NYACP Board Review Question of the Week

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Every other Tuesday, NYACP members are sent a Board Review Question from ACP's MKSAP 18 to test professional knowledge and help prepare for the exam.  Answer explanations are distributed every other Thursday in IM Connected, the Chapter's eNewsletter, and are also published on this page.

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November 23, 2021

MKSAP 18 Dermatology: Item 1


A 63-year-old man is evaluated for a skin eruption that is itchy and worsening for the past several weeks. Medical history is unremarkable, and he takes no medications.
On physical examination, vital signs are normal. There are tense bullae on an erythematous base and scattered erosions on the trunk and extremities.

Which of the following is the most appropriate diagnostic test to perform next? 
Responses Received from Members ( 482 Total):

November 23rd answer graph







The correct answer is:  C. Biopsy of lesional skin for histology and perilesional skin for direct immunofluorescence

Educational Objective

Diagnose autoimmune bullous diseases.


This patient likely has an autoimmune bullous disease, and the most sensitive method for diagnosis is with two biopsies: one of lesional skin for histology, and one of perilesional skin for direct immunofluorescence, as shown.

Biopsy image

Autoimmune blistering diseases result from autoantibodies to different antigens in the skin and have similar but distinct presentations. Clinically, they are characterized by persistent pruritic to painful blisters with erosions and variable mucosal and ocular involvement and scarring. These diseases often arise in older persons. Identification and diagnosis of these disorders are important because of the associated morbidity and mortality. Differentiation of the autoimmune blistering diseases can be made based on clinical features, but definitive diagnosis requires histopathologic examination and, in some patients, serologic testing for pathogenic antibodies.

Depending on the location of the targeted antigen, flaccid or tense bullae will be present clinically, and the corresponding separation can be appreciated using histopathology. In pemphigus, flaccid blisters correspond with suprabasilar separation, whereas tense bullae correspond with subepidermal blisters in bullous pemphigoid and epidermolysis bullosa acquisita.

A skin (shave or punch) biopsy of an intact, early vesicle or bullae with adjacent normal skin should be submitted in formalin and processed for hematoxylin and eosin to examine tissue histology. Each of the autoimmune bullous diseases has characteristic histologic findings that suggest a differential diagnosis. In addition, a perilesional skin biopsy should be submitted for direct immunofluorescence, either in saline or Michel transport medium.

The histologic findings together with the pattern on direct immunofluorescence can usually render a diagnosis. Serum from affected patients also can assist in diagnosis. The blood can be reacted with different substrates and will determine if circulating antibodies are present (indirect immunofluorescence). Tests such as serum enzyme-linked immunosorbent assays have been developed that detect the presence of specific antibodies in pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid, and may correlate with disease activity. Other studies such as salt-split skin immunofluorescence may be useful in selected instances, but overall serum studies have lower sensitivities than biopsy.

Key Point

To diagnose an autoimmune bullous disease, two biopsies often are performed: one of lesional skin for histology and one of perilesional normal skin for direct immunofluorescence.


Elston DM, Stratman EJ, Miller SJ. Skin biopsy: Biopsy issues in specific diseases. J Am Acad Dermatol. 2016;74:1-16; quiz 17-8. [PMID: 26702794] doi:10.1016/j.jaad.2015.06.033

Copyright 2018, American College of Physicians.

Last Updated:  11.10.21

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