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Anti-programmed cell death-1 therapy-associated bullous disorders

a systematic review of the literature

Zhao, Cathy Yunjiaa,c; Hwang, Shelley Ji Euna,c; Consuegra, Germanaa,c; Chou, Shaunb; Fernandez-Peñas, Pabloa,c

doi: 10.1097/CMR.0000000000000500

Bullous disorders are rare adverse events associated with anti-programmed cell death-1 (anti-PD1) therapy. This paper presents two new cases of bullous disorders under anti-PD1 therapy and systematically reviewed the literature to foster a better understanding of the presentation and pathogenesis of bullous disorders under anti-PD1. A systematic review of the literature was completed using MEDLINE, Embase, PubMed and LILACS databases. We identified 29 cases of bullous disorders under anti-PD1 therapy, including our two new cases. This includes 18 cases of bullous pemphigoid (BP), five cases of toxic epidermal necrolysis (TEN)/Stevens–Johnson syndrome (SJS) spectrum, one case of erythema multiforme (EM), four cases of bullous lichenoid reactions and one case of vesiculobullous eczema. In BP, blistering occurred by a median of 23 weeks after anti-PD1 therapy initiation and is often preceded by a prodrome, which lasts for a median of 9.5 weeks. Limbs and trunk were the most frequently involved body sites. Most cases (76%) achieved remission. In TEN/SJS/EM, blistering was usually preceded by a prodrome of interface dermatitis that lasted for a median of 1.5 weeks. Most cases (80%) died from either TEN/SJS or disease progression. Bullous disorders under anti-PD1 may be classified clinically as BP, SJS/TEN/EM, bullous lichenoid reactions and vesiculobullous eczema and histologically by intraepidermal splitting and subepidermal splitting. BP is usually preceded by a pruritic eruption and has a relatively good prognosis. SJS/TEN is usually preceded by a maculopapular eruption and has a very poor prognosis.

Departments of aDermatology

bPathology, Westmead Hospital, Westmead

cSydney Medical School, The University of Sydney, Sydney, New South Wales, Australia

Correspondence to Cathy Yunjia Zhao, MBBS, MMed, MSc, Department of Dermatology, Westmead Hospital, Hawkesbury Road and Darcy Road, Westmead Hospital, Westmead NSW 2145, Australia Tel: +61 288 905 686; fax: +61 288 909 673; e-mail:

Received May 27, 2018

Accepted July 23, 2018

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