SUPERStudy: Erythema Nodosum (EN)

By usmlevideoss

Introduction

Erythema nodosum (EN) is an acute inflammatory condition characterized by painful, red, tender nodules or plaques, most commonly found on the anterior shins. It is often a reactional process associated with systemic diseases, infections, or medications.

Etiology

  1. Infectious Causes:
    • Bacterial: Streptococcal infections (most common), tuberculosis, Yersinia, Brucella.
    • Viral: Epstein-Barr virus, hepatitis B, HIV.
    • Fungal: Histoplasmosis, coccidioidomycosis.
  2. Systemic Conditions:
    • Inflammatory diseases: Sarcoidosis (most common systemic cause), inflammatory bowel disease (IBD).
    • Autoimmune disorders: Behçet’s disease.
  3. Drug-Induced:
    • Sulfonamides, oral contraceptives, penicillins, some vaccinations.
  4. Pregnancy:
    • Hormonal changes can trigger EN.

Epidemiology

  • Age: Most common in young adults (20–40 years).
  • Gender: More prevalent in women.
  • Geography: Incidence varies; tuberculosis is a common cause in endemic regions.

Pathophysiology

  • Represents a delayed hypersensitivity reaction (Type IV) to antigens from infections, drugs, or systemic conditions.
  • Immune complexes are deposited in the subcutaneous fat, causing panniculitis (inflammation of the fat layer beneath the skin).

Clinical Manifestations

  1. Skin Lesions:
    • Tender, erythematous nodules or plaques, typically 2–5 cm in size.
    • Commonly located on the anterior shins, but may also appear on thighs, forearms, or trunk.
    • Nodules are non-ulcerative and resolve without scarring.
  2. Systemic Symptoms:
    • Fever, malaise, arthralgia, and fatigue may precede or accompany the rash.
    • Associated symptoms depend on the underlying cause (e.g., cough in tuberculosis).

Diagnosis

  1. Clinical Evaluation:
    • History of infections, drug use, or systemic symptoms.
    • Physical examination of characteristic lesions.
  2. Laboratory Tests:
    • Complete blood count: Leukocytosis.
    • ESR/CRP: Elevated inflammatory markers.
    • ASO titer: To check for recent streptococcal infection.
    • Tuberculin skin test or IGRA: To rule out tuberculosis.
    • Stool cultures: For Yersinia or other infections if gastrointestinal symptoms are present.
  3. Biopsy:
    • Rarely needed. Shows septal panniculitis without vasculitis.

Treatment

  1. Treat Underlying Cause:
    • Antibiotics for infections (e.g., streptococcal pharyngitis).
    • Corticosteroids for systemic diseases (e.g., sarcoidosis).
  2. Symptomatic Management:
    • NSAIDs (e.g., ibuprofen, naproxen) for pain and inflammation.
    • Rest and leg elevation.
    • Potassium iodide for refractory cases.

Prognosis

  • EN is self-limiting, with lesions resolving in 3–6 weeks.
  • Recurrence depends on the persistence or recurrence of the underlying condition.

SUPERPoint

Erythema nodosum is a reactive inflammatory condition often triggered by infections, systemic diseases, or medications. Identifying and addressing the underlying cause is essential for effective management.

SUPERFormula

Patient presents with tender, erythematous nodules on shins + taking oral contraceptives  Immune-mediated panniculitis + Trigger (infection, systemic disease, or drugs) + Self-limiting course = Erythema Nodosum.

Reference: 

Rojek NW, Worswick S, Shinkai K, Fox LP. Erythema Nodosum. In: Papadakis MA, Rabow MW, McQuaid KR, Gandhi M. eds. Current Medical Diagnosis & Treatment 2025. McGraw-Hill Education; 2025.