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. Self limited mucocutaneous reaction
  2. Type IV Hypersensitivity Reaction (T Lymphocyte mediated) to various antigens

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 Mutiforme Causes

VI. Symptoms

  1. 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
  2. Rash
    1. Develops 3-5 days after prodrome
    2. 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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Ontology: Erythema Multiforme (C0014742)

Definition (NCI_CTCAE) A disorder characterized by target lesions (a pink-red ring around a pale center).
Definition (NCI) A hypersensitivity reaction characterized by the sudden appearance of symmetrical cutaneous and mucocutaneous macular or papular lesions which evolve into lesions with bright red borders (target lesions). The lesions usually appear in the hands, feet, extremities, and face. Symptoms include fever, malaise, sore throat, cough, vomiting, diarrhea, arthralgia, and myalgia. Causes include infections (most commonly herpes simplex virus), drugs (e.g., sulfonamides, anticonvulsants, and antibiotics), malignancies, and collagen vascular disorders.
Definition (MSH) A skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic "bull's-eye" lesions usually occurring on the dorsal aspect of the hands and forearms.
Definition (CSP) skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic bull's-eye lesions usually occurring on the dorsal aspect of the hands and forearms.
Concepts Disease or Syndrome (T047)
MSH D004892
ICD9 695.10, 695.1
ICD10 L51 , L51.9
SnomedCT 36715001, 200919006, 156362004, 200928007, 267848009
English ERYTHEMA MULTIFORME, Erythema multiforme, unspecified, erythema multiforme, erythema multiforme (diagnosis), Erythema multiforme NOS, Erythema Multiforme [Disease/Finding], erythema polymorphe, multiforme erythema, Erythema;multiforme, erythema multiformes, Target lesion, Multiforme - erythema, Erythema multiforme NOS (disorder), Erythaema polymorphe, Erythema polymorphe, Erythema multiforme, EM - Erythema multiforme, Erythema multiforme (disorder), erythema; multiforme, multiforme; erythema, Erythema multiforme, NOS, Erythema Multiforme
Portuguese ERITEMA MULTIFORME, Eritema polimorfo, Eritema multiforme, Eritema Multiforme
Spanish ERITEMA MULTIFORME, Eritema poliforme, Eritema polimórfico, eritema multiforme, SAI (trastorno), eritema multiforme, SAI, eritema multiforme, eritema polimorfo (trastorno), eritema polimorfo, Eritema multiforme, Eritema Multiforme
Italian Eritema multiforme o polimorfo, Eritema polimorfo, Eritema essudativo polimorfo
Dutch polymorf erytheem, erytheem, polymorf, erytheem; multiforme, multiforme; erytheem, Erythema exsudativum multiforme, niet gespecificeerd, erythema multiforme, Erythema exsudativum multiforme, Erythema multiforme
German Polymorphes Erythem, Erythaema polymorphe, ERYTHEMA MULTIFORME, Erythema exsudativum multiforme, nicht naeher bezeichnet, Erythema multiforme, Erythema exsudativum multiforme
Japanese 多形紅斑, タケイコウハン
Swedish Erythema multiforme
Czech erythema multiforme, Erythema multiforme, Polymorfní erytém
Finnish Monimuotoinen punavihoittuma
Russian ERITEMA MNOGOFORMNAIA EKSSUDATIVNAIA, ЭРИТЕМА МНОГОФОРМНАЯ ЭКССУДАТИВНАЯ
French ERYTHEME POLYMORPHE, Erythème polymorphe, Érythème multiforme, Érythème exsudatif multiforme, Érythème polymorphe
Korean 상세불명의 다형홍반, 다형홍반
Croatian POLIMORFNI ERITEM, ERITEM, MULTIFORMNI
Polish Rumień wielopostaciowy
Hungarian Polymorph erythema, erythema, polymorph, Erythema multiforme
Norwegian Erythema multiforme