Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is a chronic, systemic autoimmune inflammatory disease characterized by symmetric peripheral polyarthritis, synovial inflammation (synovitis), and joint cartilage and bone destruction, leading to joint deformities and progressive functional disability.

• Symmetric joint pain, swelling, warmth, and erythema affecting small joints of the hands (metacarpophalangeal / MCP and proximal interphalangeal / PIP joints) and feet (MTP joints)
• Prolonged morning joint stiffness lasting longer than 1 hour (improving with movement)
• Fatigue, low-grade fever, anorexia, and generalized malaise
• Rheumatoid nodules: Firm, non-tender subcutaneous nodules over bony pressure points (extensor surface of elbows)
• Advanced joint deformities: Ulnar deviation of fingers, Swan-neck deformity, Boutonnière deformity, and Baker cysts behind the knee
• Extra-articular manifestations: Keratoconjunctivitis sicca (dry eyes), interstitial lung disease, pericarditis, rheumatoid vasculitis

Loss of immune self-tolerance in genetically susceptible individuals (HLA-DRB1 shared epitope alleles). Environmental triggers (tobacco smoking, periodontal disease) lead to citrullination of mucosal self-proteins, triggering production of Anti-Citrullinated Protein Antibodies (ACPA / Anti-CCP) and Rheumatoid Factor (RF). Immune complexes and activated T/B lymphocytes infiltrate synovium, forming a hypertrophic invasive "pannus" that erodes cartilage and bone.

Diagnosed based on the 2010 ACR/EULAR Classification Criteria:

• Joint involvement (number of small and large joints involved)
• Serological testing: Rheumatoid Factor (RF) and high-specificity Anti-Cyclic Citrullinated Peptide (Anti-CCP / ACPA)
• Acute phase reactants: Elevated C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR)
• Duration of symptoms (≥6 weeks)
• Plain radiographs: Periarticular osteopenia, marginal erosions, symmetric joint space narrowing

Early and aggressive "Treat-to-Target" strategy aimed at clinical remission or low disease activity:

• Conventional Synthetic DMARDs (csDMARDs): Methotrexate is the anchor drug of choice (15-25 mg weekly with Folic acid); Hydroxychloroquine, Sulfasalazine, and Leflunomide.
• Biological DMARDs (bDMARDs): TNF-alpha inhibitors (Adalimumab, Etanercept, Infliximab), IL-6 receptor antagonists (Tocilizumab), T-cell costimulation blockers (Abatacept), or B-cell depleting agents (Rituximab).
• Targeted Synthetic DMARDs (tsDMARDs): Oral JAK inhibitors (Tofacitinib, Upadacitinib).
• Symptomatic Bridging Therapy: Short courses of low-dose oral Corticosteroids (Prednisone) and NSAIDs during DMARD initiation.