What is erythema nodosum?

What is Erythema Nodosum

Erythema nodosum is a painful inflammatory condition of the subcutaneous fat (panniculitis) characterized by tender, raised, red or violet nodules of 1-5 cm diameter, typically appearing bilaterally and symmetrically on the anterior tibial areas (shins), that evolve through color changes from bright red to purplish to yellow-green (resembling a deep bruise) and resolve without ulceration or scarring over several weeks. 1, 2

Clinical Presentation

The hallmark features include:

• Nodule characteristics: Tender, erythematous, warm, raised subcutaneous nodules that are symmetrically distributed, most commonly on the shins, ankles, and knees 2, 3
• Color evolution: Lesions progress from bright red to livid red or purplish, finally exhibiting a yellow or greenish appearance resembling a deep bruise over days to weeks 2
• Key distinguishing feature: The nodules never ulcerate and heal without atrophy or scarring, which differentiates erythema nodosum from other panniculitides 2, 3

Associated Systemic Symptoms

Patients commonly experience:

• Fever (present in 60% of cases), malaise (67%), and extreme fatigue that may persist for weeks to months 1, 4
• Arthralgias affecting multiple joints (64% of cases), typically symmetrical, involving distal lower extremities without joint effusions 1, 4
• Arthritis occurs in approximately 31% of cases 4

Pathophysiology

• Histopathologic hallmark: Septal panniculitis without vasculitis, with thickened septa of subcutaneous fat infiltrated by inflammatory cells extending to periseptal areas 2
• Miescher's radial granulomas: Small, well-defined nodular aggregations of histiocytes arranged radially around a central cleft—a diagnostic histopathologic feature 2
• Immunologic mechanism: Represents a type IV delayed hypersensitivity response to numerous antigenic stimuli 3

Common Etiologies

Approximately 50% of cases are idiopathic, but when an underlying cause is identified, the most common include:

• Infections: Streptococcal pharyngitis (most common identifiable cause), tuberculosis, coccidioidomycosis, histoplasmosis 1, 3, 5
• Inflammatory conditions: Sarcoidosis, inflammatory bowel disease (ulcerative colitis and Crohn's disease, occurring in 4.2-7.5% of IBD patients), Behçet's disease 6, 1, 5
• Medications: Oral contraceptives, sulfonamides, halides, certain antibiotics 2, 3, 4
• Other: Pregnancy, malignancies (including Hodgkin's and non-Hodgkin's lymphoma) 2, 5, 7

Diagnostic Approach

• Clinical diagnosis: Made primarily on clinical grounds based on characteristic features; diagnosis of erythema nodosum is made clinically, and in atypical cases, a skin biopsy might be helpful 6, 1
• Biopsy technique: When needed, obtain a deep incisional or excisional biopsy specimen for adequate visualization of the septal panniculitis pattern 3
• Initial laboratory evaluation: Complete blood count with differential, erythrocyte sedimentation rate, C-reactive protein level, testing for streptococcal infection (throat culture, rapid antigen test, anti-streptolysin-O titer), and risk stratification for tuberculosis 3, 5

Key Differential Diagnosis

Critical distinction from gnathostomiasis: Unlike erythema nodosum which presents with fixed bilateral nodules on the anterior tibial areas, gnathostomiasis presents with recurrent painful or pruritic subcutaneous nodules that migrate to different locations over days to weeks 8

Treatment Strategy

• Address underlying cause: Treat any identified underlying condition (e.g., streptococcal infection, manage inflammatory bowel disease) 1, 2
• First-line symptomatic treatment: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin or naproxen are the cornerstone for pain and inflammation management 1, 2, 3
• Supportive measures: Bed rest is often sufficient as nodules typically regress spontaneously within a few weeks 2, 4
• Systemic corticosteroids: Reserved for severe cases with significant inflammation or IBD-associated erythema nodosum; should be used cautiously after excluding infectious causes 1, 2, 4
• Refractory cases: For persistent or recurrent disease, consider colchicine (particularly for Behçet's-associated cases), azathioprine for frequent relapses, or TNF-alpha inhibitors (infliximab or adalimumab) for IBD-associated disease 1

Important Clinical Pitfalls

• Do not use corticosteroids before ruling out infection: The danger of disseminating an underlying infectious disease (particularly tuberculosis or fungal infections) makes corticosteroids contraindicated until infection is excluded 2, 4
• Antifungal therapy not indicated: For coccidioidomycosis-associated erythema nodosum, NSAIDs alone are sufficient; antifungal therapy is not recommended for this manifestation 1
• Monitor for underlying disease activity: Recurrent erythema nodosum may indicate persistent underlying disease activity and warrants reassessment, particularly in inflammatory bowel disease or sarcoidosis 1