Diagnosis

Erythema multiforme

Etiology

Cause [ugn][fnf][kqq]

1. Virus:

   HSV-1, HSV-2, EBV, CMV, VZV, Adenovirus, Coxsackievirus, Echovirus, Hepatitis, Orf, Enterovirus, Hepatitis A/B/C viruses, Influenza, Measles, Mumps, Parvovirus B19, Poliomyelitis, HIV

2. Bacteria:

   Mycoplasma pneumoniae, Corynebacterium diphtheriae, Hemolytic streptococci, Legionella pneumophila, Salmonella, Mycobacterium leprae, Pneumococcus, Borreliosis, Catscratch disease, Diphtheria, Legionellosis, Hemolytic streptococci, Staphylococcus, Leprosy, Salmonellosis, Neisseria meningitidis, Mycobacterium avium complex, Pneumococci, Tuberculosis, Treponema avium complex, pneumococci, tuberculosis, Treponema pallidum, tularemia, and rickettsia

3. Fungus: Histoplasmosis

4. Parasites

5. Immune disease:

   Graft versus host disease, Inflammatory bowel disease, Polyarteritis nodosa, Sarcoidosis, Systemic lupus erythematous, Vaccines (Diphtheria-tetanus-pertussis, Measles-mumps-rubella, Bacille Calmette-Guerin, hepatitis B and smallpox)

6. Drugs:

   Trimethoprim, sulfamethoxazole, NSAIDs, Penicillins, Anticonvulsants (barbiturates, carbamazepine), Hydantoids, Valproic acid, Allopurinol, Antifungal (Terbinafine), Oxicama (piroxicam, tenoxicam), Imidazole, Chlormezanone, Corticosteroids, Cephalosporins, Quinolones, Tetracycline, Aspirin, Nitrofurantoin, Diphtheria-tetanus-pertussis immunization, Measles-mumps-rubella vaccine

7. Pregnancy

8. Malignancy

9. Radiotherapy

10. Menstruation

11. Idiopathic

Pathophysiology [kqq]

1. Exact pathophysiology is unknown

   • Genetic susceptibility

   • Enviromental trigger

2. Cell-mediated immune response against antigens in skin lesions

3. Influx of macrophages and CD8 T lymphocytes

4. Release of cytokines --> inflammation --> cell death

5. Steven-Johnson Syndrome and toxic epidermal necrolysis are severe variant of Erythema multiforme associated with drug therapies.

Complications [kqq]

• Strictures of the urethra, esophagus, vagina, and anus

• Eye complications: Uveitis, conjunctivitis, scarring, panophthalmitis, blindness, piphora

Epidemiology

Incidence per 100.000 [fnf]

Approach

• Dermatoscopy (clinical diagnosis)

• Blood test: Complete blood cell count, Erythrocyte sedimentation

• Skin biopsy:

  • Immunofluorescence study: Specific HSV antigens within keratinocytes

  • Polymerase chain reaction: HSV DNA primarily within the keratinocytes

• Chest x-ray

Erythema Multiforme

• Target lesions <3cm in diameter

• No or only 1 mucous membrane involvement

• <20% body are involved

• Biopsy compatible with Erythema Multiforme (PCR --> Herpes Simpex DNA?)

Stevens-Johnson syndrome

• Target lesions <3cm in diameter

• 2 or more mucous membrane involvement

• Fever

• 10-20% body are involved

• Biopsy compatible with Erythema Multiforme

Toxic Epidermal Necrolysis

• Bullae and/or erosions >3cm in diameter with erythema and desquamation as seen in exfoliative erythroderma

• Frequent mucous membrane involvement

• Fever

• >20% body are involved

• Biopsy compatible with drug-induced toxic epidermal necrolysis

Treatment

1. Acute phase --> Treat underlying disease: [kqq]

   • HSV infection: acyclovir 400 mg x 2 or valacyclovir 500 mg x 2

   • Mycoplasma pneumoniae infection

   • Drug-induced --> promptly discontinue

2. Mild case: Complete healing in 3-6 weeks and the disease may recur

   • Anti-inflammatory: Fluocinonide 0.05% or other topical steroid agents

   • Analgesic agents

   • Mouthwash containing lidocaine and diphenhydramine

3. Severe case:

   • Systemic steroids: Prednisone 40-60 mg/day, tapered over 2 to 4 weeks

   • Antiviral therapy (acyclovir, valacyclovir, or famciclovir)

   • Supportive care: liquid diet, intravenous fluids, electrolytes, and nutritional support

Differential diagnoses

Acute exanthematic pustulosis, Acute febrile neutrophilic dermatosis, Aphthous stomatitis, Behcet's disease, Bullous pemphigoid, Burn wound, Contact dermatitis, Drug eruptions, Erythroderma, Granuloma annulare, Herpes simplex, Lichen planus, Linear IgA dermatosis, Lyme disease, Meningitis, Mycoplasma infection, Necrotizing vasculitis, Pemphigus erythematosus, Pemphigus foliaceus, Pemphigus vulgaris, Pityriasis rosea, Sepsis, Serum sickness, Staphylococcal scalded skin syndrome, Stevens-Johnson syndrome, Syphilis, Systemic lupus erythematosus, Toxic epidermal necrolysis, Urticaria