Rheumatoid Arthritis: Clinical Features, ACR/EULAR Criteria & Treatment Options

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Below is a **concise but exhaustive single-place medical reference** for: # **RHEUMATOID ARTHRITIS (RA)** **Clinical Features • ACR/EULAR 2010 Criteria • Diagnosis • Management (stepwise) • Drugs with MoA, dosing, AEs, contraindications, interactions, monitoring & counselling** --- # **1. Definition** Rheumatoid arthritis is a **chronic, systemic, autoimmune inflammatory polyarthritis** primarily affecting **synovial joints**, causing **persistent symmetric polyarthritis**, progressive joint destruction, disability, and extra-articular complications. It is mediated by **autoantibodies (RF, anti-CCP)** and **pro-inflammatory cytokines (TNF-α, IL-6, IL-1)**. --- # **2. Pathophysiology (Short but Complete)** * Genetic: **HLA-DRB1 shared epitope** strongly associated * Autoantibodies: **RF (IgM anti-Fc)** and **anti-CCP** (highly specific) * Inflammatory cascade → **synovial hyperplasia (pannus formation)** → cartilage erosion → bone destruction * Cytokines: **TNF-α, IL-6, IL-1**, JAK-STAT pathway activation * Extra-articular: vasculitis, nodules, ILD, anemia of chronic disease, scleritis * Accelerated **atherosclerosis** → ↑ CV mortality --- # **3. Clinical Features** ## **A. Articular** * **Symmetric small joint polyarthritis** (MCP, PIP, wrists; usually spares DIP) * **Morning stiffness > 1 hour** * Joint tenderness, boggy swelling * **Warm joints but not red** * **Deformities** (late): * Ulnar deviation * Swan-neck deformity * Boutonnière deformity * Z-thumb deformity * Reduced grip strength * In advanced disease: rheumatoid nodules, tendon rupture (e.g., **extensor tendon**) ## **B. Extra-articular** * **Rheumatoid nodules** * **Felty syndrome**: RA + neutropenia + splenomegaly * Ocular: **scleritis, episcleritis, keratoconjunctivitis sicca** * Pulmonary: **ILD, pleural effusion (exudative, low glucose)** * Cardiac: **pericarditis, ↑ CAD risk** * Hematology: anemia of chronic disease, thrombocytosis * Neurological: carpal tunnel syndrome, cervical spine (C1–C2) subluxation * Skin: vasculitic ulcers --- # **4. Investigations & Diagnosis** ### **A. Blood Tests** * **ESR/CRP** ↑ * **RF** positive in ~70–80% * **Anti-CCP**: highly specific (~95%), predicts severe disease * **CBC**: anemia of chronic disease, thrombocytosis * **LFT/RFT** baseline before DMARD therapy ### **B. Imaging** * **X-ray early**: soft tissue swelling, peri-articular osteopenia * **X-ray late**: joint space narrowing, erosions * **Ultrasound / MRI**: detects early synovitis & erosions --- # **5. ACR/EULAR 2010 Classification Criteria for RA** A score **≥ 6/10 = definite RA** ### **A. Joint involvement (0–5 points)** * 1 large joint → 0 * 2–10 large joints → 1 * 1–3 small joints → 2 * 4–10 small joints → 3 * > 10 joints (≥1 small) → 5 ### **B. Serology (0–3 points)** * RF negative & anti-CCP negative → 0 * Low-positive RF or low-positive anti-CCP → 2 * High-positive RF or anti-CCP → 3 ### **C. Acute-phase reactants (0–1 point)** * Normal ESR/CRP → 0 * Abnormal ESR/CRP → 1 ### **D. Duration of symptoms (0–1 point)** * <6 weeks → 0 * ≥6 weeks → 1 --- # **6. Differential Diagnoses** * Osteoarthritis * Psoriatic arthritis * SLE arthritis * Reactive arthritis * Viral polyarthritis (parvovirus B19, chikungunya) * Gout/pseudogout * Polymyalgia rheumatica --- # **7. Management (Stepwise & Evidence-Based)** ## **A. General Principles** * **Early aggressive treatment** with DMARDs * Aim: **remission or low disease activity** * Regular **DAS28** monitoring * Combination DMARDs if inadequate response * Avoid long-term steroids --- # **8. Pharmacologic Treatment (Full drug-level details)** # **1) First-line: Conventional DMARDs** --- ## **A. Methotrexate (MTX) – cornerstone** **Indication:** First-line DMARD for all moderate-severe RA **Mechanism:** Inhibits dihydrofolate reductase → ↓ purine synthesis; ↑ adenosine (anti-inflammatory) **Dose:** * Start 7.5–15 mg once weekly → titrate to **25 mg weekly**; give **folic acid 1 mg/day** **PK:** Hepatic metabolism, renal excretion **Common AEs:** GI upset, stomatitis, hair loss **Serious AEs:** Hepatotoxicity, myelosuppression, pneumonitis **Contraindications:** Pregnancy, liver disease, alcohol use disorder, severe renal impairment **Interactions:** TMP-SMX ↑ MTX toxicity; avoid NSAID excess **Monitoring:** CBC, LFT, RFT every 6–12 weeks **Counselling:** Once weekly dosing, avoid alcohol, report dyspnea --- ## **B. Leflunomide** **MoA:** Inhibits dihydroorotate dehydrogenase → ↓ pyrimidine synthesis **Dose:** 10–20 mg daily **AEs:** Hepatotoxicity, diarrhea, alopecia, teratogenic **Contra:** Pregnancy; need cholestyramine washout **Monitoring:** CBC, LFT every 8 weeks --- ## **C. Sulfasalazine** **MoA:** Anti-inflammatory; modulates cytokines **Dose:** 500 mg/day → 2–3 g/day **AEs:** Rash, GI upset, reversible oligospermia **Contra:** Sulfa allergy **Monitoring:** CBC, LFT --- ## **D. Hydroxychloroquine** **MoA:** Inhibits antigen presentation & TLR pathways **Dose:** 200–400 mg/day **AEs:** Retinopathy (dose-dependent) **Monitoring:** Baseline eye exam + annual screening after 5 yrs **Use:** Mild RA or combination therapy --- # **2) Biologic DMARDs (if inadequate response to MTX)** --- ## **A. Anti-TNF Agents** * **Etanercept** * **Infliximab** * **Adalimumab** * **Golimumab** * **Certolizumab** **MoA:** TNF-α blockade **AEs:** TB reactivation, infections, demyelination, CHF worsening **Contra:** Active infection, demyelinating disease **Monitoring:** TB screening, CBC, LFT **Counselling:** Report fever; maintain vaccination --- ## **B. Anti-IL-6 (Tocilizumab, Sarilumab)** **MoA:** IL-6 receptor blockade **AEs:** ↑ cholesterol, infections, GI perforation (esp. diverticulitis) --- ## **C. Anti-CD20 (Rituximab)** **MoA:** B-cell depletion **Use:** Refractory RA or when biologics contraindicated **AEs:** Infusion reactions, hepatitis B reactivation --- ## **D. CTLA-4 Fusion Protein (Abatacept)** **MoA:** Inhibits T-cell activation **AEs:** Infections, COPD exacerbation --- # **3) Targeted Synthetic DMARDs – JAK Inhibitors** * **Tofacitinib** * **Baricitinib** * **Upadacitinib** **MoA:** JAK-STAT inhibition → ↓ cytokine signaling **AEs:** Herpes zoster, ↑ LDL/HDL, thrombosis risk **Monitoring:** CBC, lipids, LFT **Counselling:** Vaccinate for zoster before therapy --- # **4) Glucocorticoids** * Used as **bridge therapy** until DMARDs act * Dose: **Prednisolone 5–10 mg/day short-term** * AEs: osteoporosis, weight gain, infection, HTN * Avoid chronic use * Provide **calcium + vitamin D** --- # **5) NSAIDs** * Symptomatic relief only * Do NOT prevent joint damage * Contra: renal disease, peptic ulcer, CVD --- # **9. Non-Pharmacologic Management** * Physiotherapy + joint-protection exercises * Smoking cessation (smoking worsens RA) * Weight optimisation * Vaccination: influenza, pneumococcal before biologics * Occupational therapy * Surgery: joint replacement in advanced destruction --- # **10. Follow-Up & Monitoring** * DAS28 scoring every 3 months * Monitor DMARD toxicity: CBC, LFT, RFT * Eye exams for hydroxychloroquine * TB screening annually for biologics --- # **11. Prognostic Factors** **Poor prognosis indicators:** * High RF/anti-CCP titers * Early erosions on X-ray * High disease activity (DAS28) * Extra-articular disease * Smoking * Early disability --- If you want, I can also generate: ✅ **Case-based MCQs (20–40)** ✅ **HTML-CSS-JS one-file quiz** ✅ **SEO-friendly titles & tags** Just tell me!