What is the best initial treatment approach for a patient presenting with erythema nodosum?

Best Treatment for Erythema Nodosum

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

Initial Treatment Approach

First-Line Therapy: NSAIDs

• Nonsteroidal anti-inflammatory drugs (NSAIDs) should be initiated immediately for symptomatic relief of pain and inflammation. 1, 2
• The American Gastroenterological Association specifically recommends NSAIDs as the cornerstone of treatment. 2
• Options include indomethacin, naproxen, or oxyphenbutazone for enhanced analgesia and resolution. 3
• Bed rest combined with NSAIDs is often sufficient for most cases, as erythema nodosum typically regresses spontaneously within a few weeks. 3

Identify and Treat Underlying Causes

• Treatment must address any identified underlying condition, as erythema nodosum is frequently a hypersensitivity response to various triggers. 1, 4
• The most common identifiable causes include:
  • Streptococcal pharyngitis (most common infectious cause) - treat with appropriate antibiotics 4, 5
  • Sarcoidosis (11% of secondary cases) 6
  • Primary tuberculosis (7% of cases) 6
  • Inflammatory bowel disease (4.2-7.5% of IBD patients) 1, 2
  • Behçet's disease 1
  • Drug reactions (oral contraceptives, antibiotics) 4, 5

When to Escalate Treatment

Systemic Corticosteroids (Second-Line)

• Corticosteroids should be used cautiously and only after excluding infectious causes, particularly tuberculosis. 1, 3, 5
• Specific indications for systemic steroids include:
  • Severe cases with significant inflammation 1, 2
  • IBD-associated erythema nodosum with active bowel inflammation 1, 2
  • Sweet's syndrome associated with ulcerative colitis 2
• The European Crohn's and Colitis Organisation recommends treating underlying bowel inflammation with systemic steroids for IBD-associated cases. 2
• Prednisone is FDA-approved for dermatologic diseases including severe erythema multiforme and other inflammatory conditions. 7

Immunomodulators and Biologics (Third-Line)

• For frequent relapses or refractory disease, particularly IBD-associated cases, consider immunomodulators or TNF-alpha inhibitors. 1, 2
• Azathioprine can be used for frequent relapses. 1, 2
• TNF-alpha inhibitors (infliximab or adalimumab) are effective in resistant cases associated with inflammatory bowel disease. 1, 2

Disease-Specific Treatments

• Colchicine is preferred when erythema nodosum is associated with Behçet's disease. 1
• Hydroxychloroquine may be added for sarcoidosis-associated cases in addition to standard therapy. 1
• For coccidioidomycosis or histoplasmosis-associated erythema nodosum, NSAIDs alone are sufficient—antifungal therapy is not recommended. 1

Critical Pitfalls to Avoid

• Never initiate corticosteroids before ruling out infectious causes, especially tuberculosis and fungal infections. 1, 3, 5
• Do not assume idiopathic disease without proper evaluation—approximately 68% of cases have an identifiable underlying cause. 6
• Avoid neglecting to monitor for disease activity in associated conditions like inflammatory bowel disease or sarcoidosis, as recurrent erythema nodosum may indicate persistent underlying disease. 1
• Remember that erythema nodosum never ulcerates and heals without scarring—if ulceration occurs, consider alternative diagnoses like pyoderma gangrenosum. 1, 3