What is the diagnosis and treatment for a 61-year-old female with foot pain, plantar pain, bilateral ankle and toe deformities, nail changes, and backache, with lab results showing elevated RF (Rheumatoid Factor) and normal ESR (Erythrocyte Sedimentation Rate)?

Diagnosis: Seronegative Rheumatoid Arthritis

This patient has seronegative rheumatoid arthritis (RA) and requires immediate initiation of methotrexate without waiting for anti-CCP or HLA-B27 results. 1

Clinical Reasoning for Diagnosis

Meeting ACR/EULAR 2010 Classification Criteria

This patient scores 7 points on the ACR/EULAR classification criteria, exceeding the threshold of ≥6/10 points required for definite RA diagnosis: 1, 2

• Joint involvement (5 points): Multiple small joints bilaterally involved (hands and feet with MCP, PIP, DIP, and MTP joint deformities) 2
• Serology (0 points): RF 6.4 IU/mL is negative (normal), anti-CCP pending 1
• Acute phase reactants (1 point): hsCRP 0.52 mg/dL is mildly elevated (though ESR is paradoxically normal at 4 mm/hr) 1, 3
• Duration (1 point): Symptoms present for >6 weeks (several years with progressive worsening over 3-4 years) 2

Key Clinical Features Supporting RA Diagnosis

• Bilateral symmetric polyarticular involvement: Classic pattern with small joint predominance affecting hands (MCP joints with ulnar deviation, swan neck deformities) and feet (claw/hammer toes, MTP joint involvement) 1, 3
• Progressive deformities: Established joint damage including ulnar deviation, swan neck deformities, interosseous muscle wasting, hindfoot valgus, and pes planovalgus indicate aggressive disease 1
• Chronic progressive course: 3-4 years of worsening symptoms is consistent with untreated RA 3, 4

Excluding Psoriatic Arthritis

The absence of psoriatic features definitively rules out psoriatic arthritis: 1

• No skin psoriasis or plaques 5, 1
• No characteristic nail pitting or oil-drop changes (the hyperkeratosis and dystrophy present are nonspecific) 5, 1
• No dactylitis (sausage digits) 5, 1
• No enthesitis 5, 1

Understanding the Laboratory Paradox

The normal ESR (4 mm/hr) despite elevated hsCRP (0.52 mg/dL) represents a discordant pattern seen in 28% of RA cases: 6

• CRP is a more specific marker of acute inflammation than ESR 6
• ESR can be falsely normal due to factors like normal hemoglobin (14 g/dL), normal albumin, and absence of hypergammaglobulinemia 7, 6
• When ESR and CRP are discordant, CRP better reflects true disease activity 6
• The mildly elevated hsCRP (0.52 mg/dL) supports ongoing inflammation despite the normal ESR 1, 6

Poor Prognostic Indicators Present

This patient has multiple features predicting aggressive disease requiring immediate treatment: 1

• Polyarticular disease with >10 joints involved 1
• Established deformities with functional impairment 1
• Elevated inflammatory markers (hsCRP) 5, 1
• Long disease duration with progressive course 1

Immediate Management Plan

Start Methotrexate Immediately

Do not wait for anti-CCP or HLA-B27 results. The clinical diagnosis is clear based on ACR/EULAR criteria. 1

• Methotrexate 15-20 mg orally once weekly (start at 15 mg and escalate to 20 mg if tolerated) 1, 4
• Folic acid 1 mg daily (or 5 mg weekly on non-methotrexate days) to reduce side effects 1

Required Baseline Testing Before Methotrexate

• Complete blood count (CBC) 1
• Comprehensive metabolic panel (liver and renal function) 1
• Hepatitis B and C screening 1, 4
• Chest X-ray (to rule out latent tuberculosis or interstitial lung disease) 1
• Pregnancy test (if applicable) 1

Symptomatic Management

• NSAIDs for pain control: Naproxen 500 mg twice daily OR celecoxib 200 mg daily 1

  • Monitor for gastrointestinal and renal side effects 1
  • Use proton pump inhibitor if GI risk factors present 1

• Bridge therapy with low-dose prednisone: 5-10 mg daily for 4-8 weeks 1

  • Taper and discontinue once methotrexate takes effect (typically 6-12 weeks) 1
  • Avoid chronic corticosteroid use due to long-term complications 1

Monitoring Strategy

Initial Phase (First 3-6 Months)

• Clinical assessment every 1-3 months to evaluate treatment response 2
• Laboratory monitoring: CBC, liver function tests, creatinine every 4-8 weeks initially 1
• Disease activity measurement: Use DAS28, SDAI, or CDAI scores 2
• Target: DAS28 <2.6 (remission) or <3.2 (low disease activity) 1, 2

Escalation Strategy if Inadequate Response

If disease activity persists after 3-6 months on methotrexate: 1, 2

• Add TNF inhibitor biologic: Adalimumab, etanercept, infliximab, golimumab, or certolizumab 1, 8
• Continue methotrexate in combination with the TNF inhibitor for synergistic effect 1, 8
• Screen for hepatitis B, hepatitis C, and tuberculosis before starting biologics 1, 4

Long-Term Monitoring

• Radiographic monitoring: Baseline hand and foot X-rays, repeat annually or if clinical worsening 1
• Functional assessment: Health Assessment Questionnaire (HAQ) to quantify disability 1
• Cardiovascular risk management: RA increases cardiovascular disease risk 2

Critical Pitfalls to Avoid

• Do not delay treatment waiting for serology results - seronegative RA (RF and anti-CCP negative) occurs in 20-30% of cases and requires the same aggressive treatment 1, 3
• Do not dismiss the diagnosis due to normal ESR - CRP is more specific for inflammation, and discordance occurs frequently 6
• Do not use chronic corticosteroids - bridge therapy only, then taper to avoid long-term complications 1
• Do not undertreat based on "seronegative" status - seronegative RA can be equally aggressive and destructive 1, 3