Clinical meaning
Rheumatoid arthritis pathogenesis involves complex interactions between genetic susceptibility (HLA-DR shared epitope), environmental triggers (smoking, periodontal pathogens), and immune dysregulation. Citrullination of self-proteins generates neoantigens recognized by autoreactive T cells, which activate B cells to produce anti-CCP antibodies and rheumatoid factor. These immune complexes deposit in synovium, activating complement and recruiting macrophages that release TNF-α, IL-1β, IL-6, and RANKL. TNF-α and IL-6 drive systemic inflammation, while RANKL activates osteoclasts causing periarticular erosions. The JAK-STAT signaling pathway amplifies cytokine-driven inflammation. Modern targeted therapies (anti-TNF, IL-6 inhibitors, JAK inhibitors, T-cell co-stimulation blockers, B-cell depletion) directly address these mechanisms. The clinician prescribes and manages DMARD regimens, monitors for treatment toxicity and opportunistic infections, adjusts therapy based on disease activity scores, and manages comorbid cardiovascular and pulmonary complications.
Diagnosis & workup
Diagnostics & workup: - Order RF and anti-CCP antibodies for serologic classification (seropositive vs. seronegative RA) - Order ESR and CRP to assess disease activity and monitor treatment response - Order CBC with differential: anemia of chronic disease, DMARD-induced leukopenia/thrombocytopenia - Order CMP: creatinine (renal function for drug dosing), LFTs (methotrexate/leflunomide monitoring) - Order radiographs of hands and feet at baseline and periodically to assess for erosive disease progression - Consider musculoskeletal ultrasound for detecting subclinical synovitis and early erosions - Calculate DAS28 (Disease Activity Score using 28 joints) at each visit to guide treat-to-target decisions - Order screening tests before biologic therapy: TB (PPD or IGRA), hepatitis B/C serologies, CBC