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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.


RA occurs in 0.5–1.0% of the population; more common in females than in males with a 2–3:1 ratio; incidence increases between 25 and 55 year of age, plateaus until age 75 then decreases.

Articular Manifestations

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.

Extra-articular Manifestations

  • Cutaneous: rheumatoid nodules, vasculitis

  • Pulmonary: nodules, interstitial disease, bronchiolitis obliterans–organizing pneumonia (BOOP), pleural disease, Caplan’s syndrome [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

Associated Conditions

  • Cardiovascular disease: most common cause of death in RA

  • Osteoporosis: more common in RA than general population

  • Hypoandrogenism: decreased testosterone, LH, DHEA

  • Lymphoma: 2–4-fold increase risk in RA pts


  • History and physical examination with careful examination of all joints

  • Rheumatoid factor (RF) is present in 75–80% 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.


Not difficult in pts with typical established disease. May be confusing early. Classification criteria were updated in 2010 (Table 351-1, HPIM-20).


Gout, SLE, psoriatic arthritis, infectious arthritis, osteoarthritis, spondyloarthritis, sarcoid, polymyalgia rheumatica.


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 351-2, HPIM-20). All RA therapies have individual toxicities, with many requiring pretreatment screening and monitoring.

  • Pt education on disease, joint protection.

  • Physical and ...

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