The subepidermal vesiculobullous disorders that have no immunologic basis include the hereditary mechanobullous disorders in which a mutation in a keratin or an epidermal basement membrane structural component allows easy blister formation. These are:

■ Hereditary epidermolysis bullosa (EB) (simplex, junctional, and dystrophic)—EB simplex has intraepidermal blisters rather than subepidermal blisters, but it is included here for completeness.

There are also systemic metabolic disorders in which acquired alterations in the basement membrane molecules of epidermis and nearby vessels allow easy injury and blister formation. They are:

■ Porphyria and pseudoporphyria

■ Bullous drug eruption

Blisters can also form due to severe external injury to otherwise normal epidermis. These are:

■ Friction bulla

■ Thermal injury

The blisters due to the metabolic disorders and severe injury can be intraepidermal as well as subepidermal, a histologic clue to their diagnosis.

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