Pathophysiology
Genetic (HLA-DR4) and environmental (smoking, gum disease) factors trigger citrullination of self-proteins. Anti-CCP antibodies and RF drive synovial infiltration by T cells, B cells and macrophages. TNF-α, IL-6 and IL-1 activate fibroblasts and osteoclasts, producing hyperplastic synovium (pannus) that erodes cartilage and bone.
Sources: ACR 2021 Guideline for the Treatment of RA (Arthritis Rheumatol 2021;73:1108); EULAR Recommendations for RA 2022 (Ann Rheum Dis 2023;82:3)
Clinical presentation
Symmetric polyarthritis of MCPs, PIPs and wrists with morning stiffness >30-60 min, sparing DIPs. Late deformities: ulnar deviation, swan-neck, boutonnière, Z-thumb. Systemic: fatigue, low-grade fever, weight loss. Extra-articular: rheumatoid nodules, interstitial lung disease, pleuritis, pericarditis, secondary Sjögren, scleritis, Felty syndrome (RA + splenomegaly + neutropenia), amyloidosis.
Sources: ACR 2021 Guideline for the Treatment of RA (Arthritis Rheumatol 2021;73:1108); EULAR Recommendations for RA 2022 (Ann Rheum Dis 2023;82:3)
Diagnosis
ACR/EULAR 2010 criteria integrate joint involvement, serology (RF, anti-CCP), acute-phase reactants (ESR/CRP) and symptom duration. Anti-CCP is more specific than RF. X-ray: periarticular osteopenia, joint-space narrowing, marginal erosions; US or MRI detects earlier synovitis and erosions.
Sources: ACR 2021 Guideline for the Treatment of RA (Arthritis Rheumatol 2021;73:1108); EULAR Recommendations for RA 2022 (Ann Rheum Dis 2023;82:3)
Treatment
Early treat-to-target with disease-modifying anti-rheumatic drugs (DMARDs). Methotrexate is first-line (with folic acid supplementation). Combine with hydroxychloroquine or sulphasalazine if incomplete response. Persistent activity: add biologic DMARD (TNF inhibitors - etanercept, infliximab, adalimumab; anti-IL6 - tocilizumab; anti-CD20 - rituximab; anti-CTLA4 - abatacept) or JAK inhibitors (tofacitinib, baricitinib). Short courses of low-dose steroids bridge to DMARD effect. NSAIDs for symptom relief.
Sources: ACR 2021 Guideline for the Treatment of RA (Arthritis Rheumatol 2021;73:1108); EULAR Recommendations for RA 2022 (Ann Rheum Dis 2023;82:3)
Monitoring & comorbidity
Regular disease activity scoring (DAS28), CBC, LFTs and creatinine. Screen for latent TB and HBV before biologics. Address cardiovascular risk (RA doubles MI risk). Vaccinate against influenza, pneumococcus, HZV and COVID-19 before starting immunosuppression when possible.
Sources: ACR 2021 Guideline for the Treatment of RA (Arthritis Rheumatol 2021;73:1108); EULAR Recommendations for RA 2022 (Ann Rheum Dis 2023;82:3)
