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For further information, see CMDT Part 20-05: Rheumatoid Arthritis

Key Features

Essentials of Diagnosis

  • Usually insidious onset with morning stiffness and joint pain

  • Symmetric polyarthritis with predilection for small joints of the hands and feet; deformities common with progressive disease

  • Radiographic findings

    • Juxta-articular osteoporosis

    • Joint erosions

    • Joint space narrowing

  • Rheumatoid factor and antibodies to cyclic citrullinated peptides (anti-CCP) are present in 70–80%

  • Extra-articular manifestations

General Considerations

  • Cause is unknown

  • Multiple genes contribute to susceptibility; best characterized genetic risk factor is inheritance of HLA DRB1 alleles encoding a distinctive five-amino-acid sequence known as the "shared epitope"

  • The pathologic findings in the joint include

    • Chronic synovitis with formation of a pannus, which erodes cartilage, bone, ligaments, and tendons

    • Effusion and other manifestations of inflammation are common

  • In the late stage, organization may result in fibrous ankylosis; true bony ankylosis is rare


  • Prevalence is 1%

  • More common in women than men (female:male ratio of 3:1)

  • Can begin at any age, but the peak onset is in the fourth or fifth decade for women and the sixth to eighth decades for men

Clinical Findings

Symptoms and Signs

  • Joint symptoms

    • Onset of articular signs of inflammation is usually insidious, with prodromal symptoms of vague periarticular pain or stiffness

    • Symmetric swelling of multiple joints with tenderness and pain

    • Monarticular disease is occasionally seen initially

    • Stiffness

      • Prominent in the morning

      • Persists for > 30 minutes (and usually many hours)

      • May recur after daytime inactivity and be much more severe after strenuous activity

    • Distribution of affected joints

      • PIP joints of the fingers, MCP joints, wrists, knees, ankles, and MTP joints are most often involved

      • However, any diarthrodial joint may be affected

    • Synovial cysts and rupture of tendons may occur

    • Entrapment syndromes are common, particularly of the median nerve at the carpal tunnel of the wrist

    • Can affect the neck but spares other components of the spine and does not involve the sacroiliac joints

      • In advanced disease, atlantoaxial (C1–C2) subluxation can lead to myelopathy

  • Rheumatoid nodules

    • Seen in 20% of patients

    • Most commonly situated over bony prominences but also observed in the bursae and tendon sheaths

    • Occasionally seen in the lungs, the sclerae, and other tissues

    • Correlate with the presence of rheumatoid factor in serum ("seropositivity"), as do most other extra-articular manifestations

  • Ocular symptoms

    • Episcleritis

    • Scleritis

    • Scleromalacia due to scleral nodules

    • Peripheral ulcerative keratitis

    • Dryness of the eyes, mouth, and other mucous membranes, especially in advanced disease

  • Other symptoms

    • Interstitial lung disease is not uncommon; manifests clinically as cough and progressive dyspnea

    • Pericarditis and pleural disease, when present, are usually silent clinically

    • Palmar erythema seen in patients with active joint disease

    • Occasionally, a small vessel vasculitis develops and manifests as tiny hemorrhagic infarcts in the nail folds or finger pulps

    • Necrotizing arteritis is a ...

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