What is the diagnosis and treatment for a young to middle-aged woman with no significant past medical history presenting with sudden onset of painful, red nodules on the lower legs, suspected to be Erythema nodosum?

Erythema Nodosum: Diagnosis and Management

Clinical Diagnosis

Erythema nodosum is diagnosed clinically by the presence 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), without ulceration. 1, 2, 3

Key Diagnostic Features:

• Location: Predominantly anterior lower legs (pretibial areas), though can occur on extensor surfaces of extremities 2, 4
• Appearance: Nodules evolve in color from bright red → livid red/purplish → yellow/greenish (resembling deep bruises) over days 3
• Characteristics: Tender, warm, raised, never ulcerate, heal without scarring or atrophy 3, 4
• Distribution: Bilateral and symmetrical in most cases 3, 5

Associated Systemic Symptoms:

• Fever, malaise, and extreme fatigue persisting weeks to months 2
• Symmetrical arthralgias affecting distal lower extremities without joint effusions 2
• Drenching night sweats and weight loss (particularly with infectious etiologies like coccidioidomycosis) 2

Diagnostic Work-Up

Biopsy is not routinely necessary and should be reserved for atypical presentations only. 2, 4, 5

Initial Laboratory Evaluation:

• Complete blood count with differential 4, 5
• Erythrocyte sedimentation rate and/or C-reactive protein 4, 5
• Throat swab culture or rapid antigen test for streptococcal infection 4, 5
• Antistreptolysin-O (ASO) titers 6, 4
• Chest radiograph (to evaluate for sarcoidosis, tuberculosis, fungal infections) 4, 5

Additional Testing Based on Clinical Context:

• If tuberculosis risk factors present: Purified protein derivative test 4
• If gastrointestinal symptoms: Consider inflammatory bowel disease evaluation 1, 2
• If oral/genital ulcers: Consider Behçet's disease 2, 7
• If endemic area exposure: Fungal serologies (coccidioidomycosis, histoplasmosis) 2

Common Etiologies to Identify:

• Streptococcal pharyngitis (most common identifiable cause) 4, 7
• Inflammatory bowel disease (4.2-7.5% of IBD patients) 1, 2
• Sarcoidosis 4, 7
• Tuberculosis 4, 7
• Fungal infections (coccidioidomycosis, histoplasmosis) 2
• Behçet's disease 2, 7
• Medications (oral contraceptives, antibiotics) 4, 7
• Pregnancy 6, 7
• Idiopathic (approximately 50% of cases) 5, 7

Treatment Strategy

NSAIDs are the cornerstone of treatment for erythema nodosum, providing symptomatic relief for pain and inflammation. 1, 2, 3

First-Line Management:

• Bed rest and leg elevation to reduce discomfort 3, 5
• NSAIDs: Indomethacin, naproxen, or oxyphenbutazone for analgesia and resolution 3, 4
• Treat underlying cause if identified (e.g., 10-14 day course of antibiotics for streptococcal infection) 6, 4

Second-Line Options for Severe Cases:

Systemic corticosteroids should be reserved for severe cases with significant inflammation or IBD-associated erythema nodosum, and only after excluding infectious causes. 1, 2, 3

• Corticosteroids are rarely indicated and require ruling out underlying infection first 3, 4
• For IBD-associated erythema nodosum, treat underlying bowel inflammation with systemic steroids 1

Refractory or Recurrent Disease:

• Colchicine: Particularly effective for Behçet's disease-associated erythema nodosum 2
• Azathioprine: For frequent relapses or IBD-associated disease 1, 2
• TNF-alpha inhibitors (infliximab or adalimumab): For IBD-associated erythema nodosum with frequent relapses 1, 2
• Hydroxychloroquine: May be beneficial for sarcoidosis-associated erythema nodosum 2

Special Considerations:

• Streptococcal infection: 10-14 day course of antibiotics (e.g., amoxicillin 500 mg three times daily) 6
• Coccidioidomycosis: Antifungal therapy is NOT recommended; NSAIDs alone are sufficient 2
• Histoplasmosis: NSAIDs alone are sufficient 2

Clinical Pitfalls to Avoid

• Do not start corticosteroids before excluding infectious causes, particularly tuberculosis and fungal infections 3, 4
• Do not perform biopsy routinely; diagnosis is clinical in typical presentations 2, 4
• Do not overlook streptococcal infection as the most common identifiable cause 4, 7
• Do not neglect to monitor for underlying disease activity in associated conditions like IBD or sarcoidosis 2
• Do not expect immediate resolution; lesions typically resolve spontaneously within 3-6 weeks even without treatment 3, 4

Prognosis

Erythema nodosum is self-limited in most cases, with spontaneous resolution within a few weeks to months without scarring or atrophy. 3, 4, 5 Recurrent episodes may indicate persistent underlying disease activity requiring reassessment. 2