Rheumatoid arthritis Study Guide

📖 Core Concepts Rheumatoid arthritis (RA) – chronic autoimmune disease that targets synovial joints, causing symmetric polyarthritis, morning stiffness > 1 h, and systemic features. Synovitis → pannus – inflamed synovial membrane proliferates (fibroblast‑like synoviocytes) → invasive pannus destroys cartilage & bone. Key autoantibodies – Rheumatoid factor (RF, IgM anti‑IgG) (≈ 2/3 positive, nonspecific) and anti‑citrullinated protein antibodies (ACPAs, e.g., anti‑CCP) (≈ 70 % positive, 95 % specific). Classification (2010 ACR/EULAR) – ≥ 6 points from joint count, serology, acute‑phase reactants, and symptom duration ≥ 6 weeks. Disease Activity Score (DAS28) – combines 28‑joint tender/swollen counts, ESR/CRP, and patient global score; guides treatment intensity. Treat‑to‑target – aim for remission or low disease activity using early DMARDs, escalation to biologics if needed. 📌 Must Remember Morning stiffness > 1 h = red flag for RA vs osteoarthritis. ACPAs: 80 % specificity; high titres predict aggressive disease. Methotrexate = first‑line DMARD; give folic acid 1 mg daily to reduce toxicity. Biologic eligibility: failure of ≥ 2 conventional DMARDs (incl. methotrexate) after 3 months. DAS28 remission: ≤ 2.6; low activity ≤ 3.2; moderate 3.2–5.1; high > 5.1. Major risk factors: smoking (×3 risk), HLA‑DR4/shared‑epitope, family history (3‑5×). Cardiovascular disease – leading cause of death; RA doubles heart disease risk independent of traditional factors. 🔄 Key Processes Initiation – genetic (HLA‑DR4) + environmental (smoking, silica) → loss of tolerance → citrullination of proteins. Autoantibody formation – ACPAs & RF generate immune complexes → activate macrophage Fcγ receptors. Synovial amplification – CD4⁺/CD8⁺ T‑cells infiltrate; macrophages release TNF‑α, IL‑1, IL‑6; FLS become aggressive → pannus formation. Bone erosion – synovial RANKL binds RANK on osteoclast precursors → osteoclastogenesis → erosions. Systemic spill‑over – cytokines cause anemia of chronic disease, fatigue, cardiovascular inflammation, lung fibrosis. 🔍 Key Comparisons RA vs Osteoarthritis Symmetry: RA = symmetric; OA = asymmetric. Morning stiffness: RA > 1 h; OA < 30 min. Labs: RA + RF/ACPAs, ↑ESR/CRP; OA = normal. TNF inhibitor vs IL‑6 blocker Primary target: TNF‑α vs IL‑6 receptor. Lipid effect: IL‑6 blockers ↑ cholesterol (monitor lipids); TNF inhibitors minimal effect. Infection risk: both ↑ serious infection; TB screening required for TNF inhibitors. Methotrexate monotherapy vs Triple therapy Methotrexate alone: effective in 50 % remission. Triple (MTX + sulfasalazine + hydroxychloroquine): higher ACR‑50 response, useful when MTX alone insufficient. ⚠️ Common Misunderstandings “RF positive = RA” – RF can be seen in healthy adults, hepatitis C, other autoimmune diseases. “NSAIDs cure RA” – they relieve pain but do not alter disease progression. “Biologics are first‑line” – conventional DMARDs are tried first; biologics require documented inadequate response. “Pregnancy always worsens RA” – most women improve during pregnancy; flare often postpartum. 🧠 Mental Models / Intuition “Fire‑fighter” model – think of the immune system as a fire: Ignition (citrullination + genetics) → fuel (autoantibodies) → spread (synovial cytokines) → damage (pannus/erosion). Intervene early (DMARDs) to extinguish the fire before it destroys the house (joints). “Score‑Driven ladder” – each step up the DAS28 ladder demands a stronger medication rung (NSAID → MTX → combo DMARD → biologic). 🚩 Exceptions & Edge Cases Seronegative RA – RF and ACPA negative but still meet clinical & imaging criteria; rely on joint pattern and imaging. Latent TB – must be treated before initiating any TNF inhibitor; not required for IL‑6 blockers or abatacept. Pregnancy‑compatible drugs – low‑dose prednisone, hydroxychloroquine, sulfasalazine are safe; methotrexate & leflunomide are contraindicated. D2T RA – disease remains active despite ≥ 2 biologics with different mechanisms; consider JAK inhibitors or combination strategies. 📍 When to Use Which Mild‑moderate disease, early → start methotrexate + folic acid; add short‑course glucocorticoid bridge. Inadequate response after 3 mo → add sulfasalazine & hydroxychloroquine (triple therapy) or TNF inhibitor. High‑risk erosive disease (positive ACPA, early erosions) → early biologic + methotrexate. Contraindication to TNF inhibitors (e.g., demyelinating disease, heart failure) → use abatacept or tocilizumab. History of recurrent infections or malignancy → consider JAK inhibitor with careful monitoring; avoid potent biologics if possible. 👀 Patterns to Recognize Symmetric small‑joint polyarthritis + > 1 h morning stiffness → think RA. Positive ACPA + early erosions on ultrasound → predicts rapid progression; warrants aggressive therapy. New-onset dyspnea + crackles in RA patient → consider interstitial lung disease; obtain HRCT. Cervical spine pain + neurologic signs → suspect atlanto‑axial subluxation; order lateral neck X‑ray. 🗂️ Exam Traps “RF alone confirms RA” – distractor; need ACPA or imaging for specificity. “NSAIDs are disease‑modifying” – false; they only control symptoms. “All biologics require TB screening” – only TNF inhibitors (and some other agents) have mandatory TB prophylaxis; IL‑6 blockers do not. “Methotrexate is contraindicated in pregnancy” – true, but the trap may be wording that suggests all DMARDs are unsafe; hydroxychloroquine and sulfasalazine are acceptable. “Low DAS28 automatically equals remission” – DAS28 ≤ 2.6 is remission, but clinical judgment (no erosions, functional status) still needed. --- Use this guide for rapid recall before your exam – focus on the bolded key points, recognize the classic clinical pattern, and apply the decision‑tree for treatment escalation.