Erythema Multiforme Causes

Idiopathic (50%)
1. However, up to 90% of Erythema Multiforme Minor cases are thought due to infections
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
Mycoplasma pneumoniae
1. Second most common cause (esp. children)
Other infections

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
NSAIDs (esp. Ibuprofen)
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
Antiepileptics
1. Phenytoin (e.g. Dilantin)
2. Phenobarbital
3. Carbamazepine
4. Valproic Acid
Vaccinations (low overall percentage risk given the very large number of annual Immunizations)
1. Hepatitis B Vaccine
2. Small Pox Vaccine
3. Meningococcal Vaccine
4. Pneumococcal Vaccine
5. Varicella Zoster Vaccine
6. Infleunza Vaccine
7. Haemophilus Influenzae Vaccine
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

Food Allergy
Autoimmune Conditions
1. Inflammatory Bowel Disease
2. Connective Tissue Disease (e.g. Systemic Lupus Erythematosus) or Vasculitis
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
Conditions in Women
1. Pregnancy
2. Menstruation