Treatment of Erythema Nodosum
Treat the underlying cause first, then provide symptomatic relief with NSAIDs as the cornerstone of therapy, reserving systemic corticosteroids only for severe cases after excluding infectious etiologies. 1
Initial Management Approach
The primary goal is identifying and treating the underlying trigger while managing symptoms. The most common identifiable causes include streptococcal pharyngitis, tuberculosis, sarcoidosis, inflammatory bowel disease, Behçet's disease, and certain medications (oral contraceptives, antibiotics). 2, 3
First-Line Symptomatic Treatment
- NSAIDs are the cornerstone of symptomatic treatment for pain and inflammation in erythema nodosum. 1
- Indomethacin 100-150 mg/day has demonstrated dramatic response with prompt resolution of both systemic symptoms and local inflammation, likely through inhibition of prostaglandin synthesis in subcutaneous fatty tissues. 4
- Naproxen is another effective NSAID option, though some patients may require escalation to alternative therapies if symptoms recur. 5
Supportive Care Measures
- Rest and leg elevation help reduce inflammation and discomfort. 1
- Compression stockings may provide symptomatic relief. 3
- The condition is typically self-limited, resolving without ulceration, atrophy, or scarring over weeks to months. 2
Treatment Based on Underlying Etiology
IBD-Associated Erythema Nodosum
When erythema nodosum occurs with inflammatory bowel disease, successful treatment of the underlying UC or Crohn's flare usually resolves symptoms within weeks. 6
- Patients may benefit from sulphasalazine (salazosulfapyridine), which has shown effectiveness for both bone and skin lesions in refractory cases. 5
- Sulphasalazine 250-500 mg/day can achieve complete remission when NSAIDs fail. 5
Behçet's Disease-Associated Erythema Nodosum
- Colchicine is the preferred treatment when erythema nodosum is associated with Behçet's disease, particularly effective for recurrent mucocutaneous involvement. 1
Infectious Etiologies
- For streptococcal pharyngitis: treat with appropriate antibiotics. 2, 3
- For coccidioidomycosis or histoplasmosis causing erythema nodosum, antifungal therapy is NOT recommended—NSAIDs alone are sufficient. 1
- For tuberculosis: appropriate antimicrobial treatment is essential before symptomatic management. 7
Second-Line Therapies for Severe or Refractory Cases
Systemic Corticosteroids
Systemic corticosteroids should be reserved for severe cases with significant inflammation or IBD-associated erythema nodosum, and must be used cautiously after excluding infectious causes. 1
- This is critical because corticosteroids can worsen underlying infections, particularly tuberculosis and fungal diseases. 1, 2
- When indicated, corticosteroids are typically used for IBD flares where erythema nodosum is a manifestation of disease activity. 6
Alternative Agents for Refractory Disease
- Potassium iodide is an effective option for persistent cases. 7
- Colchicine can be used for frequent relapses, particularly in Behçet's syndrome. 1, 7
- Azathioprine for frequent relapses or IBD-associated cases. 1
- TNF-alpha inhibitors (infliximab or adalimumab) may be effective in resistant cases associated with inflammatory bowel disease. 1
Critical Pitfalls to Avoid
- Never initiate corticosteroids before excluding infectious causes, especially tuberculosis, coccidioidomycosis, and histoplasmosis, as this can lead to disseminated infection. 1, 2
- Do not assume idiopathic erythema nodosum without systematic evaluation for underlying systemic disease—it may be the first sign of tuberculosis, sarcoidosis, IBD, or malignancy. 2, 3
- Avoid premature discontinuation of treatment when symptoms improve; monitor for disease activity in associated conditions like IBD or sarcoidosis. 1
- Do not biopsy routinely—diagnosis is primarily clinical based on characteristic tender, erythematous subcutaneous nodules on the anterior lower extremities; biopsy is reserved only for atypical presentations. 6