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Osteoarthritis Risk factors involving the joint itself include abnormal Classification loading, injury malalignment, and intrinsic cartilage or bone tissue defects. Injury may be acute (e.g., anterior cruci- Primary Osteoarthritis ate ligament tear) or accumulate over time (e.g., physical In most cases, no identifiable proximal cause of OA is recog labor or overuse); regardless of cause, injuries have been nized. Although the term "primary OA" is commonly used for linked with the future development of OA of various sites. this category a complex interplay of genetics, age, sex, biome- Hip dislocation, congenital dysplasia, femoroacetabular chanics, biochemistry and inflammation is implicit. Primary impingement, and knee malalignment are also associated OA may affect almost any joint, but clinically significant with incident OA. presentations occur in the small joints of the hands (distal Given the multifactorial causes, OA may develop as a con- interphalangeal [DIP], proximal interphalangeal [PIP], carpo- sequence of one or more risk factors; how the interaction of metacarpal) and feet (first metatarsal phalangeal, midfoot) and these risk factors culminates in OA is complex and not fully in the spine, hips, and knees. One or more of these areas might understood. be affected and symptomatic in a given individual. TEY POIIIIt o Osteoarthritis is a chronic progressive disorder charac- Erosive Osteoarthritis terized by cartilage and meniscal degradation, subchon- Erosive (inflammatory) OA is a subset of primary hand OA. dral bone changes, osteophyte formation, and low-grade Erosive OA prominently affects the DIP and PIP joints, Ieads to

TEY POIIIIt o Osteoarthritis is a chronic progressive disorder charac- Erosive Osteoarthritis terized by cartilage and meniscal degradation, subchon- Erosive (inflammatory) OA is a subset of primary hand OA. dral bone changes, osteophyte formation, and low-grade Erosive OA prominently affects the DIP and PIP joints, Ieads to synovitis. more joint erythema and swelling than other forms of primary hand OA, and is more common in women. Radiographs reveal . Obesity is the most important modifiable risk factor for diagnosis-defining central erosions with a "seagull" or "gull osteoarthritis of the knee. wing" appearance in the finger joints (Figure 8); joint are spared' sclerosis aie present at both fir;t carpometacarpal joints (blue arows). Furthermore, metacarpophalangeal ioints 24

Osteoarthritis anMosis (bony fusion) may also occur. Whether erosive OA suggested that the aorta may serye as a mechanical barrier to comprises a separate disease entity or is part ofthe continuum the production of bony hyperostosis on the left side of the ofl OA remains controversial. spine.

anMosis (bony fusion) may also occur. Whether erosive OA suggested that the aorta may serye as a mechanical barrier to comprises a separate disease entity or is part ofthe continuum the production of bony hyperostosis on the left side of the ofl OA remains controversial. spine. TEY POITIS Secondary Osteoarthritis Secondary OA is historically defined in the presence ofa pre- . In most cases, no identifiable proximal cause of osteoar- disposing disorder; however, an increasing number of risk thritis (OA) is recognized; this form is categorized as factors for primary OA are being identified, thus blurring the primaryOA. line between the primary and secondary forms. Pathologic r Erosive osteoarthritis mostly affects the distal inter changes, clinical presentations, symptoms, and management phalangeal and proximal interphalangeal joints, is are indistinguishable between primary and secondary OA. characterized by erythema and swelling, and is more When OA occurs in a joint not typically affected by primary common in women. OA, or when it presents at a younger age, secondary causes . Commonly recognized causes of secondary osteoarthri- should be entertained. Commonly recognized causes of sec- tis include a history of joint damage; congenitally ondary OA include a history of joint damage, such as trauma, abnormal joints and/or malalignment; systemic meta- infection, or surgical repair (e.g., anterior cruciate ligament bolic, endocrine, and neuropathic disorders; and repair or meniscectomy); congenitally abnormal joints (e.g., underlying inflammatory arthritis with accompanying hip dysplasia) and/or malalignment; systemic metabolic, damage. endocrine, and neuropathic disorders, particularly those that o Diffuse idiopathic skeletal hyperostosis is a noninflam- affect cartilage (e.g., hemochromatosis and chondrocalcino matory condition characterized by calcification and sis); and underlying inflammatory arthritis with accompany ossiflcation of spinal ligaments and entheses; radio- ing damage (e.g., rheumatoid or psoriatic arthritis) (Table 15). graphs usually show confluent "flowing" ossification of at least four contiguous vertebral levels, usually on the Diffuse tdiopathic Skeletal Hyperostosis right side of the spine. Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflam- matory condition characterized by calcification and ossifica tion of spinal ligaments (especially the anterior longitudinal Diagnosis ligament) and entheses (tendon and ligament attachments to bone). DISH is more common in men. DISH usually presents Clinical Manifestations as back pain and stiffness, with the thoracic spine most often OA diagnosis is based on history and physical examination; involved. Although spinal ligamentous ossiflcation is also seen radiography is confirmatory but may be unnecessary. In early OA, clinical findings may not be accompanied by radiographic in ankylosing spondylitis, the spinal calcifications in DISH are more "flowing," wider, and less vertically oriented than those changes; conversely, some patients with prominent radio graphic changes may have minimal or no symptoms. Patients seen with ankylosing spondylitis. DISH also lacks involvement of the sacroiliac joints. with OA are typically older than 50 years of age; diagnosis at Radiographic changes characteristic of DISH include con an earlier age should prompt inquiry into a history of joint damage, endocrine or metabolic disorders, or a genetic pro fluent ossification ofat least four contiguous vertebral levels, usually on the right side of the spine (Figure 9). It has been clivity for early disease. Joints most commonly affected are the hands (DIP, PIP, and first carpometacarpal joints) (Figure 1O), feet (especially TABIE 1 5. Secondary Causes of Osteoarthritis the first metatarsophalangeal and midfoot joints), knees, hips, Secondary Cause Joint(s) Typically lnvolved and spine, but the distribution varies. When OA affects a single joint, it more often results from injury or joint asymmetry and Hemochromatosis Second/third MCP joints often occurs in weight bearing joints (hip or knee). Generalized Calcium pyrophosphate MCP joints; wrists; knees; hips; OA, which affects multiple joint groups, often symmetrically, deposition shoulders; atlanto-axial joint may be the result of a combination of genetic and environ Alkaptonuria/och ronosis Spine; hips; knees mental factors. Acromegaly Knees; shoulders; spine Patients with OA usually describe an insidious onset of Hyperparathyroidism Wrists; MCP joints intermittent symptoms, which become more persistent and Joint injury Knees severe over time. The most common symptom is joint pain Sensory neuropathy Feet; ankles; knees exacerbated by activity and alleviated with rest. Patients also (Charcot joints) describe morning stiffness usually lasting less than 30 min lnflammatory arthritis Hands; wrists; feet; knees utes, in contrast to the prolonged moming stiffness of inflam- matory arthritis. A single joint may initially be involved, with MCP = metacarpophalangeal eventual involvement of multiple loints.

TEY POITIS Secondary Osteoarthritis Secondary OA is historically defined in the presence ofa pre- . In most cases, no identifiable proximal cause of osteoar- disposing disorder; however, an increasing number of risk thritis (OA) is recognized; this form is categorized as factors for primary OA are being identified, thus blurring the primaryOA. line between the primary and secondary forms. Pathologic r Erosive osteoarthritis mostly affects the distal inter changes, clinical presentations, symptoms, and management phalangeal and proximal interphalangeal joints, is are indistinguishable between primary and secondary OA. characterized by erythema and swelling, and is more When OA occurs in a joint not typically affected by primary common in women. OA, or when it presents at a younger age, secondary causes . Commonly recognized causes of secondary osteoarthri- should be entertained. Commonly recognized causes of sec- tis include a history of joint damage; congenitally ondary OA include a history of joint damage, such as trauma, abnormal joints and/or malalignment; systemic meta- infection, or surgical repair (e.g., anterior cruciate ligament bolic, endocrine, and neuropathic disorders; and repair or meniscectomy); congenitally abnormal joints (e.g., underlying inflammatory arthritis with accompanying hip dysplasia) and/or malalignment; systemic metabolic, damage. endocrine, and neuropathic disorders, particularly those that o Diffuse idiopathic skeletal hyperostosis is a noninflam- affect cartilage (e.g., hemochromatosis and chondrocalcino matory condition characterized by calcification and sis); and underlying inflammatory arthritis with accompany ossiflcation of spinal ligaments and entheses; radio- ing damage (e.g., rheumatoid or psoriatic arthritis) (Table 15). graphs usually show confluent "flowing" ossification of at least four contiguous vertebral levels, usually on the Diffuse tdiopathic Skeletal Hyperostosis right side of the spine. Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflam- matory condition characterized by calcification and ossifica tion of spinal ligaments (especially the anterior longitudinal Diagnosis ligament) and entheses (tendon and ligament attachments to bone). DISH is more common in men. DISH usually presents Clinical Manifestations as back pain and stiffness, with the thoracic spine most often OA diagnosis is based on history and physical examination; involved. Although spinal ligamentous ossiflcation is also seen radiography is confirmatory but may be unnecessary. In early OA, clinical findings may not be accompanied by radiographic in ankylosing spondylitis, the spinal calcifications in DISH are more "flowing," wider, and less vertically oriented than those changes; conversely, some patients with prominent radio graphic changes may have minimal or no symptoms. Patients seen with ankylosing spondylitis. DISH also lacks involvement of the sacroiliac joints. with OA are typically older than 50 years of age; diagnosis at Radiographic changes characteristic of DISH include con an earlier age should prompt inquiry into a history of joint damage, endocrine or metabolic disorders, or a genetic pro fluent ossification ofat least four contiguous vertebral levels, usually on the right side of the spine (Figure 9). It has been clivity for early disease. Joints most commonly affected are the hands (DIP, PIP, and first carpometacarpal joints) (Figure 1O), feet (especially TABIE 1 5. Secondary Causes of Osteoarthritis the first metatarsophalangeal and midfoot joints), knees, hips, Secondary Cause Joint(s) Typically lnvolved and spine, but the distribution varies. When OA affects a single joint, it more often results from injury or joint asymmetry and Hemochromatosis Second/third MCP joints often occurs in weight bearing joints (hip or knee). Generalized Calcium pyrophosphate MCP joints; wrists; knees; hips; OA, which affects multiple joint groups, often symmetrically, deposition shoulders; atlanto-axial joint may be the result of a combination of genetic and environ Alkaptonuria/och ronosis Spine; hips; knees mental factors. Acromegaly Knees; shoulders; spine Patients with OA usually describe an insidious onset of Hyperparathyroidism Wrists; MCP joints intermittent symptoms, which become more persistent and Joint injury Knees severe over time. The most common symptom is joint pain Sensory neuropathy Feet; ankles; knees exacerbated by activity and alleviated with rest. Patients also (Charcot joints) describe morning stiffness usually lasting less than 30 min lnflammatory arthritis Hands; wrists; feet; knees utes, in contrast to the prolonged moming stiffness of inflam- matory arthritis. A single joint may initially be involved, with MCP = metacarpophalangeal eventual involvement of multiple loints. 2S

Osteoarthritis B € € ? € ?4 tl G U RE 9. Plain spinal radiographs showing diffuse idiopathic skeletal hyperostosis. Note the calcification at sites of tendinous and ligamentous insertion of the spine, taking the form of flowing ossification of multiple contiguous € vertebrae (yel/ow a rrows in A a nd 8). Also seen here is the typica I extensive involvement of the right side of the spine and relative sparing of the left of the thoracolumbar spine (/). (C) Calcification ol the anterior longitudinal ligament, also common, is shown in the cervical spine (redarrows).Also shown is the thick/ wide osteophytes originating from the vertebral bodies, which ditfer from those seen in ankylosing spondylitis (yel/ow arrowin C). Pdn A r0urle,y o'50lprio' Gyhopoulos llD [./lSc On joint examination, joint-line tenderness, crepitus, groin pain and decreased range of motion, especially internal decreased range of motion, bony enlargement without synovi rotation. Knee symptoms include pain on walking and clinlb- tis. and sometimes eflusion (most commonly in the knees) ing stairs and difficulty transferring from a seated to a stand may be present. Patients with long-standing hand OA may ing position. OA affecting the spine (spondylosis) can affect have Heberden and Bouchard nodes (bony enlargement ofthe the vertebral bodies, facet joints, and neural foramina and may DIP and PIP joints, respectively) and squaring ofthe first car Iead to spinal stenosis. See MKSAP 19 General Internal pometacarpal joint. FIip involvement {ypically manifests as Medicine 1 for further discussion of spinal stenosis. 26

Osteoarthritis FIGURE 10. Progressionof handosteoarthritis(0A).Thisimageillustratestheprogressionfromnormal handjoints(/eft),todistal interphalangeal (Dlp)jointbony hypertrophy (Heberden nodes) of hand 0A (middle), to extensive hand 0A findings of Heberden nodes and proximal interphalangeal (plp) joint bony hypertrophy (Bouchard nodes) (nght). Ihe hand on the right also displays a gouty nodule (tophus) overlying the Heberden node on the second Dlp joint, underlining the potential coexistence of these two arthropathies. White arrowheads = Heberden nodes; black anows = Bouchard nodes; black asterisk = tophus.

FIGURE 10. Progressionof handosteoarthritis(0A).Thisimageillustratestheprogressionfromnormal handjoints(/eft),todistal interphalangeal (Dlp)jointbony hypertrophy (Heberden nodes) of hand 0A (middle), to extensive hand 0A findings of Heberden nodes and proximal interphalangeal (plp) joint bony hypertrophy (Bouchard nodes) (nght). Ihe hand on the right also displays a gouty nodule (tophus) overlying the Heberden node on the second Dlp joint, underlining the potential coexistence of these two arthropathies. White arrowheads = Heberden nodes; black anows = Bouchard nodes; black asterisk = tophus. Patients with OA generally do not have systemic features. Pain and structural changes, however, ultimately result in Differential Diagnosis functional impairment, disability, psychosocial isolation, and Diagnosing OA can be challenging when OA is present in reduced quality of life. Inability to exercise regular$ may have atypical joints, an accurate history is difficult to obtain, or a adverse consequences for general health. concurrent inflammatory arthropathy may be present. Calcium pyrophosphate deposition disease, gout, rheumatoid arthritis, and psoriatic arthritis may coexist with OA or mimic Laboratory and lmaging Studies Laboratory testing is not necessary for diagnosis of OA but is helpful ifother causes ofarthritis are being considered, such as crystal arthropathy, rheumatoid arthritis, psoriatic arthritis, or hemochromatosis (all of which can coexist with OA). Acute phase reactant levels are not elevated in OA. Routine labora tory tests (complete blood count, kidney and hepatic function) are not necessary for diagnosing OA but may be important to help define the safety of pharmacologic therapy, especially in older persons and patients with comorbidities. If a joint effusion is present, evaluation for concurrent crystal arthropathy, infections, or other inflammatory causes should be considered, ideally by synovial fluid analysis. OA slmovial fluid is typically clear in appearance and noninflam- matory with a leukoclte count of 2000/pL (2.0 x 10e/L) or less. Although imaging is not necessary to diagnose OA, it can be helpful to confirm the diagnosis, establish baseline severity and/or monitor progressive severity, and exclude other diag noses. Radiographic features of OA include asymmetric joint- space narrowing, subchondral sclerosis, osteophytes, and bone cysts (Figure 11); however, these changes may not be present in early disease. Even in established OA, symptoms may correlate poorly with imaging findings. Although MRI and ultrasonography can detect subtle OA changes, they are ; I G U R E 1 1 . 0steoarthritis of the knee showing joint-space narrowing (JSN), not needed for routine OA diagnosis. osteophytes (0P), subchondral sclerosis (SS), and bone cysts (BC).

Patients with OA generally do not have systemic features. Pain and structural changes, however, ultimately result in Differential Diagnosis functional impairment, disability, psychosocial isolation, and Diagnosing OA can be challenging when OA is present in reduced quality of life. Inability to exercise regular$ may have atypical joints, an accurate history is difficult to obtain, or a adverse consequences for general health. concurrent inflammatory arthropathy may be present. Calcium pyrophosphate deposition disease, gout, rheumatoid arthritis, and psoriatic arthritis may coexist with OA or mimic Laboratory and lmaging Studies Laboratory testing is not necessary for diagnosis of OA but is helpful ifother causes ofarthritis are being considered, such as crystal arthropathy, rheumatoid arthritis, psoriatic arthritis, or hemochromatosis (all of which can coexist with OA). Acute phase reactant levels are not elevated in OA. Routine labora tory tests (complete blood count, kidney and hepatic function) are not necessary for diagnosing OA but may be important to help define the safety of pharmacologic therapy, especially in older persons and patients with comorbidities. If a joint effusion is present, evaluation for concurrent crystal arthropathy, infections, or other inflammatory causes should be considered, ideally by synovial fluid analysis. OA slmovial fluid is typically clear in appearance and noninflam- matory with a leukoclte count of 2000/pL (2.0 x 10e/L) or less. Although imaging is not necessary to diagnose OA, it can be helpful to confirm the diagnosis, establish baseline severity and/or monitor progressive severity, and exclude other diag noses. Radiographic features of OA include asymmetric joint- space narrowing, subchondral sclerosis, osteophytes, and bone cysts (Figure 11); however, these changes may not be present in early disease. Even in established OA, symptoms may correlate poorly with imaging findings. Although MRI and ultrasonography can detect subtle OA changes, they are ; I G U R E 1 1 . 0steoarthritis of the knee showing joint-space narrowing (JSN), not needed for routine OA diagnosis. osteophytes (0P), subchondral sclerosis (SS), and bone cysts (BC). 27

Osteoarthritis OA. Calcium pyrophosphate deposition disease may occur in receive individualized, often multidisciplinary treatment that joints also fypically affected by OA (hands or knees) but is considers their expectations, functional and activity levels, occu- associated with intermittent "flares," and radiographs show pational and vocational needs, joints affected, severity of disease, cartilage calcification (chondrocalcinosis). Gout and OA com- and any coexisting medical problems. Instead of a single algo- monly co-associate, particularly in the DIP joints. Rheumatoid rithm, the practitioner should consider the patient's clinical state and psoriatic arthritis can be differentiated from OA by pro- and institute treatment, which may include single or multiple longed morning stiffness, signs and symptoms of chronic and modalities that may be rycled in and out as needed (Figure ljl). persistent inflammation, and elevated inflammatory markers. Unlike OA, rheumatoid arthritis typically spares the DIP joints, Sttongly reommended and the presence of rheumatoid factor and/or anti-cyclic cit- rullinated peptide antibodies favors the diagnosis of rheuma Conditionally toid arthritis. Psoriatic arthritis can involve the DIP joints, but recommended

OA. Calcium pyrophosphate deposition disease may occur in receive individualized, often multidisciplinary treatment that joints also fypically affected by OA (hands or knees) but is considers their expectations, functional and activity levels, occu- associated with intermittent "flares," and radiographs show pational and vocational needs, joints affected, severity of disease, cartilage calcification (chondrocalcinosis). Gout and OA com- and any coexisting medical problems. Instead of a single algo- monly co-associate, particularly in the DIP joints. Rheumatoid rithm, the practitioner should consider the patient's clinical state and psoriatic arthritis can be differentiated from OA by pro- and institute treatment, which may include single or multiple longed morning stiffness, signs and symptoms of chronic and modalities that may be rycled in and out as needed (Figure ljl). persistent inflammation, and elevated inflammatory markers. Unlike OA, rheumatoid arthritis typically spares the DIP joints, Sttongly reommended and the presence of rheumatoid factor and/or anti-cyclic cit- rullinated peptide antibodies favors the diagnosis of rheuma Conditionally toid arthritis. Psoriatic arthritis can involve the DIP joints, but recommended dactylitis and a history of psoriasis help differentiate it from HAND KNEE HIP OA. In older patients with psoriasis and insidious-onset arthri Exarcker vl tis, OA may be a more likely diagnosis than psoriatic arthritis. u,l I U Self.Efficary and Self-Management Prognms Synovial fluid analysis can also help distinguish between OA and these inflammatory disorders. o Weight los d o- Other conditions to consider in evaluating a patient for o. Tai Chi OA include nonarticular sources of pain, such as bursitis and o Cane tendinitis. Hip pain that is not in the anterior groin but instead o lo around the lateral hip and buttock may indicate trochanteric o lstCMC Orthosis TF Knee Bmcet z bursitis or lumbosacral radiculopathy. Similarly, knee pain Heat, Th€rapeutic Cooling may be secondary to pes anserine bursitis or iliotibial band = o z syndrome rather than intra-articular pathologz, which may Cognitive Behavioral Therapy J present with medial or lateral knee pain, respectively. See s Acupuncture U MKSAP 19 General Internal Medicine 1 for further discussion o ]i Kinesiotaping of nonarticular pain conditions. o I U f,EY POIIIS vt Balance Training o- o The most common symptom of osteoarthritis is joint J Other Hand Orthosesn PF Knee Brace** pain exacerbated by activity and alleviated with rest; U 6 Pamffin Yoga morning stiffness usually lasts less than 30 minutes. I o- HVC o Laboratory testing is usually not necessary to diagnose RFA

dactylitis and a history of psoriasis help differentiate it from HAND KNEE HIP OA. In older patients with psoriasis and insidious-onset arthri Exarcker vl tis, OA may be a more likely diagnosis than psoriatic arthritis. u,l I U Self.Efficary and Self-Management Prognms Synovial fluid analysis can also help distinguish between OA and these inflammatory disorders. o Weight los d o- Other conditions to consider in evaluating a patient for o. Tai Chi OA include nonarticular sources of pain, such as bursitis and o Cane tendinitis. Hip pain that is not in the anterior groin but instead o lo around the lateral hip and buttock may indicate trochanteric o lstCMC Orthosis TF Knee Bmcet z bursitis or lumbosacral radiculopathy. Similarly, knee pain Heat, Th€rapeutic Cooling may be secondary to pes anserine bursitis or iliotibial band = o z syndrome rather than intra-articular pathologz, which may Cognitive Behavioral Therapy J present with medial or lateral knee pain, respectively. See s Acupuncture U MKSAP 19 General Internal Medicine 1 for further discussion o ]i Kinesiotaping of nonarticular pain conditions. o I U f,EY POIIIS vt Balance Training o- o The most common symptom of osteoarthritis is joint J Other Hand Orthosesn PF Knee Brace** pain exacerbated by activity and alleviated with rest; U 6 Pamffin Yoga morning stiffness usually lasts less than 30 minutes. I o- HVC o Laboratory testing is usually not necessary to diagnose RFA osteoarthritis but is helpful if other causes of arthritis are being considered or to help define the safety of Oml NSAIDs u I potential therapies. U Topical NSAIDs Topical NSAIDs . Radiographic features of osteoarthritis include asym- o cL & l-A Steroids l-A Steroids (lmaging Guidance for Hip) metric joint-space narrowing, subchondral sclerosis, osteophl'tes, and bone cysts; however, these changes I|9 Acetaminophen o I J may not be present in early disease, and symptoms may Tramadol correlate poorly with imaging findings. c=, Duloxetine I A. Management Chondroitin Topical Capsaicin

osteoarthritis but is helpful if other causes of arthritis are being considered or to help define the safety of Oml NSAIDs u I potential therapies. U Topical NSAIDs Topical NSAIDs . Radiographic features of osteoarthritis include asym- o cL & l-A Steroids l-A Steroids (lmaging Guidance for Hip) metric joint-space narrowing, subchondral sclerosis, osteophl'tes, and bone cysts; however, these changes I|9 Acetaminophen o I J may not be present in early disease, and symptoms may Tramadol correlate poorly with imaging findings. c=, Duloxetine I A. Management Chondroitin Topical Capsaicin To date, the FDA has approved no agents to prevent, delay, or remit FIGURE 1 2. Strongly and conditionally recommended therapies for osteoarthritis (0A) of hand, knee, and/or hip. The figure implies no hierarchy within the structural progression of OA. Instead, current treatment is categories; the various options may be used (and reused) at various times directed to the management of pain and disability Evidence throughout a patient's disease. lA= intra-articular; RFA= radiofrequency ablation. based guidelines for OA management are available from the *Exercise for knee and hip 0A rould include walting, strengthening, neuromuscular training, and aquatic American College of Rheumatologr and Arthritis Foundation, the erercise, with no hierarchyof0neoveranother. Exer(ise isassociated wilh better0uttomes when superuised

To date, the FDA has approved no agents to prevent, delay, or remit FIGURE 1 2. Strongly and conditionally recommended therapies for osteoarthritis (0A) of hand, knee, and/or hip. The figure implies no hierarchy within the structural progression of OA. Instead, current treatment is categories; the various options may be used (and reused) at various times directed to the management of pain and disability Evidence throughout a patient's disease. lA= intra-articular; RFA= radiofrequency ablation. based guidelines for OA management are available from the *Exercise for knee and hip 0A rould include walting, strengthening, neuromuscular training, and aquatic American College of Rheumatologr and Arthritis Foundation, the erercise, with no hierarchyof0neoveranother. Exer(ise isassociated wilh better0uttomes when superuised Osteoarthritis Research Society International, the European **Knee brace recommendations: tibiolemoral (TF) brace for TF 0A (strongly recommended), patellofemoral (PF) brace f0r PF 0A (conditionally recommended). League Against Rheumatism, and other organizations. There is *'*Hand orthosis re(0mmendati0ns: first (arpometacarpal (CMC) joinl neoprene or rigid orthoses for first CMC considerable consensus among these guidelines, particularly that joint 0A (slrongly recommended),0rthoses for joints of the hand olher than the Ii6t CMC j0int (conditionally optimal OA management requires a comprehensive plan that may recommended).

Osteoarthritis Research Society International, the European **Knee brace recommendations: tibiolemoral (TF) brace for TF 0A (strongly recommended), patellofemoral (PF) brace f0r PF 0A (conditionally recommended). League Against Rheumatism, and other organizations. There is *'*Hand orthosis re(0mmendati0ns: first (arpometacarpal (CMC) joinl neoprene or rigid orthoses for first CMC considerable consensus among these guidelines, particularly that joint 0A (slrongly recommended),0rthoses for joints of the hand olher than the Ii6t CMC j0int (conditionally optimal OA management requires a comprehensive plan that may recommended). include educational, psychological, and phlsical management, trom Kolasinski SL, Neogi I Hochberg MC, et al. 201 9 American College ol Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis 0f the hand, hip, and knee. Arthritis Care Res (Hoboken). 2020;72: along with pharmacologic interventions. Patients with OA should 149 162.IPlVlD:31908149] Reproduced with permission fromJohnWiley& 50ns, lnc. 28

Osteoarthritis Nonpharmacologic Therapy other sites. However, topical NSAIDs may be limited in use for The nonpharmacologic approach to OA starts with assessment hand OA because of practical circumstances. They also may be of physical status, activities of daily living, health education, associated with more skin reactions and are more expensive motivation, beliefs, and other biopsychosocial factors. An indi than oral NSAIDs. Other topical agents, such as capsaicin, vidualized management plan includes education on OA and lidocaine, and methyl salicylate preparations, may also be used joint protection, an exercise regimen, weight loss, proper foot- as adjunctive measures, especially when NSAIDs are ineffec wear, and assistive devices as appropriate. Recent data suggest tive or are not tolerated. that participation in self-efficacy and self-management pro Recent systematic reviews and meta analyses suggest that grams that use a format based on multidisciplinary groups is acetaminophen provides no benefit for hip or knee OA but associated with improvement in OA symptoms. Physical activ- may be considered as an add on therapy, as well as for short ity includes graduated aerobic exercise and strength training, term and episodic use. ACR guidelines conditionally recom with attention paid to strengthening periarticular structures mend acetaminophen for knee, hip, and hand OA in patients and minimizing injury. Tai chi has also been shown to be as with limited pharmacologic options. beneficial as physical therapy lbr knee OA pain and is strongly Duloxetine, a serotonin norepinephrine reuptake inhibi recommended by the American College of Rheumatologr tor with central nervous system activity, has shown efficacy for (ACR) for knee and hip OA. The combination of diet and exer pain from knee OA, suggesting a role for central sensitization cise is more effective at decreasing OA related knee pain and in OA pain modulation. dysfunction than diet or exercise alone; no evidence supports Opioids for OA should be avoided because evidence following a specific diet to decrease OA symptoms. Weight loss shows only slight benefit and a high risk for toxicity and provides meaningful improvement in symptoms that increases dependence. Opioid use should be considered only in limited with greater loss of weight. The ACR also conditionally recom- circumstances when no other alternatives exist. Tramadol. a mends cognitive behavioral therapy, acupuncture, and thermal partial opioid with fewer adverse effects and less addictive interventions (locally applied heat or cold) for knee, hip, and potential than pure opioids, may be considered in some hand OA. Balance exercises are conditionally recommended for patients in whom other analgesics have not relieved pain. knee and hip OA, and yoga is recommended for knee OA. Nonetheless, concerns about the potential for adverse effbcts of tramadol continue. Patients with OA frequently use glucosamine, an oral Pharmacologic Therapy dietary supplement. Although glucosamine appears to be safb, ln the absence of disease modiffing OA drugs, pharmacologic substantial evidence suggests that it lacks efficacy. ACR guide treatment is considered when symptoms are bothersome to the lines strongly recommend against glucosamine in patients patient and are inadequately or incompletely addressed by with knee, hip, and/or hand OA. Chondroitin sulfate is strongly nonpharmacologic interventions. Pharmacologic therapy lor recommended against in patients with knee and/or hip OA, as OA includes oral, topical, and intra-articular medications. are combination products that include glucosamine and chon Choice of treatment depends on individualized assessment, droitin sulfate, but chondroitin is conditionally recommended with particular attention to comorbidities, concomitant medi for patients with hand OA. cations, and, especially, adverse treatment effects. See Principles of Therapeutics for details on the medications used in OA. Intra-Articular Injections Patients with knee or hip OA who have inefficacy, intolerance, Oral and Topical Agents or contraindication to oral and topical therapies may benefit Oral agents for OA include NSAIDs, acetaminophen, duloxe from intra articular glucocorticoid injections. Despite the lack tine, and tramadol. NSAIDs are efficacious in OA, regardless of of formal evidence for the utility of this therapy in joints other anatomic location, and are the initial oral treatment of choice. than the knee and hip, there may be a possible benefit in other However, their side effect profiles make sustained use prob joints, such as the first carpometacarpal joint. The ACR lematic, especially in older persons and patients with comor strongly recommends using ultrasound guidance for hip-joint bidities. A proton pump inhibitor may improve tolerance and glucocorticoid injections. minimize risk; the proper choice of an NSAID should consider Long term harm from intra articular glucocorticoids has drug pharmacokinetics and gastrointestinal and cardiovascu not been consistently demonstrated; however, benefit is usu lar effects. For OA, NSAIDs should be used in the lowest pos ally short term and wanes within 3 months. Injections can be sible dose and for the shortest possible time. Nonetheless, administered repeatedly but are not usually given more often NSAIDs remain the mainstay of OA treatment. than every 3 months. At least one study has suggested that Topical NSAIDs are saf'e, associated with the least sys knee joints undergoing repeated injections may be more likely temic exposure, and effective for treatment of knee OA and to experience cartilage loss, but the effect size was small and hand OA. For OA ofthe hands and knees, they are preferable the clinical significance remains controversial. and should be considered before use oforal NSAIDs' They are Intra-articular hyaluronic acid injections are widely not effective for hip OA and have limited efficacy in OA of used for knee OA in patients with inadequate response to

Nonpharmacologic Therapy other sites. However, topical NSAIDs may be limited in use for The nonpharmacologic approach to OA starts with assessment hand OA because of practical circumstances. They also may be of physical status, activities of daily living, health education, associated with more skin reactions and are more expensive motivation, beliefs, and other biopsychosocial factors. An indi than oral NSAIDs. Other topical agents, such as capsaicin, vidualized management plan includes education on OA and lidocaine, and methyl salicylate preparations, may also be used joint protection, an exercise regimen, weight loss, proper foot- as adjunctive measures, especially when NSAIDs are ineffec wear, and assistive devices as appropriate. Recent data suggest tive or are not tolerated. that participation in self-efficacy and self-management pro Recent systematic reviews and meta analyses suggest that grams that use a format based on multidisciplinary groups is acetaminophen provides no benefit for hip or knee OA but associated with improvement in OA symptoms. Physical activ- may be considered as an add on therapy, as well as for short ity includes graduated aerobic exercise and strength training, term and episodic use. ACR guidelines conditionally recom with attention paid to strengthening periarticular structures mend acetaminophen for knee, hip, and hand OA in patients and minimizing injury. Tai chi has also been shown to be as with limited pharmacologic options. beneficial as physical therapy lbr knee OA pain and is strongly Duloxetine, a serotonin norepinephrine reuptake inhibi recommended by the American College of Rheumatologr tor with central nervous system activity, has shown efficacy for (ACR) for knee and hip OA. The combination of diet and exer pain from knee OA, suggesting a role for central sensitization cise is more effective at decreasing OA related knee pain and in OA pain modulation. dysfunction than diet or exercise alone; no evidence supports Opioids for OA should be avoided because evidence following a specific diet to decrease OA symptoms. Weight loss shows only slight benefit and a high risk for toxicity and provides meaningful improvement in symptoms that increases dependence. Opioid use should be considered only in limited with greater loss of weight. The ACR also conditionally recom- circumstances when no other alternatives exist. Tramadol. a mends cognitive behavioral therapy, acupuncture, and thermal partial opioid with fewer adverse effects and less addictive interventions (locally applied heat or cold) for knee, hip, and potential than pure opioids, may be considered in some hand OA. Balance exercises are conditionally recommended for patients in whom other analgesics have not relieved pain. knee and hip OA, and yoga is recommended for knee OA. Nonetheless, concerns about the potential for adverse effbcts of tramadol continue. Patients with OA frequently use glucosamine, an oral Pharmacologic Therapy dietary supplement. Although glucosamine appears to be safb, ln the absence of disease modiffing OA drugs, pharmacologic substantial evidence suggests that it lacks efficacy. ACR guide treatment is considered when symptoms are bothersome to the lines strongly recommend against glucosamine in patients patient and are inadequately or incompletely addressed by with knee, hip, and/or hand OA. Chondroitin sulfate is strongly nonpharmacologic interventions. Pharmacologic therapy lor recommended against in patients with knee and/or hip OA, as OA includes oral, topical, and intra-articular medications. are combination products that include glucosamine and chon Choice of treatment depends on individualized assessment, droitin sulfate, but chondroitin is conditionally recommended with particular attention to comorbidities, concomitant medi for patients with hand OA. cations, and, especially, adverse treatment effects. See Principles of Therapeutics for details on the medications used in OA. Intra-Articular Injections Patients with knee or hip OA who have inefficacy, intolerance, Oral and Topical Agents or contraindication to oral and topical therapies may benefit Oral agents for OA include NSAIDs, acetaminophen, duloxe from intra articular glucocorticoid injections. Despite the lack tine, and tramadol. NSAIDs are efficacious in OA, regardless of of formal evidence for the utility of this therapy in joints other anatomic location, and are the initial oral treatment of choice. than the knee and hip, there may be a possible benefit in other However, their side effect profiles make sustained use prob joints, such as the first carpometacarpal joint. The ACR lematic, especially in older persons and patients with comor strongly recommends using ultrasound guidance for hip-joint bidities. A proton pump inhibitor may improve tolerance and glucocorticoid injections. minimize risk; the proper choice of an NSAID should consider Long term harm from intra articular glucocorticoids has drug pharmacokinetics and gastrointestinal and cardiovascu not been consistently demonstrated; however, benefit is usu lar effects. For OA, NSAIDs should be used in the lowest pos ally short term and wanes within 3 months. Injections can be sible dose and for the shortest possible time. Nonetheless, administered repeatedly but are not usually given more often NSAIDs remain the mainstay of OA treatment. than every 3 months. At least one study has suggested that Topical NSAIDs are saf'e, associated with the least sys knee joints undergoing repeated injections may be more likely temic exposure, and effective for treatment of knee OA and to experience cartilage loss, but the effect size was small and hand OA. For OA ofthe hands and knees, they are preferable the clinical significance remains controversial. and should be considered before use oforal NSAIDs' They are Intra-articular hyaluronic acid injections are widely not effective for hip OA and have limited efficacy in OA of used for knee OA in patients with inadequate response to 29

Fibromyalgia intra articular glucocorticoids. The quality of trials assessing condition (prevalence, 2'X, 3'X,) is more predominant in women efficacy ofintra articular hyaluronic acid is variable, and the than men, and age at onset is usually be[ween the third and degree of benefit is low. Hyaluronic acid injections may be sixth decades. considered in patients with knee OA in whom other treat- Fibromyalgia is not an inflammatory condition but rather ments have failed and surgery is not feasible. appears to be a disorder ofpain perception and processing. lts Intra articular stem cells, platelet rich plasma, biologics, pathophysiologr is not well understood. However, it is thought and botulinum toxin are not ef'ficacious and are not to relate to central sensitization, characterized by amplifica recommended. tion of pain signaling within the central nervous system. Neuroimaging of patients with fibromyalgia shows abnor Surgical Therapy malities within structures responsible for pain transmission Surgery for OA is considered when nonpharmacologic and and interpretation, and accruing data demonstrate a genetic pharmacologic approaches fail to control pain or improve predisposition. functional limitation. Multiple high quality studies have shown that arthroscopic surgery for knee OA provides no bet- ter outcomes than conservative management unless there is Diagnosis joint buckling, instability, or locking, or a concomitant and The characteristic clinical features of fibromyalgia are wide symptomatic mechanical disorder. spread chronic pain; fatigue; sleep disorders (both disrupted In contrast, total joint replacement is a "curative" option and nonrestorative sleep); and cognitive symptoms, often fbr patients in whom conservative therapies have failed; it termed "fibrofog." Patients flrequently have polysymptomatic relieves pain and improves function. Overall, Iong-term out distress across multiple systems, including paresthesia, comes are excellent, although hardware loosening and inf'ec chronic headaches, temporomandibular joint disorder, irri tion may occur. table bowel syndrome, and chronic pelvic pain. Two instru Recent studies suggest that fbr patients with morbid obe ments are available to aid in the diagnosis of fibromyalgia: sity and knee OA, bariatric surgery may significantly improve one issued jointly by the American Pain Society (APS) and pain and function even without further OA management. the FDA, called the Analgesic, Anesthetic, and Addiction Clinical Trial Translations lnnovations Opportunities and l(tY PotilTs Networks (ACTTION) APS Pain Taxonomy, and a 2016 revision HVC o Nonpharmacologic therapy for osteoarthritis includes of the 2010 American College ol Rheumatologr Preliminary education, an exercise regimen, weight loss, proper Diagnostic Criteria (Table f6 and Figure 13). A diagnosis of footwear, and assistive devices as appropriate. fibromyalgia obtained by using these tools is valid irrespective . Pharmacologic therapy for osteoarthritis includes oral, of other diagnoses and does not exclude other clinically topical, and intra articular medications; choice of treat- important illnesses. ment depends on individualized assessment, with par These diagnostic tools are based entirely on patient ticular attention to comorbidities and concomitant reporting of symptoms, and they dispense with the assess medications. ment of tender points that was incorporated into prior criteria (see Table 16). Although tender points may be characteristic of HVC o NSAIDs and duloxetine are conditionally recommended for hip and knee osteoarthritis; acetaminophen is sug- fibromyalgia, especially in female patients, the finding of spe- gested as add on therapy. ciflc tender points on physical examination has multiple shortcomings in practice, including lack of reproducibility HVC o Arthroscopic surgery is not indicated in patients with (particularly in men) and greater association of tender points osteoarthritis unless there is joint buckling, instability, with anxiety than with the pain itself. Technically, tender or locking, or a concomitant and symptomatic mechan- point assessments require properly administered pressure, ical disorder. such as may be achieved with a dolorimeter, an instrument o Total joint replacement relieves pain and improves not routinely available. function in patients with osteoarthritis in whom con- Extensive laboratory studies (e.g., antinuclear antibody servative therapies have failed. [ANA] testing) should also not be performed unless other specific diagnoses are suspected. Positive ANA test results, particularly at low titers, are nonspecific and have a low

intra articular glucocorticoids. The quality of trials assessing condition (prevalence, 2'X, 3'X,) is more predominant in women efficacy ofintra articular hyaluronic acid is variable, and the than men, and age at onset is usually be[ween the third and degree of benefit is low. Hyaluronic acid injections may be sixth decades. considered in patients with knee OA in whom other treat- Fibromyalgia is not an inflammatory condition but rather ments have failed and surgery is not feasible. appears to be a disorder ofpain perception and processing. lts Intra articular stem cells, platelet rich plasma, biologics, pathophysiologr is not well understood. However, it is thought and botulinum toxin are not ef'ficacious and are not to relate to central sensitization, characterized by amplifica recommended. tion of pain signaling within the central nervous system. Neuroimaging of patients with fibromyalgia shows abnor Surgical Therapy malities within structures responsible for pain transmission Surgery for OA is considered when nonpharmacologic and and interpretation, and accruing data demonstrate a genetic pharmacologic approaches fail to control pain or improve predisposition. functional limitation. Multiple high quality studies have shown that arthroscopic surgery for knee OA provides no bet- ter outcomes than conservative management unless there is Diagnosis joint buckling, instability, or locking, or a concomitant and The characteristic clinical features of fibromyalgia are wide symptomatic mechanical disorder. spread chronic pain; fatigue; sleep disorders (both disrupted In contrast, total joint replacement is a "curative" option and nonrestorative sleep); and cognitive symptoms, often fbr patients in whom conservative therapies have failed; it termed "fibrofog." Patients flrequently have polysymptomatic relieves pain and improves function. Overall, Iong-term out distress across multiple systems, including paresthesia, comes are excellent, although hardware loosening and inf'ec chronic headaches, temporomandibular joint disorder, irri tion may occur. table bowel syndrome, and chronic pelvic pain. Two instru Recent studies suggest that fbr patients with morbid obe ments are available to aid in the diagnosis of fibromyalgia: sity and knee OA, bariatric surgery may significantly improve one issued jointly by the American Pain Society (APS) and pain and function even without further OA management. the FDA, called the Analgesic, Anesthetic, and Addiction Clinical Trial Translations lnnovations Opportunities and l(tY PotilTs Networks (ACTTION) APS Pain Taxonomy, and a 2016 revision HVC o Nonpharmacologic therapy for osteoarthritis includes of the 2010 American College ol Rheumatologr Preliminary education, an exercise regimen, weight loss, proper Diagnostic Criteria (Table f6 and Figure 13). A diagnosis of footwear, and assistive devices as appropriate. fibromyalgia obtained by using these tools is valid irrespective . Pharmacologic therapy for osteoarthritis includes oral, of other diagnoses and does not exclude other clinically topical, and intra articular medications; choice of treat- important illnesses. ment depends on individualized assessment, with par These diagnostic tools are based entirely on patient ticular attention to comorbidities and concomitant reporting of symptoms, and they dispense with the assess medications. ment of tender points that was incorporated into prior criteria (see Table 16). Although tender points may be characteristic of HVC o NSAIDs and duloxetine are conditionally recommended for hip and knee osteoarthritis; acetaminophen is sug- fibromyalgia, especially in female patients, the finding of spe- gested as add on therapy. ciflc tender points on physical examination has multiple shortcomings in practice, including lack of reproducibility HVC o Arthroscopic surgery is not indicated in patients with (particularly in men) and greater association of tender points osteoarthritis unless there is joint buckling, instability, with anxiety than with the pain itself. Technically, tender or locking, or a concomitant and symptomatic mechan- point assessments require properly administered pressure, ical disorder. such as may be achieved with a dolorimeter, an instrument o Total joint replacement relieves pain and improves not routinely available. function in patients with osteoarthritis in whom con- Extensive laboratory studies (e.g., antinuclear antibody servative therapies have failed. [ANA] testing) should also not be performed unless other specific diagnoses are suspected. Positive ANA test results, particularly at low titers, are nonspecific and have a low Fibromyalgia positive predictive value. Positive findings on ANA screening tests are highly prevalent in both the general population and patients with fibromyalgia. In addition to ANA positivity Epidemiology and driving unnecessary additional testing, patients with fibro Pathophysiology myalgia and positive ANA results are often incorrectly Fibromyalgia is characterized by widespread chronic pain, diagnosed with a connective tissue disease and given inap fatigue, disturbed sleep, and mental fbgginess. This common propriate and potentially harmfut therapy. For example,

Fibromyalgia positive predictive value. Positive findings on ANA screening tests are highly prevalent in both the general population and patients with fibromyalgia. In addition to ANA positivity Epidemiology and driving unnecessary additional testing, patients with fibro Pathophysiology myalgia and positive ANA results are often incorrectly Fibromyalgia is characterized by widespread chronic pain, diagnosed with a connective tissue disease and given inap fatigue, disturbed sleep, and mental fbgginess. This common propriate and potentially harmfut therapy. For example, 30

Fibromyalgia TABLE 16. Comparison of ACR Diagnostic Criteria and ACTTION-APS Pain Taxonomy Diagnostic Criteria for Fibromyalgia, 201 0 ACR Preliminary Diagnostic Criteria (2016 Revision) ACTTION-APS Pain Taxonomy Criteria (2019, Widespread pain by Widespread Pain lndex (19-point scale) Musculoskeletal pain defined as >6 pain sites from total o{ assessing number of regions in which patient has painb,' 9 possible sites Symptom severity by Symptom Severity Scale (1 2-point scale) Moderate to severe sleep problems orfatigue assessing fatigue, nonrestorative sleep, and cognitive symptomsb' Duration of symptoms >3 months Musculoskeletal pain plus fatigue or sleep problems must have been present for >3 months No other disorder explaining the pain ACR=AmericanCollegeofRheumatology;ACTTION=Analgesic,Anesthetic,andAddictionClinica TrialTranslationslnnovationsOppodunitiesandNetworks;APS=American "A diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses. r'Fibromyalgia is diagnosed in the setting of Widespread Pain lndex 27 plus Symptom Severity Scale score >5, or Widespread Parn lndex >3 plus Symptom Sever ty Scale score )9. Head illl,*t,,,'n ftight erm i*f cn"'t il j*ao,"n i]l unoo, back and spine ll io*u, back and spine. includangbuttocks Lert leg Right leg

i*f cn"'t il j*ao,"n i]l unoo, back and spine ll io*u, back and spine. includangbuttocks Lert leg Right leg back front FIGURE l3.Numberof painfulbodysites.Patientsareaskedtochecktheareasinwhichtheyexperiencepainonthetwoviewmanikins(ignoringthepreshadedareas). Alternatively, patients may use the checklist ol body sites. Ihe number of separate sites is summed from a maximum of nine body sites. studies have shown that many patients with fibromyalgia erythematosus, rheumatoid arthritis) are also associated with with a positive ANA result are unnecessarily treated with a higher risk for coexistent fibromyalgia than seen in the gen high dose glucocorticoids. eral population. In patients with autoimmune disease and Alternative diagnoses of treatable conditions that may comorbid fibromyalgia, it is crucial to recognize when comor provoke or be associated with fibromyalgia include hypothy bid fibromyalgia is the primary driver of musculoskeletal roidism, polymyalgia rheumatica, and depression. Multiple symptoms in order to avoid overtreatment with immunosul.l rheumatologic conditions (Slogren syndrome, systemic lupus pressive agents. 31

5 pondyloa rthritis serotonin reuptake inhibitor (e.g., sertraline) in the morning, Management may mimic the aggregate effect of the SNRIs while helping Optimal management of fibromyalgia requires a holistic normalize the sleep-wake pattern. approach, including education, exercise, and psychosocial Tramadol has a dual effect as both an agonist of p opioid support. Pharmacotherapy is often warranted, although non receptors and an SNRI. Although studies have shown tramadol pharmacologic measures remain a cornerstone of treatment. is helpful, it is now classified as an opioid, with associated concerns of class side effects, including tolerance and addic- Nonpharmacologic tion. These concerns are less extreme than with other opioids, Patients should be educated regarding their condition, with which are contraindicated in fibromyalgia. validation that their symptoms are real and reassurance that Evidence does not support NSAIDs for treating their pain is not due to tissue injury and will not lead to per fibromyalgia. manent disability. Aerobic exercise can improve well being The patient and physician should understand that fibro and function as well as reduce pain. Because patients initially myalgia is a chronic illness. The benefit of treatment will likely experience postexercise pain and thus may be unwilling to be partial and usually temporary often requiring a rotating continue, exercise must be introduced gradually and sup sequence of treatments. Nevertheless, treatment can help ported encouragingly. Although evidence supporting their use patients manage and cope with their symptoms as well as is modest, modalities that can be helpful include tai chi, medi maintain function and autonomy. tation, and acupuncture. Patients with fibromyalgia should be assessed for psycho- xtY Poil{Ts social stressors and psychiatric illness, including a history of e The characteristic features of flbromyalgia are widespread trauma and abuse. In such cases, referral for psychological chronic pain, fatigue, sleep disorders, and cognitive support is essential, although access to practitioners with symptoms. experience treating chronic pain conditions is often a barrier. r The diagnosis of fibromyalgia is no longer based on HVC Social work support may help reduce the stress burden. Even physician examination findings but rather on a careful in patients without specific psychosocial stressors, psychologi- characterization of symptoms using a validated scoring cal support for illness and pain management may be advisable. tool. Cognitive behavioral therapy has shown modest benefit in . Nonpharmacologictherapy(education,exercise,psycho- HVC reducing pain, negative mood, and disability. social support) remains a cornerstone of treatment for fibromyalgia, and pharmacotherapy is often warranted. Pharmacologic Choice of pharmacologic therapy is based on symptom profile, patient comorbidities, and medication adverse effects because no trials have directly compared the efficacy of medications. Spondyloafthritis The antiepileptic agents gabapentin and pregabalin (the latter FDA approved for fibromyalgia) improve quality of Iife Overview and decrease pain in the short term. In principle, these agents Spondyloarthritis comprises arthritic disorders classified act by reducing pain signals from the dorsal root ganglia to the together by common genetic and environmental risk factors thalamus. Adverse effects, including sedation, disequilibrium, and clinical manifestations. Spondyloarthritis includes anky weight gain, and peripheral edema, are frequent. In older losing spondylitis, psoriatic arthritis, reactive arthritis, and patients, gabapentinoid doses should initially be low and then enteropathic arthritis. Their common feature is enthesitis be slowly titrated, as appropriate. Pregabalin is now classified (inflammation at the points where tendons, ligaments, and as a controlled substance. joint capsules insert into bone). Clinically, enthesitis mani Tricyclic antidepressants (such as amitriptyline) raise fests as inflammation, pain, and new bone formation in and norepinephrine and serotonin levels and have mild benefit, around peripheral joints; dactylitis (diflfuse digital swelling, although efficacy may wane with time. These agents induce also called sausage digit, including the joint capsule, tendons, drowsiness, with potential benefit for disordered sleep, and and ligaments) (Figure 14); and, in many cases, ossiflcation at should be taken just before bedtime. Anticholinergic and anti the spinal entheses. The term spondyloarthritis reflects the histaminic adverse effects may be limiting; low doses are rec fact that most of these conditions also tend to involve the ommended (e.g., fO 25 mg of amitriptyline). spine. Two serotonin-norepinephrine reuptake inhibitors (SNRIs), duloxetine and milnacipran, are FDA approved for fibromyalgia and have modest effects on pain. They may be Pathophysiology particularly appropriate in patients with concomitant depres- Genes and the environment interact to contribute to spondy- sion. Some practitioners report that the administration of a Ioarthritis pathogenesis. The exact mechanisms of these pro tricyclic antidepressant at bedtime, combined with a selective cesses remain incompletely understood.

serotonin reuptake inhibitor (e.g., sertraline) in the morning, Management may mimic the aggregate effect of the SNRIs while helping Optimal management of fibromyalgia requires a holistic normalize the sleep-wake pattern. approach, including education, exercise, and psychosocial Tramadol has a dual effect as both an agonist of p opioid support. Pharmacotherapy is often warranted, although non receptors and an SNRI. Although studies have shown tramadol pharmacologic measures remain a cornerstone of treatment. is helpful, it is now classified as an opioid, with associated concerns of class side effects, including tolerance and addic- Nonpharmacologic tion. These concerns are less extreme than with other opioids, Patients should be educated regarding their condition, with which are contraindicated in fibromyalgia. validation that their symptoms are real and reassurance that Evidence does not support NSAIDs for treating their pain is not due to tissue injury and will not lead to per fibromyalgia. manent disability. Aerobic exercise can improve well being The patient and physician should understand that fibro and function as well as reduce pain. Because patients initially myalgia is a chronic illness. The benefit of treatment will likely experience postexercise pain and thus may be unwilling to be partial and usually temporary often requiring a rotating continue, exercise must be introduced gradually and sup sequence of treatments. Nevertheless, treatment can help ported encouragingly. Although evidence supporting their use patients manage and cope with their symptoms as well as is modest, modalities that can be helpful include tai chi, medi maintain function and autonomy. tation, and acupuncture. Patients with fibromyalgia should be assessed for psycho- xtY Poil{Ts social stressors and psychiatric illness, including a history of e The characteristic features of flbromyalgia are widespread trauma and abuse. In such cases, referral for psychological chronic pain, fatigue, sleep disorders, and cognitive support is essential, although access to practitioners with symptoms. experience treating chronic pain conditions is often a barrier. r The diagnosis of fibromyalgia is no longer based on HVC Social work support may help reduce the stress burden. Even physician examination findings but rather on a careful in patients without specific psychosocial stressors, psychologi- characterization of symptoms using a validated scoring cal support for illness and pain management may be advisable. tool. Cognitive behavioral therapy has shown modest benefit in . Nonpharmacologictherapy(education,exercise,psycho- HVC reducing pain, negative mood, and disability. social support) remains a cornerstone of treatment for fibromyalgia, and pharmacotherapy is often warranted. Pharmacologic Choice of pharmacologic therapy is based on symptom profile, patient comorbidities, and medication adverse effects because no trials have directly compared the efficacy of medications. Spondyloafthritis The antiepileptic agents gabapentin and pregabalin (the latter FDA approved for fibromyalgia) improve quality of Iife Overview and decrease pain in the short term. In principle, these agents Spondyloarthritis comprises arthritic disorders classified act by reducing pain signals from the dorsal root ganglia to the together by common genetic and environmental risk factors thalamus. Adverse effects, including sedation, disequilibrium, and clinical manifestations. Spondyloarthritis includes anky weight gain, and peripheral edema, are frequent. In older losing spondylitis, psoriatic arthritis, reactive arthritis, and patients, gabapentinoid doses should initially be low and then enteropathic arthritis. Their common feature is enthesitis be slowly titrated, as appropriate. Pregabalin is now classified (inflammation at the points where tendons, ligaments, and as a controlled substance. joint capsules insert into bone). Clinically, enthesitis mani Tricyclic antidepressants (such as amitriptyline) raise fests as inflammation, pain, and new bone formation in and norepinephrine and serotonin levels and have mild benefit, around peripheral joints; dactylitis (diflfuse digital swelling, although efficacy may wane with time. These agents induce also called sausage digit, including the joint capsule, tendons, drowsiness, with potential benefit for disordered sleep, and and ligaments) (Figure 14); and, in many cases, ossiflcation at should be taken just before bedtime. Anticholinergic and anti the spinal entheses. The term spondyloarthritis reflects the histaminic adverse effects may be limiting; low doses are rec fact that most of these conditions also tend to involve the ommended (e.g., fO 25 mg of amitriptyline). spine. Two serotonin-norepinephrine reuptake inhibitors (SNRIs), duloxetine and milnacipran, are FDA approved for fibromyalgia and have modest effects on pain. They may be Pathophysiology particularly appropriate in patients with concomitant depres- Genes and the environment interact to contribute to spondy- sion. Some practitioners report that the administration of a Ioarthritis pathogenesis. The exact mechanisms of these pro tricyclic antidepressant at bedtime, combined with a selective cesses remain incompletely understood. 32

Spondyloarthritis spondylitis. Consistent with this observation, fibrocartilage rich joint structures, such as the iiium and acetabulum, are preferentially destroyed in ankylosing spondylitis; the hyaline cartilage of the sacrum and femoral head are mostly spared. Fibrillin 1, a protein commonly found in fibrocartilage, may be a target molecule. The anterior eye, proximal aorta, and ace- tabulum are all occasionally involved in spondyloarthritis and are rich in flbrocartilage/fibrillin 1. TEY POIIT' r Spondyloarthritis comprises arthritic disorders classi- fied by common genetic and environmental risk factors and clinical manifestations; they include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis. tIGURE 14. Dactylitisor'tausagedigit"oftheleftseconddigitinpatientwith o Certain subtlpes of HLA-B27 are strongly associated psoriatic arthritis, showing {usiform swelling (swelling extending throughout the with axial spondyloarthritis; however, HLA-827 alone is digit and not limited to the joint) of the metacarpophalangeal and interphalangeal insufficient to cause axial spondyloarthritis. joints and interarticular soft tissue as compared to the normal third digit.

TEY POIIT' r Spondyloarthritis comprises arthritic disorders classi- fied by common genetic and environmental risk factors and clinical manifestations; they include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis. tIGURE 14. Dactylitisor'tausagedigit"oftheleftseconddigitinpatientwith o Certain subtlpes of HLA-B27 are strongly associated psoriatic arthritis, showing {usiform swelling (swelling extending throughout the with axial spondyloarthritis; however, HLA-827 alone is digit and not limited to the joint) of the metacarpophalangeal and interphalangeal insufficient to cause axial spondyloarthritis. joints and interarticular soft tissue as compared to the normal third digit. Genetic Factors Certain subtypes of HLA-B27, a class I major histocompatibility Classification complex (MHC) molecule that presents antigens to immune Four distinct but overlapping diseases comprise spondyloar cells, are strongly associated with spondyloarthritis with axial thritis (Table 17): involvement (most commonly ankylosing spondylitis). Up to l. Ankylosing spondylitis 90'2, of White patients with ankylosing spondylitis and 60% of 2. Psoriatic arthritis Black patients with ankylosing spondylitis are HLA-B27 posi- 3. Enteropathic arthritis tive. However, HLA 827 alone is insufficient to cause ankylos ing spondylitis: Among White persons who carryr the HIA 827 4. Reactive arthritis gene, only 6% will develop disease. Other genes are therefore Some taxonomies include a fifth, undifferentiated cate- also important to spondyloarthritis risk, some of which have gory for patients with features of spondyloarthritis but insuf- been identified (e.g., interleukin-23 receptor polymorphisms). ficient manifestations to permit classification into one of the four categories. For example, a patient with episodic dactylitis Environmental Factors and a history of uveitis would not flt neatly into one of the The prevalence of spondyloarthritis is low in West Africa, even standard categories but would be classified as having periph among HIA B27 positive people. However, when HIA B27 eral spondyloarthritis by criteria discussed below. positive West Africans immigrate to the United States or Emphasizing the relatedness of all four categories, the Europe, the prevalence of spondyloarthritis increases to the Assessment of SpondyloArthritis international Society devel local population level. This suggests acquired risk related to oped classification criteria that eschew individual diseases and environmental modifi cation. instead divide patients into those with axial involvement Intestinal dysbiosis or a proinflammatory microbiome is (Figure 15) and those with involvement of peripheral joints common in spondyloarthritis and may contribute to this only (Figure 16). Although these criteria were designed for observation. Terminal ileitis, similar to that seen in Crohn study enrollment rather than clinical practice, they demon disease, occurs in up to 60% of patients with ankylosing spon- strate the common clinical features that are part of the spon dylitis, emphasizing the overlapping nature of the spondyloar dyloarthritis family. thritis disorders. Intestinal inflammation is thought to lead to Axial spondylarthritis can be categorized as radiographic a permeable gut, allowing exposure of dysbiotic bacteria (definite radiographic sacroiliitis) or nonradiographic (mini (especially flagellated bacteria) to the intestinal immune sys mal or no radiographic sacroiliitis). Although patients with tem. Dysbiosis may also play a role in psoriatic arthritis. nonradiographic spondyloarthritis often have milder disease Similarly, reactive arthritis has a well-known association with and HLA-B27 is less common, these patients have lower rates enteropathic as well as urogenital infection. of response to current treatments.

Genetic Factors Certain subtypes of HLA-B27, a class I major histocompatibility Classification complex (MHC) molecule that presents antigens to immune Four distinct but overlapping diseases comprise spondyloar cells, are strongly associated with spondyloarthritis with axial thritis (Table 17): involvement (most commonly ankylosing spondylitis). Up to l. Ankylosing spondylitis 90'2, of White patients with ankylosing spondylitis and 60% of 2. Psoriatic arthritis Black patients with ankylosing spondylitis are HLA-B27 posi- 3. Enteropathic arthritis tive. However, HLA 827 alone is insufficient to cause ankylos ing spondylitis: Among White persons who carryr the HIA 827 4. Reactive arthritis gene, only 6% will develop disease. Other genes are therefore Some taxonomies include a fifth, undifferentiated cate- also important to spondyloarthritis risk, some of which have gory for patients with features of spondyloarthritis but insuf- been identified (e.g., interleukin-23 receptor polymorphisms). ficient manifestations to permit classification into one of the four categories. For example, a patient with episodic dactylitis Environmental Factors and a history of uveitis would not flt neatly into one of the The prevalence of spondyloarthritis is low in West Africa, even standard categories but would be classified as having periph among HIA B27 positive people. However, when HIA B27 eral spondyloarthritis by criteria discussed below. positive West Africans immigrate to the United States or Emphasizing the relatedness of all four categories, the Europe, the prevalence of spondyloarthritis increases to the Assessment of SpondyloArthritis international Society devel local population level. This suggests acquired risk related to oped classification criteria that eschew individual diseases and environmental modifi cation. instead divide patients into those with axial involvement Intestinal dysbiosis or a proinflammatory microbiome is (Figure 15) and those with involvement of peripheral joints common in spondyloarthritis and may contribute to this only (Figure 16). Although these criteria were designed for observation. Terminal ileitis, similar to that seen in Crohn study enrollment rather than clinical practice, they demon disease, occurs in up to 60% of patients with ankylosing spon- strate the common clinical features that are part of the spon dylitis, emphasizing the overlapping nature of the spondyloar dyloarthritis family. thritis disorders. Intestinal inflammation is thought to lead to Axial spondylarthritis can be categorized as radiographic a permeable gut, allowing exposure of dysbiotic bacteria (definite radiographic sacroiliitis) or nonradiographic (mini (especially flagellated bacteria) to the intestinal immune sys mal or no radiographic sacroiliitis). Although patients with tem. Dysbiosis may also play a role in psoriatic arthritis. nonradiographic spondyloarthritis often have milder disease Similarly, reactive arthritis has a well-known association with and HLA-B27 is less common, these patients have lower rates enteropathic as well as urogenital infection. of response to current treatments. I Tissue Factors Ankylosing Spondylitis : The enthesis organ has a high content of fibrocartilage, which Ankylosing spondylitis is a chronic inflammatory disease seems to be a target in spondyloarthritis, especially ankylosing affecting the axial skeleton (including sacroiliac joints),

I Tissue Factors Ankylosing Spondylitis : The enthesis organ has a high content of fibrocartilage, which Ankylosing spondylitis is a chronic inflammatory disease seems to be a target in spondyloarthritis, especially ankylosing affecting the axial skeleton (including sacroiliac joints), I 33