Erythema nodosum

Erythema nodosum is a type of panniculitis caused by a delayed hypersensitivity reaction. It characteristically manifests with the sudden onset of painful, subcutaneous nodules on the anterior aspect of the lower legs. Female individuals are most commonly affected. Erythema nodosum is often idiopathic but can be caused by a variety of conditions, including infections and autoimmune diseases (e.g., ulcerative colitis). Erythema nodosum is primarily a clinical diagnosis, but testing is recommended to confirm the diagnosis and/or exclude a serious underlying cause. Erythema nodosum typically resolves spontaneously within a few weeks; treatment is symptomatic and/or targeted to the specific cause.

• Sex: ♀ > ♂ ^[1][2]
• Peak incidence: second to fifth decade of life ^[1][2]

Epidemiological data refers to the US, unless otherwise specified.

• Idiopathic (over one-third of patients) ^[3]
• Infection (e.g., streptococcal pharyngitis, histoplasmosis, coccidioidomycosis, tuberculosis, leprosy, cat scratch disease, infectious mononucleosis)
• Autoimmune diseases (e.g., sarcoidosis, Crohn disease, ulcerative colitis, Behcet syndrome)
• Drugs (e.g., oral contraceptives, sulfonamides, penicillins, iodide)
• Pregnancy
• Malignancy (e.g., leukemia, lymphoma)

Delayed hypersensitivity reaction → panniculitis (inflammation of subcutaneous fat) ^[3][4]

• Nonspecific symptoms ^[3][5]
  • Fever
  • Arthralgia
  • Malaise
  • Lymphadenopathy
• Painful, subcutaneous nodules on both pretibial surfaces (less common on other areas of skin) ^[3][5]
  • Sudden onset (1–2 days)
  • Initially firm and erythematous
  • May become soft and purple in the second week
  • Typically resolve over several weeks, with slowly fading hyperpigmentation (e.g., yellow or brown hue)
• Recurrences are common.

Erythema nodosum is primarily a clinical diagnosis. Diagnostic testing is performed to determine the cause and/or to guide management.

Approach ^[3][5]

• Make a preliminary diagnosis based on clinical features.
• Perform a focused history. ^[2]
  • Constitutional symptoms
  • Recent drug intake or vaccinations
  • Travel history
  • Family history of autoimmune disease and/or tuberculosis exposure
  • Animals in the home
• Obtain laboratory studies and imaging based on clinical suspicion.
• Consider a skin biopsy for confirmation.

Exclude underlying disease before establishing a diagnosis of idiopathic erythema nodosum. ^[3]

Laboratory studies ^[3][4][5]

• Routine studies
  • CBC with differential
  • ESR, CRP
  • Antistreptolysin O antibody titer, throat swab culture
  • Individuals who can become pregnant: pregnancy test ^[6]
• Additional studies based on suspicion, e.g.:
  • VDRL
  • Serum AAT level ^[7]
  • Inflammatory bowel disease workup
  • Diagnostic workup for sarcoidosis
  • Diagnostic workup for tuberculosis

Imaging studies ^[3][5]

• Chest x-ray
  • Recommended as part of the initial workup
  • May show hilar lymphadenopathy (e.g., in sarcoidosis, tuberculosis)
• Consider advanced imaging (e.g., CT chest) as needed for further evaluation and/or confirmation of chest x-ray findings.

Skin biopsy ^[3][5]

• Confirmatory test: Consider if there is diagnostic uncertainty (e.g., for patients with atypical manifestations). ^[5]
• Indications and timing vary. ^[3][4][5]

• Alpha-1-antitrypsin deficiency
• Systemic lupus erythematosus
• Nodular fat necrosis ^[4]
• Nodular vasculitis ^[5]
• Thrombophlebitis
• Urticaria ^[8]
• Insect bites
• Erysipelas
• Familial Mediterranean fever
• See also “Skin nodules.”

The differential diagnoses listed here are not exhaustive.

Approach ^[3]

• Stop offending medications.
• Treat the underlying condition (if known)
• Provide supportive treatment.
• Severe and/or refractory disease: Consider additional treatment in consultation with a specialist.
  • Systemic steroids
  • Potassium iodide, colchicine, dapsone ^[3][5]

Supportive treatment ^[3][5]

• Bed rest
• Leg elevation
• Limb compression with bandages
• Heat or cool compresses
• NSAIDs (e.g., ibuprofen) ^[3]

Disposition

• Most patients can be managed as outpatients.
• Refer patients with severe, atypical, and/or recurrent symptoms to dermatology.
• Consider admission if warranted by underlying cause (e.g., need for parenteral treatment).

• Usually self-limited (within 1–8 weeks) ^[5][6][9]
• May resolve earlier with effective treatment of an underlying condition
• Recurrence after discontinued treatment is common.