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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- RA = symmetric inflammatory polyarthritis, classically MCP, PIP, wrists, and MTPs with morning stiffness >60 minutes
- Anti-CCP is highly specific and predicts erosive disease; rheumatoid factor is sensitive but less specific
- X-ray: periarticular osteopenia, marginal erosions, and symmetric joint-space narrowing
- Treatment should begin early with a treat-to-target strategy; methotrexate is first-line unless contraindicated
- Extra-articular disease includes nodules, ILD, pleuritis, pericarditis, scleritis, anemia of chronic disease, and Felty syndrome
Overview
Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic synovitis, pannus formation, cartilage destruction, and marginal bone erosions. It usually presents as an insidious symmetric inflammatory polyarthritis of small joints. Early diagnosis and prompt DMARD initiation matter because erosions and disability can develop within months.
Epidemiology
RA affects about 0.5-1% of adults, with a female predominance. Risk factors include smoking, family history, HLA-DRB1 shared epitope alleles, periodontitis, silica exposure, and obesity. Smoking is strongly associated with anti-CCP positive erosive disease.
Clinical Features
Symptoms
Symmetric pain, swelling, and stiffness of MCP, PIP, wrist, and MTP joints
Morning stiffness lasting >60 minutes and improving with activity
Fatigue, low-grade fever, malaise, and weight loss
Neck pain or neurologic symptoms from atlantoaxial instability
Eye pain or photophobia suggesting scleritis or peripheral ulcerative keratitis
Progressive dyspnea or dry cough suggesting RA-associated interstitial lung disease
Signs
Boggy synovitis of MCPs, PIPs, wrists, and MTPs; DIPs usually spared
Ulnar deviation, swan-neck deformities, boutonniere deformities, and Z-thumb deformity in chronic disease
Rheumatoid nodules over extensor surfaces or pressure points
Tenosynovitis, trigger finger, and carpal tunnel syndrome from synovial swelling
Splenomegaly with neutropenia in Felty syndrome
Mononeuritis multiplex suggesting rheumatoid vasculitis
Investigations
First-line
Anti-CCP antibodyHigh specificity for RA and predicts erosive disease; useful when RF is negative or diagnosis is uncertain
Rheumatoid factorSensitive but less specific; also seen in hepatitis C, Sjogren syndrome, endocarditis, and older age
ESR/CRP, CBC, CMPAssess inflammation, anemia of chronic disease, thrombocytosis, renal/liver function before DMARD therapy
Second-line
Plain radiographs of hands and feetEarly soft-tissue swelling and periarticular osteopenia; later marginal erosions and symmetric joint-space narrowing
Ultrasound or MRIDetects synovitis, tenosynovitis, erosions, and Doppler activity before plain-film changes
Hepatitis B/C and TB screeningRequired before biologic or targeted synthetic DMARD therapy
Specialist
Cervical spine imagingIf neck pain, neurologic symptoms, long-standing disease, or preoperative intubation risk
Chest imaging/PFTsIf respiratory symptoms or suspected RA-associated interstitial lung disease
1
Initial treatment
- Start DMARD therapy as soon as RA is diagnosed; do not wait for erosions
- Methotrexate is preferred first-line for moderate-to-high disease activity unless contraindicated
- Give folic acid with methotrexate to reduce mucositis, cytopenias, and liver toxicity
- Hydroxychloroquine can be used for low disease activity or mild disease
- Short glucocorticoid bridge may be used for severe symptoms but avoid chronic steroids
2
Treat-to-target escalation
- Target remission or low disease activity using validated measures such as DAS28 or CDAI
- Reassess every 1-3 months while active and adjust therapy if target is not achieved
- If inadequate response to methotrexate: add or switch to biologic DMARD or targeted synthetic DMARD
- Biologics include TNF inhibitors, abatacept, IL-6 inhibitors, and rituximab
3
Safety and prevention
- Monitor CBC, AST/ALT, and creatinine on methotrexate
- Avoid methotrexate in pregnancy, severe liver disease, severe renal impairment, and heavy alcohol use
- Vaccinate before immunosuppression when possible and screen cardiovascular risk aggressively
Complications
- Joint destruction: Erosions, deformity, tendon rupture, and disability
- Cervical spine disease: Atlantoaxial subluxation can cause cord compression and intubation risk
- Pulmonary: Interstitial lung disease, pleural effusion, nodules, and bronchiolitis
- Cardiovascular: Accelerated atherosclerosis and pericarditis
- Hematologic: Anemia of chronic disease and Felty syndrome
USMLE Step 2 CK Exam Tips
- 1Symmetric MCP/PIP/wrist synovitis + morning stiffness >1 hour = RA; DIPs are usually spared
- 2Anti-CCP is the most specific serologic test and predicts erosive disease
- 3First-line disease-modifying therapy is methotrexate, not NSAIDs or chronic prednisone
- 4Methotrexate is teratogenic; hydroxychloroquine and sulfasalazine are safer pregnancy-compatible options
- 5RA patient needing surgery or intubation: evaluate cervical spine instability if long-standing disease or neurologic symptoms
- 6RA + splenomegaly + neutropenia = Felty syndrome
- 7RA with acute monoarthritis still requires arthrocentesis; do not assume all hot joints are flares
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