What is the best course of treatment for a patient with arthritis, elevated C-Reactive Protein (CRP), and excessive hair loss without scalp lesions, and no significant medical history?

Treatment Approach for Arthritis with Elevated CRP and Hair Loss

Start methotrexate 15 mg weekly immediately as first-line therapy for this patient with inflammatory arthritis and elevated CRP, while simultaneously evaluating the hair loss as a separate clinical issue that may represent alopecia areata or another autoimmune condition. 1, 2

Diagnostic Clarification Required

Confirm the Type of Arthritis

The combination of arthritis and elevated CRP (93.3 mg/L represents severe systemic inflammation) requires immediate classification:

• Perform a detailed 28-joint examination assessing metacarpophalangeal joints (MCPs), proximal interphalangeal joints (PIPs), wrists, elbows, shoulders, and knees for tenderness and swelling to determine if this is rheumatoid arthritis or another inflammatory arthropathy 1
• Order rheumatoid factor (RF) and anti-citrullinated protein antibodies (anti-CCP) immediately, as these have high specificity (90%) for rheumatoid arthritis, though seronegative disease accounts for 20-30% of cases 1, 3
• Examine skin carefully for psoriatic plaques or nail changes to exclude psoriatic arthritis, which can present with polyarticular involvement, elevated CRP, and negative RF 1
• Obtain baseline bilateral hand, wrist, and foot X-rays to assess for erosions, which predict aggressive disease and guide treatment intensity 1, 2

Evaluate the Hair Loss Separately

The hair loss without scalp lesions requires distinct evaluation:

• Examine the scalp for exclamation point hairs and patches of complete hair loss characteristic of alopecia areata, an autoimmune condition that can coexist with rheumatoid arthritis 4
• Check vitamin D levels, as vitamin D deficiency is associated with alopecia areata and shows an inverse correlation with CRP levels in these patients 4
• Consider dermatology referral if alopecia areata is suspected, as this requires separate management from the arthritis 4

Immediate Treatment Strategy

First-Line DMARD Therapy

Methotrexate is the anchor drug and must be started immediately given the markedly elevated CRP indicating severe active inflammation:

• Start methotrexate 15 mg orally once weekly, with plan to escalate to 20-25 mg weekly if needed for disease control 1, 2, 5
• Add folic acid 1 mg daily to reduce methotrexate toxicity 1
• Emphasize to the patient that methotrexate is taken WEEKLY, not daily, as mistaken daily use has led to fatal toxicity 5
• Screen for hepatitis B, hepatitis C, and tuberculosis before starting therapy, as required before any DMARD or biologic 1, 2

Bridge Therapy for Symptom Control

While awaiting DMARD effect (typically 3-6 weeks):

• Consider short-term low-dose prednisone 10-20 mg daily as bridge therapy to rapidly control inflammation 2
• Plan to taper glucocorticoids to <7.5 mg/day prednisone equivalent once methotrexate takes effect, with goal of discontinuation 2
• NSAIDs may be used at minimum effective dose after evaluating gastrointestinal, renal, and cardiovascular risks 2
• Intra-articular glucocorticoid injections can provide relief for particularly inflamed individual joints 2

Monitoring Protocol

Disease Activity Assessment

• Calculate Simplified Disease Activity Index (SDAI) at baseline and every 4-6 weeks during active treatment, incorporating tender joint count, swollen joint count, patient global assessment, evaluator global assessment, and CRP 1, 2
• Target remission (SDAI ≤3.3) or low disease activity (SDAI ≤11) as the treatment goal 1, 2
• Repeat CRP and ESR every 4-6 weeks to monitor inflammatory response to treatment 2, 6

Safety Monitoring

• Obtain complete blood count with differential monthly to detect cytopenias 1, 5
• Check comprehensive metabolic panel including liver function tests and creatinine every 1-2 months during methotrexate therapy 1, 5
• Repeat hand, wrist, and foot X-rays at 6 months and 12 months to monitor for radiographic progression 1

Treatment Escalation Algorithm

If Inadequate Response After 3 Months

If SDAI remains >11 after 3 months of optimized methotrexate therapy:

• Option 1: Add triple DMARD therapy (methotrexate + sulfasalazine + hydroxychloroquine) 7, 1
• Option 2: Add a TNF inhibitor biologic (adalimumab, etanercept, infliximab, golimumab, or certolizumab pegol) 7, 1
• For psoriatic arthritis specifically: Consider IL-17 inhibitors (secukinumab, ixekizumab) or IL-12/23 inhibitor (ustekinumab) if skin involvement is significant 7

Critical Pitfalls to Avoid

• Do not delay DMARD therapy waiting for complete serologic workup - seronegative inflammatory arthritis is common and has similar prognosis requiring early aggressive treatment 1
• Do not dismiss the diagnosis based on normal ESR if CRP is elevated - CRP of 93.3 mg/L indicates severe inflammation regardless of ESR 1, 8
• Do not use NSAIDs or glucocorticoids alone without DMARDs - this allows irreversible joint damage to progress 2
• Do not attribute hair loss to methotrexate before starting therapy - the hair loss predates treatment and likely represents a separate autoimmune process 4
• Do not prescribe methotrexate on a PRN basis - prescriptions should specify weekly dosing to prevent fatal daily dosing errors 5

Addressing the Hair Loss

• If alopecia areata is confirmed, vitamin D supplementation may be beneficial given the inverse correlation between vitamin D and CRP in these patients 4
• Coordinate with dermatology for topical or intralesional corticosteroids for alopecia areata patches if present 4
• Reassure the patient that treating the underlying inflammatory arthritis may improve the autoimmune hair loss as systemic inflammation is reduced 4