What are the causes of erythema nodosum?

Causes of Erythema Nodosum

Erythema nodosum is most commonly caused by streptococcal infections, followed by sarcoidosis, inflammatory bowel disease, tuberculosis, and medications, though up to 32% of cases are idiopathic with no identifiable cause. 1, 2, 3

Clinical Presentation and Diagnosis

Erythema nodosum presents as:

• Tender, erythematous subcutaneous nodules (1-5 cm in diameter)
• Typically located symmetrically on the anterior tibial areas (shins)
• Often accompanied by systemic symptoms including arthralgia and fatigue
• More common in women than men 1

Diagnosis is primarily made on clinical grounds, with skin biopsy reserved for atypical cases 4.

Major Causes of Erythema Nodosum

1. Infections

• Streptococcal infections: Most common identifiable cause, particularly streptococcal pharyngitis 2, 3
• Tuberculosis: Particularly primary tuberculosis 3
• Mycoplasma infections 3
• Bartonella infections 3
• Other bacterial infections

2. Inflammatory Conditions

• Sarcoidosis: Second most common cause in adults 2, 3
• Inflammatory bowel disease: Including Crohn's disease and ulcerative colitis 4, 3
• Behçet's syndrome 1, 3

3. Medications

• Oral contraceptives
• Antibiotics
• Other medications 2

4. Other Causes

• Pregnancy 5
• Malignancies: Can be a paraneoplastic manifestation 2, 6

5. Idiopathic

• No identifiable cause in approximately 32% of cases 3

Diagnostic Approach

When evaluating a patient with erythema nodosum, the following investigations should be considered:

1. Basic laboratory tests:

   • Complete blood count with differential
   • Erythrocyte sedimentation rate and/or C-reactive protein
   • Testing for streptococcal infection (throat culture, rapid antigen test, antistreptolysin-O titer) 1, 2

2. Imaging:

   • Chest radiograph (to evaluate for sarcoidosis, tuberculosis) 1, 2

3. Additional testing based on clinical suspicion:

   • Tuberculin skin test for suspected tuberculosis
   • Stool cultures for suspected inflammatory bowel disease
   • Specific serologies for suspected infections 1, 2

Treatment Considerations

Treatment should focus on the underlying cause:

• Streptococcal infections should be treated with appropriate antibiotics 5
• For inflammatory bowel disease-associated erythema nodosum, treatment of the underlying IBD is usually effective 4
• Systemic corticosteroids may be required in severe cases 4, 1
• For resistant cases or frequent relapses, immunomodulators such as azathioprine or TNF-α antagonists (infliximab, adalimumab) may be considered 4, 1
• Supportive care including rest, elevation of affected limbs, and pain management with NSAIDs 1, 7

Prognosis

Erythema nodosum is typically self-limited, resolving without scarring within 3-6 weeks, though it may persist longer in some cases. Prognosis is generally good, especially when any underlying cause is identified and treated appropriately 1.