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DEFINITION AND PATHOGENESIS
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A chronic multisystem disease of unknown etiology characterized by persistent inflammatory synovitis, usually involving peripheral joints symmetrically. Although cartilaginous destruction, bony erosions, and joint deformity are hallmarks, the course of RA can be quite variable. An association with HLA-DR4 has been noted; both genetic and environmental factors may play a role in initiating disease. The propagation of RA is an immunologically mediated event in which joint injury occurs from synovial hyperplasia; lymphocytic infiltration of synovium; and local production of cytokines and chemokines by activated lymphocytes, macrophages, and fibroblasts.
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CLINICAL MANIFESTATIONS
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RA occurs in 0.5–1.0% of the population; women affected three times more often than men; prevalence increases with age, onset most frequent in fourth and fifth decades.
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Articular Manifestations
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Typically a symmetric polyarthritis of peripheral joints with pain, tenderness, and swelling of affected joints; morning stiffness is common; proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints frequently involved; joint deformities may develop after persistent inflammation.
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Extraarticular Manifestations
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Cutaneous: rheumatoid nodules, vasculitis
Pulmonary: nodules, interstitial disease, bronchiolitis obliterans–organizing pneumonia (BOOP), pleural disease, Caplan’s syndrome [sero (+) RA associated with pneumoconiosis]
Ocular: keratoconjunctivitis sicca (KCS), episcleritis, scleritis
Hematologic: anemia, Felty’s syndrome (splenomegaly and neutropenia)
Cardiac: pericarditis, myocarditis
Neurologic: myelopathies secondary to cervical spine disease, entrapment, vasculitis
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History and physical examination with careful examination of all joints.
Rheumatoid factor (RF) is present in >66% of pts; its presence correlates with severe disease, nodules, extra-articular features.
Antibodies to cyclic citrullinated protein (anti-CCP) have similar sensitivity but higher specificity than RF; may be most useful in early RA; presence most common in pts with aggressive disease with a tendency for developing bone erosions.
Other laboratory data: CBC, ESR.
Synovial fluid analysis: useful to rule out crystalline disease, infection.
Radiographs: juxta-articular osteopenia, joint space narrowing, marginal erosions. CXR should be obtained.
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Not difficult in pts with typical established disease. May be confusing early. Classification criteria were updated in 2010 (Table 380-1, p. 2143, in HPIM-19).
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DIFFERENTIAL DIAGNOSIS
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Gout, SLE, psoriatic arthritis, infectious arthritis, osteoarthritis, sarcoid.
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TREATMENT: RHEUMATOID ARTHRITIS
Goals: lessen pain, reduce inflammation, improve/maintain function, prevent long-term joint damage, control of systemic involvement. Increasing trend to treat RA more aggressively earlier in disease course (Table 380-2, HPIM-19, pp. 2146–2147). All RA therapies have individual toxicities, with many requiring pretreatment screening and monitoring.
Pt education on disease, joint protection.
Physical and occupational therapy: strengthen periarticular muscles, consider assistive devices.
Aspirin or NSAIDs.
Intra-articular glucocorticoids.
Systemic glucocorticoids.
Disease-modifying antirheumatic drugs (DMARDs): e.g., methotrexate, hydroxychloroquine, sulfasalazine, leflunomide.
Biologic therapies.
TNF-modulatory agents (etanercept, infliximab, adalimumab, golimumab, certolizumab): effective at controlling RA in many pts and can slow the rate of progression of radiographic joint damage and decrease disability; carry potential for serious infection and individual toxicities.
Abatacept (CTLA4-Ig): inhibits T-cell activation, can be given with or without methotrexate.
Rituximab: a chimeric antibody directed to CD20 that depletes mature B cells and is approved for refractory RA.
Tocilizumab: humanized monoclonal antibody directed against the IL-6 receptor.
Tofacitinib: oral small molecule inhibitor that primarily inhibits JAK1 and JAK3.
Anakinra: an IL-1 receptor antagonist approved for RA but rarely used in RA due to only modest clinical efficacy.
Surgery: may be considered for severe functional impairment due to deformity.