A Case of Nivolumab-Induced Bullous Pemphigoid: Review of Dermatologic Toxicity Associated with Programmed Cell Death Protein-1/Programmed Death Ligand-1 Inhibitors and Recommendations for Diagnosis and Management

Oncologist. 2018 Oct;23(10):1119-1126. doi: 10.1634/theoncologist.2018-0128. Epub 2018 Jul 17.

Abstract

Immunotherapy has emerged as a highly effective treatment for numerous cancers. Use of checkpoint inhibitors against various molecules including programmed cell death protein-1 (PD-1), programmed death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 have become widespread in clinical practice. Compared with conventional chemotherapy, immunotherapy is associated with a unique set of immune reactions known collectively as immune-related adverse events (irAEs). Of known irAEs, cutaneous toxicity is among the most frequently observed in patients treated with immunotherapy. Although often mild, dermatologic toxicity can occasionally be high grade and potentially life-threatening. In this article, we report a case of PD-1 inhibitor-induced bullous pemphigoid-a serious adverse event that has been increasingly observed with use of PD-1/PD-L1 inhibitors. We will also review diagnosis and management of low-grade cutaneous irAEs and bullous disease with checkpoint inhibitors.

Key points: PD-1/PD-L1 inhibitor-induced bullous pemphigoid (BP) is a rare but potentially serious dermatologic toxicity associated with checkpoint inhibitorsIn patients with pruritus or rash that is refractory to topical steroids, physicians should have a greater index of suspicion for higher-grade cutaneous immune-related adverse events.There is no standardized treatment algorithm for management of PD-1/PD-L1 inhibitor-induced BP, but patients frequently require topical and systemic steroids.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / adverse effects*
  • Antineoplastic Agents, Immunological / therapeutic use
  • B7-H1 Antigen / antagonists & inhibitors*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Clobetasol / therapeutic use
  • Female
  • Humans
  • Immunotherapy / adverse effects*
  • Immunotherapy / methods
  • Lung Neoplasms / drug therapy
  • Nivolumab / adverse effects*
  • Nivolumab / therapeutic use
  • Pemphigoid, Bullous / chemically induced*
  • Pemphigoid, Bullous / diagnosis
  • Pemphigoid, Bullous / drug therapy
  • Prednisone / therapeutic use
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Skin / pathology

Substances

  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • Clobetasol
  • Prednisone