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Approach to the Patient With Rheumatologic Disease TABLE 4. lnternal Organ lnvolvement in Rheumatologic Disease Disease Type of lnvolvement Heart Kawasaki disease Coronary artery vasculitis Systemic sclerosis Arrhythmia; myocardial fibrosis SLE Pericarditis; valvular disease; myocarditis RA Perica rditis; myocarditis Rheumatic fever; antiphospholipid syndrome Valvular disease Giant cell arteritis Aortic aneurysm/dissection; aortitis; large'vessel obstruction Sarcoidosis Atrioventricular block; a mia; cardiom Lung RA Serositis; ILD; rheumatoid nodules SLE; CTDs; myositis; Henoch-Schonlein purpura Serositis; pneumonitis; pulmonary hemorrhage from vasculitis Pulmonary hemorrhage; cavitary nodules Diffuse cutaneous systemic sclerosis ILD; pulmonary hypertension Limited cutaneous systemic sclerosis Pulmonary hypertension Antiphospholipid syndrome Pulmonary embolism; pulmonary hemorrhage in catastrophic antiphospholipid syndrome Sarcoidosis Hilar lymphadenopathy; ILD Goodpasture syndrome Pulmonary hemorrhage Kidney SLE; CTDs; AAV systemic vasculitis (except PAN) G lomeru loneph ritis PAN Renal artery vasculitis; pseudoaneurysms Antiphospholipid syndrome Renal infarct; renal vein thrombosis

Limited cutaneous systemic sclerosis Pulmonary hypertension Antiphospholipid syndrome Pulmonary embolism; pulmonary hemorrhage in catastrophic antiphospholipid syndrome Sarcoidosis Hilar lymphadenopathy; ILD Goodpasture syndrome Pulmonary hemorrhage Kidney SLE; CTDs; AAV systemic vasculitis (except PAN) G lomeru loneph ritis PAN Renal artery vasculitis; pseudoaneurysms Antiphospholipid syndrome Renal infarct; renal vein thrombosis Sjogren syndrome Acute interstitial nephritis/renal tu bular acidosis Goodpasture syndrome G lomeru lonephritis Gastrointestinal System PAN Mesenteric vasculitis Henoch-Schonlein purpura lntestinal vasculitis and ulcerations Diffuse and limited cutaneous systemic sclerosis Esophageal and small-bowel hypomotility BehEet syndrome Mucosal ulcerations Familial Mediterranean fever Peritonitis Nervous System SLE; CTDs; AAV; systemic vasculitis CNS involvement may include mental status changes, stroke, seizures; peripheral involvement may include mononeuritis multiplex and peripheral neuropathy PACNS CNS vasculitis AAV = ANCA associated vasculitis; CNS = central nervous system; CTD = con nective tissue disease; I LD = interstitial lung disease; PACNS = primar angiitis o{ the central nerous system; PAN = polyarteritis nodosa; RA = rheumatoid afthritis; SLE = systemic lupus erythematosus.

Gastrointestinal System PAN Mesenteric vasculitis Henoch-Schonlein purpura lntestinal vasculitis and ulcerations Diffuse and limited cutaneous systemic sclerosis Esophageal and small-bowel hypomotility BehEet syndrome Mucosal ulcerations Familial Mediterranean fever Peritonitis Nervous System SLE; CTDs; AAV; systemic vasculitis CNS involvement may include mental status changes, stroke, seizures; peripheral involvement may include mononeuritis multiplex and peripheral neuropathy PACNS CNS vasculitis AAV = ANCA associated vasculitis; CNS = central nervous system; CTD = con nective tissue disease; I LD = interstitial lung disease; PACNS = primar angiitis o{ the central nerous system; PAN = polyarteritis nodosa; RA = rheumatoid afthritis; SLE = systemic lupus erythematosus. In addition to inflammatory conditions, ESRs can be A markedly elevated ESR (>100 mm/h) should alert phy- elevated in pregnancy, diabetes mellitus, obesiry and end- sicians to conditions such as giant cell arteritis, multiple mye- stage kidney disease. Because ofrheostatic properties, anemia loma, metastatic cancer, or other overwhelming inflammatory and macrocytosis are also associated with an increased ESR. states (infection or autoimmune disease). ESR can be excessively low in low-fibrinogen states, such as liver or heart failure, and in conditions promoting rouleaux C-Reactive Protein formation (e.g., polycythemia vera). Sickle cell disease and C-reactive protein (CRP) is produced by the liver mainly in microcytosis (including spherocytosis) may also decrease response to interleukin-6 generated by leukocytes during ESR. the inflammatory state. CRP levels and ESR usually follow a

In addition to inflammatory conditions, ESRs can be A markedly elevated ESR (>100 mm/h) should alert phy- elevated in pregnancy, diabetes mellitus, obesiry and end- sicians to conditions such as giant cell arteritis, multiple mye- stage kidney disease. Because ofrheostatic properties, anemia loma, metastatic cancer, or other overwhelming inflammatory and macrocytosis are also associated with an increased ESR. states (infection or autoimmune disease). ESR can be excessively low in low-fibrinogen states, such as liver or heart failure, and in conditions promoting rouleaux C-Reactive Protein formation (e.g., polycythemia vera). Sickle cell disease and C-reactive protein (CRP) is produced by the liver mainly in microcytosis (including spherocytosis) may also decrease response to interleukin-6 generated by leukocytes during ESR. the inflammatory state. CRP levels and ESR usually follow a 4

Approach to the Patient With Rheumatologic Disease common pattern, but CRP is often more rapidly responsive to Antinuclear antibodies (ANAs) are directed against changes in inflammation. In rheumatologic conditions, CRP is nuclear antigens and are traditionally associated with SLE. Up typically elevated 2 to l0 times the normal level; a higher level to one third of the healthy population has a low titer (1:40) for (especially >10 mg/dl [tOO mg/L]) should prompt considera, ANA, and up to 5'X, have a titer of 1:160 or more. ANA can also tion of an alternative diagnosis, such as infection. CRP is be seen in other autoimmune conditions, infection, and thought to be a better marker than ESR for measuring inflam malignancy and may be drug induced. ANA testing should not mation in spondyloarthritis. In contrast, in some patients with be performed in a patient with nonspecific symptoms and SLE, ESR is a better marker of disease activity and the CRP normal findings on clinical examination because it does not level may remain normal despite active disease. An elevated establish the diagnosis of a connective tissue disease. CRP level in a patient with SLE is often related to infection. A higher ANA titer is more often associated with an CRP can be elevated in obesity and low with the use of certain underlying rheumatologic disease, although not always SLE. antibiotics and interleukin 6 blockers. However, almost all patients with SLE (>95'/") are positive for ANA. ANA titer does not correlate with SLE disease activi!/ Complement and should not be used fbr activity assessment. The complement system is an essential part of the immune ANA specificity or subserologz testing (i.e., testing for response, promoting vasodilation, attracting leukocy.tes, and antibodies to specific nuclear components, such as DNA or assisting in the lysis of opsonized bacteria during humoral centromeres) should be reserved for patients positive fbr ANA immunity. and a clinical syndrome suggesting an underlying connective Complement components are acute phase reactants that tissue disease. ANA subserologr testing should not be rou are synthesized in the liver and rise in many inflammatory tinely performed, even in the setting of a positive ANA result, states. However, in response to diseases that lead to immune without a strong clinical suspicion of an underlying connec complex formation (SLE; cryoglobulinemic and urticarial vas- tive tissue disease. culitis) and other states, such as infections (subacute bacterial Table 5 provides details on these and other autoantibodies endocarditis, sepsis, viremia) and glomerulonephritis, com and their associations with specific conditions. plement cascades are activated, and complement levels fall XEY POItrII because of excessive consumption. Paradoxically, genetic defi ciency of early complement components may increase the risk . Erythrocyte sedimentation rate and C-reactive protein (CRP) levels usually follow a common pattern, but CRP tbr lupus like autoimmune diseases. is often more rapidly responsive to changes in inflam- C3 and C4 are the commonly measured complement mation. components. The CH50 assay should not be perlbrmed rou tinely because of cost and limited utility. o Antinuclear antibody testing should not be perfbrmed HVC in a patient with nonspecific symptoms and normal Autoantibody Tests findings on clinical examination because it does not Rheumatologic diseases are commonly associated with establish the diagnosis of a connective tissue disease. autoantibodies, but their presence does not equate with the . Antinuclear antibody (ANA) subserologr testing should HVC diagnosis ol an underlying condition because they lack speci not be routinely performed, even in the setting of a pos ficity and may be seen in patients with other conditions and in itive ANA result, without strong clinical suspicion of an healthy persons. In commercial laboratories, autoantibody underlying connective tissue disease. testing has been automated with enzyme-linked immuno- sorbent assays in a sequential algorithm, which may simplify physician assessment but tend to have reduced sensitivity and specificity. lmaging Studies Rheumatoid lactor is an IgM antibody directed against the Radiography Fc portion of IgG. Although characteristically associated with Radiography is essential in the evaluation of many rheuma RA. rheumatoid factor is present in less than 70'X, of patients tologic diseases and can assess and differentiate inflamma with RA and is common in several other diseases, such as bac- tory arthritis, osteoarthritis, and crystal arthropathies terial endocarditis and hepatitis C vims infection' Anti cyclic (Table 6). Radiography has limitations because it gives a two

common pattern, but CRP is often more rapidly responsive to Antinuclear antibodies (ANAs) are directed against changes in inflammation. In rheumatologic conditions, CRP is nuclear antigens and are traditionally associated with SLE. Up typically elevated 2 to l0 times the normal level; a higher level to one third of the healthy population has a low titer (1:40) for (especially >10 mg/dl [tOO mg/L]) should prompt considera, ANA, and up to 5'X, have a titer of 1:160 or more. ANA can also tion of an alternative diagnosis, such as infection. CRP is be seen in other autoimmune conditions, infection, and thought to be a better marker than ESR for measuring inflam malignancy and may be drug induced. ANA testing should not mation in spondyloarthritis. In contrast, in some patients with be performed in a patient with nonspecific symptoms and SLE, ESR is a better marker of disease activity and the CRP normal findings on clinical examination because it does not level may remain normal despite active disease. An elevated establish the diagnosis of a connective tissue disease. CRP level in a patient with SLE is often related to infection. A higher ANA titer is more often associated with an CRP can be elevated in obesity and low with the use of certain underlying rheumatologic disease, although not always SLE. antibiotics and interleukin 6 blockers. However, almost all patients with SLE (>95'/") are positive for ANA. ANA titer does not correlate with SLE disease activi!/ Complement and should not be used fbr activity assessment. The complement system is an essential part of the immune ANA specificity or subserologz testing (i.e., testing for response, promoting vasodilation, attracting leukocy.tes, and antibodies to specific nuclear components, such as DNA or assisting in the lysis of opsonized bacteria during humoral centromeres) should be reserved for patients positive fbr ANA immunity. and a clinical syndrome suggesting an underlying connective Complement components are acute phase reactants that tissue disease. ANA subserologr testing should not be rou are synthesized in the liver and rise in many inflammatory tinely performed, even in the setting of a positive ANA result, states. However, in response to diseases that lead to immune without a strong clinical suspicion of an underlying connec complex formation (SLE; cryoglobulinemic and urticarial vas- tive tissue disease. culitis) and other states, such as infections (subacute bacterial Table 5 provides details on these and other autoantibodies endocarditis, sepsis, viremia) and glomerulonephritis, com and their associations with specific conditions. plement cascades are activated, and complement levels fall XEY POItrII because of excessive consumption. Paradoxically, genetic defi ciency of early complement components may increase the risk . Erythrocyte sedimentation rate and C-reactive protein (CRP) levels usually follow a common pattern, but CRP tbr lupus like autoimmune diseases. is often more rapidly responsive to changes in inflam- C3 and C4 are the commonly measured complement mation. components. The CH50 assay should not be perlbrmed rou tinely because of cost and limited utility. o Antinuclear antibody testing should not be perfbrmed HVC in a patient with nonspecific symptoms and normal Autoantibody Tests findings on clinical examination because it does not Rheumatologic diseases are commonly associated with establish the diagnosis of a connective tissue disease. autoantibodies, but their presence does not equate with the . Antinuclear antibody (ANA) subserologr testing should HVC diagnosis ol an underlying condition because they lack speci not be routinely performed, even in the setting of a pos ficity and may be seen in patients with other conditions and in itive ANA result, without strong clinical suspicion of an healthy persons. In commercial laboratories, autoantibody underlying connective tissue disease. testing has been automated with enzyme-linked immuno- sorbent assays in a sequential algorithm, which may simplify physician assessment but tend to have reduced sensitivity and specificity. lmaging Studies Rheumatoid lactor is an IgM antibody directed against the Radiography Fc portion of IgG. Although characteristically associated with Radiography is essential in the evaluation of many rheuma RA. rheumatoid factor is present in less than 70'X, of patients tologic diseases and can assess and differentiate inflamma with RA and is common in several other diseases, such as bac- tory arthritis, osteoarthritis, and crystal arthropathies terial endocarditis and hepatitis C vims infection' Anti cyclic (Table 6). Radiography has limitations because it gives a two citrullinated peptide antibodies are more specific (95%) for RA dimensional picture of three dimensional structures, is lim- but less sensitive (67'7,). The presence of both autoantibodies ited in its ability to visualize soft tissues, and may not detect together increases the Iikelihood of RA. Patients with RA who early or small erosive changes. Despite these limitations, have anti cyclic citrullinated peptide antibodies are more radiography is usually the first imaging test ordered in the likely to experience rapid joint damage from erosive disease. evaluation of rheumatologic diseases because it is readily Patients with hepatitis C virus infection alone are typically available, is inexpensive, exposes patients to only a low level positive for rheumatoid factor but negative for anti-cyclic of ionizing radiation, and is useful in monitoring arthritis citrullinated peptide antibodies. progression.

citrullinated peptide antibodies are more specific (95%) for RA dimensional picture of three dimensional structures, is lim- but less sensitive (67'7,). The presence of both autoantibodies ited in its ability to visualize soft tissues, and may not detect together increases the Iikelihood of RA. Patients with RA who early or small erosive changes. Despite these limitations, have anti cyclic citrullinated peptide antibodies are more radiography is usually the first imaging test ordered in the likely to experience rapid joint damage from erosive disease. evaluation of rheumatologic diseases because it is readily Patients with hepatitis C virus infection alone are typically available, is inexpensive, exposes patients to only a low level positive for rheumatoid factor but negative for anti-cyclic of ionizing radiation, and is useful in monitoring arthritis citrullinated peptide antibodies. progression. 5

1 I 'l 1 Approach to the Patient With Rheumatologic Disease I a I I It Autoantibody Rheumatologic Disease Sensitivity/Specificity Comments I SLE: >95% sensitivity, Poor Does not correlate with disease activity \I ANA SLE; also SSc, Sjogren syndrome, MCTD specificity; indirect IFA is the most appropriate method i t

SLE: >95% sensitivity, Poor Does not correlate with disease activity \I ANA SLE; also SSc, Sjogren syndrome, MCTD specificity; indirect IFA is the most appropriate method i t Anti-double-stranded SLE 507"- 60"/" se nsitivity, >9 5% Found in more severe disease, especially kidney DNA specificity; Crithidia IFA or disease; antibody levels commonly follow disease I Farr assays more specific than ELISA activity and are usefulto monitor l I

Anti-double-stranded SLE 507"- 60"/" se nsitivity, >9 5% Found in more severe disease, especially kidney DNA specificity; Crithidia IFA or disease; antibody levels commonly follow disease I Farr assays more specific than ELISA activity and are usefulto monitor l I Most specific test for SLE; does not correlate Anti-Smith SLE 30% sensitivity,99% specificity with disease activity I Anti-U 1-RNP MCTD; SLE High sensitivity for MCTD High titer seen in MCTD (>1 :1 0,000); does not I correlate with disease activity 1 I Anti-Ro/SSA; Sjogren syndrome; SLE; Sjogren syndrome: 7095 Sicca symptoms; in SLE, associated with anti-La/SSB RA; SSC sensitivity; SLE:20% photosensitive rash; offspring of mothers who sensitivity are positive for anti-Ro/SSA or anti-La/SSB are at ) increased risk for neonatal lupus erythematosus t I (rash and congenital heart block)

Most specific test for SLE; does not correlate Anti-Smith SLE 30% sensitivity,99% specificity with disease activity I Anti-U 1-RNP MCTD; SLE High sensitivity for MCTD High titer seen in MCTD (>1 :1 0,000); does not I correlate with disease activity 1 I Anti-Ro/SSA; Sjogren syndrome; SLE; Sjogren syndrome: 7095 Sicca symptoms; in SLE, associated with anti-La/SSB RA; SSC sensitivity; SLE:20% photosensitive rash; offspring of mothers who sensitivity are positive for anti-Ro/SSA or anti-La/SSB are at ) increased risk for neonatal lupus erythematosus t I (rash and congenital heart block) Antiribosomal P SLE 15% sensitivity Associated with CNS lupus and lupus hepatitis l I ,,]

Antiribosomal P SLE 15% sensitivity Associated with CNS lupus and lupus hepatitis l I ,,] Anti-Scl-70 DcSSc 10%-30% sensitivity Seen more often in patients with DcSSc who have (antitopoisomerase-1 ) ILD leading to pulmonary fibrosis ; Anticentromere LcSSc (CREST) 10%-30% sensitivity Patients with LcSSc with this antibody are more likely to develop pulmonary arterial hypertension c-ANCA GPA 90% sensitivity when disease Correlation with disease activity is unclear (antiproteinase-3) is active; high specificity in classic presentations

c-ANCA GPA 90% sensitivity when disease Correlation with disease activity is unclear (antiproteinase-3) is active; high specificity in classic presentations p-ANCA MPA; EGPA MPA: 80% sensitivity; Atypical p-ANCA (antimyeloperoxidase (antimyeloperoxidase) EGPA: 60% sensitivity; less negative) can be seen in inflammatory bowel I specific than c-ANCA disease and with positivity for ANA; may be seen in drug-induced vasculitis Anti-Jo-1 Polymyositis 20%-30% sensitivity Associated with antisynthetase syndrome, which may include mechanic! hands, Raynaud phenomenon, and lung inflammation Anti-SRP Polymyositis Found in 5% of patients with Associated with immune-mediated necrotizing myositis myopathy with muscle fiber necrosis and minimal inflammation on biopsy Anti-Mi-2 Dermatomyositis Rare Acute onset of skin rash in shawl distribution, usually responsive to treatment Anti-TlF-1-1 Dermatomyositis Approximately 70% lncreased risk for malignancy; also seen in sensitivity and 90% specificity juvenile dermatomyositis Anti-MDA-5 Dermatomyositis Rare Associated with rapid lLD, cutaneous ulcerations, Gottron papules; poorer prognosis Rheumatoid factor RA; Sjogren syndrome; RA: 70% sensitivity; limited RF is common in multiple other diseases (e.9., cryoglobulinemia specificity, especially in hepatitis C virus infection, endocarditis, SLE); patients without a classic 30% of patients with RA are RF negative but may disease presentation become positive later in RA course Anti-cyclic RA 70% sensitivity; Can be positive in RF-negative patients with RA; citrullinated peptide 95% speciflcity often present before RF becomes positive; associated with erosions; predicts disease progression in undifferentiated arthritis Antihistone DILE 95% sensitivity; poor Also seen in primary SLE specificity Cryoglobulins Vasculitis; hepatitis C Type ll or lll cryoglobulins May be present in connective tissue diseases in virus infection; myeloma; seen in cryoglobulinemic the absence of vasculitis SLE; RA vasculitis ANA = antinuclear antibody; CNS = central nerous system; CREST = calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia; DcSSc = difuse cutaneous systemic sclerosis; DILE = drug induced lupus erythematosus; EGPA = eosinophilic granulomatosis with polyangiitis; ELISA = enzyme-linked immunosorbent assay;

p-ANCA MPA; EGPA MPA: 80% sensitivity; Atypical p-ANCA (antimyeloperoxidase (antimyeloperoxidase) EGPA: 60% sensitivity; less negative) can be seen in inflammatory bowel I specific than c-ANCA disease and with positivity for ANA; may be seen in drug-induced vasculitis Anti-Jo-1 Polymyositis 20%-30% sensitivity Associated with antisynthetase syndrome, which may include mechanic! hands, Raynaud phenomenon, and lung inflammation Anti-SRP Polymyositis Found in 5% of patients with Associated with immune-mediated necrotizing myositis myopathy with muscle fiber necrosis and minimal inflammation on biopsy Anti-Mi-2 Dermatomyositis Rare Acute onset of skin rash in shawl distribution, usually responsive to treatment Anti-TlF-1-1 Dermatomyositis Approximately 70% lncreased risk for malignancy; also seen in sensitivity and 90% specificity juvenile dermatomyositis Anti-MDA-5 Dermatomyositis Rare Associated with rapid lLD, cutaneous ulcerations, Gottron papules; poorer prognosis Rheumatoid factor RA; Sjogren syndrome; RA: 70% sensitivity; limited RF is common in multiple other diseases (e.9., cryoglobulinemia specificity, especially in hepatitis C virus infection, endocarditis, SLE); patients without a classic 30% of patients with RA are RF negative but may disease presentation become positive later in RA course Anti-cyclic RA 70% sensitivity; Can be positive in RF-negative patients with RA; citrullinated peptide 95% speciflcity often present before RF becomes positive; associated with erosions; predicts disease progression in undifferentiated arthritis Antihistone DILE 95% sensitivity; poor Also seen in primary SLE specificity Cryoglobulins Vasculitis; hepatitis C Type ll or lll cryoglobulins May be present in connective tissue diseases in virus infection; myeloma; seen in cryoglobulinemic the absence of vasculitis SLE; RA vasculitis ANA = antinuclear antibody; CNS = central nerous system; CREST = calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia; DcSSc = difuse cutaneous systemic sclerosis; DILE = drug induced lupus erythematosus; EGPA = eosinophilic granulomatosis with polyangiitis; ELISA = enzyme-linked immunosorbent assay; tissue diseasei MDA = melanoma diferentiation-associated; MPA = microscopic polyangiitis; RA = rheumatoid arthritis; RF = rheumatoid factor; RNp = ribonucleoprotein; SLE = systemic lupus erythematosus; SRP = signal recognition particle; SSc = systemic sclerosis; TIF = transcription intermediary factor.

p-ANCA MPA; EGPA MPA: 80% sensitivity; Atypical p-ANCA (antimyeloperoxidase (antimyeloperoxidase) EGPA: 60% sensitivity; less negative) can be seen in inflammatory bowel I specific than c-ANCA disease and with positivity for ANA; may be seen in drug-induced vasculitis Anti-Jo-1 Polymyositis 20%-30% sensitivity Associated with antisynthetase syndrome, which may include mechanic! hands, Raynaud phenomenon, and lung inflammation Anti-SRP Polymyositis Found in 5% of patients with Associated with immune-mediated necrotizing myositis myopathy with muscle fiber necrosis and minimal inflammation on biopsy Anti-Mi-2 Dermatomyositis Rare Acute onset of skin rash in shawl distribution, usually responsive to treatment Anti-TlF-1-1 Dermatomyositis Approximately 70% lncreased risk for malignancy; also seen in sensitivity and 90% specificity juvenile dermatomyositis Anti-MDA-5 Dermatomyositis Rare Associated with rapid lLD, cutaneous ulcerations, Gottron papules; poorer prognosis Rheumatoid factor RA; Sjogren syndrome; RA: 70% sensitivity; limited RF is common in multiple other diseases (e.9., cryoglobulinemia specificity, especially in hepatitis C virus infection, endocarditis, SLE); patients without a classic 30% of patients with RA are RF negative but may disease presentation become positive later in RA course Anti-cyclic RA 70% sensitivity; Can be positive in RF-negative patients with RA; citrullinated peptide 95% speciflcity often present before RF becomes positive; associated with erosions; predicts disease progression in undifferentiated arthritis Antihistone DILE 95% sensitivity; poor Also seen in primary SLE specificity Cryoglobulins Vasculitis; hepatitis C Type ll or lll cryoglobulins May be present in connective tissue diseases in virus infection; myeloma; seen in cryoglobulinemic the absence of vasculitis SLE; RA vasculitis ANA = antinuclear antibody; CNS = central nerous system; CREST = calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia; DcSSc = difuse cutaneous systemic sclerosis; DILE = drug induced lupus erythematosus; EGPA = eosinophilic granulomatosis with polyangiitis; ELISA = enzyme-linked immunosorbent assay; tissue diseasei MDA = melanoma diferentiation-associated; MPA = microscopic polyangiitis; RA = rheumatoid arthritis; RF = rheumatoid factor; RNp = ribonucleoprotein; SLE = systemic lupus erythematosus; SRP = signal recognition particle; SSc = systemic sclerosis; TIF = transcription intermediary factor. 6

Approach to the Patient With Rheumatologic Disease TABLE 6. Standard Radiographic Findings of Common Rheumatologic Diseases RheumatologicDisease RadiographicFindings Rheumatoid arthritis Soft-tissue swelling and periarticular osteopenia early; bony marginal erosions and uniform joint-space narrowing later Swan neck deformity and ulnar deviation if unresponsive or untreated; MCB PIB wrist, and MTP involvement; noncalcified soft-tissue nodules Osteoarthritis Asymmetric joint space narrowing; osteophytes; subchondral sclerosis and cystic changes; degenerative disk disease with collapse of disks; degenerative joint disease with facet joint osteophytes; spondylolisthesis (anterior/posterior misalignment of the spine); kyphosis Diffuse idiopathic skeletal Calcification (ossification)o{ anterior longitudinal ligament (bone spurs); bridging horizontal hyperostosis syndesmophytes; usually seen in thoracic spine and more prominent on right side of spine Ankylosing spondylitis Sacroiliitis best seen on modified anteroposterior Ferguson view of sacrum on radiograph, usually bilateral; squaring o{ the vertebral bodies in early disease; bridging vertical syndesmophytes (ossification o{ annulus fibrosus) in later disease; shiny corners; ankylosis does not skip veftebrae

TABLE 6. Standard Radiographic Findings of Common Rheumatologic Diseases RheumatologicDisease RadiographicFindings Rheumatoid arthritis Soft-tissue swelling and periarticular osteopenia early; bony marginal erosions and uniform joint-space narrowing later Swan neck deformity and ulnar deviation if unresponsive or untreated; MCB PIB wrist, and MTP involvement; noncalcified soft-tissue nodules Osteoarthritis Asymmetric joint space narrowing; osteophytes; subchondral sclerosis and cystic changes; degenerative disk disease with collapse of disks; degenerative joint disease with facet joint osteophytes; spondylolisthesis (anterior/posterior misalignment of the spine); kyphosis Diffuse idiopathic skeletal Calcification (ossification)o{ anterior longitudinal ligament (bone spurs); bridging horizontal hyperostosis syndesmophytes; usually seen in thoracic spine and more prominent on right side of spine Ankylosing spondylitis Sacroiliitis best seen on modified anteroposterior Ferguson view of sacrum on radiograph, usually bilateral; squaring o{ the vertebral bodies in early disease; bridging vertical syndesmophytes (ossification o{ annulus fibrosus) in later disease; shiny corners; ankylosis does not skip veftebrae Psoriatic arthritis Destructive arthritis with erosions and osteophytes; DIP involvement is common; pencil-in-cup deformity on hand radiograph; arthritis mutilans; syndesmophytes Gout Soft-tissue swelling; punched-out erosions with sclerotic borders and overhanging edges; periarticular tophi appear as high-density radiopaque deposits Calcium pyrophosphate Chondrocalcinosis, most commonly of knees, shoulders, wrists, pubic symphysis; osteoarthritis, including deposition in locations atypical for primary osteoarthritis (MCPs, wrists, shoulders); hooked osteophytes of second and third MCP joints DIP = distal interphalangeal; MCP = metacarpophalangeal; MTP = metatarsophalangeal; PIP = proximal interphalangeal.

Psoriatic arthritis Destructive arthritis with erosions and osteophytes; DIP involvement is common; pencil-in-cup deformity on hand radiograph; arthritis mutilans; syndesmophytes Gout Soft-tissue swelling; punched-out erosions with sclerotic borders and overhanging edges; periarticular tophi appear as high-density radiopaque deposits Calcium pyrophosphate Chondrocalcinosis, most commonly of knees, shoulders, wrists, pubic symphysis; osteoarthritis, including deposition in locations atypical for primary osteoarthritis (MCPs, wrists, shoulders); hooked osteophytes of second and third MCP joints DIP = distal interphalangeal; MCP = metacarpophalangeal; MTP = metatarsophalangeal; PIP = proximal interphalangeal. CT structures, and can provide real time data in the clinic with- CT provides multiple views and orientations from a single out exposure to ionizing radiation. It can assess soft tissue study but is more useful fbr bony abnormalities than for soft abnormalities, including synovitis, tendonitis, bursitis, crystal tissue inflammation or fluid collections. CT is more sensitive deposition, and effusions; assess disease activity using Doppler for detecting bone erosions than is radiography or MRI. technolory; and assist with tendon or joint injections. However, CT is more expensive than radiography and exposes Howeveq it is operator dependent, and training and practice the patient to more radiation. It is mainly used in acute trauma are needed to achieve competence. or when a patient cannot undergo MRl. Dual ener$/ CT may t(tY P0t xTs be used to detect tissue urate deposits but is not indicated in routine testing. r Radiography is usually the first imaging test ordered in HVC the evaluation of rheumatologic diseases because it is readily available, is inexpensive, exposes patients to MRI only a low level of ionizing radiation, and is useful in MRI is the most sensitive routine radiologic technique fbr moniloring arthril is progression. detecting soft tissue abnormalities, inflammation, and fluid collections but is Iess eflective than CT in demonstrating bony o CT is more sensitive for detecting bony abnormalities or HVC

CT structures, and can provide real time data in the clinic with- CT provides multiple views and orientations from a single out exposure to ionizing radiation. It can assess soft tissue study but is more useful fbr bony abnormalities than for soft abnormalities, including synovitis, tendonitis, bursitis, crystal tissue inflammation or fluid collections. CT is more sensitive deposition, and effusions; assess disease activity using Doppler for detecting bone erosions than is radiography or MRI. technolory; and assist with tendon or joint injections. However, CT is more expensive than radiography and exposes Howeveq it is operator dependent, and training and practice the patient to more radiation. It is mainly used in acute trauma are needed to achieve competence. or when a patient cannot undergo MRl. Dual ener$/ CT may t(tY P0t xTs be used to detect tissue urate deposits but is not indicated in routine testing. r Radiography is usually the first imaging test ordered in HVC the evaluation of rheumatologic diseases because it is readily available, is inexpensive, exposes patients to MRI only a low level of ionizing radiation, and is useful in MRI is the most sensitive routine radiologic technique fbr moniloring arthril is progression. detecting soft tissue abnormalities, inflammation, and fluid collections but is Iess eflective than CT in demonstrating bony o CT is more sensitive for detecting bony abnormalities or HVC abnormalities or erosions. MRI is sensitive for detecting early erosions than is radiography or MRI, whereas MRI is the spine and sacroiliac joint inflammation and may be indicated most sensitive routine radiologic technique for detect for the evaluation of suspected spondyloarthritis ifradiographs ing soft tissue abnormalities, inflammation, and fluid are negative. MRI is also indicated in the evaluation of osteo- collections. necrosis if the findings on plain imaging are normal and sus, o Ultrasonography is an inexpensive means to assess soft HVC picion is high. MRI does not expose patients to radiation but is tissue abnormalities, assess disease activity, and assist associated with high cost, limited availability, and possible with tendon or joint injections, but it is operator patient intolerance due to claustrophobia or body habitus. The dependent. American College of Rheumatolos/ Choosing Wisely list rec ommends against routine MRI of the peripheral joints to mon- itor RA because of inadequate data supporting its use. Joint Aspiration Joint aspiration and synovial fluid analysis are essential for Ultrasonography discriminating between inflammatory and noninflammatory The use of ultrasonography to evaluate patients with rheuma efTusions and for distinguishing between infectious arthritis tologic diseases has expanded dramatically. Ultrasonography is and acute crystal arthropathies. ln the evaluation of any relatively inexpensive, can scan across three-dimensional monoarthritis or when infection is being considered, joint

abnormalities or erosions. MRI is sensitive for detecting early erosions than is radiography or MRI, whereas MRI is the spine and sacroiliac joint inflammation and may be indicated most sensitive routine radiologic technique for detect for the evaluation of suspected spondyloarthritis ifradiographs ing soft tissue abnormalities, inflammation, and fluid are negative. MRI is also indicated in the evaluation of osteo- collections. necrosis if the findings on plain imaging are normal and sus, o Ultrasonography is an inexpensive means to assess soft HVC picion is high. MRI does not expose patients to radiation but is tissue abnormalities, assess disease activity, and assist associated with high cost, limited availability, and possible with tendon or joint injections, but it is operator patient intolerance due to claustrophobia or body habitus. The dependent. American College of Rheumatolos/ Choosing Wisely list rec ommends against routine MRI of the peripheral joints to mon- itor RA because of inadequate data supporting its use. Joint Aspiration Joint aspiration and synovial fluid analysis are essential for Ultrasonography discriminating between inflammatory and noninflammatory The use of ultrasonography to evaluate patients with rheuma efTusions and for distinguishing between infectious arthritis tologic diseases has expanded dramatically. Ultrasonography is and acute crystal arthropathies. ln the evaluation of any relatively inexpensive, can scan across three-dimensional monoarthritis or when infection is being considered, joint 7