Background: Direct immunofluorescence (DIF) is considered pivotal in diagnosing autoimmune blistering diseases. Our goal was to examine the necessity of DIF in intraepidermal bullous cases, of which pemphigus vulgaris (PV) is the prototype. Methods: Sixty-six cases from 2010 to 2014 submitted for DIF with an intraepidermal blistering disease listed in the differential diagnosis were reviewed by 2 board-certified dermatopathologists to see if they would order DIF based on routine histologic findings. If either pathologist requested DIF, it was considered required. Results: DIF was "required" in 29% (19/66) (94% intraobserver concordance) and was positive in 16% (3/19) of those "required," leading to a diagnosis of PV (2/3) or pemphigus foliaceus [(PF) 1/3]. DIF was "not required" in 71% (47/66). Of these, 37/47 had negative/nonspecific DIF findings (79%). Of the 10 DIF+ cases, 8 were accurately diagnosed as PV based solely on the hematoxylin and eosin (H&E) findings. Three of 47 "not required" cases were misdiagnosed. Two (2/10 DIF+) were called "spongiotic dermatitis" by H&E interpretation yet had DIF consistent with PF. One case of acantholytic pityriasis rubra pilaris was diagnosed as PV on H&E, an error that may have been avoided with real-time clinical correlation. Conclusions: H&E diagnosis was 80% sensitive and 97% specific for intraepidermal blistering diseases. Positive predictive value was 89%; negative predictive value was 95%. H&E triaging could significantly reduce the need for DIF, especially in PV. If PF is in the differential diagnosis, DIF is necessary. In certain settings, triaging by H&E can obviate the need for DIF, resulting in significant savings. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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