Erythema Nodosum

Aka: Erythema Nodosum, Erythema Nodosum Migrans, Subacute Nodular Migratory Panniculitis, Chronic Erythema Nodosum

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II. Epidemiology

  1. Incidence: 1-5 per 100,000
  2. Age: Peaks in 20-30 year range (up to age 50 years)
  3. Gender
    1. Adults: Women predominate by a factor of 6 fold
    2. Children: Boys and girls are equally affected

III. Pathophysiology

  1. Prototype of septal Panniculitis
  2. Erythema Nodosum is the most common cause of Paniculitis (subcutaneous fat inflammation)
  3. Cutaneous Type IV delayed Hypersensitivity response

IV. Causes

  1. Idiopathic or primary (up to 55% of cases)
    1. All other causes are considered secondary
  2. Infection
    1. Streptococcal Pharyngitis (up to 48% of EM cases, most common cause in children)
    2. Infectious Mononucleosis
    3. Mycoplasma
    4. Chlamydia
    5. Coccidioidomycosis
    6. Histoplasmosis
    7. Yersinia enterocolitis (in europe)
    8. MycobacteriaTuberculosis (see Granulomatous disease)
  3. Granulomatous disease
    1. Tuberculosis
    2. Sarcoidosis (up to 25% of cases)
    3. Behcet Syndrome
    4. Inflammatory Bowel Disease
  4. Drug Reaction (up to 10% of cases)
    1. Halides
    2. Sulfonamides
    3. Penicillins (e.g. Amoxicillin)
    4. Cephalosporins
    5. Gold
    6. Oral Contraceptives
    7. Angiotensin Converting Enzyme Inhibitors (ACE Inhibitors)
    8. Proton Pump Inhibitors
  5. Miscellaneous
    1. Pregnancy
    2. Malignancy (e.g. Leukemia)

V. Symptoms

  1. Prodrome: Acute phase response (1-3 weeks before rash)
    1. Fever
    2. Arthralgia
  2. Rash
    1. Painful "bumps" on legs

VI. Signs

  1. Characteristics
    1. Erythematous Nodules
    2. Nodules are deep, warm
    3. Nodules are exquisitely tender to touch
    4. Nodules 1 to 10 cm (typically 2 to 6 cm diameter)
  2. Course
    1. Initially firm
    2. Later become fluctuant
    3. Involute over 2 week period
    4. May appear Bruised during healing
    5. Heal completely within 2 months
      1. No ulcerations, atrophy or scarring
  3. Distribution
    1. Most common on bilateral lower legs
      1. Pretibial area, anterior shins
    2. Other area involved
      1. Extensor Forearm
      2. Thighs
      3. Trunk
  4. Lesions change color over time
    1. Evolve from red to purple to brown
    2. Typically fades without scarring in a few weeks (up to 6 weeks)

VII. Clinical variants

  1. Erythema Nodosum Migrans
    1. Persistent and minimally symptomatic lesions
  2. Subacute Nodular Migratory Panniculitis
    1. Coalescing Nodules form large Plaques on legs
  3. Chronic Erythema Nodosum

VIII. Labs

  1. Complete Blood Count (CBC) with Leukocytosis
  2. Sedimentation Rate (ESR) increased
  3. C-Reactive Protein increased
  4. Tuberculin Skin Test (PPD)
  5. Antistreptolysin-O titer and streptococcal throat swab
    1. Titer increase 30% at four weeks after onset suggests Streptococcus as cause
  6. Consider sending stool for Ova and Parasites
  7. Skin Biopsy (indicated in atypical cases)
    1. Inflammation confined to subcutaneous fat
    2. Acute lesions
      1. Septal widening
      2. Vessel wall inflammation
      3. NO Vasculitis
    3. Chronic lesions
      1. Giant cells
      2. Granulomas may be present

IX. Imaging

  1. Chest XRay

X. Differential Diagnosis

  1. Common
    1. Alpha-1 Antitrypsin Deficiency
    2. Lupus Panniculitis
    3. Lymphoma (cytophagic histiocytic Panniculitis)
  2. Less common
    1. Necrobiosis Lipoidica
    2. Scleroderma

XI. Management

  1. NSAIDs
  2. Bed rest with leg elevation
  3. Support stockings
  4. Treat underlying cause
  5. Potassium Iodide 300-900 mg/day for one month
    1. Risk of Hyperthyroidism
  6. Consider Systemic Corticosteroids
    1. Contraindicated in Bacterial Infection or cancer
    2. Prednisone 60 mg daily and taper
  7. Intralesional injections of Corticosteroids

XII. Course

  1. Most often resolves in 3-6 weeks

XIII. References

  1. Cribier (1998) Int J Dermatol 37:667-72 [PubMed]
  2. Do (2022) Am Fam Physician 106(3): 329-30 [PubMed]
  3. Mert (2004) Scand J Infect Dis 36:424-7 [PubMed]
  4. Schwartz (2007) Am Fam Physician 75:695-700 [PubMed]

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