What is the diagnosis and best course of action for a 49-year-old female with morning stiffness, swelling in hands and feet, a positive Antinuclear Antibody (ANA) test, and an elevated Rheumatoid Factor (RF) of 58?

Diagnosis: Rheumatoid Arthritis

This 49-year-old female has rheumatoid arthritis (RA) based on morning-predominant symmetric polyarthritis of hands and feet with elevated RF of 58, and she requires immediate initiation of methotrexate as first-line disease-modifying therapy. 1, 2

Diagnostic Confirmation

This patient meets the 2010 ACR/EULAR classification criteria for RA with a score ≥6/10 points 1:

• Joint involvement: Hands and feet with multiple small joints = 3 points 1
• Serology: RF of 58 (low positive, >ULN but ≤3× ULN) = 2 points 1, 3
• Acute phase reactants: Need to measure ESR/CRP, but if elevated = 1 point 1
• Duration: Morning stiffness and pain pattern suggests ≥6 weeks = 1 point 1, 2

The positive ANA is not uncommon in RA and does not change the diagnosis, though it warrants monitoring for overlap syndromes 4, 3.

Essential Immediate Workup

Complete the following laboratory tests before starting treatment 1, 3:

• Anti-CCP antibodies (critical for prognosis; high specificity 90% for RA) 1, 3
• ESR and CRP (quantify inflammation; CRP preferred for ongoing monitoring) 4, 1
• Complete blood count with differential (assess for cytopenias before DMARD initiation) 1, 3
• Comprehensive metabolic panel (liver and renal function required for methotrexate safety) 1, 3
• Hepatitis B, Hepatitis C, and tuberculosis screening (mandatory before any DMARD or biologic therapy) 1, 3
• Urinalysis (standard baseline assessment) 1, 3

Obtain baseline imaging 1, 2:

• Bilateral hand, wrist, and foot X-rays (presence of erosions predicts aggressive disease and persistence) 4, 1, 2
• Repeat X-rays at 6 and 12 months to monitor radiographic progression 1

Treatment Plan: Immediate Initiation

Start methotrexate 15 mg weekly as first-line DMARD immediately 1, 2. Do not delay treatment waiting for complete serologic workup, as early treatment within the "window of opportunity" prevents irreversible joint damage 2, 5.

Methotrexate Protocol 1:

• Start 15 mg weekly, escalate to 20-25 mg weekly based on response 1
• Add folic acid 1 mg daily to reduce side effects 1
• Bridge therapy: Add prednisone 10-20 mg daily for 4-6 weeks while awaiting DMARD effect, then taper 1
• Consider intra-articular glucocorticoid injections for severely affected joints 1

Symptomatic Management 1, 3:

• NSAIDs (naproxen 500 mg twice daily) after evaluating GI, renal, and cardiovascular status 3
• Occupational therapy referral for joint protection education and splinting 1
• Dynamic exercise program with aerobic and progressive resistance training 1

Disease Activity Monitoring

Reassess every 4-6 weeks using composite measures 1:

• Simplified Disease Activity Index (SDAI) is preferred when CRP is elevated 1
• Target: Remission (SDAI ≤3.3) or low disease activity (SDAI ≤11) 1
• SDAI = tender joint count (28 joints) + swollen joint count (28 joints) + patient global (0-10) + evaluator global (0-10) + CRP (mg/dL) 1

If inadequate response after 3 months of methotrexate 1:

• Add triple DMARD therapy (methotrexate + hydroxychloroquine + sulfasalazine), OR
• Add biologic agent (TNF inhibitor: adalimumab, etanercept, or infliximab) 1

Critical Pitfalls to Avoid

Do not delay treatment based on serology 1. Seronegative RA accounts for 20-30% of cases and has similar prognosis to seropositive disease 1. This patient is already RF-positive, confirming the diagnosis.

Do not dismiss the diagnosis if ESR/CRP are normal 1. Acute phase reactants are poor predictors and can be normal even in active disease; prioritize clinical synovitis over laboratory values 1.

Do not wait for erosions to develop 2. The presence of clinical synovitis with RF positivity and symptom duration >6 weeks is sufficient to diagnose RA and initiate DMARDs 1, 2.

Refer to rheumatology within 6 weeks of symptom onset 2, 3. Earlier specialist involvement and treatment initiation significantly improves long-term outcomes and prevents irreversible joint damage 2, 5.

Prognostic Factors

This patient has poor prognostic indicators 1, 2:

• RF positivity predicts more aggressive disease and erosive progression 4, 1
• Polyarticular involvement of small joints (hands and feet) predicts persistence 4, 2
• Morning stiffness >30 minutes indicates active inflammatory disease 4, 2
• If anti-CCP is also positive, risk of severe disease and radiographic progression increases substantially 1, 3

Monitor for extra-articular manifestations 6, 7: rheumatoid nodules, pulmonary involvement, ocular complications, and vasculitis, which indicate severe disease requiring aggressive treatment 6, 7.