Rheumatoid Arthritis ✅

Related Subjects: |Polyarticular arthritis |Rheumatoid arthritis |Systemic Sclerosis (Scleroderma) |RA vs OA |Acute and Chronic Gout |Calcium Pyrophosphate Deposition (Pseudogout) |Osteoporosis |Rheumatology Autoantibodies

🔥 Rheumatoid Arthritis (RA) is a chronic systemic autoimmune inflammatory arthritis characterised by persistent synovitis and progressive joint destruction. Symptoms must persist >6 weeks for classification. 🧪 Anti-CCP antibodies are highly specific (≥95%) and may appear years before symptoms. Early recognition and prompt DMARD initiation prevent irreversible erosions and improve long-term function.

📊 Epidemiology & Hallmarks

• Prevalence ≈ 0.8–1% in UK 🇬🇧; female:male ratio ≈ 3:1.
• Peak onset: 30–50 yrs; can present at any age.
• ⏰ Morning stiffness ≥60 min; improves with activity.
• Symmetrical small-joint polyarthritis: MCP, PIP, wrists; DIP usually spared.
• Extra-articular involvement reflects systemic inflammation (lungs, heart, eyes, vasculitis).

🧬 Aetiology & Risk Factors

• Genetic: HLA-DRB1 “shared epitope” (e.g., DR4) → higher risk of seropositive RA.
• Environmental: 🚬 Smoking (major modifiable risk factor, especially anti-CCP+ RA).
• Autoimmunity: RF (70–80% sensitive, less specific), anti-CCP (high specificity, predicts erosive disease).
• Pathogenesis: Loss of tolerance → autoantibody production → immune complex deposition → synovial inflammation → pannus formation.

🔬 Pathology – Joint Damage Mechanism

• Hyperplastic synovium forms pannus, invading cartilage and bone.
• Osteoclast activation via TNF-α, IL-6, RANKL → erosions + joint space narrowing.
• Rheumatoid nodules: central fibrinoid necrosis with palisading histiocytes.
• Synovial angiogenesis → inflammatory cell recruitment → chronic inflammation.

🩺 Clinical Features (persistent >6 weeks)

• Joints: Warm, tender, boggy; reduced grip strength; MCP/PIP/wrist involvement.
• Deformities: ulnar deviation, swan-neck, Boutonnière, MTP subluxation.
• Systemic: Fatigue, low-grade fever, weight loss.
• Extra-articular: Lung (ILD, nodules), pericarditis, vasculitis, anaemia of chronic disease, accelerated atherosclerosis.
• Eyes: Episcleritis, scleritis, secondary Sjögren’s syndrome.
• Neuro: Carpal tunnel, atlantoaxial subluxation (screen before GA).

🧪 Investigations – NICE & EULAR Guidance

• Bloods:
  • ESR/CRP: disease activity.
  • RF: supportive, monitor titers.
  • Anti-CCP: diagnostic and prognostic.
  • FBC: anaemia of chronic disease; neutropenia in Felty’s.
  • LFTs/renal for DMARD monitoring.
• Synovial fluid analysis: exclude septic arthritis and crystal arthropathies.
• Imaging:
  • X-ray: peri-articular osteopenia, joint space narrowing, erosions (classic RA changes).
  • MRI/US: detect early synovitis, erosions, tenosynovitis before X-ray changes.
• Screen for comorbidities: CVD risk, osteoporosis, infection history before DMARDs/biologics.

💊 Management – Treat-to-Target (T2T) Strategy

• 📌 Early, aggressive DMARD therapy within 3 months of diagnosis (NICE recommendation).
• First-line: Methotrexate (anchor drug) + folic acid.
• Combination DMARDs: Sulfasalazine, Leflunomide, Hydroxychloroquine.
• Biologics/targeted therapy: TNF inhibitors (etanercept, adalimumab), IL-6 inhibitors (tocilizumab), rituximab, abatacept, JAK inhibitors (if inadequate DMARD response).
• Steroids: short course bridging therapy or intra-articular injections for flares; lowest effective dose, taper rapidly to reduce long-term complications.
• NSAIDs: symptom relief only; do not modify disease.
• Non-pharmacological: smoking cessation, physiotherapy, occupational therapy, cardiovascular risk optimisation, joint protection strategies.

⚡ Acute RA Flare Management

📉 Prognosis & Monitoring

• Worse prognosis: high RF/anti-CCP titres, early erosions, polyarticular involvement, smoking.
• DAS28 to monitor disease activity and guide treatment escalation.
• Regular blood monitoring for DMARD/biologic toxicity (FBC, LFTs, renal).
• Mortality: primarily cardiovascular disease (accelerated atherosclerosis).
• Long-term monitoring: bone density, eye exams if hydroxychloroquine, infection surveillance if immunosuppressed.

🔎 RA vs OA – Clinical Shortcut

• RA: inflammatory, symmetrical, small joints, morning stiffness >60 min, systemic features, erosive on imaging.
• OA: degenerative, mechanical pain, stiffness <30 min, DIP involvement, bony enlargement, minimal systemic features.

📚 References

• NICE CKS – Rheumatoid Arthritis (UK management guidance)
• EULAR 2022 RA Management Recommendations
• Smolen JS et al., Treat-to-Target Recommendations in RA, Ann Rheum Dis 2020;79:685–699.