Development of Bullous Pemphigoid While Receiving PD-1 Checkpoint Inhibitor Nivolumab

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Zachary P Nahmias
Eric D Merrill
Cristopher C Briscoe
Charles E Mount
Sabra Abner
Andras Schaffer
Milan J Anadkat


oncology, bullous pemphigoid, adverse drug reaction


Monoclonal antibodies against PD-1 are becoming increasingly important agents in the oncologist's armamentarium against a variety of cancers, including melanoma and squamous cell carcinoma. Most reported cutaneous reactions to these agents are mild and resolve with a conservative treatment approach. We present two cases of patients treated with anti-PD-1 agents who developed bullous pemphigoid shortly after initiation of therapy. We then review the literature of anti-PD-1-associated bullous pemphigoid, which is likely a bona fide side effect of anti-PD-1 therapy. Finally, we discuss management of these cases, where the risks of bullous pemphigoid must be weighed against the benefits of anti-PD-1 treatment. As the number of indications for PD-1 monoclonal antibodies expands, dermatologists will need to recognize their cutaneous adverse events and assist oncologists in the management of such complications.


1. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–264.

2. Sibaud V, Meyer N, Lamant L, Vigarios E, Mazieres J, Delord JP. Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies. Curr Opin Oncol. 2016;28(4):254–263.

3. Sowerby L, Dewan AK, Granter S, Gandhi L, LeBoeuf NR. Rituximab Treatment of Nivolumab-Induced Bullous Pemphigoid. JAMA Dermatol. 2017;153(6):603–605.

4. Damsky W, Kole L, Tomayko MM. Development of bullous pemphigoid during nivolumab therapy. JAAD Case Rep. 2016;2(6):442–444.

5. Naidoo J, Schindler K, Querfeld C, Busam K, Cunningham J, Page DB, Postow MA, Weinstein A, Lucas AS, Ciccolini KT, Quigley EA, Lesokhin AM, Paik PK, Chaft JE, Segal NH, D'Angelo SP, Dickson MA, Wolchock JD, Lacouture ME. Autoimmune Bullous Skin Disorders with Immune Checkpoint Inhibitors Targeting PD-1 and PD-L1. Cancer Immunol Res. 2016;4(5):383–389.

6. Kwon CW, Land AS, Smoller BR, Scott G, Beck LA, Mercurio MG. Bullous pemphigoid associated with nivolumab, a programmed cell death 1 protein inhibitor. J Eur Acad Dermatol Venereol. 2017;31(8):e349-e350.

7. Jour G, Glitza IC, Ellis RM, Torres-Cabala CA, Tetzlaff MT, Li JY, Nagarajan P, Huen A, Aung PP, Ivan D, Drucker CR, Prieto VG, Rapini RP, Patel A, Curry JL. Autoimmune dermatologic toxicities from immune checkpoint blockade with anti-PD-1 antibody therapy: a report on bullous skin eruptions. J Cutan Pathol. 2016;43(8):688–696.

8. Mochel MC, Ming ME, Imadojemu S, Gangadhar TC, Schuchter LM, Elenitsas R, Payne AS, Chu EY. Cutaneous autoimmune effects in the setting of therapeutic immune checkpoint inhibition for metastatic melanoma. J Cutan Pathol. 2016;43(9):787–791.

9. Parakh S, Nguyen R, Opie JM, Andrews MC. Late presentation of generalised bullous pemphigoid-like reaction in a patient treated with pembrolizumab for metastatic melanoma. Australas J Dermatol. 2017;58(3):e109-e112.

10. Hwang SJ, Carlos G, Chou S, Wakade D, Carlino MS, Fernandez-Peñas P. Bullous pemphigoid, an autoantibody-mediated disease, is a novel immune-related adverse event in patients treated with anti-programmed cell death 1 antibodies. Melanoma Res. 2016;26(4):413–416.

11. Carlos G, Anforth R, Chou S, Clements A, Fernandez-Peñas P. A case of bullous pemphigoid in a patient with metastatic melanoma treated with pembrolizumab. Melanoma Res. 2015;25(3):265–268.

12. Cugno M, Marzano AV, Bucciarelli P, Balice Y, Cianchini G, Quaglino P, Calzavara Pinton P, Caproni M, Alaibac M, De Simone C, Patrizi A, Cozzani E, Papini M, Tedeschi A, Berti E, Rosendaal FR. Increased risk of venous thromboembolism in patients with bullous pemphigoid. The INVENTEP (INcidence of VENous ThromboEmbolism in bullous Pemphigoid) study. Thromb Haemost. 2016;115(1):193–199.

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