History
Appearance of an unusual rash, usually without itching, particularly in a patient who has herpes simplex.

ALERT
Because it is an immunologic reaction, drug-related erythema multiforme will not occur until 7–14 days after exposure to the offending agent, unless the patient has had the medication previously.

Physical Exam

• Typical pleomorphic eruption is a mixture of macules of various sizes and target lesions. These consist of a central inflamed and superficially necrotic area, surrounded by a halo of less inflamed skin, enclosed within an outer erythematous rim.
  • Purpuric lesions are uncommon, and vesicles may be related to antecedent herpes 1 infections.
  • Rash occurs on the palms, soles, dorsum of the hands, and extensor surface of the extremities and the face; often recurrent, following a viral infection.
• In erythema multiforme there may be involvement of one mucus membrane. This consists of target lesions of the lips or herpetic lesions without extensive necrosis. This may cause confusion with Stevens-Johnson syndrome in which two or more mucus membranes are involved, often with deep ulceration and necrosis.
• Corneal ulceration is a serious complication.

Diagnostic Tests and Interpretation

Lab
Initial Labs
No lab tests have been found to be useful in making the diagnosis or monitoring the progress of erythema multiforme.

Diagnostic Procedures/Other
Skin biopsy

Pathological Findings
A predominantly inflammatory pattern characterized by a lichenoid infiltrate, which is of high density and rich in T lymphocytes, and epidermal necrosis that mainly affects the basal layer

Differential Diagnosis

• Stevens-Johnson syndrome
• Urticaria
• Necrotizing vasculitis
• Drug eruptions
• Contact dermatitis
• Pityriasis rosea
• Secondary syphilis
• Ringworm
• Pemphigus vulgaris
• Pemphigoid
• Dermatitis herpetiformis
• Herpes gestationis
• Septicemia
• Serum sickness
• Viral exanthems
• Rocky Mountain spotted fever
• Collagen vascular diseases
• Mucocutaneous lymph node syndrome
• Meningococcemia
• Lichen planus
• Behçet syndrome
• Recurrent aphthous ulcers
• Herpetic gingivostomatitis
• Granuloma annulare