Erythema Multiforme Causes

Aka: Erythema Multiforme Causes, Medication Causes of Erythema Mutiforme, Infectious Causes of Erythema Multiforme

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II. Causes: Infections

  1. Idiopathic (50%)
    1. However, up to 90% of Erythema Multiforme Minor cases are thought due to infections
  2. Herpes Simplex Virus (>50%)
    1. Occurs 10 days after acute eruption, and resolves over a 2 week period
    2. HSV may be cause even without active lesions
    3. Typically associated with HSV-1, but HSV-2 can also cause Erythema Multiforme
  3. Mycoplasma pneumoniae
    1. Second most common cause (esp. children)
  4. Other infections
    1. Varicella Zoster Virus
    2. Hepatitis A Virus
    3. Hepatitis CVirus
    4. Mononucleosis (Epstein-Barr Virus)
    5. Cytomegalovirus
    6. Human Immunodeficiency Virus (HIV Infection)
    7. Vulvovaginal Candidiasis

III. Causes: Drug Sensitivity

  1. Background
    1. Occurs 1-3 weeks after intake
    2. Highest risk with higher doses and rapid drug introduction
    3. Most common cause of erythema mutiforme major
      1. Contrast with Erythema Multiforme Minor which is typically caused infections (esp. HSV, Mycoplasma)
      2. Medications cause 50% of Stevens Johnson
      3. Medications cause 90% of Toxic Epidermal Necrolysis)
    4. Most common with NSAIDS, antiepileptics and Antibiotics
  2. NSAIDs (esp. Ibuprofen)
  3. Antibiotics
    1. Sulfonamides (e.g. Septra)
      1. Trimethoprim-Sulfamethoxazole (Bactrim) is the most common cause of Erythema Multiforme Major
      2. Risk of Erythema Multiforme Major with Trimethoprim-Sulfamethoxazole is up to 40 fold higher in HIV
    2. Penicillins
    3. Erythromycin
    4. Nitrofurantoin
    5. Tetracyclines
    6. Ciprofloxacin
  4. Antiepileptics
    1. Phenytoin (e.g. Dilantin)
    2. Phenobarbital
    3. Carbamazepine
    4. Valproic Acid
  5. Vaccinations (low overall percentage risk given the very large number of annual Immunizations)
    1. Hepatitis B Vaccine
    2. Small PoxVaccine
    3. Meningococcal Vaccine
    4. Pneumococcal Vaccine
    5. Varicella Zoster Vaccine
    6. Infleunza Vaccine
    7. Haemophilus InfluenzaeVaccine
  6. Miscellaneous Medications
    1. Acetaminophen
    2. Phenothiazines
    3. Bextra (FDA black box warning)
    4. Allopurinol
    5. Candesartan (Atacand)
    6. Metformin (Glucophage)
    7. TNF-alpha inhibitors (e.g. Adalimumab or Humira)
    8. Checkpoint Inhibitors (e.g. Pembrolizumab)
    9. Bupropion (Wellbutrin)
    10. Statins
    11. Corticosteroids

IV. Causes: Miscellaneous Causes

  1. Food Allergy
  2. Autoimmune Conditions
    1. Inflammatory Bowel Disease
    2. Connective Tissue Disease (e.g. Systemic Lupus Erythematosus) or Vasculitis
  3. Neoplasm
    1. Associated with Leukemia, Lymphoma
    2. Solid organ neoplasms (Renal Cell Carcinoma, Gastric Adenocarcinoma) may cause persistent and refractory cases
    3. May also be associated with Radiotherapy
  4. Conditions in Women
    1. Pregnancy
    2. Menstruation

V. References

  1. Long (2016) Crit Dec Emerg Med 30(7):3-10
  2. Lamoreux (2006) Am Fam Physician 74:1883-8 [PubMed]
  3. Leaute-Labreze (2000) Arch Dis Child 83:347-52 [PubMed]
  4. Trayes (2019) Am Fam Physician 100(2): 82-8 [PubMed]
  5. Williams (2005) Dent Clin North Am 49:67-76 [PubMed]

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