II. Epidemiology

  1. Age: Peaks age 20-40 (20% of cases under age 18)
  2. Gender: Males affected more often than females

III. Pathophysiology

  1. Type IV Hypersensitivity Reaction (T Lymphocyte mediated) to various Antigens
  2. Self limited mucocutaneous reaction
    1. Reaction to Antigen deposition within the skin
    2. Triggers cell-mediated Immunity

IV. Types

  1. Erythema Multiforme Minor
    1. Now known simply as Erythema Multiforme
    2. Other forms below are distinct entities
  2. Erythema Multiforme Major (Stevens Johnson Syndrome)
    1. Previously thought to be along same spectrum as minor
    2. Now thought to be distinct entity, with mucous membrane involvement
    3. May include Toxic Epidermal Necrolysis

V. Causes

  1. See Erythema Multiforme Causes
  2. Infections (90% of cases)
    1. Herpes Simplex Virus and Mycoplasma pneumoniae are most common
  3. Medications (10% of cases)

VI. Symptoms

  1. Lesion onset typically 3 to 5 days after initial exposure
    1. Onset up to 1 to 3 weeks after medication exposure
  2. Mild prodrome for 7-10 days may be present (more common with mucosal lesions, Erythema Multiforme Major)
    1. Malaise
    2. Fever
    3. Headache
    4. Rhinorrhea
    5. Cough
  3. Rash
    1. Develops 3-5 days after prodrome
    2. Lesions persist up to 1 to 2 weeks
    3. Rash may burn or itch

VII. Signs

  1. Distinctive Target or Iris skin lesion
    1. Starts as a dull erythematous (pink or red) Macule that becomes raised
    2. Centripetal spread (extremities to trunk) into target lesion over 3-5 days (often by day 2)
      1. Center: Dusky erythema or Vesicle
      2. Middle: Pale edematous ring
      3. Outer: Dark band of erythema
    3. Distribution: Symmetrical involvement with centripetal spread
      1. Onset on distal extremities (often dorsal hands, as well as palms and soles)
      2. Progress proximally (often extensor surfaces)
        1. However, trunk is typically affected less than extremities
        2. Predilection for current areas of Trauma or Sunburn
      3. Features absent in Erythema Multiforme Minor (contrast with EM Major and TEN)
        1. Oral Mucosal involvement is absent in Erythema Multiforme Minor
        2. Nikolsky Sign is absent in Erythema Multiforme Minor
        3. Non-toxic patient appearance
    4. Progresses
      1. Central necrosis
      2. Some lesions may coalesce into annular Plaques
    5. Healing
      1. Most lesions heal without complication
      2. Scarring or Postinflammatory Hyperpigmentation may occur
  2. Alternative presentations
    1. Non-transient Urticarial Plaques
    2. Vesicles or bullae form in prior Macule or wheal

VIII. Labs: None are necessary (use for differential diagnosis)

  1. Complete Blood Count
  2. Skin Biopsy (if diagnosis unclear)
    1. Biopsy with direct immunofluorescence distinguishes Bullous Diseases
  3. Consider evaluating for underlying etiology
    1. Herpes Simplex Virus
      1. Tzanck Preparation of skin lesion
    2. Mycoplasma pneumoniae
      1. Complement fixation
      2. Cold Agglutinins
      3. Chest XRay

IX. Differential Diagnosis

  1. See Erythema Multiforme Differential Diagnosis
  2. Erythema Multiforme Major
    1. Associated with mucosal lesions (distinguishes from Erythema Multiforme Major)
    2. Mucosal lesions (esp mouth) are seen in 25-60% of Erythema Multiforme cases

X. Management: Acute Erythema Multiforme Minor

  1. Elimination of precipitating factors
    1. Herpes Simplex Virus
    2. Mycoplasma pneumoniae
    3. Suspected drug or food item
  2. Mild Involvement: Supportive care
    1. Analgesics
    2. Oral Antihistamines
    3. Skin lesions
      1. Wet Dressings or soaks
      2. Topical Corticosteroids (questionable efficacy)
  3. Moderate Erythema Multiforme Minor
    1. Oral Acyclovir
    2. Prednisone (controversial, not typically recommended)
      1. Dose: 40-80 mg PO daily for 1-2 weeks, then taper
    3. Oral Lesions (Erythema Multiforme Major)
      1. See Erythema Multiforme Major
      2. Saline mouth rinses
  4. Home Precautions
    1. Return for fever, new systemic symptoms, large bullae or Oral Lesions

XI. Management: Recurent Erythema Multiforme Minor

  1. Background
    1. In some patients, may recur multiple times in one year (mean 6 episodes/year over 6-10 years)
    2. Conditions associated with recurrent Erythema Migrans (idiopathic in 60% of cases)
      1. Herpes Simplex Virus (thought to be related to many recurrence episodes, even without outbreak)
      2. Mycoplasma pneumoniae
      3. Hepatitis C
      4. Menstruation
  2. Systemic antivirals
    1. Continue until lesion-free for 4 months
      1. Then taper dose gradually
    2. First-line
      1. Acyclovir 400 mg orally twice daily
    3. Second-line if Acyclovir ineffective
      1. Valacyclovir 500 mg orally twice daily
      2. Famciclovir 250 mg orally twice daily
    4. References
      1. Tatnail (1995) Br J Dermatol 132(2): 267-70 [PubMed]
  3. Other agents in refractory cases
    1. Prescribed by Dermatology
    2. Agents (high rate of adverse effects)
      1. Dapsone
      2. Hydroxychloroquine
      3. Azathoprine
      4. Cyclosporine
      5. Thalidomide

XII. Course

  1. New lesions occur over 3-5 days
  2. Lesions persist for 1-2 weeks (non-migratory)
    1. Contrast with Urticaria that last <24 hours
  3. Resolves spontaneously in 3-5 weeks
    1. HSV related lesions typically resolve by 2 weeks
  4. Recurrence
    1. See above

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