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• Erythema multiforme (EM) – EM has characteristic target lesions (3 concentric colors that are round and well-demarcated) and occur on the extremities more often than the trunk. Precipitating factors are usually infectious (HSV, mycoplasma, etc) and not drug induced. Lesions may be papular or centrally bullous. Note that EM is not considered within the same disease spectrum as Steven-Johnson syndrome (SJS) / TEN and confers no risk in progressing to TEN. Nikolsky sign negative. Mucosal involvement with EM is termed EM major. Mucosal involvement may resemble that of SJS/TEN.
• Staphylococcal scalded skin syndrome – Usually occurs in newborns, infants, and young children; mucous membranes and palms / soles are spared. The exfoliated skin is significantly more superficial (subcorneal vs epidermal-dermal). Also look for purulent discharge from nose, and histologically very different from SJS/TEN. Nikolsky sign can be positive.
• Consider streptococcal toxic-shock-like syndrome, which has a similar clinical presentation. Patients are usually aged 20-50 years and have a deep soft-tissue infection.
• Neonatal candidiasis
• KID syndrome
• Acute generalized exanthematous pustulosis (AGEP) – Look for neutrophilia, eosinophilia, almost confluent erythema with overlying nonfollicular pustules. Nikolsky sign can be positive. Histology will clearly differentiate AGEP vs SJS/TEN.
• Generalized fixed drug eruption – Look for erythematous plaques that develop on the lips, face, distal extremities, and genitalia 1-2 weeks after drug ingestions. Oral mucosa can be involved. Histology will differentiate fixed drug versus SJS/TEN.
• Toxic shock syndrome (TSS) and toxic shock-like syndrome – Look for sudden onset of exanthematous eruption. Histology will help differentiate TSS and SJS/TEN.
• Drug hypersensitivity syndrome – Look for facial edema (hallmark), eosinophilia, hepatitis, and other visceral involvement.
• Exanthematous drug eruption
• Drug-induced erythroderma
• Erythrodermic psoriasis
• Atopic dermatitis with erythroderma
• Contact dermatitis
• Erysipelas
• Necrotizing fasciitis – Rapidly progressing necrosis of fascia and subcutaneous fat.
• Intrauterine epidermal necrosis
• Aplasia cutis congenita
• Dystrophic epidermolysis bullosa
• Epidermolytic ichthyosis
• Congenital erosive and vesicular dermatosis

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