her clinical presentation is not suggestive of an roidism as a cause of the patient's recent symptoms. AN(.A associ:rted rast'ulitis. Primary Sjogren syndrome occurs in isolation; second Rheumatoid arthritis (RA) (Option C) cirn also cause la (l, ary Sjogren syndrome occurs in the setting of other rheu joint findings in the distribution describecl. lncl lacli of 3 ET matologic diseases, most commonly rheumatoid arthritis rheunratoicl factor ar.rd anti cy,clic citrullinatcci pcpticle .= (Option D) and systemic Iupus erythematosus. Patients with antiboclies does not rule out ItA. This cliagnosis coulcl llso L' rheumatoid arthritis and Sj0gren syndrome may have lab be considere<l if'synovitis persists aftcr discontinuation ol E' oratory findings similar to those found in this patient, but mir.rocycline. E .E this patient has Sj0gren syndrome antibodies and negative SLE (Option D) is also in the diflerer.rlirrl diagnosis. ra (I, results fbr anti cyclic citrullinated peptide antibodies. In although it is lcss likely than clrug induced lupus erytl.re addition, examination does not suggest synovitis (the patient lr:ltoslls in x patient t:rking urirrocl,clir.rc. [t shou]d be c<ln- = Ut has arthralgia rather than arthritis). The recent onset of sidered if syn.rptoms fail to inrprove after discontinuation of weight loss, fbver, and night sweats in the absence of syno- minocycline. vitis favors the diagnosis ol lymphoma over rheumatoid XEY POIilT arthritis. o DruB induced lupus erythematosus is often milder XEY POITIT than idiopathic systemic lupus erythematosus and is . Patients with Sjogren syndrome are at high risk for characterized by more skin and joint symptoms and a lymphoma (5% lifetime risk). much lower risk for organ involvement or damage. o Risk factors for lymphoma in patients with Sj0gren syndrome include parotid gland enlargement, Bibliography depressed C4 complement level, elevated rheumatoid Kawktt t.. Mertz tl Chasset F. et al. Charucterization of drug induced cutane ous lupus: analysis of 199,1 cases using the WHO pharmacovigilance factor level, elevated anti-Ro/SSA and/or anti-La/SSB database [Letter]. Autoimmun Rev 2021;20:102705. IPMll): 33188917] antibody levels, monoclonal gammopathy, and cryo globulinemic vasculitis. Item 81 Answer: A Bibliography Educational Obiective: Diagnose fibromyalgia. Fragkioudaki S, M:rvragani CP, Moutsopoulos llM. Predicting the risk fbr lymphoma clevelopment in Sjogren syndrome: an easy tool for clinical The most likely diagnosis is fibromyalgia (Option A). This use. Medicine (Baltinrore). 2016i95 r3766. lPMlDt 273368631 doi:10.1097, M D.0000000000003766 patient presents with ',r,idespread pain, fatigue, poor sleep, and cognitive symptoms of 1 year's duration. These symp- toms are the hallmarks of flbromyalgia, a poorly understood

has arthralgia rather than arthritis). The recent onset of sidered if syn.rptoms fail to inrprove after discontinuation of weight loss, fbver, and night sweats in the absence of syno- minocycline. vitis favors the diagnosis ol lymphoma over rheumatoid XEY POIilT arthritis. o DruB induced lupus erythematosus is often milder XEY POITIT than idiopathic systemic lupus erythematosus and is . Patients with Sjogren syndrome are at high risk for characterized by more skin and joint symptoms and a lymphoma (5% lifetime risk). much lower risk for organ involvement or damage. o Risk factors for lymphoma in patients with Sj0gren syndrome include parotid gland enlargement, Bibliography depressed C4 complement level, elevated rheumatoid Kawktt t.. Mertz tl Chasset F. et al. Charucterization of drug induced cutane ous lupus: analysis of 199,1 cases using the WHO pharmacovigilance factor level, elevated anti-Ro/SSA and/or anti-La/SSB database [Letter]. Autoimmun Rev 2021;20:102705. IPMll): 33188917] antibody levels, monoclonal gammopathy, and cryo globulinemic vasculitis. Item 81 Answer: A Bibliography Educational Obiective: Diagnose fibromyalgia. Fragkioudaki S, M:rvragani CP, Moutsopoulos llM. Predicting the risk fbr lymphoma clevelopment in Sjogren syndrome: an easy tool for clinical The most likely diagnosis is fibromyalgia (Option A). This use. Medicine (Baltinrore). 2016i95 r3766. lPMlDt 273368631 doi:10.1097, M D.0000000000003766 patient presents with ',r,idespread pain, fatigue, poor sleep, and cognitive symptoms of 1 year's duration. These symp- toms are the hallmarks of flbromyalgia, a poorly understood tr Item 80 Ed ucationa I Objective Answer: A : Diagnose drug-induced lupus but common chronic pain syndrome affecting 2"/,, to 3"/,, of the population. Diagnosis is suggested by history and can be conlirmed with validated criteria (e.g., the 2016 revisions to erythematosus. the American College of Rheumatologz Preliminary Diag The nrost likelv diagnosis is clrug induced lupus erythen-ra nostic Criteria). This illness is not autoimmune or inflamma tosus (Option A). Several medications, inclucling nrinoc)- tory and extensive laboratory testing is not advised unless cline, can cause drug induced lupus erythenratosus. This another comorbid disease is suggested. Although some syndrome is often r.nilcler tl.ran idiopathic systemic lupus patients may have tender points, assessment of tender points erythematosus (SLE). Patients may hirve skin ar.rd joint on examination is unreliable (particularly in men) and no symptoms but are at a mucl.r lower risk for organ dam Ionger among the clinical criteria for diagnosis. Fibromyal- age. Patients u,ith drug induced lupus erl,thematosus oflen gia tends to be associated with other medically unexplained have transiently positive antinuclear arltibodies but may lack syndromes, including irritable bowel syndrome, and is espe- typicirl aukrantibodies specific to Sl.E. Classically, paticnts cially common in patients with migraine headaches. with drug induced lupus erytl.rematosus may have antihis Generalized osteoarthritis (Option B) affects multiple tone antibodies. although these :rntibodies arc' not always joint groups. On joint examination, crepitus, decreased

tr Item 80 Ed ucationa I Objective Answer: A : Diagnose drug-induced lupus but common chronic pain syndrome affecting 2"/,, to 3"/,, of the population. Diagnosis is suggested by history and can be conlirmed with validated criteria (e.g., the 2016 revisions to erythematosus. the American College of Rheumatologz Preliminary Diag The nrost likelv diagnosis is clrug induced lupus erythen-ra nostic Criteria). This illness is not autoimmune or inflamma tosus (Option A). Several medications, inclucling nrinoc)- tory and extensive laboratory testing is not advised unless cline, can cause drug induced lupus erythenratosus. This another comorbid disease is suggested. Although some syndrome is often r.nilcler tl.ran idiopathic systemic lupus patients may have tender points, assessment of tender points erythematosus (SLE). Patients may hirve skin ar.rd joint on examination is unreliable (particularly in men) and no symptoms but are at a mucl.r lower risk for organ dam Ionger among the clinical criteria for diagnosis. Fibromyal- age. Patients u,ith drug induced lupus erl,thematosus oflen gia tends to be associated with other medically unexplained have transiently positive antinuclear arltibodies but may lack syndromes, including irritable bowel syndrome, and is espe- typicirl aukrantibodies specific to Sl.E. Classically, paticnts cially common in patients with migraine headaches. with drug induced lupus erytl.rematosus may have antihis Generalized osteoarthritis (Option B) affects multiple tone antibodies. although these :rntibodies arc' not always joint groups. On joint examination, crepitus, decreased 165

Answers and Critiques range of motion. bony enlargement, and sometimes effu program is likely the one to which the patient will adhere. sion may be present. Ger.reralized osteoarthritis is an unlikely Walking is the most common form o1'aerobic exercise eval- diagnosis because it would not cause the widespread pain uated in studies, either on a treadmill or as part of a super- seen in this patient and occurs in older patients. In addition, vised community program. Strengthening exercises with the examination demonstrates no evidence of osteoarthritis the use of isokinetic weight machines, resistance exercises, in any joint. and isometric exercise also provide value. Aquatic exercise Polymyalgia rheumatica (PMR) (Option C) is a clinical often encompasses aspects of aerobic fitness exercises and diagnosis based on characteristic symptoms in a patient exercises fbr enhancing joint range of motion in a low older than 50 years and is supported by an elevated eryth impact environment. The ACR/AF guideline notes a dose rocyte sedimentation rate. PMR is associated with pain and response relationship of weight loss and resultant symptom stiffness of the shoulder girdle and hip girdle. This patient's and functional improvement in patients with OA who have age, difiuse pain, and normal erythrocyte sedimentation rate overweight or obesity. Weight loss attempts coupled with an are not compatible with PMR. exercise program increase the benefit to the patient. Even UI Rheumatoid arthritis (Option D) is an inflammatory small amounts of weight loss (5'1,) can have a positive elfect € o arthritis that primarily affects small joints. Patients with on pain and function. ta rheumatoid arthritis present r,r,ith discomfort in discrete The ACR/AF recommends against the use of massage q, 3 joints. not di{fuse pain. In addition, rheumatoid arthritis therapy (Option B) in the treatment of OA because elficacy EL does not cause axial pain or myalgia. The musculoskele data are lacking. Massage therapy may have other benefits, n tal examination in a ptrtient u,ho has a l-year history of' but none that pertain to outcomes speciflc to knee OA have i. untreated rheumatoid arthritis should reveal multiple yet been demonstrated. tt tr swollen joints. The ACR/AF recommends against mobilization/manip o ulation and passive range of motion (Option C) for knee and/ ta Systemic lupus erythematosus (SLE) (Option E) is an autoimmune disease that can allect any system in the body, or hip OA. Although manual therapy can be of benefit for including the skin, blood cells, joints, lung, central nervous certain conditions, such as chronic low back pain, data show systenl. and kidneys. Although patients with SLE can have little additional benefit over exercise alone lor managing OA concurrent fibromyalgia, patients with fibromyalgia rarely symptoms. have SLE. This patient also has none ol the hallmarks ol Studies examining the use of transcutaneous electrical SLE. such as autoimmune c).topenia, inflammatory arthritis. nerve stimulation (TENS) (Option D) have failed to demon- rash, kidney disease, or systemic inflammation. strate benefit in patients with knee OA. The ACR/AF guide line strongly recommends against the use of TENS. [[Y P0lilrt . Fibromyalgia is characterized by widespread pain, rEY POIlIIS fatigue, poor sleep, and cognitive symptoms; diagno- . Exercise is beneficial in hip, knee, and hand osteoar sis is suggested by history and can be confirmed with thritis; no one exercise program is superior. a validated questionnaire. o There is a dose-response relationship of weight loss and . Assessment of tender points on examination is unreliable slmptom and functional improvement in patients with and no longer among the clinical criteria for diagnosis overweight or obesity and osteoarthritis that begins of fibromyalgia. with 5'7, loss of bodyweight.

range of motion. bony enlargement, and sometimes effu program is likely the one to which the patient will adhere. sion may be present. Ger.reralized osteoarthritis is an unlikely Walking is the most common form o1'aerobic exercise eval- diagnosis because it would not cause the widespread pain uated in studies, either on a treadmill or as part of a super- seen in this patient and occurs in older patients. In addition, vised community program. Strengthening exercises with the examination demonstrates no evidence of osteoarthritis the use of isokinetic weight machines, resistance exercises, in any joint. and isometric exercise also provide value. Aquatic exercise Polymyalgia rheumatica (PMR) (Option C) is a clinical often encompasses aspects of aerobic fitness exercises and diagnosis based on characteristic symptoms in a patient exercises fbr enhancing joint range of motion in a low older than 50 years and is supported by an elevated eryth impact environment. The ACR/AF guideline notes a dose rocyte sedimentation rate. PMR is associated with pain and response relationship of weight loss and resultant symptom stiffness of the shoulder girdle and hip girdle. This patient's and functional improvement in patients with OA who have age, difiuse pain, and normal erythrocyte sedimentation rate overweight or obesity. Weight loss attempts coupled with an are not compatible with PMR. exercise program increase the benefit to the patient. Even UI Rheumatoid arthritis (Option D) is an inflammatory small amounts of weight loss (5'1,) can have a positive elfect € o arthritis that primarily affects small joints. Patients with on pain and function. ta rheumatoid arthritis present r,r,ith discomfort in discrete The ACR/AF recommends against the use of massage q, 3 joints. not di{fuse pain. In addition, rheumatoid arthritis therapy (Option B) in the treatment of OA because elficacy EL does not cause axial pain or myalgia. The musculoskele data are lacking. Massage therapy may have other benefits, n tal examination in a ptrtient u,ho has a l-year history of' but none that pertain to outcomes speciflc to knee OA have i. untreated rheumatoid arthritis should reveal multiple yet been demonstrated. tt tr swollen joints. The ACR/AF recommends against mobilization/manip o ulation and passive range of motion (Option C) for knee and/ ta Systemic lupus erythematosus (SLE) (Option E) is an autoimmune disease that can allect any system in the body, or hip OA. Although manual therapy can be of benefit for including the skin, blood cells, joints, lung, central nervous certain conditions, such as chronic low back pain, data show systenl. and kidneys. Although patients with SLE can have little additional benefit over exercise alone lor managing OA concurrent fibromyalgia, patients with fibromyalgia rarely symptoms. have SLE. This patient also has none ol the hallmarks ol Studies examining the use of transcutaneous electrical SLE. such as autoimmune c).topenia, inflammatory arthritis. nerve stimulation (TENS) (Option D) have failed to demon- rash, kidney disease, or systemic inflammation. strate benefit in patients with knee OA. The ACR/AF guide line strongly recommends against the use of TENS. [[Y P0lilrt . Fibromyalgia is characterized by widespread pain, rEY POIlIIS fatigue, poor sleep, and cognitive symptoms; diagno- . Exercise is beneficial in hip, knee, and hand osteoar sis is suggested by history and can be confirmed with thritis; no one exercise program is superior. a validated questionnaire. o There is a dose-response relationship of weight loss and . Assessment of tender points on examination is unreliable slmptom and functional improvement in patients with and no longer among the clinical criteria for diagnosis overweight or obesity and osteoarthritis that begins of fibromyalgia. with 5'7, loss of bodyweight. Bibliography Bibliography Wolfe F, Clauu,l)J. Fitzcharlcs MA. et aI.2016 Revisions to the 2010/2011 Kohsinski Sl.. Neogi li llochberg MC, et al.2019 American College of fibnrmyalgia dixgnostic criteria. Semin Arthritis Rheum. 2ol6r.t6::ll9 Rheumirkrlol5,', Arthritis Foundation guideline for the mrnagemrnt of 329. IP1\{lD:')79l6278ldoi:10.1016 j.scmarthrit.20l6.08.0l2 osteoarthritis ofthe hand. hip. and knee. Arthritis Care Res (Hoboken). 2O2OJ2:149 162. [PI\'Ill): 31908149]

Bibliography Bibliography Wolfe F, Clauu,l)J. Fitzcharlcs MA. et aI.2016 Revisions to the 2010/2011 Kohsinski Sl.. Neogi li llochberg MC, et al.2019 American College of fibnrmyalgia dixgnostic criteria. Semin Arthritis Rheum. 2ol6r.t6::ll9 Rheumirkrlol5,', Arthritis Foundation guideline for the mrnagemrnt of 329. IP1\{lD:')79l6278ldoi:10.1016 j.scmarthrit.20l6.08.0l2 osteoarthritis ofthe hand. hip. and knee. Arthritis Care Res (Hoboken). 2O2OJ2:149 162. [PI\'Ill): 31908149] Item 82 Answer: A : Treat osteoarthritis with exercise Ed u catio na I O bjective Item 83 Answer: D and weight loss. Educational Objective: Evaluate rheumatoid arthritis with hand radiography. The most appropriate additional treatment for this patient is exercise and weight toss (Option A). The 2019 Ameri The most appropriate diagnostic test to perfbrm next is can College of Rheumatolory (ACR)/Arthritis Foundation plain radiography of the hands (Option D). No single (AF) guideline strongly recommends exercise for all patients radiographic feature is diagnostic of rheumatoid arthritis. with osteoarthritis (OA). The most robust evidence supports However, f'eatures such as periarticular osteopenia, joint exercise in the treatment of knee and hip OA: less evi space narrowing, and bony erosions are characteristic of dence is available for hand OA. Many helpful exercises are established disease and may help solidify the diagnosis of available for knee and hip OA, and the evidence indicates rheumatoid arthritis when physical examination findings that no one exercise program is superior. However. the best :rre equivocal. Ifpresent, they can also underscore the need 155

Answers and Critiques for early treatment with disease modifying agents. which variants: annular and polycyclic photosensitive plaques can include biologics, because the presence ofradiographic on the back, chest, and extremities, or psoriasiform scaly damage at the time of diagnosis of rheumatoid arthritis plaques in a similar distribution. SCLE does not scar but predicts a more severe course of disease. Thus, plain radi may resolve with temporary pigmentary changes. Fewer ography may aid in both diagnostic and therapeutic deci than one in four patients with SCLE has systemic lupus ery- sion making as well as help establish a baseline to assist in thematosus (SLE), and as many as one in three SCLE cases monitoring disease activity. are drug induced. The latter may resolve with withdrawal of ANCAs (Option A) are directed against antigens fbund the causative agent. Up to 70'7, of patients with SCLE have an i in the cytoplasmic granules of neutrophils and monocytes. elevated antinuclear antibody titer, with anti RoTSSA and ANCA testing is usually performed to help diagnose or anti La/SSB being overrepresented. exclude granulomatosis with polyangiitis and microscopic The malar "butterfly" rash is characteristic of acute polyangiitis. However, polyarticular, symmetric inflamma cutaneous lupus erythematosus (ACLE) (Option A); holt' tory arthritis of the small joints of the hands as seen in ever, ACLE can also manifest as a maculopapular variant t,l G, this patient is not a feature of ANCA positive vasculitis. that is photosensitive and distributed over the chest, upper C' The choice of which autoantibody tests to order should be back, and arms. Both rashes have a range ol presentation guided by an accurate history and careful physical exanrina from pink-to-violet macules to scaly papules and plaques. tr, tion. ln this case, ANCA testing is not the most appropriate Essentially all patients with ACI-E have SLE and as such ter.rd rE : diagnostic test. to have systemic symptoms and positive serologic results. .g , Anti double stranded DNA antibody testing (Option The rash ofACLE does not scar. B) is not indicated. Antinuclear antibody (ANA) specificiff Cutaneous leukocytoclastic vasculitis (Option B) o testing (i.e., testing fcrr antibodies to specific nuclear com results from inflammation of small blood vessels and can ta = j ponents, such as DNA or centromeres) should be reserved be seen in isolation or in association with a variety of for patients with a positive ANA test result and a clinical systemic diseases, including autoimmune disorders (such syndrome suggesting an underlying rheumatologic disease. as SI-E, rheumatoid arthritis, inflammatory bowel disease, An anti double stranded DNA antibody test should not be and systemic vasculitides), but also infection, hypersen perfbrmed in the absence of a positive ANA result. sitivity to medications, and malignancy. Rashes consist of MRI (Option C) can be a valuable tool in the evaluation red or purple discrete skin lesions, are more common on of specific concerns in patients with musculoskeietal dis the lor.r,er extremities than on the trunk or fbrearms. and ease, but it lacks speciflcity fbr the diagnosis of rheumatoid rarely occur on the face. arthritis. The first step in radiologic evaluatior.r of a patient Chronic cutaneous lupus erythematosus (CCLE) with joint symptoms is usually plain radiography because defines a category of related skin diseases of which dis it is relatively inexpensive, is readily available, and per, coid lupus erythematosus (DI-E) (Option C) is the most mits assessment for findings characteristic of rheumatoid common. DLE lesions start as red to violet plaques that arthritis. develop a hyperpigmented border and thick adherent scale in the center. The centers of the lesions eventually become r(EY POt t{IS atrophic and depigmer.rted, causing permanent alopecia if . No single radiographic feature is diagnostic of rheu- occurring in hair bearing areas. Plaques favor the head and matoid arthritis, but features such as periarticular neck, particularly the scalp and the hollow ot the auricle osteopenia, joint-space narrowing, and bony erosions of the ear. CCLE in general has a low association with Sl.E, are characteristic of established disease. and t)LE poses approximately a 10'X, risk for underlying . Radiographic features of rheumatoid arthritis can systemic disease. underscore the need for early treatment with disease I(EY POIilTS modi8zing agents because radiographic damage at o Subacute cutaneous lupus erythematosus is a photo the time of diagnosis predicts a more severe disease sensitive rash occurring especially on the arms, neck, course. and upper trunk, usually sparing the central face and consisting of erythematous annular/polycyclic or Bibliography patchy papulosquamous lesions. Aletaha D, Smolen JS. Diagnosis ancl management of rheul.uirtoid artltritis: a review. JAMA.2018 Oct 2:320(13):1360 1372. IPMID:3028.51831 cloi: 10. . Fewer than 25'l. of patients with subacute cutaneous 1001 iama.20lB.l3103 Iupus erythematosus have systemic lupus ery.thematosus. Item 84 Answer: D Ed ucationa I Objective: Diagnose subacute cutaneous Bibliography lupus erythematosus. Alniemi l)T. Gutierrez A Jr. l)ruge I-A. el xl. Subrcule cutilncous lupus ery themrtosus: clinic:rl cluracteristics. clisease associatior.ts. treiltnlents. The most likely diagnosis is subacute cutaneous lupus ery- and outcomes in a series ol'90 patients at Meyo Clinic. 1996 2011. l\,hyo thematosus (SCLE) (Option D). SCLE appears as one of two CIin l)roc. 20l7;92:,106 41.1. IPl\4lD: 2U1856561

for early treatment with disease modifying agents. which variants: annular and polycyclic photosensitive plaques can include biologics, because the presence ofradiographic on the back, chest, and extremities, or psoriasiform scaly damage at the time of diagnosis of rheumatoid arthritis plaques in a similar distribution. SCLE does not scar but predicts a more severe course of disease. Thus, plain radi may resolve with temporary pigmentary changes. Fewer ography may aid in both diagnostic and therapeutic deci than one in four patients with SCLE has systemic lupus ery- sion making as well as help establish a baseline to assist in thematosus (SLE), and as many as one in three SCLE cases monitoring disease activity. are drug induced. The latter may resolve with withdrawal of ANCAs (Option A) are directed against antigens fbund the causative agent. Up to 70'7, of patients with SCLE have an i in the cytoplasmic granules of neutrophils and monocytes. elevated antinuclear antibody titer, with anti RoTSSA and ANCA testing is usually performed to help diagnose or anti La/SSB being overrepresented. exclude granulomatosis with polyangiitis and microscopic The malar "butterfly" rash is characteristic of acute polyangiitis. However, polyarticular, symmetric inflamma cutaneous lupus erythematosus (ACLE) (Option A); holt' tory arthritis of the small joints of the hands as seen in ever, ACLE can also manifest as a maculopapular variant t,l G, this patient is not a feature of ANCA positive vasculitis. that is photosensitive and distributed over the chest, upper C' The choice of which autoantibody tests to order should be back, and arms. Both rashes have a range ol presentation guided by an accurate history and careful physical exanrina from pink-to-violet macules to scaly papules and plaques. tr, tion. ln this case, ANCA testing is not the most appropriate Essentially all patients with ACI-E have SLE and as such ter.rd rE : diagnostic test. to have systemic symptoms and positive serologic results. .g , Anti double stranded DNA antibody testing (Option The rash ofACLE does not scar. B) is not indicated. Antinuclear antibody (ANA) specificiff Cutaneous leukocytoclastic vasculitis (Option B) o testing (i.e., testing fcrr antibodies to specific nuclear com results from inflammation of small blood vessels and can ta = j ponents, such as DNA or centromeres) should be reserved be seen in isolation or in association with a variety of for patients with a positive ANA test result and a clinical systemic diseases, including autoimmune disorders (such syndrome suggesting an underlying rheumatologic disease. as SI-E, rheumatoid arthritis, inflammatory bowel disease, An anti double stranded DNA antibody test should not be and systemic vasculitides), but also infection, hypersen perfbrmed in the absence of a positive ANA result. sitivity to medications, and malignancy. Rashes consist of MRI (Option C) can be a valuable tool in the evaluation red or purple discrete skin lesions, are more common on of specific concerns in patients with musculoskeietal dis the lor.r,er extremities than on the trunk or fbrearms. and ease, but it lacks speciflcity fbr the diagnosis of rheumatoid rarely occur on the face. arthritis. The first step in radiologic evaluatior.r of a patient Chronic cutaneous lupus erythematosus (CCLE) with joint symptoms is usually plain radiography because defines a category of related skin diseases of which dis it is relatively inexpensive, is readily available, and per, coid lupus erythematosus (DI-E) (Option C) is the most mits assessment for findings characteristic of rheumatoid common. DLE lesions start as red to violet plaques that arthritis. develop a hyperpigmented border and thick adherent scale in the center. The centers of the lesions eventually become r(EY POt t{IS atrophic and depigmer.rted, causing permanent alopecia if . No single radiographic feature is diagnostic of rheu- occurring in hair bearing areas. Plaques favor the head and matoid arthritis, but features such as periarticular neck, particularly the scalp and the hollow ot the auricle osteopenia, joint-space narrowing, and bony erosions of the ear. CCLE in general has a low association with Sl.E, are characteristic of established disease. and t)LE poses approximately a 10'X, risk for underlying . Radiographic features of rheumatoid arthritis can systemic disease. underscore the need for early treatment with disease I(EY POIilTS modi8zing agents because radiographic damage at o Subacute cutaneous lupus erythematosus is a photo the time of diagnosis predicts a more severe disease sensitive rash occurring especially on the arms, neck, course. and upper trunk, usually sparing the central face and consisting of erythematous annular/polycyclic or Bibliography patchy papulosquamous lesions. Aletaha D, Smolen JS. Diagnosis ancl management of rheul.uirtoid artltritis: a review. JAMA.2018 Oct 2:320(13):1360 1372. IPMID:3028.51831 cloi: 10. . Fewer than 25'l. of patients with subacute cutaneous 1001 iama.20lB.l3103 Iupus erythematosus have systemic lupus ery.thematosus. Item 84 Answer: D Ed ucationa I Objective: Diagnose subacute cutaneous Bibliography lupus erythematosus. Alniemi l)T. Gutierrez A Jr. l)ruge I-A. el xl. Subrcule cutilncous lupus ery themrtosus: clinic:rl cluracteristics. clisease associatior.ts. treiltnlents. The most likely diagnosis is subacute cutaneous lupus ery- and outcomes in a series ol'90 patients at Meyo Clinic. 1996 2011. l\,hyo thematosus (SCLE) (Option D). SCLE appears as one of two CIin l)roc. 20l7;92:,106 41.1. IPl\4lD: 2U1856561 167

Answers and Critiques tr Item 85 Answer: A Educational Objective: Diagnose giant cell arteritis. Item 86 Answer: A Educational Objective: Diagnose the cause of acute tx monoarthritis by using arthrocentesis. The rnost likely diagnosis is giant cell arteritis (GCA) (Option A). 'lhis patient h:rs polymyalgia rl.reumatica. and 10'/, to The most appropriate diagnostic test to perfbrm next is 20'll, of patients n,ith polyntyalgia rheumatica have con aspiration of the left knee (Option A). This patient has collritilnt CCA at presentatior.r or dcvelop GCA later in the acute inf lammatory arthritis of the knee characlerized by disc:rse course. Ileadachc is present in mure than 607, o1' pain. swelling, and redness for less than 1 rveek. Physical paticnts r,r'ith GCA and may be frontal, occipital, unilateral. examination shows swelling r,rritl-r warmtl-r ancl redness. or gcneralized; it nra1,' be constant, intermittent, or waxing as well as tenderness with palprrtion and limited range and u'aning. Ihe irnpofiant point is that the headache is of' motion. The clifl'erential diagnosis ol acute monoar ner,ri A frecluent nor.rheadache manif'estation of GCA is jaw thritis includes crystal induced disease (gout or calciunr D clauclication, or,r,ing to decreased blood flow to the muscles pl,rophosphate deposition), infection. and hemarthrosis ut of mirstication. Jar,r'claudication is ttrund in nearly 50?; of (bleeding into the joint). Joint aspiration is necessary' to E patients with GCA, and this symptom should always be make an accurate diagnosis and distinguish amor.rg these .D UI explored on revie\.t, ol svstems in a patient with polymyal causes. Synovial fluid should be analyzecl for cell count o, gia rheun.ratica. Other key questions to ask such patients ar.rd diflerential. crystal examination, Cram stain, and =L C include whcther thcy havc recent changes in vision (e.g., culture. n short lir,ecl episodes of amaurosis firgax. diplopia. or blur Erythrocyte sedimer-rtation rate (Option B) is a blood =. lr3. g riness) ancl scalp tenderness (e.g., r,r,ith hair brushing). A blood C-reactive protein level of l2.B mg/dl (128 mgil) test that indicates systemic inflammation. It may be elevatecl in any inflammatory process. inclucling crystal induced dis (D Ut r'rru-rld be unusual lbr polvml,algia rheunratica alor.re; this ease and intectiorr. but docs r.rot distinguish betu,een the t$o 1 degree of systemic inflammation is r.nore in keeping with a diagnoses. vasculitis. such as (lCA. Radiography ol the knee (Option C) rnay be a useful Granulomatosis r,r,ith polyangiitis (GPA) (Option B) is test but is not adequate to distinguish the cause of acute the n-rost common ANCA associatecl vasculitis. Typical age monoarthritis unless there is a history of traunra and frac at onset is bctu,een .15 ancl 60 !'ears. GPA afl'ects the upper ture lvith hemarthrosis is suspected. This patient has no and lorter ainr,ays. kidneys, eyes. and ears. At least 50u/. of hislory ol trauma. paticnts havc constitutional symptoms. GPA can cause visual Serum urate (Option D) is not l-relpful for deterntining chxnges bllt is not t1'picall1.'associated \vith ncrn onset head the causc of this patient's acute ntonoarthritis. Although ache or jau, claudication. an elevated level might increase clinical suspicion of goul Like (lPA. microscopic polyangiitis (MtA) (Option C) as the cause, only knee aspiration with fluid analysis fbr is a small vessel r,asculitis that characteristically aflects thc cell count and crystals can determine the cause of the knee lungs anci kidneys, along with other organ systems. Absence intlammation. The presence of soclium urate crystals in thc of granulonras distinguishes N,IPA iiom GPA. MPA cannot synovial fluid polymorphonuclear cells is diagnostic for account ibr tl-tis patient's syrnptoms. gout. Gout and infection may coexist. so aspirati<tn wottld Polyrrteritis r.rodosa (Option D) is a medium be indicatcd even if the serum urate lcvcl was elevated. l,essel lasculitis tlrat can af fect any organ in the body but Finall1,, evcn in patients with acute gout. scrum urate level most comnronly involves the renal vasculirture (resulting rnny be normal at the tirne of the flare. Thus, a norntirl irr renal insufficicncy and hypertcnsion), skin (produc serunl urate level would not rule out gout as the cause ol ing nodular skin lesions). mesenteric vessels (causing acute monoarthritis. abdominal pain, including postprandial abdominal pain), TEY POTITI ancl peripheral ncrves (typically presentir.rg as mononeu ritis multiplex). The patient does not have this symp o Joint aspiration is necessary to make an accurate toln compler, making polyarteritis nodosa an unlikely diagnosis and distinguish among causes of acute dirrgr-rosis. monoarthritis, including crystal-induced disease (gout or calcium pyrophosphate deposition), infec- KEY POIilTS tion, and hemarthrosis. o Concomitant giant cell arteritis develops in 10'2, to . ln patients with an acute inflammatory arthritis, 20% of patients with polymyalgia rheumatica. synovial fluid should be ana\zed for cell count and o Common symptoms of giant cell arteritis include differential, crystal examination, Gram stain, and headache, jaw claudication, and changes in vision. culture.

tr Item 85 Answer: A Educational Objective: Diagnose giant cell arteritis. Item 86 Answer: A Educational Objective: Diagnose the cause of acute tx monoarthritis by using arthrocentesis. The rnost likely diagnosis is giant cell arteritis (GCA) (Option A). 'lhis patient h:rs polymyalgia rl.reumatica. and 10'/, to The most appropriate diagnostic test to perfbrm next is 20'll, of patients n,ith polyntyalgia rheumatica have con aspiration of the left knee (Option A). This patient has collritilnt CCA at presentatior.r or dcvelop GCA later in the acute inf lammatory arthritis of the knee characlerized by disc:rse course. Ileadachc is present in mure than 607, o1' pain. swelling, and redness for less than 1 rveek. Physical paticnts r,r'ith GCA and may be frontal, occipital, unilateral. examination shows swelling r,rritl-r warmtl-r ancl redness. or gcneralized; it nra1,' be constant, intermittent, or waxing as well as tenderness with palprrtion and limited range and u'aning. Ihe irnpofiant point is that the headache is of' motion. The clifl'erential diagnosis ol acute monoar ner,ri A frecluent nor.rheadache manif'estation of GCA is jaw thritis includes crystal induced disease (gout or calciunr D clauclication, or,r,ing to decreased blood flow to the muscles pl,rophosphate deposition), infection. and hemarthrosis ut of mirstication. Jar,r'claudication is ttrund in nearly 50?; of (bleeding into the joint). Joint aspiration is necessary' to E patients with GCA, and this symptom should always be make an accurate diagnosis and distinguish amor.rg these .D UI explored on revie\.t, ol svstems in a patient with polymyal causes. Synovial fluid should be analyzecl for cell count o, gia rheun.ratica. Other key questions to ask such patients ar.rd diflerential. crystal examination, Cram stain, and =L C include whcther thcy havc recent changes in vision (e.g., culture. n short lir,ecl episodes of amaurosis firgax. diplopia. or blur Erythrocyte sedimer-rtation rate (Option B) is a blood =. lr3. g riness) ancl scalp tenderness (e.g., r,r,ith hair brushing). A blood C-reactive protein level of l2.B mg/dl (128 mgil) test that indicates systemic inflammation. It may be elevatecl in any inflammatory process. inclucling crystal induced dis (D Ut r'rru-rld be unusual lbr polvml,algia rheunratica alor.re; this ease and intectiorr. but docs r.rot distinguish betu,een the t$o 1 degree of systemic inflammation is r.nore in keeping with a diagnoses. vasculitis. such as (lCA. Radiography ol the knee (Option C) rnay be a useful Granulomatosis r,r,ith polyangiitis (GPA) (Option B) is test but is not adequate to distinguish the cause of acute the n-rost common ANCA associatecl vasculitis. Typical age monoarthritis unless there is a history of traunra and frac at onset is bctu,een .15 ancl 60 !'ears. GPA afl'ects the upper ture lvith hemarthrosis is suspected. This patient has no and lorter ainr,ays. kidneys, eyes. and ears. At least 50u/. of hislory ol trauma. paticnts havc constitutional symptoms. GPA can cause visual Serum urate (Option D) is not l-relpful for deterntining chxnges bllt is not t1'picall1.'associated \vith ncrn onset head the causc of this patient's acute ntonoarthritis. Although ache or jau, claudication. an elevated level might increase clinical suspicion of goul Like (lPA. microscopic polyangiitis (MtA) (Option C) as the cause, only knee aspiration with fluid analysis fbr is a small vessel r,asculitis that characteristically aflects thc cell count and crystals can determine the cause of the knee lungs anci kidneys, along with other organ systems. Absence intlammation. The presence of soclium urate crystals in thc of granulonras distinguishes N,IPA iiom GPA. MPA cannot synovial fluid polymorphonuclear cells is diagnostic for account ibr tl-tis patient's syrnptoms. gout. Gout and infection may coexist. so aspirati<tn wottld Polyrrteritis r.rodosa (Option D) is a medium be indicatcd even if the serum urate lcvcl was elevated. l,essel lasculitis tlrat can af fect any organ in the body but Finall1,, evcn in patients with acute gout. scrum urate level most comnronly involves the renal vasculirture (resulting rnny be normal at the tirne of the flare. Thus, a norntirl irr renal insufficicncy and hypertcnsion), skin (produc serunl urate level would not rule out gout as the cause ol ing nodular skin lesions). mesenteric vessels (causing acute monoarthritis. abdominal pain, including postprandial abdominal pain), TEY POTITI ancl peripheral ncrves (typically presentir.rg as mononeu ritis multiplex). The patient does not have this symp o Joint aspiration is necessary to make an accurate toln compler, making polyarteritis nodosa an unlikely diagnosis and distinguish among causes of acute dirrgr-rosis. monoarthritis, including crystal-induced disease (gout or calcium pyrophosphate deposition), infec- KEY POIilTS tion, and hemarthrosis. o Concomitant giant cell arteritis develops in 10'2, to . ln patients with an acute inflammatory arthritis, 20% of patients with polymyalgia rheumatica. synovial fluid should be ana\zed for cell count and o Common symptoms of giant cell arteritis include differential, crystal examination, Gram stain, and headache, jaw claudication, and changes in vision. culture. Bibliography Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatologr/ Bibliography Vrsculitis l.bundation guideline fbr the nlanagement ofgiant cell arte Singh N. Vrgelgesang SA. Monoarticuhr arthritis. Med (llin North ritis and Takayasu irrteritis. Arthritis RheumrtOl. 2021. fPMID: Am. 20l7: lOl :607 6 13. IPMI I): 283727 16l doi:lo. I Ol 6,'i.mcnir.2016. 12. 3123s8841 00,1

Bibliography Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatologr/ Bibliography Vrsculitis l.bundation guideline fbr the nlanagement ofgiant cell arte Singh N. Vrgelgesang SA. Monoarticuhr arthritis. Med (llin North ritis and Takayasu irrteritis. Arthritis RheumrtOl. 2021. fPMID: Am. 20l7: lOl :607 6 13. IPMI I): 283727 16l doi:lo. I Ol 6,'i.mcnir.2016. 12. 3123s8841 00,1 168

t Answers and 9'r!qv.:: I I i t i \ tr Item 87 Answer: D Educational Objective: Evaluate new monoarticular pain Bibliography Ross JJ. Septic arthritis of native joints. lnfect Dis Clin North Am. 2017; 31:203,218. IpMID, ZSgOOZ:2t] doi:10.1016/j.idc.2017.01.001 I in a patient with rheumatoid arthritis. The nrost appropridte diagnostic test to perfbrm next :

t i \ tr Item 87 Answer: D Educational Objective: Evaluate new monoarticular pain Bibliography Ross JJ. Septic arthritis of native joints. lnfect Dis Clin North Am. 2017; 31:203,218. IpMID, ZSgOOZ:2t] doi:10.1016/j.idc.2017.01.001 I in a patient with rheumatoid arthritis. The nrost appropridte diagnostic test to perfbrm next : \ is synovial fluid analysis (Option D). 'lhe abrupt onset of Item 88 Answer: D acllte nronoarticular inllamnratory rrthritis in any patient Educational Objective: Treat systemic lupus shor-rld suggest a joint inf'ection. llris patient has a history e4rthematosus in a patient planning pregnancy. o1' krng standing rheumatoid arthritis that has damaged The most appropriate preconception management is to nurrerous joints. Previiius joint clamage incre:rses the risk discontinue mycophenolate mofetil and add azathioprine tbr joint inf'ection. 'lhe patient irlso reccives multiple inrnru- (Option D). In some very stable patients with systemic nosupirressive irgents. u{rich also increase risk fbr joint : lupus erythematosus (SLE), mycophenolate mofetil could intbction. tier joint ex:rmination, apart from the left knee, ra be discontinued with maintenance on hydroxychloroquine (l, suggests quiescent rhcumatoicl arthritis rather than a gcn alone. SLE is associated with increased risk for miscarriage, CT eralizecl flirre of disease. turther raising suspicion lor an :

\ is synovial fluid analysis (Option D). 'lhe abrupt onset of Item 88 Answer: D acllte nronoarticular inllamnratory rrthritis in any patient Educational Objective: Treat systemic lupus shor-rld suggest a joint inf'ection. llris patient has a history e4rthematosus in a patient planning pregnancy. o1' krng standing rheumatoid arthritis that has damaged The most appropriate preconception management is to nurrerous joints. Previiius joint clamage incre:rses the risk discontinue mycophenolate mofetil and add azathioprine tbr joint inf'ection. 'lhe patient irlso reccives multiple inrnru- (Option D). In some very stable patients with systemic nosupirressive irgents. u{rich also increase risk fbr joint : lupus erythematosus (SLE), mycophenolate mofetil could intbction. tier joint ex:rmination, apart from the left knee, ra be discontinued with maintenance on hydroxychloroquine (l, suggests quiescent rhcumatoicl arthritis rather than a gcn alone. SLE is associated with increased risk for miscarriage, CT eralizecl flirre of disease. turther raising suspicion lor an : premature delivery and other pregnancy complications. inlected joint. In patients suspectecl of having infections ; Patients with SLE who desire pregnancy should be advised rr, arthritis. the most important cliagnostic proceclure is crpe E to wait until disease has been well controlled for at least ditious afihrocentesis to obtiiin joint lluid :rncl conduct syncr .g 6 months to reduce these risks. Certain therapies, such vi:rl fluid analysis (Cram stain. culture lbacterial and. when tl : as mycophenolate mofetil, belimumab, and methotrex o indicated, mvcobacterial and,or fungall. leukocyte count. ate, should be avoided in patients considering pregnancy and crystal analysis). t = : because they are teratogenic. Cyclophosphamide is associ (l reactive protein (CRP) (Option A) is ar.r acute phase ated with age and dose-dependent infertility and should reactant. Although elevation oI CRP level can signal ar.r irrfec not be used in patients contemplating pregnancy without tion, it is a nonspecific indicator. Indeed. an elevated CRP a compelling life or organ threatening indication. This level can be seen in a Ilare of rheumatoicl arthritis. as well as patient has well controlled SLE but is taking mycopheno in other conditions. and may not help distinguish betr,r,een late mofetil, which should be discontinued 3 months before iniL'ction and a rheunratoid arthritis Ilare. conception is attempted. Routine use of azathioprine in Measurenrent of serum procalcitonin levels (Option B) pregnancy is not advised; however, this drug is safer than has lreen proposed to help clistinguish ini'ectious arthritis other agents and can be used if necessary. In this patient tiom inflan.rmatory arthritis. Ilowever, serum procalcitonin with a history of Iupus nephritis, azathioprine can reduce is 11ot sensitivc lor the presencc of joint infectir>n. and ir neg the risk for flare or disease progression. Hydroxychloro atir,e result cloes not elirr.rinate infectioLrs arthritis. quine can be safely used during pregnancy in most patients ln patients suspccted ot having lr joint inf'ection. a to reduce the risk for SLE flare or other complications and sy'no','ial biopsy (Option C) is rarell, necessaryi Syr.ulvial should be continued. biopsies may be helpfll in patients in r,r,hont concurrent Patients should be advised about the risks of preg- contiguous osteomyelitis or tubercukrsis (or infection with nancy in the setting of an SLE diagnosis (Option A), but arrother 5low grou'ing organism, such as a fungus) is a given this patient's excellent disease control, a careful diagnostic possibility. 'lhe paticrrt's shrtrt durati<ln olsymp decision to proceed with attempts to conceive would be toms nrakes concurrent ostcomyelitis or ir.rf'ection witl-r reasonable. slorv gror,.",ing organisms unlikell,. Although tulterculosis This patient's current medications (Option B) must be or fLngal infection callnot be absolutely excluded irr this changed before conception given the risk for teratogenicity patient receiving intr.nunosuppressallt clrugs. the first cliag, associated with mycophenolate mofetil. Azathioprine is the nostic test remains a synovial fluid analysis. A syr.rovial best option to control the patient's lupus nephritis and may biopsy may be consiclered in patients without an cstab be considered following a frank discussion with the patient lishecl diagnosis after joint f luicl analysis or those in rvhom regarding risks and beneflts and shared decision making. antibiotic therapy has failed. Patients who have SLE flares during pregnancy can be treated with prednisone or other glucocorticoids. If the risk rEY POIilIS for flare is considered high, empiric addition of low-dose . The abrupt onset of acute monoarticular inflamma- prednisone (Option C) could be considered, but this patient tory arthritis in any patient should suggest a joint currently has no indication for a glucocorticoid. infection. . In patients suspected of having infectious arthritis, ftY Pottrs the most important diagnostic procedure is expedi- . Systemic lupus erythematosus is associated with tious arthrocentesis to obtain joint fluid and conduct increased risk for miscarriage, premature delivery synovial fluid analysis (Gram stain, culture, leukocyte and other pregnancy complications. count, and crystal analysis). (Continued)

premature delivery and other pregnancy complications. inlected joint. In patients suspectecl of having infections ; Patients with SLE who desire pregnancy should be advised rr, arthritis. the most important cliagnostic proceclure is crpe E to wait until disease has been well controlled for at least ditious afihrocentesis to obtiiin joint lluid :rncl conduct syncr .g 6 months to reduce these risks. Certain therapies, such vi:rl fluid analysis (Cram stain. culture lbacterial and. when tl : as mycophenolate mofetil, belimumab, and methotrex o indicated, mvcobacterial and,or fungall. leukocyte count. ate, should be avoided in patients considering pregnancy and crystal analysis). t = : because they are teratogenic. Cyclophosphamide is associ (l reactive protein (CRP) (Option A) is ar.r acute phase ated with age and dose-dependent infertility and should reactant. Although elevation oI CRP level can signal ar.r irrfec not be used in patients contemplating pregnancy without tion, it is a nonspecific indicator. Indeed. an elevated CRP a compelling life or organ threatening indication. This level can be seen in a Ilare of rheumatoicl arthritis. as well as patient has well controlled SLE but is taking mycopheno in other conditions. and may not help distinguish betr,r,een late mofetil, which should be discontinued 3 months before iniL'ction and a rheunratoid arthritis Ilare. conception is attempted. Routine use of azathioprine in Measurenrent of serum procalcitonin levels (Option B) pregnancy is not advised; however, this drug is safer than has lreen proposed to help clistinguish ini'ectious arthritis other agents and can be used if necessary. In this patient tiom inflan.rmatory arthritis. Ilowever, serum procalcitonin with a history of Iupus nephritis, azathioprine can reduce is 11ot sensitivc lor the presencc of joint infectir>n. and ir neg the risk for flare or disease progression. Hydroxychloro atir,e result cloes not elirr.rinate infectioLrs arthritis. quine can be safely used during pregnancy in most patients ln patients suspccted ot having lr joint inf'ection. a to reduce the risk for SLE flare or other complications and sy'no','ial biopsy (Option C) is rarell, necessaryi Syr.ulvial should be continued. biopsies may be helpfll in patients in r,r,hont concurrent Patients should be advised about the risks of preg- contiguous osteomyelitis or tubercukrsis (or infection with nancy in the setting of an SLE diagnosis (Option A), but arrother 5low grou'ing organism, such as a fungus) is a given this patient's excellent disease control, a careful diagnostic possibility. 'lhe paticrrt's shrtrt durati<ln olsymp decision to proceed with attempts to conceive would be toms nrakes concurrent ostcomyelitis or ir.rf'ection witl-r reasonable. slorv gror,.",ing organisms unlikell,. Although tulterculosis This patient's current medications (Option B) must be or fLngal infection callnot be absolutely excluded irr this changed before conception given the risk for teratogenicity patient receiving intr.nunosuppressallt clrugs. the first cliag, associated with mycophenolate mofetil. Azathioprine is the nostic test remains a synovial fluid analysis. A syr.rovial best option to control the patient's lupus nephritis and may biopsy may be consiclered in patients without an cstab be considered following a frank discussion with the patient lishecl diagnosis after joint f luicl analysis or those in rvhom regarding risks and beneflts and shared decision making. antibiotic therapy has failed. Patients who have SLE flares during pregnancy can be treated with prednisone or other glucocorticoids. If the risk rEY POIilIS for flare is considered high, empiric addition of low-dose . The abrupt onset of acute monoarticular inflamma- prednisone (Option C) could be considered, but this patient tory arthritis in any patient should suggest a joint currently has no indication for a glucocorticoid. infection. . In patients suspected of having infectious arthritis, ftY Pottrs the most important diagnostic procedure is expedi- . Systemic lupus erythematosus is associated with tious arthrocentesis to obtain joint fluid and conduct increased risk for miscarriage, premature delivery synovial fluid analysis (Gram stain, culture, leukocyte and other pregnancy complications. count, and crystal analysis). (Continued) 169

Answers and Critiques l(E? P0IXIS (onfinucdl 'lhe ACR conditionally recornmends against su,itching o Certain therapies used to treat systemic lupus ery- statill agents. such as aton,astirtilt. to fenoflbrate (Option C). I,'errofibrute has urate lowering ellects. but the ACR has thematosus, including mycophenolate mofetil, beli, deterrninecl that the risks (inclucling aclverse eff'ects of the mumab, and methotrexate, should be avoided in tnedication) outweigh potcntial benefits of sr,r,ilching among patients contemplating pregnancy becrruse they are patients u'ith gout. regarclless of clisease activitl: teratogenic; cyclophosphamide is associated with age- and dose-dependent infertility and should not XEY POIXIS be used in patients contemplating pregnancy . For patients with gout, the American College of without compelling life- or organ threatening Rheumatologz conditionally recommends switching indications. hydrochlorothiazide to an alternate antihypertensive agent when feasible. D Bibliography . For patients with gout, the American College of UI Lazzaroni MG, Dall'Ara F, Fredi M, et al. A comprehensive revieu, ot the clinical approach to pregnancy and systemic lupus erythematosus. J Rheumatologr conditionally recommends switching E (D Autoimmun. 2016;74:106 117. [PMID: 273774*l hydrochlorothiazide to losartan as an antihypertensive UI o, agent when feasible. CL n 4t tr Item 89 Answer: D Educational Objective: Treat gout by switching Bibliography Fitzcerald JD, Dalbeth N, Mikuls T. et al. 2020 American College of Rheumatolos/ guideline for the management of gout. Arthritis C:lre Res hydrochlorothiazide to losartan. (Hoboken). 2020;72:744 760. IPMID: 323919341 doi:10.1002r'acr.2,ll80 (D Ut lhe most appropriate treatment is to stop hl.drocl.rlorothia zide ancl start losartan (Option D). 'lhis patient has had a first Item 9O Answer: D episode of poclagra (gout of'tl.re gre:rt toe) treated efl'ectir.ely, Educational Objective: Diagnose rheumatoid arthritis with colchicine. He has a nrininrally elevated senul urate with appropriate imaging studies. level. Flvdrochlorothiazide lr.rd clther loop diuretics cluse hyperuricen.ria and miry have contributed to this gout epi The most appropriate next step in diagnosis is no lurther sode. l-osartan is an angiotensin receptor blocker that lray imaging (Option D). The history physical examination, l.tltre sorne uricosuric effect in adciition to lorvering bkrod and laboratory studies are all consistent with a diagnosis of pressure. For patients with gout. the Arnerican College of rheumatoid arthritis. Plain radiography of the hands and/or Rheun.rirblory (ACR) concli t ional h, reconr mends sr,r,itch i ng feet is the standard imaging study for rheumatoid arthritis hydroch krroth i azide to an irlt ernate anti hyperterlsive r,r,hen and can aid in diagnosis. Radiography ofthe hands and/or feasibte.'lire ACR also conditionalh' recornmends sr,vitchir.rg feet may also detect changes suggesting other diseases that to losartan prefbrentially as an antihypertensi\€ agent rvhen may mimic rheumatoid arthritis, such as psoriatic arthri t'easibtc. Although this patient has had rlnly a single flure. tis, spondyloarthritis, gout, or chondrocalcinosis. Although nrodifying his iatrogenic risk factors for gout is reasorrable early radiographs may be normal, this patient has the typi at this time. cal radiographic changes of rheumatoid arthritis, including Alkrpurinol (Option A) is a urate kxrering lgent. but periarticular osteopenia. marginal erosions, and joint-space this therapy is r.rot inclicated after rr single gout episode in a narrowing. These radiographic flndings add to the diagnostic pltienl rvithont tophi or radiographic damage. Urate lor,rerir.rg certainty that the patient has rheumatoid arthritis and are therapy is strorrgly recomrnended by the ACR fbr patients helpful not only in establishing the diagnosis but in moni with one or more subcutaneous topl-ri: evidence <tf raclio toring the course ofthe disease. graphic damage (an1- ntodality) attributable to gouti or fie Bone scanning (Option A) has no diagnostic value in quenl gout llares. with "fiecluent" being definecl ils two or rheumatoid arthritis and is not used in evaluation of this rnore iurnually. Urate lou,ering therripl,' is conclitionallt, rec disease. No speciflc flndings on bone scanning would point ommencied filr patients erperiencing their first flare when to the diagnosis of rheumatoid arthritis. moderate to severe chronic kidnel, disease (stage 213). serr_rm In the setting of characteristic features of rheuma- urate concentralion greater than 9.0 mgidl_ (0.511 nrrnoliL), toid arthritis seen on plain radiographs, MRI of the hands or urolithiasis is present. (Option B) has no additional diagnostic value. Although MRI l.irr patients with gor-rt. the A(.R conditionirlly recolll- can show flndings that cannot be visualized on plain radio- nrends against aclding vitamin C sr-rpplententation (Option graphs, such as bone edema and inflammatory synovitis. B) to decrease serulr urate levels. The ACR conclr.rdecl tl.rat these are not diagnostic of rheumatoid arthritis and are not clrrta on vitanlin C wcre insufficierrt to sLlpport continued needed to confirm the diagnosis. recornrnendation of its usc in paticnts rt'itlt gout. Tu'o stud Musculoskeletal ultrasonography (Option C) has ies showed clinically insignificant changes in senlm urlte gained popularity in the diagnosis and treatment of rheu- concentrations fbr patients rvith gout taking vitantin C sup matoid arthritis because it is noninvasive and may demon plementation. strate a variety ofsoft-tissue flndings not visualized on plain

l(E? P0IXIS (onfinucdl 'lhe ACR conditionally recornmends against su,itching o Certain therapies used to treat systemic lupus ery- statill agents. such as aton,astirtilt. to fenoflbrate (Option C). I,'errofibrute has urate lowering ellects. but the ACR has thematosus, including mycophenolate mofetil, beli, deterrninecl that the risks (inclucling aclverse eff'ects of the mumab, and methotrexate, should be avoided in tnedication) outweigh potcntial benefits of sr,r,ilching among patients contemplating pregnancy becrruse they are patients u'ith gout. regarclless of clisease activitl: teratogenic; cyclophosphamide is associated with age- and dose-dependent infertility and should not XEY POIXIS be used in patients contemplating pregnancy . For patients with gout, the American College of without compelling life- or organ threatening Rheumatologz conditionally recommends switching indications. hydrochlorothiazide to an alternate antihypertensive agent when feasible. D Bibliography . For patients with gout, the American College of UI Lazzaroni MG, Dall'Ara F, Fredi M, et al. A comprehensive revieu, ot the clinical approach to pregnancy and systemic lupus erythematosus. J Rheumatologr conditionally recommends switching E (D Autoimmun. 2016;74:106 117. [PMID: 273774*l hydrochlorothiazide to losartan as an antihypertensive UI o, agent when feasible. CL n 4t tr Item 89 Answer: D Educational Objective: Treat gout by switching Bibliography Fitzcerald JD, Dalbeth N, Mikuls T. et al. 2020 American College of Rheumatolos/ guideline for the management of gout. Arthritis C:lre Res hydrochlorothiazide to losartan. (Hoboken). 2020;72:744 760. IPMID: 323919341 doi:10.1002r'acr.2,ll80 (D Ut lhe most appropriate treatment is to stop hl.drocl.rlorothia zide ancl start losartan (Option D). 'lhis patient has had a first Item 9O Answer: D episode of poclagra (gout of'tl.re gre:rt toe) treated efl'ectir.ely, Educational Objective: Diagnose rheumatoid arthritis with colchicine. He has a nrininrally elevated senul urate with appropriate imaging studies. level. Flvdrochlorothiazide lr.rd clther loop diuretics cluse hyperuricen.ria and miry have contributed to this gout epi The most appropriate next step in diagnosis is no lurther sode. l-osartan is an angiotensin receptor blocker that lray imaging (Option D). The history physical examination, l.tltre sorne uricosuric effect in adciition to lorvering bkrod and laboratory studies are all consistent with a diagnosis of pressure. For patients with gout. the Arnerican College of rheumatoid arthritis. Plain radiography of the hands and/or Rheun.rirblory (ACR) concli t ional h, reconr mends sr,r,itch i ng feet is the standard imaging study for rheumatoid arthritis hydroch krroth i azide to an irlt ernate anti hyperterlsive r,r,hen and can aid in diagnosis. Radiography ofthe hands and/or feasibte.'lire ACR also conditionalh' recornmends sr,vitchir.rg feet may also detect changes suggesting other diseases that to losartan prefbrentially as an antihypertensi\€ agent rvhen may mimic rheumatoid arthritis, such as psoriatic arthri t'easibtc. Although this patient has had rlnly a single flure. tis, spondyloarthritis, gout, or chondrocalcinosis. Although nrodifying his iatrogenic risk factors for gout is reasorrable early radiographs may be normal, this patient has the typi at this time. cal radiographic changes of rheumatoid arthritis, including Alkrpurinol (Option A) is a urate kxrering lgent. but periarticular osteopenia. marginal erosions, and joint-space this therapy is r.rot inclicated after rr single gout episode in a narrowing. These radiographic flndings add to the diagnostic pltienl rvithont tophi or radiographic damage. Urate lor,rerir.rg certainty that the patient has rheumatoid arthritis and are therapy is strorrgly recomrnended by the ACR fbr patients helpful not only in establishing the diagnosis but in moni with one or more subcutaneous topl-ri: evidence <tf raclio toring the course ofthe disease. graphic damage (an1- ntodality) attributable to gouti or fie Bone scanning (Option A) has no diagnostic value in quenl gout llares. with "fiecluent" being definecl ils two or rheumatoid arthritis and is not used in evaluation of this rnore iurnually. Urate lou,ering therripl,' is conclitionallt, rec disease. No speciflc flndings on bone scanning would point ommencied filr patients erperiencing their first flare when to the diagnosis of rheumatoid arthritis. moderate to severe chronic kidnel, disease (stage 213). serr_rm In the setting of characteristic features of rheuma- urate concentralion greater than 9.0 mgidl_ (0.511 nrrnoliL), toid arthritis seen on plain radiographs, MRI of the hands or urolithiasis is present. (Option B) has no additional diagnostic value. Although MRI l.irr patients with gor-rt. the A(.R conditionirlly recolll- can show flndings that cannot be visualized on plain radio- nrends against aclding vitamin C sr-rpplententation (Option graphs, such as bone edema and inflammatory synovitis. B) to decrease serulr urate levels. The ACR conclr.rdecl tl.rat these are not diagnostic of rheumatoid arthritis and are not clrrta on vitanlin C wcre insufficierrt to sLlpport continued needed to confirm the diagnosis. recornrnendation of its usc in paticnts rt'itlt gout. Tu'o stud Musculoskeletal ultrasonography (Option C) has ies showed clinically insignificant changes in senlm urlte gained popularity in the diagnosis and treatment of rheu- concentrations fbr patients rvith gout taking vitantin C sup matoid arthritis because it is noninvasive and may demon plementation. strate a variety ofsoft-tissue flndings not visualized on plain 170

I Answers and Critiques \ t radiographs. However, similar to MRI, when diagnostic fea supporting evidence is otten not s<lught because ot t'ost ancl I tures of rheumatoid arthritis are seen on plain radiographs, lack o{'efll'ct on therapy or prognosis' in this patient with I lrthralgia, cytopcrtirt, ar.rtl llossible kidne-v" tlisease. SI-E is musculoskeletal ultrasonography is not needed to confirm \ I the diagnosis. high rin the list of clilgnostic possibilities. irnd a positive SLll cliirgnosis r,rould exclude idiopath ic pcricarditis. \ I XEY POI l{TS o Plain radiography of the hands and/or feet is a stan I(EY POIIIT \ dard imaging study for rheumatoid arthritis and can o Pericarditis is a relatively common manifestation of \ I detect typical radiographic changes, including periar systemic lupus erythematosus that can be asympto ticular osteopenia, marginal erosions, and joint-space matic (most commonly) or can cause chest pain and r myopericarditis. narrowing. L . Hand and/or feet radiography can detect changes sug Bibliography UI gesting other diseases that may mimic rheumatoid (l, t Dein E. DouglasI I. Petri l\,1. et al. Pericarditis in lupus. Cureus. 2019:11:e4166 3 arthritis, such as psoriatic arthritis, spondyloarthritis, IPMID: 310867511 ET : I gout. or chondrocalcinosis. (J \ Item 92 Answer: C t, Bibliography .9 Shiraishi M, Irukuda T. Igarashi T. et al. Differentiating rheumrtoid and Ed u cati o na I O bj ective : Diagnose rclapsing polychondritis. UI : psoriatic arthritis of the hand: multimodality imaging characteristics. (l, I Rxdiographics. 2020 Sep Oct:,10:1339 1354. [PMID: i27351741 The most likely diagnosis is relapsing polychondritis (Option B vl \ C). This patient has a chronic inflammatory disease involv c ing the cartilage (but not noncartilaginous structures) ofthe tr Item 91 Answer: D Edu cational Objective: Diagnose systemic lupus ears, nasal bridge (saddle nose deformity), joints, and tra chea. as well as involvement of the connective tissue of the i erythematosus as the cause ofacute pericarditis. eye. Hearing loss is likely related to inflammation of the car 'lhe mosl lil<ely cause ol 1his patient's pcricrrditis is systemic tilage of the middle ear. Because relapsing polychondritis is i lupus cn,thcrnatosus (Sl.fl) (Option D). 'lhe nranv possible a clinical diagnosis for which no speciflc tests exist (although I causcs of' acute pericarditis includc idiopathic pericarditis, certain autoantibodies, including those to lype 2 collagen, irrlt'ction. nredications. neolrlasm. injury fiom trrluma or may be supportive), other causes should be considered and ischcnria. rncl irutoirnrnune irnd inf lanrmatory diseases. Fac ruled out as appropriate. Management depends on severit5z: tors that suggest SLli as the cituse ol't his patit:nt's pericarditis NSAIDs and dapsone for mild symptoms and high dose glu inclucle joint s,,velling, eviclence of' lrossiblc l<idney cliseasc, cocorticoids for initial management of acute and/or severe ancl cytopcnias. particularly thrornbocykrpeniir. All of these involvement. Oral immunosuppressants (e.g., methotrexate) arc scen in Sl.Fl. Pericarditis is a relatively colrmon manif'es may be added. The tumor necrosis factor inhibitors inflix- tation ol SLli ancl can be asynrptorllatic (rnosl conrmonly) or imab and adalimumab and the anti-interleukin 6 agent can ci"luse chcst pain rnd myollericarditis; tlrnponacle is rare. tocilizumab may also be effective. Aclnlt onset Still disease (Option A) is another rheu Like relapsing polychondritis, cryoglobulinemia mrrtologic cliagnosis that can present u,ith Icver. synovitis. (Option A) can affect the ears and nose. However, cryoglob irncl serclsitis. including acute pericarclitis. Ilowever, patients ulinemic involvement of these tissues is typically ischemic/ lrrith aclult onset Still disease gencrally havc high platelet necrotic rather than inflammatory and usually affects the coLlnts. suggcsting a generalized inllanrmatorv statc. Many tip rather than the bridge of the nose. Cryoglobulinemia paticnts irlso have a rash thirt occurs ltrith ltvcrs. Thcse fea can affect the lungs but not the trachea. Moreover, most trlres are nol present in tl-ris patier-rt. cryoglobulinemias (excepting type I cryoglobulinemia) are (loxsackievirus (Option B) is onc of the nrost common secondary to hepatitis C virus infection or primary autoim infbctious lgcrrts tlut can cruse acute pericarclitis: as rtith mune disease; testing for hepatitis C virus and autoimmune milnt'other pathogens, it cirn also cause fevers and musculo antibodies can be considered. ske le tal p:rin. It woulcl be reasonablc to considcr coxsackievi Like relapsing polychondritis, granulomatosis with rus irrlection. but he lacks other features suc'h ls exanthem. polyangiitis (GPA) (Option B) can afiect the upper and lower oropharyngell lesions, ancl nreningitic or encephalitic symp airways, ears, and eyes and can cause a saddle nose defor toms. \,'iral infbctions can cause ll,mphopc'uia, but <lther mity. It can also cause arthralgia, although the arthralgia is finclings prescnt in this paticnt. including thrombocytopenia usually migratory. However, GPA involvement of the lungs ancl rbnornral urinalysis, wonld r.rol bc expected with a viral is typically parenchymal and does not involve the trachea. intbction. Because 90'7, of patients with GPA are positive for antipro Although most cases of acute pericarclitis lre icliopatl.ric teinase 3 antibodies, testing can be considered. (Option C), a search fbr otl.rer causes is appropriate; a cause Rheumatoid arthritis (Option D) can involve the is tirund in about 16')ti, of patients. lhe cause of isolated ircute knees symmetrically and in severe presentations can pericarditis in most patients is presunted to be viral, but cause a systemic illness that involves the eyes and glottis

I Answers and Critiques \ t radiographs. However, similar to MRI, when diagnostic fea supporting evidence is otten not s<lught because ot t'ost ancl I tures of rheumatoid arthritis are seen on plain radiographs, lack o{'efll'ct on therapy or prognosis' in this patient with I lrthralgia, cytopcrtirt, ar.rtl llossible kidne-v" tlisease. SI-E is musculoskeletal ultrasonography is not needed to confirm \ I the diagnosis. high rin the list of clilgnostic possibilities. irnd a positive SLll cliirgnosis r,rould exclude idiopath ic pcricarditis. \ I XEY POI l{TS o Plain radiography of the hands and/or feet is a stan I(EY POIIIT \ dard imaging study for rheumatoid arthritis and can o Pericarditis is a relatively common manifestation of \ I detect typical radiographic changes, including periar systemic lupus erythematosus that can be asympto ticular osteopenia, marginal erosions, and joint-space matic (most commonly) or can cause chest pain and r myopericarditis. narrowing. L . Hand and/or feet radiography can detect changes sug Bibliography UI gesting other diseases that may mimic rheumatoid (l, t Dein E. DouglasI I. Petri l\,1. et al. Pericarditis in lupus. Cureus. 2019:11:e4166 3 arthritis, such as psoriatic arthritis, spondyloarthritis, IPMID: 310867511 ET : I gout. or chondrocalcinosis. (J \ Item 92 Answer: C t, Bibliography .9 Shiraishi M, Irukuda T. Igarashi T. et al. Differentiating rheumrtoid and Ed u cati o na I O bj ective : Diagnose rclapsing polychondritis. UI : psoriatic arthritis of the hand: multimodality imaging characteristics. (l, I Rxdiographics. 2020 Sep Oct:,10:1339 1354. [PMID: i27351741 The most likely diagnosis is relapsing polychondritis (Option B vl \ C). This patient has a chronic inflammatory disease involv c ing the cartilage (but not noncartilaginous structures) ofthe tr Item 91 Answer: D Edu cational Objective: Diagnose systemic lupus ears, nasal bridge (saddle nose deformity), joints, and tra chea. as well as involvement of the connective tissue of the i erythematosus as the cause ofacute pericarditis. eye. Hearing loss is likely related to inflammation of the car 'lhe mosl lil<ely cause ol 1his patient's pcricrrditis is systemic tilage of the middle ear. Because relapsing polychondritis is i lupus cn,thcrnatosus (Sl.fl) (Option D). 'lhe nranv possible a clinical diagnosis for which no speciflc tests exist (although I causcs of' acute pericarditis includc idiopathic pericarditis, certain autoantibodies, including those to lype 2 collagen, irrlt'ction. nredications. neolrlasm. injury fiom trrluma or may be supportive), other causes should be considered and ischcnria. rncl irutoirnrnune irnd inf lanrmatory diseases. Fac ruled out as appropriate. Management depends on severit5z: tors that suggest SLli as the cituse ol't his patit:nt's pericarditis NSAIDs and dapsone for mild symptoms and high dose glu inclucle joint s,,velling, eviclence of' lrossiblc l<idney cliseasc, cocorticoids for initial management of acute and/or severe ancl cytopcnias. particularly thrornbocykrpeniir. All of these involvement. Oral immunosuppressants (e.g., methotrexate) arc scen in Sl.Fl. Pericarditis is a relatively colrmon manif'es may be added. The tumor necrosis factor inhibitors inflix- tation ol SLli ancl can be asynrptorllatic (rnosl conrmonly) or imab and adalimumab and the anti-interleukin 6 agent can ci"luse chcst pain rnd myollericarditis; tlrnponacle is rare. tocilizumab may also be effective. Aclnlt onset Still disease (Option A) is another rheu Like relapsing polychondritis, cryoglobulinemia mrrtologic cliagnosis that can present u,ith Icver. synovitis. (Option A) can affect the ears and nose. However, cryoglob irncl serclsitis. including acute pericarclitis. Ilowever, patients ulinemic involvement of these tissues is typically ischemic/ lrrith aclult onset Still disease gencrally havc high platelet necrotic rather than inflammatory and usually affects the coLlnts. suggcsting a generalized inllanrmatorv statc. Many tip rather than the bridge of the nose. Cryoglobulinemia paticnts irlso have a rash thirt occurs ltrith ltvcrs. Thcse fea can affect the lungs but not the trachea. Moreover, most trlres are nol present in tl-ris patier-rt. cryoglobulinemias (excepting type I cryoglobulinemia) are (loxsackievirus (Option B) is onc of the nrost common secondary to hepatitis C virus infection or primary autoim infbctious lgcrrts tlut can cruse acute pericarclitis: as rtith mune disease; testing for hepatitis C virus and autoimmune milnt'other pathogens, it cirn also cause fevers and musculo antibodies can be considered. ske le tal p:rin. It woulcl be reasonablc to considcr coxsackievi Like relapsing polychondritis, granulomatosis with rus irrlection. but he lacks other features suc'h ls exanthem. polyangiitis (GPA) (Option B) can afiect the upper and lower oropharyngell lesions, ancl nreningitic or encephalitic symp airways, ears, and eyes and can cause a saddle nose defor toms. \,'iral infbctions can cause ll,mphopc'uia, but <lther mity. It can also cause arthralgia, although the arthralgia is finclings prescnt in this paticnt. including thrombocytopenia usually migratory. However, GPA involvement of the lungs ancl rbnornral urinalysis, wonld r.rol bc expected with a viral is typically parenchymal and does not involve the trachea. intbction. Because 90'7, of patients with GPA are positive for antipro Although most cases of acute pericarclitis lre icliopatl.ric teinase 3 antibodies, testing can be considered. (Option C), a search fbr otl.rer causes is appropriate; a cause Rheumatoid arthritis (Option D) can involve the is tirund in about 16')ti, of patients. lhe cause of isolated ircute knees symmetrically and in severe presentations can pericarditis in most patients is presunted to be viral, but cause a systemic illness that involves the eyes and glottis 171

Answers and Critiques (cricoarytenoid joints). However, it does not typically Pantoprazole, a proton pump inhibitor, is useful for affect the ears or trachea. This patient also lacks the classic gastrointestinal reflux disease. This patient's reflux disease is l symmetric polyarthritis of the hands, and his knee pain stable: flurther reducing gastric acid production by increas : severity is not commensurate with severe rheumatoid ing the pantoprazole dosage (Option C) may contribute to arthritis. bacterial overgrowth and may worsen the problem. TEY POIf,I Loperamide (Option D), an opioid agonist, will slow intestinal motility further and potentially worsen SIBO. . Relapsing polychondritis is a chronic inflammatory disease involving the cartilage (but not noncartilagi- TEY POII'IS nous structures) ofthe ears, nasal bridge (saddle nose o Small intestinal bacterial overgrowth affects patients deformity), joints, and trachea, as well as involvement with systemic sclerosis, causing diarrhea, abdominal of the connective tissue of the eye. pain, bloating, and nausea. D r Small intestinal bacterial overgrowth is best treated tt Bibliography with monthly antibiotics in a rotating fashion to E o Borgia F. Ciuffrida R, Guarneri F, et al. Relapsing polychondritis: an updated review. Biomedicines. 2018r6. IPMID: 3007259t]l decrease the bacterial load in the small intestine. Ut o, Bibliography EL a.l Item 93 Answer: B lblkou,ska Pruszynska B, Gerkowicz A. Szczepanik Kulak P et al. Small intestinal bacterial overgrowth in systemic sclerosis: a revie\\'of the liI Educational Objective: Treat small intestinal bacterial erature. Arch Dermatol Res. 2o191311:l 8. IPMID, 30382339] doi:lo.loo7, a overgrowth in a patient with dilluse cutaneous systemic s00'10:l 018 1874 0 E (D Ut sclerosis.

(cricoarytenoid joints). However, it does not typically Pantoprazole, a proton pump inhibitor, is useful for affect the ears or trachea. This patient also lacks the classic gastrointestinal reflux disease. This patient's reflux disease is l symmetric polyarthritis of the hands, and his knee pain stable: flurther reducing gastric acid production by increas : severity is not commensurate with severe rheumatoid ing the pantoprazole dosage (Option C) may contribute to arthritis. bacterial overgrowth and may worsen the problem. TEY POIf,I Loperamide (Option D), an opioid agonist, will slow intestinal motility further and potentially worsen SIBO. . Relapsing polychondritis is a chronic inflammatory disease involving the cartilage (but not noncartilagi- TEY POII'IS nous structures) ofthe ears, nasal bridge (saddle nose o Small intestinal bacterial overgrowth affects patients deformity), joints, and trachea, as well as involvement with systemic sclerosis, causing diarrhea, abdominal of the connective tissue of the eye. pain, bloating, and nausea. D r Small intestinal bacterial overgrowth is best treated tt Bibliography with monthly antibiotics in a rotating fashion to E o Borgia F. Ciuffrida R, Guarneri F, et al. Relapsing polychondritis: an updated review. Biomedicines. 2018r6. IPMID: 3007259t]l decrease the bacterial load in the small intestine. Ut o, Bibliography EL a.l Item 93 Answer: B lblkou,ska Pruszynska B, Gerkowicz A. Szczepanik Kulak P et al. Small intestinal bacterial overgrowth in systemic sclerosis: a revie\\'of the liI Educational Objective: Treat small intestinal bacterial erature. Arch Dermatol Res. 2o191311:l 8. IPMID, 30382339] doi:lo.loo7, a overgrowth in a patient with dilluse cutaneous systemic s00'10:l 018 1874 0 E (D Ut sclerosis. The most appropriate treatment is ciprofloxacin (Option Item 94 Answer: A B). This patient is experiencing the manifestations of small intestinal bacterial overgrowth (SIBO), which affects 39'l, Ed u catio na I Obj ective : Diagnose ankylosing spondylitis. of patients with systemic sclerosis. SIBO occurs in both the The most appropriate diagnostic test to perform next is limited and diffuse cutaneous forms of systemic sclerosis. anteroposterior radiography of the pelvis (Option A). This The most frequent symptoms include diarrhea, abdominal patient has had classic inflammatory low back pain for pain, bloating, and nausea. The diarrhea is often explosive several years. Flexion, external rotation, and abduction of and typically follows a meal. Over time, SIBO can lead to the hips elicit pain in this patient's right hip as well as lor,r' malabsorption, malnutrition, and weight loss. Jejunal aspi back pain. These flndings, along with involvement of the rate is considered the gold standard but is often not used in right hip, suggest ankylosing spondylitis (AS). This patient clinical practice because ofthe requirement for endoscopy was diagnosed with uveitis. Spondyloarthritis accounts to obtain cultures and the patchy nature of small intesti for approximately 40'l" of cases of acute anterior uveitis nal overgrowth. Glucose and lactulose breath tests have in the United States, and most of these patients will have acceptable speciflcity (around B0'/,) but poor sensitivity AS. Acute anterior uveitis has been reported to affect 27'f,' (30'/,, 40"1,) fbr diagnosing SIBO. Diagnosis requires typi of patients with AS and rarely causes permanent visual cal symptoms and a confirmatory test, although empiric damage. antibiotic therapy with monitoring for improvement in An antinuclear antibody test (Option B) can help symptoms may be reasonable in patients with a high prob evaluate for autoimmune diseases, such as systemic lupus ability of SIBO, such as this patient. The protocol is to a ery.thematosus, but these diseases rarely cause uveitis. More take a different antibiotic with activity against bowel flora over, the patient's inflammatory back pain symptoms and (e.g., ciprofloxacin, doxycycline, amoxicillin/clavulanic right hip restriction of motion are more compatible with acid, and rifaximin) for the flrst 10 days of the month for a spondyloarthropathy than an autoantibody associated 4 months. Systemic sclerosis affects both smooth muscle rheumatologic disease. and autonomic nerves and leads to small intestine hypo The prevalence of AS in the HLA B27 positive popula motility. Hypomotility results in food and liquid stasis, tion is only about 5'2,; positive results for HLA B27 may be which then fosters bacterial overgrowth. SIBO also causes absent in up to 15'1, of patients with confirmed AS. There bile acid deconjugation, leading to dietary malabsorption fore, HLA-B27 testing (Option C) cannot independently con of fats and fat soluble vitamins. A low lat diet may help flrm or exclude a diagnosis of AS. According to Assessment reduce the intensity ofthe diarrhea. of SpondyloArthritis international Society (ASAS) criteria, Cholestyramine (Option A) is often prescribed for bile HLA-827 positivity would be helpful if the pelvis radiograph acid diarrhea following limited ileal resection, after abdom. is normal in a patient with high likelihood of AS. The pres inal radiation therapy, or for postcholecystectomy diarrhea. ence of back pain plus HLA-B27 positivity plus two other Patients with SIBO have bile acid insufficiency, and treat features of spondyloarthritis (in this case, uveitis and hip ment with a bile acid binding resin, such as cholestyramine, arthritis) would classifz this patient's disease as an axial is likely to worsen this patient's symptoms. spondyloarthritis.

The most appropriate treatment is ciprofloxacin (Option Item 94 Answer: A B). This patient is experiencing the manifestations of small intestinal bacterial overgrowth (SIBO), which affects 39'l, Ed u catio na I Obj ective : Diagnose ankylosing spondylitis. of patients with systemic sclerosis. SIBO occurs in both the The most appropriate diagnostic test to perform next is limited and diffuse cutaneous forms of systemic sclerosis. anteroposterior radiography of the pelvis (Option A). This The most frequent symptoms include diarrhea, abdominal patient has had classic inflammatory low back pain for pain, bloating, and nausea. The diarrhea is often explosive several years. Flexion, external rotation, and abduction of and typically follows a meal. Over time, SIBO can lead to the hips elicit pain in this patient's right hip as well as lor,r' malabsorption, malnutrition, and weight loss. Jejunal aspi back pain. These flndings, along with involvement of the rate is considered the gold standard but is often not used in right hip, suggest ankylosing spondylitis (AS). This patient clinical practice because ofthe requirement for endoscopy was diagnosed with uveitis. Spondyloarthritis accounts to obtain cultures and the patchy nature of small intesti for approximately 40'l" of cases of acute anterior uveitis nal overgrowth. Glucose and lactulose breath tests have in the United States, and most of these patients will have acceptable speciflcity (around B0'/,) but poor sensitivity AS. Acute anterior uveitis has been reported to affect 27'f,' (30'/,, 40"1,) fbr diagnosing SIBO. Diagnosis requires typi of patients with AS and rarely causes permanent visual cal symptoms and a confirmatory test, although empiric damage. antibiotic therapy with monitoring for improvement in An antinuclear antibody test (Option B) can help symptoms may be reasonable in patients with a high prob evaluate for autoimmune diseases, such as systemic lupus ability of SIBO, such as this patient. The protocol is to a ery.thematosus, but these diseases rarely cause uveitis. More take a different antibiotic with activity against bowel flora over, the patient's inflammatory back pain symptoms and (e.g., ciprofloxacin, doxycycline, amoxicillin/clavulanic right hip restriction of motion are more compatible with acid, and rifaximin) for the flrst 10 days of the month for a spondyloarthropathy than an autoantibody associated 4 months. Systemic sclerosis affects both smooth muscle rheumatologic disease. and autonomic nerves and leads to small intestine hypo The prevalence of AS in the HLA B27 positive popula motility. Hypomotility results in food and liquid stasis, tion is only about 5'2,; positive results for HLA B27 may be which then fosters bacterial overgrowth. SIBO also causes absent in up to 15'1, of patients with confirmed AS. There bile acid deconjugation, leading to dietary malabsorption fore, HLA-B27 testing (Option C) cannot independently con of fats and fat soluble vitamins. A low lat diet may help flrm or exclude a diagnosis of AS. According to Assessment reduce the intensity ofthe diarrhea. of SpondyloArthritis international Society (ASAS) criteria, Cholestyramine (Option A) is often prescribed for bile HLA-827 positivity would be helpful if the pelvis radiograph acid diarrhea following limited ileal resection, after abdom. is normal in a patient with high likelihood of AS. The pres inal radiation therapy, or for postcholecystectomy diarrhea. ence of back pain plus HLA-B27 positivity plus two other Patients with SIBO have bile acid insufficiency, and treat features of spondyloarthritis (in this case, uveitis and hip ment with a bile acid binding resin, such as cholestyramine, arthritis) would classifz this patient's disease as an axial is likely to worsen this patient's symptoms. spondyloarthritis. 172

Answers and ues MRI of the sacroiliac joint (Option D) can identify sac also be considered if diagnostic unccrlainty remains. Bkrod roiliac inflammation even in the absence of radiographic pressure managemellt with labetalol would be inclicatecl lor changes. However, 25')1, of healthy individuals can have MRI systolic blood pressure of. l60 nrnr Hg or grcater <lr diastolic changes that meet criteria for sacroiliitis, and up to 47"/,, of bkxrd pressurc of 110 mm I lg or greater. persons who regularly participate in impact loading athlet lntralenous cyclophospharnide (Option A) r'voulcl be ics may have similar MRI changes. The extent of involvement a reasonable consiclcratiotl fbr treatmellt o1 a flirre of lupus and presence of erosions on MRI increase the speciflcity of ncphritis in a nonpregt.tant patient. In screre cases. cyclophos the result. However, plain radiography remains the corner phamide could be considcred itl pregnancy afler tlle first tri stone of radiographic diagnosis in spondyloarthritis and nresler bLlt is zrssociated rvith an illcreasecl risk fbr fetal detnise. 'Ihe best treatmcnt fbr preeclampsia is clelivery (Option has sufficient specificity to confirm a diagnosis. Sacroiliitis shown by MRI is included in the ASAS classification criteria B) if the baby is adecluately n1atLlre. Al 26 r,t'eeks. this letus is and would be useful ilthe plain radiograph was normal. In not adequatelv mature lbr delivcry I)elivery is lil<cly ttl lead this case, checking HLA P27 antigen would be more cost- to little ur no improvemcnt in her lupus nephritis; other UI 6' effective lor classiflcation as an axial spondyloarthritis if the therapies are rrcedecl. ET plain radiograph was normal. Plain radiography is the initial lntravenous magnesium sulfate (Option C) can be used L. imaging choice in patients suspected olhaving AS because of to pre.ucnt seizures in preeclanrpsia ancl rrigl.rt be appro (J its relatively low cost and safety. priate trcatmer.rt if this patient's findings were related to preeclampsiir rathcr thart SLfi. Ir-r sonle cllses, it rlll' be t =l .E XEY POIilTt t,l lppl'opriate to treat lbr both cortditions. . Spondyloarthritis accounts for BS'X, ofcases ofacute o XEY POIf,IS B tt anterior uveitis in the United States, and most of these patients will have ankylosing spondylitis. o In pregnant women, differentiating a flare of lupus o Anteroposterior radiography of the pelvis is the nephritis from preeclampsia can be difficult; a lupus initial imaging examination for suspected ankylosing flare may be identified by rising anti-double-stranded DNA antibody titers and falling complement levels. spondylitis. o In a pregnant patient with a life or organ threatening Bibliography flare of systemic lupus erythematosus, first-line treat- Mandl P, Nxvarro Compdn V, Terslev L, et alr l.)uropern League Agtinst ment is the addition of glucocorticoid therapy. Rheumatism (tlULAR). IjULAR recomnrendations lbr the use of imalling in the diagnosis rnd managenrcnt of spondvkr:rrthritis in clinical prac tice. Ann Rheum Dis.2015;74:1327 39. IPMID:258371481 Bibliography Lazzaroni MG. Dall'Ara H Fredi M. et al. A comprehensive review of the clinicirl approlch to pregnancy and systemic lupus erythematosus. J Autoinrmun. ')016;74:106 ll7. [PM]l): 273774fi1 \

MRI of the sacroiliac joint (Option D) can identify sac also be considered if diagnostic unccrlainty remains. Bkrod roiliac inflammation even in the absence of radiographic pressure managemellt with labetalol would be inclicatecl lor changes. However, 25')1, of healthy individuals can have MRI systolic blood pressure of. l60 nrnr Hg or grcater <lr diastolic changes that meet criteria for sacroiliitis, and up to 47"/,, of bkxrd pressurc of 110 mm I lg or greater. persons who regularly participate in impact loading athlet lntralenous cyclophospharnide (Option A) r'voulcl be ics may have similar MRI changes. The extent of involvement a reasonable consiclcratiotl fbr treatmellt o1 a flirre of lupus and presence of erosions on MRI increase the speciflcity of ncphritis in a nonpregt.tant patient. In screre cases. cyclophos the result. However, plain radiography remains the corner phamide could be considcred itl pregnancy afler tlle first tri stone of radiographic diagnosis in spondyloarthritis and nresler bLlt is zrssociated rvith an illcreasecl risk fbr fetal detnise. 'Ihe best treatmcnt fbr preeclampsia is clelivery (Option has sufficient specificity to confirm a diagnosis. Sacroiliitis shown by MRI is included in the ASAS classification criteria B) if the baby is adecluately n1atLlre. Al 26 r,t'eeks. this letus is and would be useful ilthe plain radiograph was normal. In not adequatelv mature lbr delivcry I)elivery is lil<cly ttl lead this case, checking HLA P27 antigen would be more cost- to little ur no improvemcnt in her lupus nephritis; other UI 6' effective lor classiflcation as an axial spondyloarthritis if the therapies are rrcedecl. ET plain radiograph was normal. Plain radiography is the initial lntravenous magnesium sulfate (Option C) can be used L. imaging choice in patients suspected olhaving AS because of to pre.ucnt seizures in preeclanrpsia ancl rrigl.rt be appro (J its relatively low cost and safety. priate trcatmer.rt if this patient's findings were related to preeclampsiir rathcr thart SLfi. Ir-r sonle cllses, it rlll' be t =l .E XEY POIilTt t,l lppl'opriate to treat lbr both cortditions. . Spondyloarthritis accounts for BS'X, ofcases ofacute o XEY POIf,IS B tt anterior uveitis in the United States, and most of these patients will have ankylosing spondylitis. o In pregnant women, differentiating a flare of lupus o Anteroposterior radiography of the pelvis is the nephritis from preeclampsia can be difficult; a lupus initial imaging examination for suspected ankylosing flare may be identified by rising anti-double-stranded DNA antibody titers and falling complement levels. spondylitis. o In a pregnant patient with a life or organ threatening Bibliography flare of systemic lupus erythematosus, first-line treat- Mandl P, Nxvarro Compdn V, Terslev L, et alr l.)uropern League Agtinst ment is the addition of glucocorticoid therapy. Rheumatism (tlULAR). IjULAR recomnrendations lbr the use of imalling in the diagnosis rnd managenrcnt of spondvkr:rrthritis in clinical prac tice. Ann Rheum Dis.2015;74:1327 39. IPMID:258371481 Bibliography Lazzaroni MG. Dall'Ara H Fredi M. et al. A comprehensive review of the clinicirl approlch to pregnancy and systemic lupus erythematosus. J Autoinrmun. ')016;74:106 ll7. [PM]l): 273774fi1 \ tr Item 95 Answer: D Educational Objective: Treat a flare of systemic lupus erythematosus during pregnancy. Item 96 Answer: A a Educational Objective: Diagnose hemochromatosis as a The lnost appropriatc marlagenrent is prednisonc (Option cause of secondary osteoarthritis. D). I rngrkgid, to trext a llare o( systernic lupus erythentirto sus (SI-h-) durirrg pregnanc): An St-E fhre during pregnancy The most appropriate diagnostic test to perform next is HFE carr be difficult to clistinguish fiorn precchntpsia. (lonrnron gene testing (Option A). Underlying disorders can predis I'eatures inclucle proteinuria u'ith hl,perterrsion ancl ederna pose patients to the development ofsecondary osteoarthritis as well ls heaclachcs and othcr nonspecific svntptolrs. (OA) and should be suspected when OA occurs at an early Thronrbocy'topenia is ir relltively conlnlon feature oISLE but age or involves joints not typical for OA, such as the meta is also sect.t with preeclampsia, cspecially with progression carpophalangeal (MCP) or shoulder joints. Hereditary hemo to the HF.l.l.P (llcmoll'sis. Iilerratecl Lir:cr enz_r,mes. and l.on chromatosis can be associated with an arthropathy that Platelets) syndrome. Clues to an Sl"Fl f lare include rnarkcrs causes symptoms of arthritis, arthralgia, and accompanying of lupus activitli snch as rising anti ckruble strirnrled I)NA radiologic findings. These patients particularly develop OA in antil)ody titers and falling serunt contplement levels. 'll.re the hands, where characteristic hook like osteophytes com serunr urate level is often cler,ated ir-r preeclarlpsiu but not monly in the second and third MCP joints and sometimes in Sl,E tlares. this patient's clinicirl features suggest a f lare the fourth MCP joint can be seen on radiographs (Figure [top ol'lupus nephritis. l'reatmcnt oI SLL during pregnancl is of next pagel). Men are more commonly affected. and the dillicult lrccausc many meclications that could otherwise symptoms usually appear in the lourth to fifth decades. This be r:sed to trext a flare are colrtraindicrlted in ltrcgnanct. patient has hook shaped osteophytes of the second, third, including cvclophosphamiclc, mvcophenolate rnolbtil. metl.r- and fourth MCP joints; onset of type 2 diabetes mellitus in otrexate. and belimunrab. In this casc. first line treatnrcnt the last few years; abnormal aspartate and aminotransferase would ir.rclude addition of high closc or "pulse" glucocor levels: and elevated serum ferritin and transf'errin saturation ticoicl therap1,. Concurrent treatnrcnt fbr preeclanrpsia rlrr\' levels, all suggesting hereditary hemochromatosis. The HFE

tr Item 95 Answer: D Educational Objective: Treat a flare of systemic lupus erythematosus during pregnancy. Item 96 Answer: A a Educational Objective: Diagnose hemochromatosis as a The lnost appropriatc marlagenrent is prednisonc (Option cause of secondary osteoarthritis. D). I rngrkgid, to trext a llare o( systernic lupus erythentirto sus (SI-h-) durirrg pregnanc): An St-E fhre during pregnancy The most appropriate diagnostic test to perform next is HFE carr be difficult to clistinguish fiorn precchntpsia. (lonrnron gene testing (Option A). Underlying disorders can predis I'eatures inclucle proteinuria u'ith hl,perterrsion ancl ederna pose patients to the development ofsecondary osteoarthritis as well ls heaclachcs and othcr nonspecific svntptolrs. (OA) and should be suspected when OA occurs at an early Thronrbocy'topenia is ir relltively conlnlon feature oISLE but age or involves joints not typical for OA, such as the meta is also sect.t with preeclampsia, cspecially with progression carpophalangeal (MCP) or shoulder joints. Hereditary hemo to the HF.l.l.P (llcmoll'sis. Iilerratecl Lir:cr enz_r,mes. and l.on chromatosis can be associated with an arthropathy that Platelets) syndrome. Clues to an Sl"Fl f lare include rnarkcrs causes symptoms of arthritis, arthralgia, and accompanying of lupus activitli snch as rising anti ckruble strirnrled I)NA radiologic findings. These patients particularly develop OA in antil)ody titers and falling serunt contplement levels. 'll.re the hands, where characteristic hook like osteophytes com serunr urate level is often cler,ated ir-r preeclarlpsiu but not monly in the second and third MCP joints and sometimes in Sl,E tlares. this patient's clinicirl features suggest a f lare the fourth MCP joint can be seen on radiographs (Figure [top ol'lupus nephritis. l'reatmcnt oI SLL during pregnancl is of next pagel). Men are more commonly affected. and the dillicult lrccausc many meclications that could otherwise symptoms usually appear in the lourth to fifth decades. This be r:sed to trext a flare are colrtraindicrlted in ltrcgnanct. patient has hook shaped osteophytes of the second, third, including cvclophosphamiclc, mvcophenolate rnolbtil. metl.r- and fourth MCP joints; onset of type 2 diabetes mellitus in otrexate. and belimunrab. In this casc. first line treatnrcnt the last few years; abnormal aspartate and aminotransferase would ir.rclude addition of high closc or "pulse" glucocor levels: and elevated serum ferritin and transf'errin saturation ticoicl therap1,. Concurrent treatnrcnt fbr preeclanrpsia rlrr\' levels, all suggesting hereditary hemochromatosis. The HFE 173

tl:}t9tsgl{_c,t!iqy.: Hlperparathyroidism can be associated with calcium pyrophosphate deposition (CPPD) disease and can cause secondary osteoarthritis. Calcifl cation of articular cartilage (chondrocalcinosis), most commonly affecting the wrists and knees. would be seen in a patient with CPPD and hyper parathyroidism but is absent in this patient. Furthermore, this patient has a normal serum calcium level, and measur ing the serum parathyroid hormone level (Option C) is not indicated. Inflammatory arthritis, such as rheumatoid arthritis, can lead to secondary joint damage and OA. This patient, however. has no history physical examination, or laboratory findings suggesting rheumatoid arthritis. Measuring rheu- UI matoid factor (Option D) is not indicated. E .D IEY Ut o, 'OIITI osteoarthritis (OA) should be suspected . Secondary CL when OA occurs at an early age or involves joints not a.l typical for OA. gene mutation is diagnostic for this condition, and testing It should be performed. o Hereditary hemochromatosis can be associated with .D Acromegaly due to growth hormone excess is a rare an arthropathy that causes arthritis, arthralgia, and tr secondary cause of secondary OA. These patients present radiologic findings, such as characteristic hook-like with enlarged hands, feet, jaw and other bones. Joint symp osteophytes in the second and third metacarpophalangeal toms may be the presenting feature of the disease, and back joints. pain with spinal kyphosis or scoliosis is frequently reported. Testing for insulin-like growth factor 1 (Option B) would be Bibliography appropriate if there were a high suspicion lor the disorder, Kiely PD. Haemochromatosis arthropathy a conundrum of the Celtic but this patient has no findings of acromegaly. curse. J R Coll Physicians Edinb. 2018:48:233-238. IPMID:30191911]

Hlperparathyroidism can be associated with calcium pyrophosphate deposition (CPPD) disease and can cause secondary osteoarthritis. Calcifl cation of articular cartilage (chondrocalcinosis), most commonly affecting the wrists and knees. would be seen in a patient with CPPD and hyper parathyroidism but is absent in this patient. Furthermore, this patient has a normal serum calcium level, and measur ing the serum parathyroid hormone level (Option C) is not indicated. Inflammatory arthritis, such as rheumatoid arthritis, can lead to secondary joint damage and OA. This patient, however. has no history physical examination, or laboratory findings suggesting rheumatoid arthritis. Measuring rheu- UI matoid factor (Option D) is not indicated. E .D IEY Ut o, 'OIITI osteoarthritis (OA) should be suspected . Secondary CL when OA occurs at an early age or involves joints not a.l typical for OA. gene mutation is diagnostic for this condition, and testing It should be performed. o Hereditary hemochromatosis can be associated with .D Acromegaly due to growth hormone excess is a rare an arthropathy that causes arthritis, arthralgia, and tr secondary cause of secondary OA. These patients present radiologic findings, such as characteristic hook-like with enlarged hands, feet, jaw and other bones. Joint symp osteophytes in the second and third metacarpophalangeal toms may be the presenting feature of the disease, and back joints. pain with spinal kyphosis or scoliosis is frequently reported. Testing for insulin-like growth factor 1 (Option B) would be Bibliography appropriate if there were a high suspicion lor the disorder, Kiely PD. Haemochromatosis arthropathy a conundrum of the Celtic but this patient has no findings of acromegaly. curse. J R Coll Physicians Edinb. 2018:48:233-238. IPMID:30191911] 174

lndex Note: Page numbers followed by f and t denote figure and table, respectiveiy. Anti-Scl-70 antibody, 6t Test questions are indicated by Q. Anti-Smith antibody, 6t, 48t Anti-SRP antibody,6t A Antisynthetase syndrcme, 54, 57 Abatacept, 141, 16t Anti TIF 1 Tantibody,6t ACE inhibitors.64 Anti-U1-ribonucleoprotein, 6t, 48t Acetaminophen, 10, 161, 29 Anxiety, fibromyalgia and, Q4o Achilles tendon, 361 38 Aortic valve regurgitation, 36 Acromegaly, OA and, 25t Apremilast, 11t, 12, Q1 Acro-osteolysis, 62, 62f Arthritis. See olso Specific forms of Acute cutaneous lupus erythematosus (ACLE), 43, Q31 Ieatures ol 1-2 Acute gouty arthritis, 67-68 Arthritis mutilans. 37 Acute monoarthritis, Q86 Arthrocentesis, 68 69, Q86 Adalimumab, l3t. Q36 Asymmetric oligoarthritis, 36 Adenocarcinoma, 63 Atherosclerotic heart disease, 21 Adult onset Still disease (AOSD), 3t, 90, Q39 Atrioventricular block, 36 Aerobic exercise for fibromyalgia, 32 Autoinflammatory diseases, 89-90, 89t Alcohol, myopathy induced by, 54t Axial spine, sacroiliitis, 37 Aldolase levels, 57 Azathioprine Alendronate, Q41 for AAV. 84 Alkaptonuria/ochronosis, 25t adverse effects, 49t Allopurinol, 13-14, 161, 70 71, Q2l, Q49 characteristics of. 11t Alternati\€ medicine, 17 [br enteropathic arthritis, 42 Amoxrcrllrn_ // /l{ for tgG4 related disease, 92, 92t Amyopathic dermatomyositis, Q10 during pregnancy, 16t, 50 Anakinra,14t, 16t, Q23 toxicity of, 10-11 Analgesics for rheumatoid diseases, 9-10 use ol 10 11 ANcA-associated vasculitis (AAV), 4t, 83-85, 84t, Q33 Ankylosing spondylitis, 33-34, 39f, 40f B diagnosis ol Q94 Baricitinib, 111, 16t enteropathic arthritis and, 37 Barrett esophagus, 63 hip involvement, 36f Basic calcium phosphate (BCP),73 inflammatory bowel disease in, Qll Behqet syndrome, 87 88, 87f management of, 41, 4lf criteria for, 88t ocular manifestations of, 3t internal organ involvement in, 4t radiologic findings, 7t ocular manil'estations of, 3t renal amyloidosis in, Q72 patherry associated with, 88f treatment oi Q14, Q78 ulcerations in, Q1 Anterior uveitis, ankylosing spondylitis and, 341, 35 Belimumab, 141, 161, 49t, 50 Antibody tests, 5, 6t Biologic disease-modifying antirheumatic drugs, 12 13, Anticentromere antibody, 6t 12f,22 Anticoagulants, drug interactions with, 17 Biosimilar drugs, 13 Anti cyclic citrullinated peptide Bor re lia burgdorfer i, 7 3, 7 8t diagnostic use o{ 19, Q44, Q70 Bouchard nodes, 26 specificity oftests, 5, 6t Bronchiectasis. 21 Anti-double-stranded DNA, 6t, 48t Bronchiolitis. 21, 64 Antihistone. 6t Budd Chiari syndrome, 87 Anti inflammatory agents, 8 9 Anti Jo 1 antibody,6t c Anti-La/SSB antibody, 6t, 48t, 50, 52 Calcineurin inhibitors, 12, 50 Antimalarials, 54t Calcinosis,60, 62f Anti-MDA-5 antibody, 6t Calcinosis cutis. 55 Anti Mi 2 antibody,6t Calcium phosphate-associated arthritis, Q35 Antimyeloperoxidase antibody, 6t Calcium pyrophosphate deposition (CPPD), Q13, Q27 Antinuclear antibodies (ANA) management of, 72t in inclusion body myositis, 57 manifestations of, 71 in mixed connective tissue disease, 66 osteoarthritis secondary to, 25t,27 28 in Sjdgren syndrome, 52-53 physiolory of,71 in SLE, 42-43, 46-48, Q6 radiographic fi ndings, 7t in systemic sclerosis, 6lt CampAlobacte r jejuni, 38 targets ol 5, 6t, 30-31 c ANCA antibody, 6t Antiphospholipid antibodies, 45 Canakinumab, 14t,16t Antiphospholipid syndrome, 3t, 4t, 45 Cancer in dermatomyositis, Q38 Antiproteinase 3 antibody, 6t Capsaicin for osteoarthritis, 29 Antiribosomal P antibody. 6t,48t Captopril for scleroderma renal crisis, Q15 Anti Ro/SSA antibody, Q60 Cardiovascular disease risk, Q19 in pregnancy,50 Carpal tunnel release, 17 in rheumatologic diseases, 6t Cauda equine syndrome, 36 in Sjogren syndrome, 52 Celuroxime axetil. 77 78 in SLE,48t, 49t Certolizumab pegol, 13t in subacute cutaneous lupus erythematosus, 44 Cevimeline, Q26

Note: Page numbers followed by f and t denote figure and table, respectiveiy. Anti-Scl-70 antibody, 6t Test questions are indicated by Q. Anti-Smith antibody, 6t, 48t Anti-SRP antibody,6t A Antisynthetase syndrcme, 54, 57 Abatacept, 141, 16t Anti TIF 1 Tantibody,6t ACE inhibitors.64 Anti-U1-ribonucleoprotein, 6t, 48t Acetaminophen, 10, 161, 29 Anxiety, fibromyalgia and, Q4o Achilles tendon, 361 38 Aortic valve regurgitation, 36 Acromegaly, OA and, 25t Apremilast, 11t, 12, Q1 Acro-osteolysis, 62, 62f Arthritis. See olso Specific forms of Acute cutaneous lupus erythematosus (ACLE), 43, Q31 Ieatures ol 1-2 Acute gouty arthritis, 67-68 Arthritis mutilans. 37 Acute monoarthritis, Q86 Arthrocentesis, 68 69, Q86 Adalimumab, l3t. Q36 Asymmetric oligoarthritis, 36 Adenocarcinoma, 63 Atherosclerotic heart disease, 21 Adult onset Still disease (AOSD), 3t, 90, Q39 Atrioventricular block, 36 Aerobic exercise for fibromyalgia, 32 Autoinflammatory diseases, 89-90, 89t Alcohol, myopathy induced by, 54t Axial spine, sacroiliitis, 37 Aldolase levels, 57 Azathioprine Alendronate, Q41 for AAV. 84 Alkaptonuria/ochronosis, 25t adverse effects, 49t Allopurinol, 13-14, 161, 70 71, Q2l, Q49 characteristics of. 11t Alternati\€ medicine, 17 [br enteropathic arthritis, 42 Amoxrcrllrn_ // /l{ for tgG4 related disease, 92, 92t Amyopathic dermatomyositis, Q10 during pregnancy, 16t, 50 Anakinra,14t, 16t, Q23 toxicity of, 10-11 Analgesics for rheumatoid diseases, 9-10 use ol 10 11 ANcA-associated vasculitis (AAV), 4t, 83-85, 84t, Q33 Ankylosing spondylitis, 33-34, 39f, 40f B diagnosis ol Q94 Baricitinib, 111, 16t enteropathic arthritis and, 37 Barrett esophagus, 63 hip involvement, 36f Basic calcium phosphate (BCP),73 inflammatory bowel disease in, Qll Behqet syndrome, 87 88, 87f management of, 41, 4lf criteria for, 88t ocular manifestations of, 3t internal organ involvement in, 4t radiologic findings, 7t ocular manil'estations of, 3t renal amyloidosis in, Q72 patherry associated with, 88f treatment oi Q14, Q78 ulcerations in, Q1 Anterior uveitis, ankylosing spondylitis and, 341, 35 Belimumab, 141, 161, 49t, 50 Antibody tests, 5, 6t Biologic disease-modifying antirheumatic drugs, 12 13, Anticentromere antibody, 6t 12f,22 Anticoagulants, drug interactions with, 17 Biosimilar drugs, 13 Anti cyclic citrullinated peptide Bor re lia burgdorfer i, 7 3, 7 8t diagnostic use o{ 19, Q44, Q70 Bouchard nodes, 26 specificity oftests, 5, 6t Bronchiectasis. 21 Anti-double-stranded DNA, 6t, 48t Bronchiolitis. 21, 64 Antihistone. 6t Budd Chiari syndrome, 87 Anti inflammatory agents, 8 9 Anti Jo 1 antibody,6t c Anti-La/SSB antibody, 6t, 48t, 50, 52 Calcineurin inhibitors, 12, 50 Antimalarials, 54t Calcinosis,60, 62f Anti-MDA-5 antibody, 6t Calcinosis cutis. 55 Anti Mi 2 antibody,6t Calcium phosphate-associated arthritis, Q35 Antimyeloperoxidase antibody, 6t Calcium pyrophosphate deposition (CPPD), Q13, Q27 Antinuclear antibodies (ANA) management of, 72t in inclusion body myositis, 57 manifestations of, 71 in mixed connective tissue disease, 66 osteoarthritis secondary to, 25t,27 28 in Sjdgren syndrome, 52-53 physiolory of,71 in SLE, 42-43, 46-48, Q6 radiographic fi ndings, 7t in systemic sclerosis, 6lt CampAlobacte r jejuni, 38 targets ol 5, 6t, 30-31 c ANCA antibody, 6t Antiphospholipid antibodies, 45 Canakinumab, 14t,16t Antiphospholipid syndrome, 3t, 4t, 45 Cancer in dermatomyositis, Q38 Antiproteinase 3 antibody, 6t Capsaicin for osteoarthritis, 29 Antiribosomal P antibody. 6t,48t Captopril for scleroderma renal crisis, Q15 Anti Ro/SSA antibody, Q60 Cardiovascular disease risk, Q19 in pregnancy,50 Carpal tunnel release, 17 in rheumatologic diseases, 6t Cauda equine syndrome, 36 in Sjogren syndrome, 52 Celuroxime axetil. 77 78 in SLE,48t, 49t Certolizumab pegol, 13t in subacute cutaneous lupus erythematosus, 44 Cevimeline, Q26 175

lndex Charcot joints, 25t Enthesis.2 Chikungunya virus, 76, Q66 Enthesitis, 35, 37, 87 Childbirth, SLE and, 50 Eosinophilic fasciitis, 61t Chlamy dia trochomotis, 38, 42 Eosinophilic granulomatosis with polyangiitis (EGPA), Chondroitin sulfate. 29 85 Chronic graft-versus-host disease, 6lt Epicondyliris, lateral, Q42 Chronic infantile neurologic, cutaneous, articular syndrome (CINCA), 89t Episcleritis, 21 Circinate balanitis, 38, 38f Epstein Barrvirus, 17 Citrulline, lT Erythema nodosum,9lf Clostridtoides dfficile, 38 Erlthrocyte sedimentation rate (ESR), 2 4, 19 Cocaine, myopathy induced by, 54t Esophageal dysmotility, 63 Cognitive behavioral therapy, 32 Estrogen receptors, 17 Colchicine Etanercept, 13t for acute gout, Q76 Exercise for osteoarthritis, 29, Q82 adverse effects of, 9 Eyes, rheumatologic disease and. 2, 20 2l for Behqet syndrome, 88 for familial Mediterranean fever, Q2 f function of. 9 Facet joints, synovial, 34-35 for gout, 69-70 Familial cold autoinflammatory syndrome (FCAS), 89, 89f myopathy induced by, 54t Familial Mediterranean fever, 4t, 9, 89. 89t, Q2 in pregnancy, 16t Fatigue. rheumatologic disease and, 2 Complement,5,48 Febuxostat, Q21, Q61 Complementary medicine, 17 contraindications. 1l Conjunctivitis, 37, 38 description o[ 14 Connective tissue disease,4t, 92 93 urate-lowering therapy with, 16t,70 7l Constipation, treatment options, 65t Felty syndrome, 21, Q29 Corneal melt.21 Ferritin, serum, Q27 c-reactive protein (cRP),4-5, 19 Fever, rheumatologic disease and, 2 Creatine kinase, 53 Fibrillin 1, fibromyalgia and, 33 CREST syndrome,60 Fibromyalgia, Q81 Cricoarytenoid arthritis, 21 classifi cation of. 33-38 Cryoglobulinemia, 86 diagnosis of,30 31, 311,311, Q81 Cryoglobulinemic vasculitis, 86, Q56 epidemiolos/ ol 30 Cryoglobulins, 6t, 86 genetic factors, 33 crystal arthritis, 721 Q27 management ol 32 Crystal arthropathies, T, 67 -73 milancipran for, 10 Crystal deposition, T pain taxonomy for, 31f cf,7, 40, s8, 64, 69 SLE and. 44 Cutaneous lupus erythematosus (CLE), Q31 treatment of, Q7, Q40 Cutaneous systemic sclerosis, Q69 Fungal infections, 75 7 6, 7 at Cyclooxygenase, 9t Cyclophosphamide G adverse effects ol 11, 49t Gabapentin, 10,32 for Behqet syndrome, 88 Cabapentinoids, 10 characteristics ol 11, 11t Gastroesophageal reflux disease, 65t for IlM. 59 Gastrointestinal dysmotiliry 65t in prcgnancy, 16t Genital ulcerc, 87, 87f for SSc. 64 Giant cell arteritis (GCA), Q16, Q85 Cyclosporine, 111, 161, 59 cardiac manifestations of. 4t C)topenia, SLE and, 45 diagnosis of,79-80 epidemiolory ol 79 D management ol 80 1 Dactylitis, 2, 32, 33f , 37f ocular manifestations of. 3t Dengue virus, 76 pathophysiolog/ of.79 Depression, Q40 Glucocorticoids : Dermatomyositis, 54, 55, 58 for AAV Q33 amyopathic, Ql0 adverse effects. 8 cancer in, Q38 for enteropathic arthritis, 42 : cutaneous manifestations of 561 56t immunosuppression by, 8-9 dermatologic manifestations of, 3t intra-articular iniections of, 29 30 treatment of, Q28 myopathy induced by, 54t Diffuse cutaneous systemic sclerosis (DcSSc), 4t, 611, Q93 osteoporosis induced by, Q4l Diffuse idiopathic skeletal hyperostosis (DISH), 7t, 25, 26f. Q8 during pregnancy, l6t, 50 Digital pitting, 63f RA management and, 22 - 23 i Discoid lupus erlthematosus (DLE), 44, 44f for reactive arthritis. 42 Disease-modifuing antirheumatic drugs (DMARDs), 10-13, Q73 for rheumatologic diseases, 8-9 Distal interphalangeal joints (DIP), 36, 37f for SLE. 49 Doxycycline, 77 -78 , Ql2 tapering of, 50 DRESS (drug reaction with eosinophilia and systemic symptoms), Glucocorticoid-sparing agents, Q16 70-71 Glucosamine for osteoarthritis. 29 Drug-induced hypersensitivity syndrome (DIHS), 13 14,49t,70 77 Golimumab. 13t Drug-induced lupus erythematosus (DILE), 48, 49t Gonococcal arthritis,73, 75t, Q63 Dryeye,20 27,52 Goodpasrure syndrome, 4t Dry mouth, 20-27, 52, Q26, Q47 Gottron papules, 55, 56f Duloxetine,10,29, Q40 Cottron sign, 55,56f Dysbiosis,33 Gout,36,67 71 Dyspnea, SLE and,45 acute flare of, 69 70,69t chronic recurrent, Q52 E intercritical. 68 Ehlers-Danlos syndrome, 92, 93t management of, 9, 13 15, 69 77 Electromyography, 58 radiologic findings, 7t Enteropathic arthritis, 34t, 37 -38, 42 refractory Q23

Charcot joints, 25t Enthesis.2 Chikungunya virus, 76, Q66 Enthesitis, 35, 37, 87 Childbirth, SLE and, 50 Eosinophilic fasciitis, 61t Chlamy dia trochomotis, 38, 42 Eosinophilic granulomatosis with polyangiitis (EGPA), Chondroitin sulfate. 29 85 Chronic graft-versus-host disease, 6lt Epicondyliris, lateral, Q42 Chronic infantile neurologic, cutaneous, articular syndrome (CINCA), 89t Episcleritis, 21 Circinate balanitis, 38, 38f Epstein Barrvirus, 17 Citrulline, lT Erythema nodosum,9lf Clostridtoides dfficile, 38 Erlthrocyte sedimentation rate (ESR), 2 4, 19 Cocaine, myopathy induced by, 54t Esophageal dysmotility, 63 Cognitive behavioral therapy, 32 Estrogen receptors, 17 Colchicine Etanercept, 13t for acute gout, Q76 Exercise for osteoarthritis, 29, Q82 adverse effects of, 9 Eyes, rheumatologic disease and. 2, 20 2l for Behqet syndrome, 88 for familial Mediterranean fever, Q2 f function of. 9 Facet joints, synovial, 34-35 for gout, 69-70 Familial cold autoinflammatory syndrome (FCAS), 89, 89f myopathy induced by, 54t Familial Mediterranean fever, 4t, 9, 89. 89t, Q2 in pregnancy, 16t Fatigue. rheumatologic disease and, 2 Complement,5,48 Febuxostat, Q21, Q61 Complementary medicine, 17 contraindications. 1l Conjunctivitis, 37, 38 description o[ 14 Connective tissue disease,4t, 92 93 urate-lowering therapy with, 16t,70 7l Constipation, treatment options, 65t Felty syndrome, 21, Q29 Corneal melt.21 Ferritin, serum, Q27 c-reactive protein (cRP),4-5, 19 Fever, rheumatologic disease and, 2 Creatine kinase, 53 Fibrillin 1, fibromyalgia and, 33 CREST syndrome,60 Fibromyalgia, Q81 Cricoarytenoid arthritis, 21 classifi cation of. 33-38 Cryoglobulinemia, 86 diagnosis of,30 31, 311,311, Q81 Cryoglobulinemic vasculitis, 86, Q56 epidemiolos/ ol 30 Cryoglobulins, 6t, 86 genetic factors, 33 crystal arthritis, 721 Q27 management ol 32 Crystal arthropathies, T, 67 -73 milancipran for, 10 Crystal deposition, T pain taxonomy for, 31f cf,7, 40, s8, 64, 69 SLE and. 44 Cutaneous lupus erythematosus (CLE), Q31 treatment of, Q7, Q40 Cutaneous systemic sclerosis, Q69 Fungal infections, 75 7 6, 7 at Cyclooxygenase, 9t Cyclophosphamide G adverse effects ol 11, 49t Gabapentin, 10,32 for Behqet syndrome, 88 Cabapentinoids, 10 characteristics ol 11, 11t Gastroesophageal reflux disease, 65t for IlM. 59 Gastrointestinal dysmotiliry 65t in prcgnancy, 16t Genital ulcerc, 87, 87f for SSc. 64 Giant cell arteritis (GCA), Q16, Q85 Cyclosporine, 111, 161, 59 cardiac manifestations of. 4t C)topenia, SLE and, 45 diagnosis of,79-80 epidemiolory ol 79 D management ol 80 1 Dactylitis, 2, 32, 33f , 37f ocular manifestations of. 3t Dengue virus, 76 pathophysiolog/ of.79 Depression, Q40 Glucocorticoids : Dermatomyositis, 54, 55, 58 for AAV Q33 amyopathic, Ql0 adverse effects. 8 cancer in, Q38 for enteropathic arthritis, 42 : cutaneous manifestations of 561 56t immunosuppression by, 8-9 dermatologic manifestations of, 3t intra-articular iniections of, 29 30 treatment of, Q28 myopathy induced by, 54t Diffuse cutaneous systemic sclerosis (DcSSc), 4t, 611, Q93 osteoporosis induced by, Q4l Diffuse idiopathic skeletal hyperostosis (DISH), 7t, 25, 26f. Q8 during pregnancy, l6t, 50 Digital pitting, 63f RA management and, 22 - 23 i Discoid lupus erlthematosus (DLE), 44, 44f for reactive arthritis. 42 Disease-modifuing antirheumatic drugs (DMARDs), 10-13, Q73 for rheumatologic diseases, 8-9 Distal interphalangeal joints (DIP), 36, 37f for SLE. 49 Doxycycline, 77 -78 , Ql2 tapering of, 50 DRESS (drug reaction with eosinophilia and systemic symptoms), Glucocorticoid-sparing agents, Q16 70-71 Glucosamine for osteoarthritis. 29 Drug-induced hypersensitivity syndrome (DIHS), 13 14,49t,70 77 Golimumab. 13t Drug-induced lupus erythematosus (DILE), 48, 49t Gonococcal arthritis,73, 75t, Q63 Dryeye,20 27,52 Goodpasrure syndrome, 4t Dry mouth, 20-27, 52, Q26, Q47 Gottron papules, 55, 56f Duloxetine,10,29, Q40 Cottron sign, 55,56f Dysbiosis,33 Gout,36,67 71 Dyspnea, SLE and,45 acute flare of, 69 70,69t chronic recurrent, Q52 E intercritical. 68 Ehlers-Danlos syndrome, 92, 93t management of, 9, 13 15, 69 77 Electromyography, 58 radiologic findings, 7t Enteropathic arthritis, 34t, 37 -38, 42 refractory Q23 176

lndex tophaceous, Q21 osteoarthritis and, 25t treatment ol Q76, Q89 rheumatoid arthritis, 20 Gouty arthritis, Q18 Granulomatosis with polyangiitis, 31,83-8s, Q4, Q33 l( Granulomatous myocarditis, 21 Kawasaki disease, 4t, 83 Gullwing erosions, 24, 24f Keratitis, ocular manifestations of, 21 Guselkumab, l4t,16t Knees Lyme arthritis,75f H monosodium urate deposition, 70f Hands osteoarthritis of, 27\ Q24, Q34 acro-osteolysis, 62f osteoarthritis of 24f,26f, Q24 I rheumatoid arthritis, l8t 19t 20f, Q83 Laboratory studies systemic sclerosis, 62f in osteoarthritis, 27 Heart, RA and, 21 in rheumatoid arthritis, 19 Heberden nodes, 26 in rheumatologic disease, 2-5 Hemochromatosis, 251, Q96 in spondylitis,38 Henoch-Sch0nlein purpura, 4t, 86 in systemic lupus erJ,thematosus, 46 Hepatitis, SLE and, 46 Large granular lymphoryte leukemia, 21 Hepatitis B virus, 76, 81-82 Iarge granular lymphoclte syn&ome, 21 Hepatitis C virus,76 lateral epicondylitis, Q42 Herbal supplements, 17 Leflunomide, 10, 11t, 161, 50 Hip. anlVlosing spondylitis. 36f Leukopenia, SLE and,45 Histopatholos/ in IIM, 58 Libman Sacks endocarditis, 45 HlV, musculoskeletal disorders in, 76 Lidocaine for osteoarthritis, 29 H[A-B27 testing,37, Qs Limited cutaneous systemic sclerosis (LcSSc),41, 6ft, Q59 HI-A-B'58:01 allele, 14,70, Q49 Linear scleroderma, 61t Hormones, RA and, U Livedo reticularis, 44, 82f Hyaluronic acid, 29-30 Losartan, Q89 Hydrochlorothiazide, Q89 Lungs,21,36 Hydrorychloroquine Lupus er,'thmatosus, drug-induced, Q80 adverse effects,49t Lupus nephritis, 12,14t,44, Q46, Q77 characteristics of, llt Lupus pernio,9l, 91f for nephritis in SLE, Q46 Lyme arthritis, 75, 751 Q12 during pregnency, 16t, 50 Lyme disease, 3t for SLE, 46,49, Q75 Lymphomas toxicity,49 RA and, 21 use of 10 in Sjogen syndrome, Q79 Hyperparathyroidism, 25t Lymphopenia,45 Hlpersensitivity vasculitis, 9, 87, Q48 Hlperuricemia, 36, 67, 67t ]t MAGIC (mouth and genital ulcerations with inflamed cartilage), 88 I Malignanry, SLE and, 46 Idiopathic inflammatory myopathies olM), 53-59, 55t,58f Marfan syndrome, 92 IgA nephropathy,36 Measles, mumps, and rubella vaccine, Q43 IgA vasculitis, 86-87 Mechanic's hands, 3t, 55,551,56f IgG4 related diseases, 3t, 92, 921, Q68 Meditation, 17 lmmune complex mediated vasculitis, 85-87, 86f Mental health screening, 8 Immune-mediated necrotizing myopathy, 57 Mepolizumab, 14t Immunosuppression, 15 Metacarpophalangeal joints, I 8l' Inclusion body myositis, 57, 59, Q45, Q65 Metalloproteinases, joint damage and, 20 Infectious arthritis, 73-78, 73f Methicillin-resistant S. oureus (MRSA), 78t causes of,74-z Methicillin-sensitive S. oureus (MSSA), 78t joint aspiration in,7 Methotrexate, l0 management of 77-78 for AAV, 84 pathogens, T8t adverse effects of, 10 risk factors, 74t characteristics of,llt lnllammation for dermatomyositis, Q28 pain ol 1, 1t for enteropathic arthritis, 42 persistent, l9t for polymyalgia rheumatica, 80 signs of, I in pregnancy, 16t Infl ammatory arthritis, 25t for psoriatic arthritis, 42 Inflammatory bowel disease, 3t, 37, Q1l for RA, 22, Q73 lnfl ammatory sacroiliitis, Q30 for reactive arthritis, 42 ankylosing spondylitis and, 7t for SLE, 50 radiographic imaging, 33 use of,10 Infliximab, l3t Methylsalicylate, 29 Intercritical gout, 68 Microscopic polyangiitis, 84-85 Interleukin-1 receptor antegonists, 891, Q23 Milnacipran, 10 Interleukin-17 inhibitors, 41, 42 Milwaukee shoulder, 73, Q35 Interstitial lung disease (lLD), 21,54, 64,651, Q17, Q62 Mind-body interactions, 17 Intestinal bacterial overgrowth, Q93 Mixed connective tissue disease (MCTD), 66-67, 66t, Q64 lxekizumab Monoarthritis, 1 characteristics of, l4t Monosodium urate deposition, 67-68 in pregnancy, 16t Morphea,6lt MRI,7,20,40, s8, Q2s, Q30 J Muckle-Wells syndrome (MWS), 89t Janus kinase inhibitors, 12 Muscle pain, evaluation ol 53 Joint replacement surgery Q50 Musculoskeletal examination, 1 Joints Mycobacteria, T3 aspiration ol 1,7-8 MAcobacterium marinum, 7 5 inflammation of, 7, 19t Ml.tcobacterium fuberculosis, 75, 78t

tophaceous, Q21 osteoarthritis and, 25t treatment ol Q76, Q89 rheumatoid arthritis, 20 Gouty arthritis, Q18 Granulomatosis with polyangiitis, 31,83-8s, Q4, Q33 l( Granulomatous myocarditis, 21 Kawasaki disease, 4t, 83 Gullwing erosions, 24, 24f Keratitis, ocular manifestations of, 21 Guselkumab, l4t,16t Knees Lyme arthritis,75f H monosodium urate deposition, 70f Hands osteoarthritis of, 27\ Q24, Q34 acro-osteolysis, 62f osteoarthritis of 24f,26f, Q24 I rheumatoid arthritis, l8t 19t 20f, Q83 Laboratory studies systemic sclerosis, 62f in osteoarthritis, 27 Heart, RA and, 21 in rheumatoid arthritis, 19 Heberden nodes, 26 in rheumatologic disease, 2-5 Hemochromatosis, 251, Q96 in spondylitis,38 Henoch-Sch0nlein purpura, 4t, 86 in systemic lupus erJ,thematosus, 46 Hepatitis, SLE and, 46 Large granular lymphoryte leukemia, 21 Hepatitis B virus, 76, 81-82 Iarge granular lymphoclte syn&ome, 21 Hepatitis C virus,76 lateral epicondylitis, Q42 Herbal supplements, 17 Leflunomide, 10, 11t, 161, 50 Hip. anlVlosing spondylitis. 36f Leukopenia, SLE and,45 Histopatholos/ in IIM, 58 Libman Sacks endocarditis, 45 HlV, musculoskeletal disorders in, 76 Lidocaine for osteoarthritis, 29 H[A-B27 testing,37, Qs Limited cutaneous systemic sclerosis (LcSSc),41, 6ft, Q59 HI-A-B'58:01 allele, 14,70, Q49 Linear scleroderma, 61t Hormones, RA and, U Livedo reticularis, 44, 82f Hyaluronic acid, 29-30 Losartan, Q89 Hydrochlorothiazide, Q89 Lungs,21,36 Hydrorychloroquine Lupus er,'thmatosus, drug-induced, Q80 adverse effects,49t Lupus nephritis, 12,14t,44, Q46, Q77 characteristics of, llt Lupus pernio,9l, 91f for nephritis in SLE, Q46 Lyme arthritis, 75, 751 Q12 during pregnency, 16t, 50 Lyme disease, 3t for SLE, 46,49, Q75 Lymphomas toxicity,49 RA and, 21 use of 10 in Sjogen syndrome, Q79 Hyperparathyroidism, 25t Lymphopenia,45 Hlpersensitivity vasculitis, 9, 87, Q48 Hlperuricemia, 36, 67, 67t ]t MAGIC (mouth and genital ulcerations with inflamed cartilage), 88 I Malignanry, SLE and, 46 Idiopathic inflammatory myopathies olM), 53-59, 55t,58f Marfan syndrome, 92 IgA nephropathy,36 Measles, mumps, and rubella vaccine, Q43 IgA vasculitis, 86-87 Mechanic's hands, 3t, 55,551,56f IgG4 related diseases, 3t, 92, 921, Q68 Meditation, 17 lmmune complex mediated vasculitis, 85-87, 86f Mental health screening, 8 Immune-mediated necrotizing myopathy, 57 Mepolizumab, 14t Immunosuppression, 15 Metacarpophalangeal joints, I 8l' Inclusion body myositis, 57, 59, Q45, Q65 Metalloproteinases, joint damage and, 20 Infectious arthritis, 73-78, 73f Methicillin-resistant S. oureus (MRSA), 78t causes of,74-z Methicillin-sensitive S. oureus (MSSA), 78t joint aspiration in,7 Methotrexate, l0 management of 77-78 for AAV, 84 pathogens, T8t adverse effects of, 10 risk factors, 74t characteristics of,llt lnllammation for dermatomyositis, Q28 pain ol 1, 1t for enteropathic arthritis, 42 persistent, l9t for polymyalgia rheumatica, 80 signs of, I in pregnancy, 16t Infl ammatory arthritis, 25t for psoriatic arthritis, 42 Inflammatory bowel disease, 3t, 37, Q1l for RA, 22, Q73 lnfl ammatory sacroiliitis, Q30 for reactive arthritis, 42 ankylosing spondylitis and, 7t for SLE, 50 radiographic imaging, 33 use of,10 Infliximab, l3t Methylsalicylate, 29 Intercritical gout, 68 Microscopic polyangiitis, 84-85 Interleukin-1 receptor antegonists, 891, Q23 Milnacipran, 10 Interleukin-17 inhibitors, 41, 42 Milwaukee shoulder, 73, Q35 Interstitial lung disease (lLD), 21,54, 64,651, Q17, Q62 Mind-body interactions, 17 Intestinal bacterial overgrowth, Q93 Mixed connective tissue disease (MCTD), 66-67, 66t, Q64 lxekizumab Monoarthritis, 1 characteristics of, l4t Monosodium urate deposition, 67-68 in pregnancy, 16t Morphea,6lt MRI,7,20,40, s8, Q2s, Q30 J Muckle-Wells syndrome (MWS), 89t Janus kinase inhibitors, 12 Muscle pain, evaluation ol 53 Joint replacement surgery Q50 Musculoskeletal examination, 1 Joints Mycobacteria, T3 aspiration ol 1,7-8 MAcobacterium marinum, 7 5 inflammation of, 7, 19t Ml.tcobacterium fuberculosis, 75, 78t 177

lndex Mycophenolate mofetil Peripheral neuropathy, 45 adverse effects, 49t characteristics ol 11t, 12 Periungual erythema, 55 Physical therapy \ for IlM, 59 for ankylosing spondylitis, 41 for ILD, Q62 for inclusion body myositis, Q65 I I for nephritis in sLE, Q46 for osteoarthritis, Q82 in pregnancy, 16t in rheumatic disease, 15-17 \ for SLE, 50 Pleural effusions I

Mycophenolate mofetil Peripheral neuropathy, 45 adverse effects, 49t characteristics ol 11t, 12 Periungual erythema, 55 Physical therapy \ for IlM, 59 for ankylosing spondylitis, 41 for ILD, Q62 for inclusion body myositis, Q65 I I for nephritis in sLE, Q46 for osteoarthritis, Q82 in pregnancy, 16t in rheumatic disease, 15-17 \ for SLE, 50 Pleural effusions I for SSc, 64 Mucoplosmo spp., 17, 38 RA and.21 \It SLE and. 45 Myelosuppression, 10, 11 Myocardial fibrosis, 63 SSc and, 64 Pleuritis, SSc and, 64 \ Myocardial infarction, 36 Poikiloderma,55, 60 Myocarditis, SLE and, 45 '1 Polyarteritis nodosa (PAN), 4t, 81 82, 821, esl Myopathies Polyadhritis,2 differential diagnoses, s3t drug-induced,54t Polyarticular arthritis, 36 \ Polymyalgia rheumatica (PMR), 79, 80, Qss, Q8S )

for SSc, 64 Mucoplosmo spp., 17, 38 RA and.21 \It SLE and. 45 Myelosuppression, 10, 11 Myocardial fibrosis, 63 SSc and, 64 Pleuritis, SSc and, 64 \ Myocardial infarction, 36 Poikiloderma,55, 60 Myocarditis, SLE and, 45 '1 Polyarteritis nodosa (PAN), 4t, 81 82, 821, esl Myopathies Polyadhritis,2 differential diagnoses, s3t drug-induced,54t Polyarticular arthritis, 36 \ Polymyalgia rheumatica (PMR), 79, 80, Qss, Q8S ) T Polymyositis, 54-58 \ Po rphgromonos gingiv alis, 17 I Naproxen, Q78 Prednisone Neisserio gonorrhoe ae, 7 4, 7 8t adverse effects,49t 1 Neonatal lupus erlthematosus, 50 I Neonatal onset multisystem inflammatory syndrome (NOMID), 89t Nephrogenic systemic fibrosis, 6lt long term use, 9 for nephritis in sLE, Q46 \ for polymyalgia rheumatica, Q55 Neutrophilic dermatoses, 20 Nintedanib.64 for SLE, 44, Q75 Pregabalin, 10, 32, Q7 \l Nonbiologic disease modirying antirheumatic drugs, lO-t2, 22 Noninflammatory pain, l, lt Pregnancy ! medications in, 15, 16t I Nonselective COX inhibitors, 9t Nonsteroidal antiinJlammatory drugs (NSAIDs), S preconception planning, Q88 RA in,23 \ adverse effects. 49t i RA treatment during, Q57 for anlgilosing spondylitis, Q78 for osteoarthritis, 29, Q24, Q54 SLE and, 50 \I SLE flares in, Q95 for parvovirus B19 arthropathy, Q53 in pregnancy, 16t RA management and, 22 SSc in.65 Primary angiitis ofthe central nervous system (PACNS),4t. 82-83 i: Probenecid, 161, 7l 1 for reactive arthritis, Q67 Prosthetic ioint infections, 77, Q74 I topical,9 Proteinuria, 36, 44, 45, 50 toxicities, 9t Proton pump inhibitors, 29 Pse udomonos oeruginoso, 78t : 0 Obesity, osteoarthritis and, 23 Psoriasis, Q18, Q58 \ Occupational therapy, l5 17 Psoriatic arthritis. 36 37 Oligoarthritis, fearures of, 2 dermatologic manifestations of, 3t Opiates in pregnancy, 16t description ol 2 I Opioids for osteoarthritis, 29 features ol 34t gouty arthritis in patients with, Q18 Optic neuritis, 87 l Oral ulcers,38,87 joint pain in, Q58 Osteoarthritis (OA) radiologic flndings, 7t classification of. 24-25 risk factors,36 sex and. 36 i diagnosisof,25 27,Q2O differential diagnosis of, 27-28 subtypes, Q3 \ epidemiolory, 23-25 treatment of, 42,42t Pulmonary arterial hypertension (PAH), 64, 651, Q69 \I erosive, 24-25 hand,24f,27f Pulmonary veno occlusive disease, 64 joint pain in, Q58 Pyoderma gangrenosum, 20 \ knee,27f, Q34 Pyrin mutations, 89 management of 28 30 NSAIDs for. 29, Q54 o : pathophysiolory ol 23 Quinacrine,50 primary 24 \ radiologic findings, 7t R I risk factors,23 25 Radiography secondary 25,251, Q96 in calcium pyrophosphate deposition disease, 71 :

T Polymyositis, 54-58 \ Po rphgromonos gingiv alis, 17 I Naproxen, Q78 Prednisone Neisserio gonorrhoe ae, 7 4, 7 8t adverse effects,49t 1 Neonatal lupus erlthematosus, 50 I Neonatal onset multisystem inflammatory syndrome (NOMID), 89t Nephrogenic systemic fibrosis, 6lt long term use, 9 for nephritis in sLE, Q46 \ for polymyalgia rheumatica, Q55 Neutrophilic dermatoses, 20 Nintedanib.64 for SLE, 44, Q75 Pregabalin, 10, 32, Q7 \l Nonbiologic disease modirying antirheumatic drugs, lO-t2, 22 Noninflammatory pain, l, lt Pregnancy ! medications in, 15, 16t I Nonselective COX inhibitors, 9t Nonsteroidal antiinJlammatory drugs (NSAIDs), S preconception planning, Q88 RA in,23 \ adverse effects. 49t i RA treatment during, Q57 for anlgilosing spondylitis, Q78 for osteoarthritis, 29, Q24, Q54 SLE and, 50 \I SLE flares in, Q95 for parvovirus B19 arthropathy, Q53 in pregnancy, 16t RA management and, 22 SSc in.65 Primary angiitis ofthe central nervous system (PACNS),4t. 82-83 i: Probenecid, 161, 7l 1 for reactive arthritis, Q67 Prosthetic ioint infections, 77, Q74 I topical,9 Proteinuria, 36, 44, 45, 50 toxicities, 9t Proton pump inhibitors, 29 Pse udomonos oeruginoso, 78t : 0 Obesity, osteoarthritis and, 23 Psoriasis, Q18, Q58 \ Occupational therapy, l5 17 Psoriatic arthritis. 36 37 Oligoarthritis, fearures of, 2 dermatologic manifestations of, 3t Opiates in pregnancy, 16t description ol 2 I Opioids for osteoarthritis, 29 features ol 34t gouty arthritis in patients with, Q18 Optic neuritis, 87 l Oral ulcers,38,87 joint pain in, Q58 Osteoarthritis (OA) radiologic flndings, 7t classification of. 24-25 risk factors,36 sex and. 36 i diagnosisof,25 27,Q2O differential diagnosis of, 27-28 subtypes, Q3 \ epidemiolory, 23-25 treatment of, 42,42t Pulmonary arterial hypertension (PAH), 64, 651, Q69 \I erosive, 24-25 hand,24f,27f Pulmonary veno occlusive disease, 64 joint pain in, Q58 Pyoderma gangrenosum, 20 \ knee,27f, Q34 Pyrin mutations, 89 management of 28 30 NSAIDs for. 29, Q54 o : pathophysiolory ol 23 Quinacrine,50 primary 24 \ radiologic findings, 7t R I risk factors,23 25 Radiography secondary 25,251, Q96 in calcium pyrophosphate deposition disease, 71 : in gout, 69 treatment of, 281, Q24, Q82 Osteogenesis imperfecta, 92 in infectious arthritis. 73 l Osteonecrosis, 7, 44, Q25 in osteoarthritis, 27 Osteoporosis, drug-induced, Q41 in rheumatoid arthritis, 19, Q83, Q90 in rheumatologic diseases, 5-6, 7t P in sarcoidosis. 90f Pain in spondyloarthritis, 39, Q94 inflammatory vs. noninflammatory I Raynaud phenomenon, 44, 46, 62 63 pathway modulators, 9-10 Reactive arthritis, 3t, 34t, 38, 42, Q67 soft tissue abnormalities and. 2 Receptor activator of nuclear factor kappa B ligand (RANKL), 20 p ANCA antibody,6t Relapsing polychondritis, 3t, 88-89, 88f, Q92 Panuveitis,87 Renal amyloidosis, Q72 Parvovirus 819, 17,76, Q53 Patient history Repetitive motion, OA and, 23 Retiform purpura,82f \: musculoskeletal examination and, 1, Q2o Retinal vasculitis. 87 Pegloticase, 15, 161,71, Q61 Rheumatic disease ..

in gout, 69 treatment of, 281, Q24, Q82 Osteogenesis imperfecta, 92 in infectious arthritis. 73 l Osteonecrosis, 7, 44, Q25 in osteoarthritis, 27 Osteoporosis, drug-induced, Q41 in rheumatoid arthritis, 19, Q83, Q90 in rheumatologic diseases, 5-6, 7t P in sarcoidosis. 90f Pain in spondyloarthritis, 39, Q94 inflammatory vs. noninflammatory I Raynaud phenomenon, 44, 46, 62 63 pathway modulators, 9-10 Reactive arthritis, 3t, 34t, 38, 42, Q67 soft tissue abnormalities and. 2 Receptor activator of nuclear factor kappa B ligand (RANKL), 20 p ANCA antibody,6t Relapsing polychondritis, 3t, 88-89, 88f, Q92 Panuveitis,87 Renal amyloidosis, Q72 Parvovirus 819, 17,76, Q53 Patient history Repetitive motion, OA and, 23 Retiform purpura,82f \: musculoskeletal examination and, 1, Q2o Retinal vasculitis. 87 Pegloticase, 15, 161,71, Q61 Rheumatic disease .. Pencil-in-cup deformity, 40f MMR vaccine in, Q43 Pericarditis, SLE and, 45, Q91 physical therapy,15 u Periodontal disease, RA and, 17 therapeutics, S 17 ; l 178 \

lndex Rheumatic fever. 3t ocular manifestations of, 3t Rheumatoid arthritis (RA) pathophysiolos/,32 33 approach to, 22f Staphylococcus oureus, 74 classification criteria, 18t Staphylococcus epidermidis, 74 , Q74 diagnosis of, 18-20, Q32, Q37, Q44 Statins, myopathy induced by, 54t evaluation of, Q83 Stiffness, morning,2 hands, 18f Still disease, adult-onset, 3t, 90, Q39 imaging studies, 19-20, Q90 Subacute cutaneous lupus erythematosus (SCLE), 43, Q84 inflammatory cascade in, 12f Sulfasaiazine, 10, 111, 161, 42 internal organ involvement in,4t Surgery interstitial lung disease in, Q17 ioint replacement, Q50 laboratory studies, 19, Q70 for osteoarthritis, 30 management of, 21-23 for RA, 23 monoarticular pain, Q87 Sweet syndrome, 20 ocular manifestations o[, 3t Synovial fluid, 1, 8, 8t, 73 patholory of, 17 Synovitis, 7, 20 radiologic findings, 7t Systemic lupus erythematosus (SLE) risk factors, 17, Q9 autoantibodies in, 48t treatment during pregnancy, Q57 cardiovascular involvement. 45 treatment of, Q36 ciassiflcation of. 47t Rheumatoid factor, 5, 61, 19, Q44, Q7o clinical manifestations, 43-46 Rheumatoid nodules. 21f dermatologic manifestations of, 3t Rheumatologic disease diagnosis ol 46 48 extra-articular features of 2 epidemiolog/ of, 42 43 laboratory studies in, 2 5 flares in pregnancy, Q95 Rilonacept, 14t,16t hematologic involvement, 45 46 Rituximab internal organ involvement in, 4t for AAV 84, Q33 ioint pain in, Q25 characteristics of, 14t kidney involvement, 44 45 for IgG4 related diseases, 92, 92t, Q68 lupus nephritis, Q77 for IIM. 59 medications tirr. 49t in pregnancy, 16t musculoskeletal in\,0lvement, 44 for RA. 22 nephritis in, Q46 for SLE. 50 neuropsychiatric involvement, 45 for SSc. 64 65 ocular manifestations of. 3t Rotator cufftendon repair, 17 osteonecrosis and. 4'l Rubella, T6 pathophysiolog/ of l2-43 patient assessment, Q19 5 pericarditis in, Q91 Sacroiliac joints, 391 pregnancy and, Q88 Sacroiliitis, 37, 39f prognosis, 51 Saliva, artificial, 52 pulmonary involvement. 45 Solmonello,38 subcutaneous. 43f Sarcoidosis. 3t, 4t, 90 92, gof, Q71 treatment of, Q75 Sariiumab, 14t, 16t Systemic sclerosis (SSc), 59 65 Sausage digits, 2 capillary loops in. 63f Sclerederma, 61t classiflcation ln.60t Scleritis, 21 cutaneous, Q59 Scleroderma spectrum disorders, 611, 63 64, Q15 digital pitting. 63f Scleromyxedema, 61t internal organ involvement in, 4t Seagull erosions, 24, 24f interstitial lung disease in, Q62 Secukinumab, l4t, l6t manifestations of, 3t, 60-64 Sensory neuropathy, 25t treatment of, 65t Serotonin-norepinephrine reuptake inhibitors (SNRIs), Systemic sclerosis sine scleroderma, 60, 61t 10,32 Systemic vasculitis. 3t, 78-87 Shawl sign, 56f Shigello,38 T Sicca, management of, 52 Tacrolimus, fbr llM, 59 Sjogren syndrome Tai chi, 17, Q34 diagnosis of, Q60 Takayasu arteritis, 81.811. Q22 epidemiolory, Sl Telangiectasias, mat like. 60 Iymphomas in,51, Q79 Tendonitis, ultrasonography of, 7 ocular manifestations of, 3t, 21 Thalidomide for Behqet syndrome, 88 oral dryness in, Q26 Thrombocytopenia. SLE and. 45 prognosis,52 53 Tissue biopsies, 8 Skin Tocilizumab, 141, 161, 22. 88 rheumatoid arthritis, 20 Toes rheumatologic disease and, 2 dactylitis, 37f Sleep hygiene, 9 gout,68,68f Small vessel cutaneous vasculitis, 21 Tofacitinib, 11t, 16t Smoking, inflammation and, u Tophaceous gout, Q21, Qbl Smoking cessation, Q9 Tophi,68 Soft-tissue abnormalities, 2 Total ioint arthroplasty. 17 Soft tissue iniuries, mechanical, Q42 Tramadol, 10, 161. 29. 32 Spine, ossification ol 35 TRAPS (tumor necrosis factor receptor-associated periodic fever Spondyloarthritis, 2 syndrome), 89,891 assessment of 35t Tricyclic antidepressants, 32 features of. 34t Tumor necrosis factor inhibitors, 13, 13t, 161, 41, 42t, Q14 HLA-B27 testing, QS imaging studies, 39-41 U laboratory studies in, 38 39 Ulcerations in Behqet syndrome, Q1 MRI.7 Ultrasonography, 7. 79 20, 69

Rheumatic fever. 3t ocular manifestations of, 3t Rheumatoid arthritis (RA) pathophysiolos/,32 33 approach to, 22f Staphylococcus oureus, 74 classification criteria, 18t Staphylococcus epidermidis, 74 , Q74 diagnosis of, 18-20, Q32, Q37, Q44 Statins, myopathy induced by, 54t evaluation of, Q83 Stiffness, morning,2 hands, 18f Still disease, adult-onset, 3t, 90, Q39 imaging studies, 19-20, Q90 Subacute cutaneous lupus erythematosus (SCLE), 43, Q84 inflammatory cascade in, 12f Sulfasaiazine, 10, 111, 161, 42 internal organ involvement in,4t Surgery interstitial lung disease in, Q17 ioint replacement, Q50 laboratory studies, 19, Q70 for osteoarthritis, 30 management of, 21-23 for RA, 23 monoarticular pain, Q87 Sweet syndrome, 20 ocular manifestations o[, 3t Synovial fluid, 1, 8, 8t, 73 patholory of, 17 Synovitis, 7, 20 radiologic findings, 7t Systemic lupus erythematosus (SLE) risk factors, 17, Q9 autoantibodies in, 48t treatment during pregnancy, Q57 cardiovascular involvement. 45 treatment of, Q36 ciassiflcation of. 47t Rheumatoid factor, 5, 61, 19, Q44, Q7o clinical manifestations, 43-46 Rheumatoid nodules. 21f dermatologic manifestations of, 3t Rheumatologic disease diagnosis ol 46 48 extra-articular features of 2 epidemiolog/ of, 42 43 laboratory studies in, 2 5 flares in pregnancy, Q95 Rilonacept, 14t,16t hematologic involvement, 45 46 Rituximab internal organ involvement in, 4t for AAV 84, Q33 ioint pain in, Q25 characteristics of, 14t kidney involvement, 44 45 for IgG4 related diseases, 92, 92t, Q68 lupus nephritis, Q77 for IIM. 59 medications tirr. 49t in pregnancy, 16t musculoskeletal in\,0lvement, 44 for RA. 22 nephritis in, Q46 for SLE. 50 neuropsychiatric involvement, 45 for SSc. 64 65 ocular manifestations of. 3t Rotator cufftendon repair, 17 osteonecrosis and. 4'l Rubella, T6 pathophysiolog/ of l2-43 patient assessment, Q19 5 pericarditis in, Q91 Sacroiliac joints, 391 pregnancy and, Q88 Sacroiliitis, 37, 39f prognosis, 51 Saliva, artificial, 52 pulmonary involvement. 45 Solmonello,38 subcutaneous. 43f Sarcoidosis. 3t, 4t, 90 92, gof, Q71 treatment of, Q75 Sariiumab, 14t, 16t Systemic sclerosis (SSc), 59 65 Sausage digits, 2 capillary loops in. 63f Sclerederma, 61t classiflcation ln.60t Scleritis, 21 cutaneous, Q59 Scleroderma spectrum disorders, 611, 63 64, Q15 digital pitting. 63f Scleromyxedema, 61t internal organ involvement in, 4t Seagull erosions, 24, 24f interstitial lung disease in, Q62 Secukinumab, l4t, l6t manifestations of, 3t, 60-64 Sensory neuropathy, 25t treatment of, 65t Serotonin-norepinephrine reuptake inhibitors (SNRIs), Systemic sclerosis sine scleroderma, 60, 61t 10,32 Systemic vasculitis. 3t, 78-87 Shawl sign, 56f Shigello,38 T Sicca, management of, 52 Tacrolimus, fbr llM, 59 Sjogren syndrome Tai chi, 17, Q34 diagnosis of, Q60 Takayasu arteritis, 81.811. Q22 epidemiolory, Sl Telangiectasias, mat like. 60 Iymphomas in,51, Q79 Tendonitis, ultrasonography of, 7 ocular manifestations of, 3t, 21 Thalidomide for Behqet syndrome, 88 oral dryness in, Q26 Thrombocytopenia. SLE and. 45 prognosis,52 53 Tissue biopsies, 8 Skin Tocilizumab, 141, 161, 22. 88 rheumatoid arthritis, 20 Toes rheumatologic disease and, 2 dactylitis, 37f Sleep hygiene, 9 gout,68,68f Small vessel cutaneous vasculitis, 21 Tofacitinib, 11t, 16t Smoking, inflammation and, u Tophaceous gout, Q21, Qbl Smoking cessation, Q9 Tophi,68 Soft-tissue abnormalities, 2 Total ioint arthroplasty. 17 Soft tissue iniuries, mechanical, Q42 Tramadol, 10, 161. 29. 32 Spine, ossification ol 35 TRAPS (tumor necrosis factor receptor-associated periodic fever Spondyloarthritis, 2 syndrome), 89,891 assessment of 35t Tricyclic antidepressants, 32 features of. 34t Tumor necrosis factor inhibitors, 13, 13t, 161, 41, 42t, Q14 HLA-B27 testing, QS imaging studies, 39-41 U laboratory studies in, 38 39 Ulcerations in Behqet syndrome, Q1 MRI.7 Ultrasonography, 7. 79 20, 69 179

lndex Undifferentiated connective tissue disease (ICTD), 66t Viral infections, T6-z Upadacitinib, 111, 16t Vision loss, 2 Urate-lowering therapy, 13-15, 70, Q52 Vitamin D, intake of 50 Uric acid, gout and, 67 Voclosporin, Ut Uricosuric agents, 15, 71 Ustekinumab, 141, 16t w Uveitis, treatment of, 41 Weight loss for osteoarthritis, Q82 U x Vaccination in immunosuppression, 15 Xanthine oxidase inhibitors, 70-71 Vasculitis Xerostoma, medication-induced, Q47 derrnatologic manifestations of, 3t Y differential diagnoses, 79t Yamaguchi criteria, 90 hypersensitivity, 9 Yersinio spp., 38 ocular manifestations of, 3t Yoga,77 RA and,21 secondary 79t z skin manifestations, 20 Zidorudine, myopathy induced by, 54t Vertebral fractures, 36 Zika virus.76 l i i : 180 a i i