Rheumatoid Arthritis (RA)

Pathophysiology

• Autoimmune disease affecting joints via synovial inflammation, leading to progressive cartilage, bone, and tendon destruction.

• Characterised by chronic, symmetrical polyarthritis.

Presentation

Demographics

• Predominantly women > men, peak onset age 40–60.

Risk Factors

• Family history

• Smoking

• HLA-DR4 positivity

Joint Involvement

• Symmetrical inflammatory arthritis involving ≥5 joints (often small joints of hands/feet).

• Common sites: MCP, MTP, PIP; rarely DIP.

• Morning stiffness >1 hour, improves with activity.

• Squeeze test: Pain on squeezing MCP/MTP joints suggests active synovitis.

Extra-Articular Features

• Haematological: Anaemia of chronic disease

• Skin: Rheumatoid nodules

• Ocular: Sjögren’s syndrome (dry eyes, mouth), episcleritis, keratoconjunctivitis sicca

• Respiratory: Interstitial lung disease (ILD) → bilateral “velcro” crackles, possible nodules

• Cardiovascular: Accelerated atherosclerosis → ↑ CVD risk

Diagnosis

Serology

• Rheumatoid Factor (RF): Positive in ~70–80%

• Anti-CCP Antibody: High specificity (~80% positivity)

• ESR/CRP: Typically elevated, indicating inflammation

Imaging

• X-ray: Joint space narrowing, marginal erosions, periarticular osteopenia (late changes)

• Ultrasound/MRI: More sensitive for early synovitis, erosions

Differential Diagnoses

• Psoriatic Arthritis: Asymmetric, DIP involvement, psoriasis

• Reactive Arthritis: Post-infective, often oligoarthritis

• Gout/Pseudogout: Typically monoarthritis, acute flares

• Osteoarthritis: Non-inflammatory, DIP and carpometacarpal joint involvement

• CTDs: SLE, Sjögren’s, scleroderma

Prognostic Indicators

• RF/Anti-CCP positive

• 20 swollen joints at diagnosis

• Erosions on X-ray early

• Smoking

• Impaired function at an early stage

Treatment

Non-Pharmacological

• Healthy BMI (20–25); consider Mediterranean diet

• Aerobic and resistance exercise tailored to tolerance

• Smoking cessation crucial

• Joint Protection: Ice during flares, rest, splinting or orthoses

Pharmacological

• Analgesia: Paracetamol or NSAIDs for flares

• DMARDs (Disease-Modifying Anti-Rheumatic Drugs):

  • Methotrexate (+ folinic acid once weekly on a separate day) is first-line

  • Other DMARDs: Leflunomide, sulfasalazine, hydroxychloroquine

• Glucocorticoids: Oral or intra-articular for acute inflammation or bridging therapy before DMARDs take effect

Biologic Therapies

• TNF inhibitors, IL-6 inhibitors, JAK inhibitors for moderate-severe RA or DMARD-refractory disease

Complications

Joint Deformities

• Swan neck, Boutonnière deformities, ulnar deviation

• Can lead to significant disability

Extra-Articular

• Respiratory: ILD, fibrosis

• Secondary Sjögren’s syndrome: Dry eyes (keratoconjunctivitis sicca), dryness in mouth

• Vasculitis: May affect skin, nerves, organs

• CVD: Increased mortality from ischaemic events

• Infection Risk: Immunosuppression from disease ± treatment

Notes

• Methotrexate: Monitor LFTs (hepatotoxicity), FBC (cytopenias), and for pulmonary fibrosis.

• Dry eyes (burning, irritation) often present; early treatment for Sjögren’s symptoms.

• Early, aggressive control of inflammation slows progression and improves outcomes.