What is the appropriate evaluation and management of erythema nodosum in a child?

Erythema Nodosum in Children: Evaluation and Management

Clinical Diagnosis

Erythema nodosum (EN) is diagnosed clinically based on the sudden onset of tender, raised, red or violet subcutaneous nodules measuring 1-5 cm in diameter, typically bilateral and symmetrical on the anterior tibial areas (pretibial surfaces). 1, 2, 3

• The nodules do not ulcerate, do not migrate over time, and resolve without scarring or atrophy 2, 3, 4
• Skin biopsy is reserved only for atypical presentations where the diagnosis is uncertain 1, 3
• Systemic symptoms commonly include fever, malaise, extreme fatigue lasting weeks to months, and symmetrical arthralgias affecting distal lower extremities without joint effusions 2, 5

Initial Diagnostic Workup

All children with EN require a standardized basic laboratory evaluation to identify underlying causes, as approximately 45-55% of pediatric cases are idiopathic while the remainder have identifiable secondary causes. 6, 7

Essential First-Line Tests (perform in all patients):

• Complete blood count with differential 3, 4
• Erythrocyte sedimentation rate and/or C-reactive protein 3, 6, 4
• Throat swab culture and anti-streptolysin O titers (streptococcal infection is the most common identifiable cause) 3, 4
• Chest radiograph (to evaluate for tuberculosis, sarcoidosis, hilar adenopathy) 3, 6
• Tuberculin skin test or interferon-gamma release assay 6, 4
• Serum aminotransferases, lactate dehydrogenase, creatinine 6
• Protein electrophoresis and immunoglobulins 6

Additional Testing Based on Clinical Context:

• If gastrointestinal symptoms present: Evaluate for inflammatory bowel disease (Crohn's disease occurs in 4.2-7.5% of IBD patients with EN) 2, 8
• If respiratory symptoms or endemic exposure: Consider coccidioidomycosis serology (particularly in southwestern United States) or histoplasmosis testing 1, 2
• If recurrent oral/genital ulcers: Evaluate for Behçet's disease 2
• If constitutional symptoms with lymphadenopathy: Consider malignancy evaluation (though rare, Hodgkin lymphoma has been reported) 7

Important caveat: No laboratory differences distinguish idiopathic from secondary EN, so a thorough etiologic search is mandatory in all cases 7

Treatment Approach

First-Line Management (all patients):

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of symptomatic treatment for pain and inflammation in EN. 2, 8, 3

• Bed rest and leg elevation to reduce discomfort 3, 4
• Most cases are self-limited and resolve spontaneously within 2-6 weeks without specific treatment 6, 4
• Address any identified underlying condition (e.g., treat streptococcal pharyngitis with antibiotics) 2, 3

Second-Line Management (severe cases):

Systemic corticosteroids should be reserved for severe cases with significant inflammation or IBD-associated EN, and must only be used after infectious causes—particularly tuberculosis—have been definitively excluded. 2, 8, 4

• The risk of exacerbating undiagnosed tuberculosis or fungal infections makes premature steroid use dangerous 4, 5
• For IBD-associated EN, treat the underlying bowel inflammation with systemic steroids 1, 8

Refractory or Recurrent Disease:

For frequent relapses or resistant cases, particularly when associated with inflammatory bowel disease, escalate to immunomodulators or biologic therapy. 2, 8

• Colchicine: Preferred when EN is the dominant lesion or associated with Behçet's disease 2, 8
• Azathioprine: Consider for patients with frequent relapses 2, 8
• TNF-α inhibitors (infliximab or adalimumab): Effective for IBD-associated EN refractory to conventional therapy 2, 8

Common Pitfalls to Avoid

• Do not perform routine skin biopsy for typical presentations; clinical diagnosis is sufficient 1, 3
• Do not initiate corticosteroids before excluding tuberculosis and other treatable infections 2, 4, 5
• Do not assume idiopathic EN without completing the basic diagnostic workup, as underlying systemic disease may not be immediately apparent 6, 7
• Do not neglect follow-up: Over 50% of patients experience recurrent episodes, which may indicate persistent underlying disease activity requiring reassessment 2, 5

Prognosis

The prognosis of EN in children is excellent, with spontaneous resolution in most patients within 2-6 weeks, though recurrence occurs in over half of cases. 6, 5

• EN does not cause permanent scarring or atrophy 3, 4
• Recurrent episodes warrant re-evaluation for underlying systemic conditions 2, 5