RHEUMATOID ARTHRITIS: PATHOGENESIS, CLINICAL COURSE, AND MODERN TREATMENT APPROACHES
Keywords:
Rheumatoid arthritis, autoimmunity, citrullination, anti-citrullinated protein antibodies, synovitis, methotrexate, biologic DMARD, treat-to-target.Abstract
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by symmetric inflammatory polyarthritis, progressive synovial proliferation, and destruction of cartilage and juxta-articular bone, frequently accompanied by extra-articular manifestations affecting the lungs, skin, cardiovascular system, and hematologic profile. This narrative review synthesizes current evidence on the immunopathogenesis, clinical course, classification, and contemporary management of RA, drawing on the 2010 ACR/EULAR classification criteria and the 2021 American College of Rheumatology (ACR) guideline for the treatment of rheumatoid arthritis. Disease pathogenesis reflects the interaction of genetic susceptibility (notably the HLA-DRB1 shared epitope) and environmental triggers, principally cigarette smoking, which promote citrullination of self-proteins, loss of immune tolerance, and production of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). These autoantibodies, together with activated T and B lymphocytes, drive synovial inflammation, fibroblast-like synoviocyte proliferation and pannus formation, and cytokine-mediated amplification through tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1, culminating in osteoclast-mediated bone erosion and cartilage destruction. Management has shifted decisively toward early diagnosis and a treat-to-target strategy: methotrexate remains the anchor drug for patients with moderate-to-high disease activity, with prompt escalation to biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for patients with an inadequate response, while glucocorticoids are reserved for short-term bridging use only. A mechanism-based understanding of RA, combined with early, individualized, guideline-directed treatment, is central to preventing irreversible joint damage and improving long-term functional outcomes, including within the healthcare system of Uzbekistan.
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