A chronic multisystem disease of unknown etiology characterized by persistent inflammatory synovitis, usually involving peripheral joints in a symmetric fashion. 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.

RA occurs in ~0.8% of the population; women affected 3 times more often than men; prevalence increases with age, onset most frequent in fourth and fifth decades.

Articular manifestations-typically a symmetric polyarthritis of peripheral joints with pain, tenderness, and swelling of affected joints; morning stiffness is common; PIP and MCP joints frequently involved; joint deformities may develop after persistent inflammation.

Extraarticular manifestations:

• 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, episcleritis, scleritis
• Hematologic-anemia, Felty's syndrome (splenomegaly and neutropenia)
• Cardiac-pericarditis, myocarditis
• Neurologic-myelopathies secondary to cervical spine disease, entrapment, vasculitis.

• Hx and physical exam with careful examination of all joints.
• Rheumatoid factor (RF) is present in >66% of pts; its presence correlates with severe disease, nodules, extraarticular 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-juxtaarticular osteopenia, joint space narrowing, marginal erosions. Chest x-ray should be obtained.

Not difficult in pts with typical established disease. May be confusing early. Classification criteria were developed for investigational purposes, but may be useful (Table 314-1, p. 2089, in HPIM-17).

DIFFERENTIAL DIAGNOSIS
Gout, SLE, psoriatic arthritis, infectious arthritis, osteoarthritis, sarcoid.

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 (Fig. 167-1).

• Pt education on disease, joint protection
• Physical and occupational therapy-strengthen periarticular muscles, consider assistive devices.
• Aspirin or NSAIDs.
• Intraarticular glucocorticoids.
• Systemic glucocorticoids.
• Disease-modifying antirheumatic drugs (DMARDs)-e.g., methotrexate; IM gold compounds; hydroxychloroquine; sulfasalazine; d-penicillamine. Each agent has individual toxicities-pt education and monitoring required. Have been used in combination but with increased toxicity.
• Biologic therapy-TNF modulatory agents (etanercept, infliximab, adalimumab) effective at controlling RA in many pts and can slow the rate of progression of radiographic joint damage and decrease disability; carries potential for serious infection and individual toxicities. IL-1 receptor antagonist (anakinra) can improve the signs and symptoms of RA. Rituximab, a chimeric antibody directed to CD20 that depletes mature B cells, has been approved for RA patients who have failed anti-TNF therapy. Abatacept (CTLA4-Ig)-inhibits T cell activation, can be given with or without methotrexate, and is usually given in those who have failed or have contraindications to anti-TNF therapy.
• Immunosuppressive therapy-e.g., azathioprine, leflunomide, cyclosporine, and cyclophosphamide. Generally reserved for pts who have failed DMARDs and biologics.
• Surgery-may be considered for severe functional impairment due to deformity.

Figure 167-1
Algorithm for the medical management of rheumatoid arthritis. Coxib, COX-2 inhibitors; DMARD, disease-modifying anti-rheumatic drug; CCP, cyclic citrullinated polypeptide; MTX, methotrexate; SSA, sulfasalazine; TNF, tumor necrosis factor.

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SLE, RA, and Other Connective Tissue Diseases