What is the diagnosis and management for a [AGE]-year-old female with morning stiffness in fingers and hands lasting 30 minutes, normal Rheumatoid Factor (RF) and C-Reactive Protein (CRP), elevated ferritin, and no known co-morbidities?

Seronegative Inflammatory Arthritis with Elevated Ferritin

This presentation is most consistent with early seronegative rheumatoid arthritis (RA), and you should initiate DMARD therapy promptly while investigating the elevated ferritin as a separate issue. 1

Clinical Diagnosis

Morning stiffness lasting 30 minutes is a validated predictor of persistent inflammatory arthritis and strongly suggests an inflammatory arthropathy rather than osteoarthritis or mechanical causes. 2, 1 The combination of:

• Morning stiffness >30 minutes (validated predictor of persistent inflammatory arthritis) 2, 1
• Painful hand and finger involvement (small joint involvement is an independent predictor of persistent inflammatory arthritis) 1
• Disease duration likely >6 weeks (independent predictor of persistent inflammatory arthritis) 2, 1

These features meet criteria for early inflammatory arthritis requiring urgent rheumatology evaluation, ideally within 6 weeks of symptom onset. 1

Critical Diagnostic Considerations

Why Normal RF and CRP Don't Exclude RA

• Up to 30% of RA patients are seronegative (RF and ACPA negative), particularly in early disease 2
• CRP can be normal in early RA - ESR and CRP should both be measured, as they can be discordant 3
• The absence of these markers does not exclude the diagnosis when clinical features are compelling 1

The Elevated Ferritin Issue

Elevated ferritin in this context is most likely a marker of inflammation (acute phase reactant) rather than iron overload. 4 However, you must differentiate:

• Inflammatory causes: RA itself causes ferritin elevation as an acute phase reactant 3
• Adult-onset Still's disease: Can present with arthritis and markedly elevated ferritin (often >1000 µg/L), though typically has fever and rash 3
• True iron overload: Less likely without elevated transferrin saturation 2, 4

Check transferrin saturation immediately - if <20% with ferritin elevated, this confirms inflammation rather than iron overload. 2, 4

Immediate Diagnostic Workup

Essential Laboratory Tests

• Anti-CCP antibodies (more specific than RF for RA and strongest predictor when combined with clinical features) 1, 5
• ESR (should be measured even if CRP is normal, as they can be discordant) 1, 3
• Complete blood count (assess for anemia of chronic disease) 3
• Transferrin saturation and iron studies (to characterize the ferritin elevation) 2, 4
• Comprehensive metabolic panel (baseline for DMARD therapy) 3

Imaging Studies

Plain radiographs of hands, wrists, and feet should be obtained immediately - the presence of erosions is predictive for development of RA and indicates need for aggressive therapy. 1

MRI of hands and wrists should be strongly considered when RA is suspected but doesn't yet meet full classification criteria. 1 Specifically:

• Flexor tenosynovitis on MRI is a powerful predictor of early RA (sensitivity 60%, specificity 73%) 5
• When combined with positive anti-CCP, flexor tenosynovitis increases diagnostic accuracy to 79% sensitivity and 73% specificity 5
• Ultrasound with power Doppler can identify active synovitis and is useful when patients don't meet 2010 ACR/EULAR criteria 1

Management Approach

Urgent Rheumatology Referral

Refer to rheumatology within 6 weeks of symptom onset - there is a critical "window of opportunity" for DMARD therapy to prevent joint destruction. 2, 1

Early DMARD Initiation

Patients at risk of developing persistent or erosive arthritis should be started with DMARDs as early as possible, even if they do not yet fulfill established classification criteria. 1 The predictors present in this patient include:

• Morning stiffness >30 minutes 2, 1
• Small joint involvement 1
• Disease duration likely >6 weeks 2, 1

Monitoring Strategy

• Measure ESR and CRP at baseline and every 1-3 months during active disease until remission is achieved 3
• Monitor disease activity systematically using validated measures, though no specific tool is fully validated for undifferentiated arthritis 2
• Repeat imaging at 3-6 months if erosions were absent initially, as their development indicates need for treatment intensification 1

Common Pitfalls to Avoid

Do not delay treatment waiting for positive serology - seronegative RA is common and responds equally well to early DMARD therapy. 2, 1

Do not attribute symptoms to osteoarthritis based on age alone - the 30-minute morning stiffness duration clearly indicates inflammatory disease, not mechanical joint disease. 2

Do not pursue iron overload workup aggressively unless transferrin saturation is elevated - 90% of elevated ferritin is due to non-iron overload conditions. 4 Refer to gastroenterology/hematology only if ferritin >1000 µg/L or if transferrin saturation suggests true iron overload. 4

Do not order unnecessary tests - ANA, ANCA, and HLA-B27 are not indicated unless specific clinical features suggest alternative diagnoses (e.g., inflammatory back pain for spondyloarthritis). 2