What is the initial workup for a patient presenting with erythema nodosum?

Initial Workup for Erythema Nodosum

The initial workup for erythema nodosum should include a comprehensive evaluation for underlying causes, starting with a complete blood count with differential, erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), streptococcal testing, and chest radiography. 1

Clinical Presentation and Diagnosis

Erythema nodosum (EN) is characterized by:

• Tender, erythematous, subcutaneous nodules
• Typically located symmetrically on the anterior surface of lower extremities (pretibial areas)
• Nodules range from 1-5 cm in diameter
• Does not ulcerate and usually resolves without scarring

The diagnosis is primarily clinical, with biopsy reserved for atypical cases 1, 2.

Etiology

Erythema nodosum is often a cutaneous manifestation of an underlying systemic condition. Common causes include:

• Idiopathic (32-50% of cases)
• Infections:
  • Streptococcal pharyngitis (most common identifiable cause, ~32%)
  • Tuberculosis (7%)
  • Mycoplasma infection (3%)
  • Bartonella infection (3%)
• Systemic diseases:
  • Sarcoidosis (11-28%)
  • Inflammatory bowel disease (2%)
  • Behçet's syndrome (2-3.8%)
• Medications:
  • Oral contraceptives
  • Antibiotics
• Pregnancy
• Malignancy

3, 4

Diagnostic Algorithm

Step 1: Initial Laboratory Testing

• Complete blood count with differential
• ESR and/or CRP (elevated in secondary cases) 3
• Streptococcal testing:
  • Throat culture
  • Rapid antigen test
  • Antistreptolysin-O (ASO) titer
• Chest radiography (to evaluate for sarcoidosis, tuberculosis)

Step 2: Risk Stratification for Tuberculosis

• Tuberculin skin test (PPD) for patients with risk factors or from endemic areas
• Interferon-gamma release assay if indicated

Step 3: Additional Testing Based on Clinical Suspicion

• Stool cultures if gastrointestinal symptoms (for inflammatory bowel disease)
• Specific autoimmune and infectious serology when appropriate
• CT scan of chest if sarcoidosis is suspected

Step 4: Biopsy Considerations

• Deep incisional or excisional biopsy if diagnosis is uncertain
• Histopathology shows inflammatory process involving septa between subcutaneous fat lobules with absence of vasculitis and presence of radial granulomas 1

Management Approach

Treatment should focus on:

1. Identifying and treating the underlying cause
2. Providing symptomatic relief

For symptom management:

• Bed rest and leg elevation to reduce discomfort
• Nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line treatment for pain 2
• Systemic corticosteroids may be required in severe cases 5
• For resistant cases or frequent relapses, immunomodulators (azathioprine) or anti-TNF agents may be considered 5

Clinical Pearls and Pitfalls

• Secondary cases of EN typically have higher levels of CRP and leukocytes than idiopathic cases 3
• EN is more common in females (female-to-male ratio approximately 6:1) 3
• Seasonal variation exists with more cases occurring in winter and spring 3
• Most cases are self-limited but may recur if the underlying condition is not addressed
• EN associated with inflammatory bowel disease often correlates with disease activity 5
• Avoid attributing EN to idiopathic causes before completing a thorough evaluation for underlying systemic diseases

Remember that erythema nodosum may be the first sign of a serious systemic disease, making identification of the underlying cause crucial for appropriate management and prevention of complications.