Erythema Multiforme

Descriptive text is not available for this image BASICS

DESCRIPTION

  • An acute, uncommon, and usually self-limiting inflammatory skin condition that presents with discrete targetoid lesions; cutaneous and/or mucosal sites can be involved.
    • 90% of cases triggered by infectious agents (1).
    • 10% are drug associated.
  • 3 clinically recognized erythema multiforme (EM) subtypes:
    • Acute EM:
      • EM minor (EMm)—predominantly cutaneous involvement
      • EM major (EMM)—predominantly mucosal involvement, often severe
    • Recurrent EM—frequent occurrences over a period of years
    • Persistent EM—continuous EM lesions, marked resistance to therapy

EPIDEMIOLOGY

Incidence

Annual U.S. incidence <1% (1)

Prevalence

  • Most common in adults aged 20 to 40 years; rare <3 years old and >50 years of age
  • >20% of cases occur in children >3 years old and in adolescents, associated with Mycoplasma pneumoniae infection
  • Recurs in 37% of cases, usually in spring and autumn (2)

ETIOLOGY AND PATHOPHYSIOLOGY

  • Etiology (2),(3)
    • Viral infections: herpes simplex virus (HSV-1 most common and HSV-2), SARS-CoV-2, Epstein-Barr, hepatitis C, coxsackievirus, varicella, mumps, poliovirus, cytomegalovirus, HIV, parvovirus B19
    • Bacterial infections: M. pneumoniae, Yersinia enterocolitica, Mycobacterium tuberculosis, Streptococcus
    • Fungal infections: Histoplasma, Candida
    • Drugs: NSAIDs, anticonvulsants, antibiotics (penicillin, sulfonamides, erythromycin, nitrofurantoin, tetracyclines), statins allopurinol, tumor necrosis factor (TNF)-α inhibitors, barbiturates
    • Vaccines: stronger association with HPV, MMR, and small pox vaccines, infrequently associated with hepatitis B, meningococcal, pneumococcal, varicella, influenza, diphtheria-pertussis-tetanus, Haemophilus influenzae, and COVID-19
    • Other: inflammatory bowel disease, autoimmune diseases, malignancies (lymphoma, leukemia, solid organ tumors), high benzoic acid (a food preservative) consumption, polymorphous light eruption
    • Idiopathic: no identifiable cause
  • Pathophysiology: (1)
    • Herpes-associated EM (HAEM): HSV antigens incite a cell-mediated delayed hypersensitivity reaction, generating cytotoxic T-cells, cytokines, and cell death
    • Drug-induced EM: keratinocytes positive for TNF-α toxic cell injury and necrosis

Genetics

  • Familial tendency documented in EMm
  • HLA-B62 found in patients with recurrent EM and in patients with recurrent HSV infection
  • HAEM: strong association with the HLA-DQB1*0301 allele

RISK FACTORS

Age 20 to 40 years or >65 years, prior EM, immunosuppression, prior acute or recurrent HSV-1 or HSV-2 infection, current infection with known associated pathogens, drug-induced

GENERAL PREVENTION

  • Safe sex practice, good handwashing hygiene, sun protection on exposed areas, avoidance of flare-causing drugs
  • Suppression of HSV with oral acyclovir or valacyclovir may help prevent herpes-related recurrent EM episodes (2).

COMMONLY ASSOCIATED CONDITIONS

See “Etiology and Pathophysiology.”

There's more to see -- the rest of this topic is available only to subscribers.