What is the initial management for a patient presenting with Erythema Nodosum?

Initial Management of Erythema Nodosum

Begin with NSAIDs for symptomatic relief while simultaneously investigating for underlying causes, as erythema nodosum is a hypersensitivity reaction that resolves spontaneously in most cases but may signal serious systemic disease. 1, 2

Immediate Clinical Actions

Symptomatic Treatment

• Initiate NSAIDs (indomethacin, naproxen, or aspirin) as first-line therapy for pain and inflammation 1, 3
• Prescribe bed rest and leg elevation to reduce discomfort 4
• The nodules typically resolve spontaneously within weeks without ulceration or scarring 3, 2

Essential Diagnostic Workup

Perform the following baseline investigations to identify underlying causes 2, 4:

• Complete blood count with differential 2
• Erythrocyte sedimentation rate and/or C-reactive protein (elevated in most cases) 2, 4
• Throat swab culture and antistreptococcal O titers (streptococcal pharyngitis is the most common identifiable cause) 5, 2
• Chest radiograph (to screen for sarcoidosis, tuberculosis, and fungal infections) 2, 4

Targeted History Elements

Document the following specific details 1, 5:

• All medications taken in the previous 2 months, including oral contraceptives, sulfonamides, and halides 3, 6
• Systemic symptoms: fever, malaise, extreme fatigue persisting weeks to months 1
• Arthralgias: symmetrical involvement of distal lower extremities without effusions 1
• Infectious symptoms: drenching night sweats and weight loss (suggesting coccidioidomycosis or histoplasmosis) 1
• Gastrointestinal symptoms: suggesting inflammatory bowel disease (occurs in 4.2-7.5% of IBD patients) 1
• Oral and genital ulcers: suggesting Behçet's disease 1

Physical Examination Findings

Confirm the diagnosis clinically based on 5, 4:

• Tender, erythematous, raised subcutaneous nodules 1-5 cm in diameter 1
• Bilateral and symmetrical distribution on pretibial areas (anterior lower legs) 5, 4
• Color evolution: bright red → livid/purplish → yellow/greenish (resembling deep bruise) 3
• Absence of ulceration (key distinguishing feature) 3, 2

When to Escalate Therapy

Severe Cases Requiring Corticosteroids

Reserve systemic corticosteroids for severe inflammation or IBD-associated erythema nodosum, and only after excluding infectious causes 1, 3

• Corticosteroids are highly effective but carry risk of disseminating underlying infections 6
• Critical pitfall: Never initiate steroids before ruling out tuberculosis and fungal infections 3, 6

Refractory or Recurrent Cases

Consider the following for persistent disease 1:

• Colchicine: particularly effective when associated with Behçet's syndrome 1
• Azathioprine: for frequent relapses 1
• TNF-alpha inhibitors (infliximab or adalimumab): for IBD-associated cases resistant to standard therapy 1
• Hydroxychloroquine: specifically for sarcoidosis-associated erythema nodosum 1

Special Considerations by Etiology

Fungal Infections

• Coccidioidomycosis and histoplasmosis: NSAIDs alone are sufficient; antifungal therapy is NOT recommended for erythema nodosum itself 1

Inflammatory Bowel Disease

• Erythema nodosum may be the presenting sign of IBD 5, 2
• Requires treatment of the underlying IBD flare, not just the skin manifestations 1

Idiopathic Cases

• Approximately 50% of cases have no identifiable cause 5, 4
• Supportive care with NSAIDs is appropriate after reasonable workup excludes serious conditions 2, 6

Critical Pitfalls to Avoid

• Do not perform biopsy routinely—diagnosis is clinical; reserve biopsy only for atypical presentations 1, 5
• Do not neglect monitoring for disease activity in associated conditions like IBD or sarcoidosis, as recurrent erythema nodosum indicates persistent underlying disease 1
• Do not use corticosteroids as first-line therapy given the benign, self-limited nature and risk of worsening occult infections 3, 6