## Serological Markers and Diagnostic Criteria in RA **Key Point:** Serology alone is never sufficient for RA diagnosis. Clinical arthritis, imaging findings, and temporal criteria must all be integrated. ### Serological Markers in RA | Marker | Sensitivity | Specificity | Clinical Significance | |---|---|---|---| | Rheumatoid Factor (RF) | 70–80% | 80–85% | Present in ~70% of RA; also in SLE, Sjögren's, infections | | Anti-CCP | 60–70% | >95% | Highly specific; precedes clinical disease; predicts erosions | | Anti-CCP + RF | — | >99% | Double-positive = very high risk of erosive disease | | Seronegative RA | 20–30% of RA cases | — | Diagnosis requires clinical + imaging criteria; same prognosis as seropositive | **High-Yield:** RF positivity **without clinical arthritis is NOT diagnostic of RA**. RF can be positive in: - Healthy individuals (especially elderly, smokers) - Chronic infections (TB, endocarditis, hepatitis C) - Other autoimmune diseases (SLE, Sjögren's, vasculitis) - Malignancy Diagnosis of RA requires **clinical arthritis** (swollen, tender joints) + imaging evidence (erosions, joint space narrowing) + supportive serology, evaluated over ≥6 weeks. ### 2015 ACR/EULAR Classification Criteria for RA Score ≥6/10 = definite RA diagnosis. Components: 1. **Joint involvement** (0–4 points) - 1 large joint: 0 pts - 2–10 large or 1–3 small: 1 pt - 4–10 small (including ≥1 PIP/MCP/wrist): 2 pts - >10 joints (including ≥1 small): 3 pts 2. **Serology** (0–3 points) - Negative RF and anti-CCP: 0 pts - Low-positive RF or anti-CCP: 2 pts - High-positive RF or anti-CCP: 3 pts 3. **Acute phase reactants** (0–1 point) - Normal ESR and CRP: 0 pts - Elevated ESR or CRP: 1 pt 4. **Symptom duration** (0–1 point) - <6 weeks: 0 pts - ≥6 weeks: 1 pt **Clinical Pearl:** Seronegative RA (RF− and anti-CCP−) accounts for 20–30% of RA cases and has the same prognosis and treatment response as seropositive disease. Diagnosis relies on clinical arthritis pattern (symmetric, small joints), imaging (erosions), and exclusion of other causes. **Mnemonic:** **JASS** = **J**oint involvement, **A**cute phase reactants, **S**erology, **S**ymptom duration (the 4 pillars of 2015 ACR/EULAR criteria).
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