Rheumatoid Arthritis

Overview – Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that primarily targets synovial joints, causing symmetrical, polyarticular inflammation and joint destruction. RA is the most common form of inflammatory arthritis and affects young to middle-aged adults, especially women. The disease is characterised by morning stiffness, progressive joint deformity, and multi-organ involvement. Early diagnosis and treatment are essential to prevent long-term disability.

Definition

Rheumatoid arthritis is a seropositive, autoimmune, inflammatory arthritis that leads to chronic synovitis, joint destruction, and systemic manifestations. It typically involves the small joints of the hands in a symmetrical pattern.

Aetiology

  • Genetic Autoimmune Disorder
  • HLA-DR4 and HLA-DR1 associated
  • Environmental triggers (e.g. smoking, infections)
  • Autoantibody formation, notably:
    • Rheumatoid factor (RF): IgM antibodies targeting Fc portion of IgG
    • ACPA: Often detectable years before clinical onset
  • Mechanisms include:
    • Immune complex formation (RF:IgG) → deposition in joints
    • Complement activation → chondrocyte lysis
    • CD4 T-cell activation → macrophage cytokine release (TNFα, IL-1, IL-6)
    • Osteoclast activation → bone erosion
    • Plasma cell activation → sustained antibody production
Binding of RF-IgG Complexes to Articular Cartilage
Source: Labpedia

Pathogenesis

  1. Autoimmune activation → Rheumatoid Factor (IgM against IgG)
  2. Anti-CCP antibodies target citrullinated peptides
  3. Macrophage-mediated synovial inflammation → pannus formation
  4. Cartilage erosion, joint destruction, and fibrous ankylosis
RHEUMATOID ARTHRITIS
 https://curearthritis.org/what-is-the-difference-between-osteoarthritis-and-other-forms-of-autoimmune-arthritis-such-as-rheumatoid-arthritis/

Morphology

  • Pannus: thickened, inflamed synovium with papillary projections
  • Articular cartilage erosion
  • Fibrous and bony ankylosis
  • Joint deformity and subluxation
RA - Cartilage Destruction
RHEUMATOID ARTHRITIS

Clinical Features

  • Age of onset: 20–40 years
  • Pattern: Symmetrical polyarthritis, particularly MCP, PIP, and wrists
  • Morning stiffness lasting >1 hour
  • Joint findings:
    • Joint pain, swelling, and morning stiffness
    • Symmetrical involvement of small joints (hands and feet)
    • Ulnar deviation, joint deformities
    • Erosions visible on X-ray
    • Functional disability and intrinsic muscle wasting
  • Systemic involvement:
    • Dermatologic: Rheumatoid nodules (commonly elbows)
    • Vasculitis: Digital infarcts, gangrene
    • Ophthalmologic: Dry eyes, scleritis
    • Pulmonary: Fibrosis, pleural effusion, nodules
    • Cardiac: Pericarditis, valvular disease
    • GI: PUD (from NSAIDs), dry mouth
    • Renal: Amyloidosis → proteinuria
    • Liver: Portal fibrosis, nodular hyperplasia
    • Neuro: Cervical spine instability, nerve entrapment
    • Haematologic: Splenomegaly, lymphadenopathy, anaemia, leukopenia
RHEUMATOID ARTHRITIS
User:Phoenix119, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons

Diagnosis

Diagnostic Criteria (≥4 required):

  • Morning stiffness
  • Arthritis of ≥3 joint areas
  • Involvement of MCP, PIP or wrist joints
  • Symmetrical arthritis
  • Rheumatoid nodules
  • RA seropositivity (RF)
  • Radiographic erosions

Laboratory Tests

  • Anti-Citrullinated Protein Antibody (ACPA/Anti-CCP)
    • Highly specific
    • May be positive years before onset
  • Rheumatoid Factor (RF) – positive in ~70%
  • ESR & CRP – non-specific inflammation markers

Differential Diagnosis

Management

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

  • COX inhibition → ↓ prostaglandin synthesis → pain/inflammation relief

Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

  • Methotrexate – inhibits folate metabolism, ↓ lymphocyte proliferation
  • Sulfasalazine – anti-inflammatory and immunomodulatory
  • Hydroxychloroquine – ↓ lysosomal acidity
  • Leflunomide – inhibits pyrimidine synthesis
  • Cyclosporin – blocks IL-2 receptor signalling

Corticosteroids

  • Potent immunosuppressants
  • Inhibit cytokine secretion and immune cell activation
  • Used for acute flare control

Biologics

  • Cytokine inhibitors:
    • TNFα inhibitors
    • IL-1 inhibitors
    • IL-6 inhibitors
  • Co-stimulation blockers (e.g. abatacept)
  • Monoclonal antibodies targeting:
    • B-cells (e.g. rituximab)
    • Osteoclasts (prevent bone erosion)
    • Pro-inflammatory cytokines

Complications

  • Joint deformity and disability
  • Atlantoaxial subluxation → spinal cord compression
  • Extra-articular organ damage (lungs, heart, eyes)
  • Amyloidosis
  • Increased cardiovascular risk

Summary – Rheumatoid Arthritis

Rheumatoid arthritis is a seropositive autoimmune condition that causes chronic, symmetrical joint inflammation and systemic complications. Early recognition, serological testing, and initiation of DMARDs are critical to slowing progression and preserving joint function. For a broader context, see our Musculoskeletal Overview and Immune & Rheumatology Overview pages.

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