Bullous disorders associated with anti-PD-1 and anti-PD-L1 therapy: A retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy

J Am Acad Dermatol. 2018 Dec;79(6):1081-1088. doi: 10.1016/j.jaad.2018.07.008. Epub 2018 Jul 17.


Background: Bullous disorders associated with anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) therapy are increasingly reported and may pose distinct therapeutic challenges. Their frequency and impact on cancer therapy are not well established.

Objective: To evaluate the clinical and histopathologic findings, frequency, and impact on cancer therapy of bullous eruptions due to anti-PD-1/PD-L1 therapy.

Methods: We retrospectively reviewed the medical records of patients evaluated by the oncodermatology clinic and consultative service of Yale New Haven Hospital from 2016 to 2018.

Results: We identified 9 of 853 patients who developed bullous eruptions (∼1%) that were treated with an-PD-1/PD-L1 therapy at our institution during the study period: 7 presented with bullous pemphigoid, 1 presented with bullous lichenoid dermatitis, and 1 presented with linear IgA bullous dermatosis in the context of vancomycin therapy. In all, 8 patients required systemic steroids, 5 required maintenance therapy, and 8 required interruption of immunotherapy. All 9 patients had an initial positive tumor response or stable disease, but 4 went on to develop disease progression.

Limitations: This was a retrospective study from a single tertiary care center.

Conclusions: Bullous disorders developed in approximately 1% of patients treated with anti-PD-1/PD-L1 therapy at our institution and frequently resulted in interruption of immune therapy and management with systemic corticosteroids and occasionally steroid-sparing agents.

Keywords: bullous pemphigoid; immunotherapy; medical dermatology; programmed cell death 1; programmed cell death ligand 1.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Aged
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Agents, Immunological / adverse effects*
  • B7-H1 Antigen / antagonists & inhibitors*
  • Drug Eruptions / drug therapy
  • Drug Eruptions / etiology*
  • Female
  • Humans
  • Lichenoid Eruptions / chemically induced
  • Male
  • Middle Aged
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasms / complications*
  • Neoplasms / drug therapy
  • Nivolumab / adverse effects
  • Pemphigoid, Bullous / chemically induced
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Retrospective Studies
  • Skin Diseases, Vesiculobullous / chemically induced*
  • Skin Diseases, Vesiculobullous / drug therapy
  • Tertiary Care Centers
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • Neoplasm Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • durvalumab
  • Nivolumab
  • atezolizumab
  • pembrolizumab