Blistering Diseases and Severe Adverse Cutaneous Drug Reactions
Split the blister
Start by asking where the split occurs: intraepidermal (fragile blisters, positive Nikolsky) versus subepidermal (tense blisters, often negative Nikolsky). Then use direct immunofluorescence to name the disease.
Concepts to master
- Pemphigus vulgaris: intraepidermal, flaccid blisters, mucosal involvement, DIF shows intercellular IgG (chicken-wire).
- Bullous pemphigoid: subepidermal, tense blisters in older adults, DIF shows linear IgG and C3 along the basement membrane.
- Dermatitis herpetiformis: grouped vesicles on extensor surfaces with celiac disease; granular IgA in dermal papillae.
- Linear IgA disease: linear IgA at the basement membrane.
- Stevens-Johnson syndrome and toxic epidermal necrolysis: mucosal erosions plus epidermal detachment; classify by body surface area detached (<10% SJS, 10-30% overlap, >30% TEN).
- Drug reaction with eosinophilia and systemic symptoms (DRESS): facial edema, morbilliform eruption, eosinophilia, and internal organ involvement.
- Acute generalized exanthematous pustulosis (AGEP): numerous small nonfollicular pustules on an erythematous base.
Traps
Nikolsky sign is positive in pemphigus and TEN but usually negative in pemphigoid - questions exploit this. SJS/TEN is a dermatologic emergency: stop the culprit drug, provide burn-unit-level supportive care, and do not rely on corticosteroids as definitive therapy. DRESS has a delayed onset (weeks) and can reactivate herpesviruses.
Worked example
An elderly patient with tense bullae on normal-appearing skin and no mucosal lesions. Diagnosis: bullous pemphigoid. Confirm with perilesional punch biopsy for DIF showing linear IgG and C3 at the basement membrane zone.