What is erythema nodosum and how is it treated?

Erythema Nodosum: Definition and Treatment

Erythema nodosum is a septal panniculitis presenting as tender, raised, red or violet subcutaneous nodules (1-5 cm diameter) typically on the anterior lower legs, diagnosed clinically, and treated primarily by addressing the underlying trigger—with systemic corticosteroids reserved for severe cases and immunomodulators or anti-TNF agents for relapsing or resistant disease. 1

What is Erythema Nodosum?

Erythema nodosum (EN) is the most common form of panniculitis, characterized by specific clinical and pathological features 2, 3:

Clinical Presentation

• Raised, tender, erythematous or violet subcutaneous nodules measuring 1-5 cm in diameter 1
• Location: Predominantly affects the extensor surfaces of extremities, particularly the anterior tibial areas (shins) 1, 3
• Distribution: Usually bilateral and symmetrical 3
• Evolution: Nodules initially appear bright red, then become livid red or purplish, and finally exhibit a yellow or greenish appearance resembling a deep bruise 3
• Key feature: Lesions heal without ulceration, atrophy, or scarring 3

Associated Symptoms

• Systemic manifestations commonly include arthralgia, fatigue, fever, malaise, and weakness 1, 4
• Often occurs during disease flares of underlying conditions 1

Pathophysiology

• Represents a type IV hypersensitivity reaction in approximately 40% of cases where a trigger can be identified 1
• Histologically shows septal panniculitis without vasculitis, with thickened septa infiltrated by inflammatory cells 3
• Miescher's radial granulomas (small histiocytic aggregations arranged radially around a central cleft) are a histopathologic hallmark 3

Diagnosis

Diagnosis is made on clinical grounds based on the characteristic appearance and location of lesions 1:

When to Biopsy

• Biopsy is not usually appropriate when clinical diagnosis is firm 1
• Consider skin biopsy only in atypical cases to confirm diagnosis 1
• If performed, histology reveals non-specific focal panniculitis 1

Differential Diagnosis

Critical to exclude metastatic Crohn's disease, which may appear as nodules, plaques, ulcers, or violaceous perifollicular papules with non-caseating granulomas on histology 1

Underlying Causes to Investigate

EN can be idiopathic (23-55% in children, up to 50% in adults) or secondary to 2, 5, 6:

• Infections: Streptococcal infections (most common), tuberculosis, Borrelia burgdorferi 2, 7
• Inflammatory diseases: Sarcoidosis, Behçet disease, inflammatory bowel disease (4.2-7.5% prevalence in IBD, higher in Crohn's than UC) 1, 2
• Medications: Various drugs including bisphosphonates (rare) 2, 8
• Pregnancy 2, 5
• Malignancy (maintain oncological vigilance) 4

Treatment Algorithm

Step 1: Address the Underlying Cause

Treatment is primarily based on managing the underlying condition 1, 3:

• EN typically parallels disease activity of associated conditions 1
• Successful treatment of the underlying trigger usually resolves symptoms within weeks 1

Step 2: Supportive Care for Mild Cases

For mild, self-limited disease 3, 5:

• Bed rest is often sufficient 3
• NSAIDs (aspirin, indomethacin, naproxen, oxyphenbutazone) for analgesia and enhanced resolution 3
• Potassium iodide may be helpful 3
• Elastic web bandages for symptom control 5

Step 3: Systemic Corticosteroids for Severe Cases

Systemic corticosteroids are required in severe cases 1:

• Reserved for patients with significant symptoms or when conservative measures fail 1
• Rule out underlying infection before administering corticosteroids 3

Step 4: Immunomodulators or Anti-TNF for Refractory Disease

For relapsing and resistant forms, escalate to immunomodulation 1:

• Azathioprine 1
• Infliximab 1
• Adalimumab 1

This stepwise approach is particularly relevant in IBD-associated EN, where the prevalence is 4.2-7.5% and occurs more commonly in females and Crohn's disease patients 1

Clinical Pearls and Pitfalls

Important Considerations

• Natural history: EN typically regresses spontaneously within 2-6 weeks in most patients 6
• Prognosis: Excellent, with complete resolution expected 6
• IBD context: EN may occur during IBD flares but not always with disease severity 1
• Pregnancy: Some treatments are contraindicated; consult obstetrics and perform risk-benefit analysis 5

Common Pitfall

Do not confuse EN with pyoderma gangrenosum, which presents as pustules that become burrowing ulcers with violaceous edges and can expose deep tissues—a completely different entity requiring different management 1