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May 25, 2022

Association of Bullous Pemphigoid With Immune Checkpoint Inhibitor Therapy in Patients With Cancer: A Systematic Review

Author Affiliations
  • 1Harvard Medical School, Boston, Massachusetts
  • 2Department of Dermatology, Massachusetts General Hospital, Boston
  • 3Virginia Commonwealth University School of Medicine, Richmond
  • 4University of Hawaii at Manoa John A. Burns School of Medicine, Honolulu
  • 5Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center, Boston
JAMA Dermatol. 2022;158(8):933-941. doi:10.1001/jamadermatol.2022.1624
Key Points

Question  What are common characteristics associated with immune checkpoint inhibitor–induced bullous pemphigoid (ICI-BP) in patients with cancer?

Findings  In this systematic review of 70 studies reporting data on 127 ICI-treated patients with cancer, ICI-BP was found to occur after all types of immunotherapy, including cytotoxic T lymphocyte–associated antigen inhibitors. Immunotherapy was discontinued for most patients after ICI-BP diagnosis, and common treatments included systemic and topical corticosteroids, followed by antibiotics, antihistamines, systemic immunomodulators, and biologics.

Meaning  This systematic review summarizes the literature base and published studies reporting the development of ICI-BP in patients with cancer; its results can potentially aid in informing disease-specific guidelines for affected patients.


Importance  There is limited information on immune checkpoint inhibitor–induced bullous pemphigoid (ICI-BP) in patients with cancer, with most existing studies being case reports or small case series from a single institution. Prior review attempts have not approached the literature in a systematic manner and have focused only on ICI-BP secondary to anti–programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) therapy. The current knowledge base of all aspects of ICI-BP is limited.

Objective  To characterize the risk factors, clinical presentation, diagnostic findings, treatments, and outcomes of ICI-BP in patients with cancer as reported in the current literature.

Evidence Review  A systematic review was performed using PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Articles reporting data on individual patients who met preestablished inclusion criteria were selected, and a predefined set of data was abstracted. When possible, study results were quantitatively combined.

Findings  In total, 70 studies reporting data on 127 individual patients undergoing ICI therapy for cancer (median [IQR] age, 71 [64-77] years; 27 women [21.3%]) were included. In pooled analyses, patients ranged in age from 35 to 90 years. Immune checkpoint inhibitor–induced bullous pemphigoid often occurred during the course of anti-PD-1, PD-L1, or cytotoxic T lymphocyte–associated antigen 4 therapy but was also found to develop up to several months after treatment cessation. Prodromal symptoms, such as pruritus or nonspecific skin eruptions, were found in approximately half of the patient population. Histopathologic or serologic testing, when undertaken, was a helpful adjunct in establishing diagnosis. Treatment with immunotherapy was discontinued after ICI-BP development in most patients. The most common treatments were systemic and topical corticosteroids. Steroid-sparing therapies, such as antibiotics and other systemic immunomodulators, were also used as adjuvant treatment modalities. Biologic and targeted agents, used predominantly in cases refractory to treatment with corticosteroids, were associated with marked symptomatic improvement in most patients.

Conclusions and Relevance  The results of this systematic review suggest that ICI-BP often poses a therapeutic challenge for patients with cancer who are receiving immunotherapy. Further research on the early recognition, diagnosis, and use of targeted treatment modalities will be essential in developing more personalized treatment options for affected patients while minimizing morbidity and mortality.

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