What are the management options for Erythema nodosum (EN)?

Management of Erythema Nodosum

NSAIDs are the cornerstone of treatment for erythema nodosum, with systemic corticosteroids reserved only for severe cases after infectious causes have been excluded. 1, 2

Initial Assessment and Diagnostic Priorities

Before initiating treatment, identify and address any underlying trigger, as erythema nodosum represents a hypersensitivity response rather than a primary disease process. 3, 4

Key underlying causes to evaluate:

• Streptococcal pharyngitis (most common identifiable cause) - obtain throat culture, rapid antigen test, or anti-streptolysin-O titer 4
• Tuberculosis - stratify patients by TB risk and perform purified protein derivative test and chest radiography in high-risk individuals 4
• Sarcoidosis - consider chest imaging and further evaluation if systemic symptoms present 3, 4
• Inflammatory bowel disease (occurs in 4.2-7.5% of IBD patients) - assess for gastrointestinal symptoms 1, 2
• Behçet's disease - look for oral and genital ulcers 5, 1
• Medications - review recent drug exposures, particularly oral contraceptives, sulfonamides, and antibiotics 4, 6
• Fungal infections (coccidioidomycosis, histoplasmosis) - consider in endemic areas 1

First-Line Treatment: Symptomatic Management

NSAIDs are the primary treatment for pain and inflammation in all cases of erythema nodosum. 1, 2, 4, 6

Supportive measures:

• Bed rest and leg elevation to reduce inflammation and discomfort 4
• Compression stockings (20-30 mmHg) worn daily can provide significant symptom relief and accelerate resolution 7
• Topical measures for localized lesions if needed 4

The condition is typically self-limited, resolving within 3-6 weeks without ulceration or scarring. 4

Treatment of Underlying Conditions

When a specific etiology is identified, treat the underlying disease:

• Streptococcal infection - appropriate antibiotic therapy 4
• Tuberculosis - standard anti-tuberculous therapy 4
• IBD-associated erythema nodosum - treat the underlying bowel inflammation with systemic steroids 2
• Behçet's disease with erythema nodosum as dominant lesion - colchicine is the preferred agent 5, 1
• Fungal infections (coccidioidomycosis, histoplasmosis) - NSAIDs alone are sufficient; antifungal therapy is not recommended for the erythema nodosum itself 1

Second-Line Treatment: Systemic Corticosteroids

Systemic corticosteroids should be used cautiously and only in specific circumstances: 1, 2, 4

• Severe cases with significant inflammation that do not respond to NSAIDs 1, 2
• IBD-associated erythema nodosum requiring treatment of underlying bowel disease 2
• Critical caveat: Exclude infectious causes (particularly tuberculosis and fungal infections) before initiating steroids to avoid disseminating underlying infection 4, 6

Third-Line Treatment: Immunomodulators and Biologics

For frequent relapses or refractory disease, particularly when associated with IBD: 1, 2

• Colchicine - particularly effective when erythema nodosum is associated with Behçet's syndrome 5, 1
• Azathioprine - for frequent relapses or IBD-associated disease 5, 1, 2
• TNF-alpha inhibitors (infliximab or adalimumab) - may be effective in resistant cases associated with inflammatory bowel disease 5, 1, 2
• Hydroxychloroquine - may be beneficial when erythema nodosum is associated with sarcoidosis 1

Special Considerations and Common Pitfalls

Avoid these critical errors:

• Do not use corticosteroids as first-line therapy - the benign, self-limited nature of erythema nodosum and the risk of disseminating underlying infections make steroids inappropriate for routine use 4, 6
• Do not neglect to monitor for disease activity in associated conditions like inflammatory bowel disease or sarcoidosis, as recurrent erythema nodosum may indicate persistent underlying disease 1
• Do not assume idiopathic disease without completing appropriate diagnostic evaluation - approximately 50% of cases have an identifiable underlying cause that requires specific treatment 4, 6

Recurrent erythema nodosum warrants reassessment for persistent underlying disease activity and consideration of immunomodulatory therapy. 1