SN4 SHORT NOTE 5M ★ High-yield

Describe the pathogenesis and morphology of rheumatoid arthritis.

Pathology · 2nd Professional — Para-Clinical

Definition

Rheumatoid arthritis is a chronic, symmetrical, inflammatory polyarthritis with systemic features, characterised by synovitis that progressively destroys articular cartilage and bone.

Prevalence about 1%; female to male ratio 3:1; peak onset in the fourth and fifth decades

Pathogenesis

Genetic susceptibility — HLA-DR4 and DR1; the "shared epitope" → An environmental trigger — notably smoking — causes citrullination of self proteins → Loss of tolerance; anti-CCP antibodies and rheumatoid factor appear, often years before symptoms → CD4 T cells and macrophages infiltrate the synovium → TNF, IL-1 and IL-6 drive synovial proliferation and angiogenesis → pannus — inflamed, proliferating synovium — grows over the cartilage → Matrix metalloproteinases and osteoclast activation (RANKL) destroy cartilage and bone → erosions

Morphology

Synovium — thickened, oedematous, with villous projections; dense infiltrate of lymphocytes, plasma cells and macrophages, sometimes with lymphoid follicles
Pannus — the destructive layer of granulation tissue that erodes cartilage and subchondral bone
Fibrinoid necrosis and fibrin exudate on the synovial surface
Late — fibrous then bony ankylosis
Rheumatoid nodule — central fibrinoid necrosis surrounded by palisading epithelioid macrophages and a lymphocyte collar; over pressure points such as the olecranon; occurs in about a quarter, and only in seropositive patients

Clinical Features

Site	Features
Joints	Symmetrical small joint involvement — MCP, PIP and wrist; spares the dip joints; morning stiffness over an hour
Deformities	Ulnar deviation, swan-neck and boutonniere deformities, Z-thumb, subluxation
Cervical spine	Atlanto-axial subluxation — dangerous during intubation
Systemic	Nodules, vasculitis, pleural effusion, interstitial lung disease, pericarditis, scleritis, amyloidosis (AA), anaemia of chronic disease
Named associations	FELTY syndrome — rheumatoid arthritis + splenomegaly + neutropenia. CAPLAN syndrome — rheumatoid arthritis + pneumoconiosis

CLINICAL PEARL

Rheumatoid arthritis spares the distal interphalangeal joints; osteoarthritis and psoriatic arthritis do not. That single observation at the bedside separates them before any test. Rheumatoid disease is also symmetrical and erosive with soft-tissue swelling, whereas osteoarthritis is asymmetrical with osteophytes and joint space narrowing.

Applied Aspects

Anti-CCP is far more specific than rheumatoid factor (about 95% against 70%) and predicts erosive disease; rheumatoid factor is also positive in infection, Sjogren syndrome and in healthy elderly people
Radiographs show soft tissue swelling, periarticular osteopenia, joint space narrowing and marginal erosions; ultrasound and MRI detect these far earlier
Early aggressive treatment with disease-modifying drugs changes the outcome — the "window of opportunity" in the first months; methotrexate is first-line
Biological agents against TNF, IL-6 and B cells have transformed refractory disease, but reactivate latent tuberculosis, so screening before starting them is mandatory in India
Secondary AA amyloidosis should be suspected if proteinuria develops
Cardiovascular disease is the leading cause of death, from accelerated atherosclerosis driven by chronic inflammation

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