To the Editor: Direct immunofluorescence of perilesional uninvolved skin (PS) is performed in most vesiculobullous dermatoses (VBL). Although immunopathologic and ultrastructural changes are described in PS, there is no data on histopathologic changes.1–3 The few studies available affirm the absence of changes on morphology.1,2 We studied hematoxylin and eosin–stained frozen sections of perilesional skin biopsies from 36 VBL, the majority of which were pemphigus (19) and bullous pemphigoid (9). In cases of pemphigus, we observed incipient acantholysis (18) (Fig. 1A), clefts between strata basale and spinosum (18) (Fig. 1B), adnexal involvement (9) (Fig. 1C), and suprabasal vesicles (5) (Fig. 1D). PS in pemphigoid showed spongiosis (4) (Fig. 2A), sub/intraepidermal clefts (4), eosinophils in the papillary dermis (3) (Fig. 2D), and frank subepidermal vesicles (4) (Fig. 2C). Eosinophils sticking to the basement membrane were noted in 2 cases of pemphigoid (Fig. 2B). Dermal melanophages were noted in most sections of both pemphigus and pemphigoid. We had 2 cases of bullous vasculitis that showed spongiotic vesicles and leukocytoclastic vasculitis. Freezing artifacts were noted in some cases but did not hamper interpretation. The only confounding factor among these was the nuclear/cytoplasmic vacuolization (Fig. 1B) that was difficult to tell apart from early suprabasal clefting. The presence of acantholysis came to rescue in such instances. We also examined frozen sections from 12 samples sent for vasculitis as a control group. None of the above changes were seen in these biopsies, except for focal nuclear and cytoplasmic vacuoles.FIGURE 1: Morphologic changes in cases of pemphigus. A, Incipient acantholysis involving suprabasal and spinous keratinocytes [hematoxylin and eosin (H&E), ×200]. B, Vacuoles between strata basale and spinosum, along with intranuclear vacuoles (H&E, ×200). C, Acantholysis involving a hair follicle (H&E, ×100). D, Suprabasal vesicle (H&E, ×200).FIGURE 2: Morphologic changes in cases of pemphigoid. A, Foci of spongiosis within epidermis [hematoxylin and eosin (H&E), ×200]. B, Eosinophils adherent to basement membrane (H&E, ×400). C, Subepidermal vesicle (H&E, ×100). D, Eosinophils in the dermal infiltrate (H&E, ×400).Significant morphologic changes are seen in perilesional skin of VBL, which are representative of the etiology and not due to freezing artifact. Credence to this observation comes from another study, which concluded that the number of mononuclear inflammatory cells was greater in perilesional than in clinically uninvolved pemphigus skin.4 The proportions of CD4+, CD8+, and Langerhans cells were also higher.4 It is particularly useful to study the morphologic features when a biopsy of lesional skin is not done simultaneously or is inconclusive. It is also potentially useful in identifying sample mix-ups and errors. Hence, we conclude that a detailed histologic evaluation of perilesional skin is pertinent in bullous lesions.