Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the bilateral shins. The underlying etiology varies and may be associated with infection, drug exposure, irritable bowel disease, pregnancy, or malignancy. These lesions often self-resolve within 8 weeks without scarring. Management focuses on identifying and treating the underlying cause.

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erythema nodosum

Image: “Erythema Nodosum.” by Norman Purvis Walker – Walker, Norman Purvis (1905) An introduction to dermatology (3rd ed.), William Wood and company Retrieved on 26 September 2010. License: Public Domain


Epidemiology and Etiology

Epidemiology

  • Most common in women in their second and the fourth decade of life
  • Most common form of panniculitis (inflammation of subcutaneous fat)

Etiology

30-50% of erythema nodosum cases are idiopathic. These are the common etiologies.

Classification Etiologies Examples
Infectious causes Bacterial 
Viral 
Fungal 
  • Coccidomycosis 
  • Histoplasmosis 
  • Blastomycosis 
Noninfectious causes  Drugs 
  • Penicillins 
  • Sulfonamide
  • Oral contraceptive pills 
Malignancy 
  • Leukemia
  • Lymphoma
  • Solid malignancies 
Inflammatory bowel disease
Miscellaneous 

Pathophysiology

Immune-mediated reaction to various antigens resulting in subcutaneous fat inflammation.

  • Type IV hypersensitivity reaction (delayed-type hypersensitivity)
  • Causes erythematous, tender nodule on the shins
  • Histology shows septal panniculitis without primary vasculitis

Video Gallery

Erythema Nodosum by Carlo Raj, MD

Clinical Presentation

  • Prodromal symptoms may precede the eruption of skin lesions
    • Fatigue
    • Fever
    • Malaise
    • Arthralgia/arthritis 
  • Characteristic skin lesions:
    • Erythematous, tender nodules on the bilateral shins
      • Nonulcerated
      • Immobile
      • Slightly raised
      • Typically 2-5 cm
    • Develop over several days
      • Usually self-resolve without scarring within 8 weeks of presentation
      • Bruising or residual hyperpigmentation may occur during resolution.
    • Less common sites of nodules:
      • Ankles
      • Thighs
      • Buttocks
      • Calves
      • Face

Diagnostics and Management

Diagnostics

Erythema nodosum is usually diagnosed clinically. Skin biopsy may be used for confirming diagnosis if the patient has an atypical presentation.

  • Patients should be evaluated for underlying disease:
    • Thorough history and physical examination including
      • Medication history
      • Travel history
      • ROS of respiratory, gastrointestinal, and constitutional symptoms
      • Examination of the throat and tonsils (to rule out streptococcal infection)
    • Laboratory workup may include
      • CBC
      • ESR and/or CRP
      • Throat culture and antistreptolysin-O (ASO) titers 
      • Tuberculin skin test/interferon-gamma release assay 
      • Pregnancy test
    • Imaging may include
      • Chest radiographs

Management

Erythema nodosum is self-limiting and usually resolves within 8 weeks.

  • Symptomatic treatment includes
    • Rest and leg elevation
    • Venous compression by stocking (if tolerable)
    • Analgesics (e.g., NSAIDs) or potassium iodide for pain
  • The underlying causes should also be identified and treated.

Differential diagnosis

Nodular vasculitis: 

Lobular panniculitis is frequently associated with tuberculosis. Often occurs on the posterior calves with ulcerated, draining nodules. Patients would be expected to have a positive tuberculin skin test.

Subcutaneous infections: 

May be due to a bacterial, fungal, or mycobacterial infection. Often occurs on the legs/feet with fluctuant, ulcerated, draining lesions. Patients would be expected to have systemic signs of infection.

Cutaneous polyarteritis nodosa: 

Characterized by painful subcutaneous nodules on the legs. However, these nodules are also associated with livedo racemosa, necrosis, and ulcerations. Histology shows segmental necrotizing medium artery vasculitis. 

Pancreatic panniculitis: 

These nodules differ in that they are fluctuant and ulcerative with oily fluid drainage. They often heal with scarring. Patients would be expected to have symptoms of pancreatitis including fever and abdominal pain. Labs would reveal elevated lipase and amylase.

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