Atlas of pathophysiology, 2 Edition

Part II - Disorders

Immunologic Disorders

Rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that primarily attacks peripheral joints and the surrounding muscles, tendons, ligaments, and blood vessels. Partial remissions and unpredictable exacerbations mark the course of this potentially crippling disease. Rheumatoid arthritis strikes women three times more often than it does men.

Age Alert

RA can occur at any age, but it begins most often between ages 25 and 55.


Direct cause unknown

Proposed mechanisms

·   Abnormal immune activation (in a genetically susceptible person) leading to inflammation, complement activation, and cell proliferation in joints and tendon sheaths

·   Infection (viral or bacterial), hormone action, or lifestyle factors


The body develops immunoglobulin (Ig) M antibody against the body's own IgG (also called rheumatoid factor [RF]). RF aggregates into complexes, generates inflammation, causing eventual cartilage damage and triggering other autoimmune responses.

If not arrested, the inflammatory process in the joints occurs in four stages:

·   Congestion and edema of the synovial membrane and joint capsule cause synovitis. Infiltration by lymphocytes, macrophages, and neutrophils continues the local inflammatory response. These cells, as well as fibroblast-like synovial cells, produce enzymes that help to degrade bone and cartilage.

·   Pannus—thickened layers of granulation tissue—covers and invades cartilage and eventually destroys the joint capsule and bone.

·   Fibrous ankylosis—fibrous invasion of the pannus and scar formation—occludes the joint space. Bone atrophy and misalignment cause visible deformities and disrupt the articulation of opposing bones, causing muscle atrophy and imbalance and, possibly, partial dislocations (subluxations).

·   Fibrous tissue calcifies, resulting in bony ankylosis and total immobility.

Signs and symptoms

·   Nonspecific symptoms (most likely related to the initial inflammatory reactions) precede inflammation of the synovium, including fever, weight loss, malaise, fatigue, and lymphadenopathy

As the disease progresses

·   Specific localized, bilateral, and symmetric articular symptoms, frequently in the fingers at the proximal interphalangeal, metacarpophalangeal, and metatarsophalangeal joints, possibly extending to the wrists, knees, elbows, and ankles from inflammation of the synovium

·   Stiffening of affected joints after inactivity, especially on arising in the morning

·   Joint pain and tenderness, at first only with movement but eventually even at rest

·   Flexion deformities or hyperextension of metacarpophalangeal joints, subluxation of the wrist, and stretching of tendons pulling the fingers to the ulnar side (ulnar drift), or characteristic “swan's neck” appearance or “boutonnire” deformity

Extra-articular findings

·   Gradual appearance of rheumatoid nodules—subcutaneous, round or oval, nontender masses (20% of RF-positive patients), usually on elbows, hands, or Achilles' tendon

·   Vasculitis possibly leading to skin lesions, leg ulcers, and multiple systemic complications

·   Pericarditis, pulmonary nodules or fibrosis, pleuritis, or inflammation of the sclera and overlying tissues of the eye

·   Peripheral neuropathy with numbness or tingling in the feet or weakness and loss of sensation in the fingers

Diagnostic test results

·   X-rays show bone demineralization and soft-tissue swelling (early stages), cartilage loss and narrowed joint spaces and, finally, cartilage and bone destruction and erosion, subluxations, and deformities (later stages).

·   RF titer is positive in 75% to 80% of patients (titer of 1:160 or higher).

·   Synovial fluid analysis shows increased volume and turbidity but decreased viscosity and elevated white blood cell counts (usually greater than l0,000/l).

·   Serum protein electrophoresis shows elevated serum globulin levels.

·   Erythrocyte sedimentation rate and C-reactive protein levels are elevated in 85% to 90% of patients (may be useful to monitor response to therapy because elevation frequently parallels disease activity).

·   Complete blood count reveals moderate anemia, slight leukocytosis, and slight thrombocytosis.


·   Salicylates, particularly aspirin; nonsteroidal anti-inflammatory agents

·   Antimalarials

·   Corticosteroids

·   Disease-modifying anti-rheumatic drugs

·   Cox-2 inhibitors

·   Tumor necrosis factor inhibitors

·   Methotrexate, cyclosporine, azathioprine in early disease

·   Supportive measures, including rest, splinting to rest inflamed joints, range-of-motion exercises, physical therapy, heat applications for chronic disease and ice application for acute episodes

·   Synovectomy, osteotomy, tendon transfers

·   Joint reconstruction or total joint replacement

·   Arthrodesis (joint fusion)





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