Erythema Multiforme
Prevalence and Demographics:
- Affects less than 1% of the population.
- Most common in young adults (20–40 years).
- Slight male predominance.
- No racial association.
Genetic Predisposition:
- Associated with HLA-DQB1*0301 allele.
- Stronger association with herpes-related erythema multiforme.
- Other alleles linked to recurrent erythema multiforme.
Causes: Infections (90% of cases):
- HSV type 1 (predominant cause)
- HSV type 2
- Cytomegalovirus
- Epstein-Barr virus
- Influenza virus
- Vulvovaginal candidiasis
- SARS-CoV-2
- Orf
- Mycoplasma pneumoniae (classified as MIRM)
Medications:
- Antibiotics (erythromycin, nitrofurantoin, penicillins, sulfonamides, tetracyclines)
- Anti-epileptics
- NSAIDs
- Vaccinations (common in infants)
Associated Conditions:
- Inflammatory bowel disease
- Hepatitis C
- Leukemia
- Lymphoma
- Solid organ cancer
Pathophysiology:
- Herpes virus phagocytosed by mononuclear cells with cutaneous lymphocyte antigen.
- Viral DNA transferred to epidermis and keratinocytes.
- Cell-mediated immune response with interferon-γ production.
Clinical Features:
Prodromal Symptoms:
- Fatigue, malaise, myalgia, fever
Cutaneous Features:
- Lesions start peripherally, spread centrally.
- Symmetrical distribution, preference for extensor surfaces.
- Painful, pruritic, or swollen.
- Early lesions: round, erythematous papules -> target lesions.
- Target lesions: central dusky area, lighter edematous area, peripheral erythematous margin.
- Atypical lesions: raised, poorly defined borders, fewer color zones.
- Severe cases: hundreds of lesions, different stages.
Mucosal Features:
- Blisters -> shallow erosions with white pseudo-membrane.
- Favors oral membranes, can involve urogenital and ocular mucosa.
- Painful, limits oral intake.
- Lesions may precede or follow cutaneous lesions.
- Self-resolve within 4-6 weeks.
Complications:
- Cutaneous lesions resolve without scarring; hyperpigmentation may persist.
- Ocular complications: keratitis, conjunctival scarring, uveitis, visual impairment.
Diagnosis:
- Based on history and clinical examination.
- Consider complete blood examination, liver function tests, ESR, serology, chest x-ray if in doubt.
- Skin biopsy: upper dermal edema, epidermal keratinocyte necrosis.
- Test for herpes simplex virus in recurrent cases.
- Workup for malignancies in recurrent/persistent cases.
Differential Diagnosis:
- Urticaria
- Viral exanthem
- Stevens-Johnson syndrome
- Fixed drug eruption
- Bullous pemphigoid
- Paraneoplastic pemphigus
- Polymorphous light eruption
- Rowell syndrome
Treatment:
Mild Cases:
- Itch: oral antihistamines, topical steroids
- Pain: oral antiseptic or local anesthetic washes
Other Treatments:
- Treat precipitating infections.
- Cease offending medications.
Severe Mucosal Disease:
- Hospital admission for oral intake support.
- Prednisone for symptom severity and duration reduction.
Recurrent Disease:
- 6 months of continuous oral antiviral therapy (acyclovir/aciclovir).
- Trial of prolonged therapy or alternative antiviral if needed.
- Other systemic agents: azathioprine, dapsone, mycophenolate mofetil, antimalarials.
Outcome:
- Self-limiting with little to no ongoing complications in most patients.
- Recurrent/persistent disease requires additional treatment; remission achievable.