Development of bullous pemphigoid during nivolumab therapy

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

“…Of reported cases, BP most frequently developed within the first 6–8 months of treatment; however, a smaller subset of patients did not present until 1–1.5 years later . In many patients, development of bullae was preceded by prodromal pruritus and nonspecific rash, as observed in this case .…”

Novel use of combination therapeutic plasma exchange and rituximab in the treatment of nivolumab‐induced bullous pemphigoid

“…Autoimmune bullous dermatoses are a recently described adverse event to the PD‐1/PD‐L1 inhibitors . The pathogenesis of BP may be due to excessive B‐cell costimulation and increased autoantibody production with blockade of PD‐1/PD‐L1 receptors . None of the prior patients mentioned neurologic or cutaneous metastases, which potentially could have an effect on exposing epitopes for the development of BP.…”

“…Of the reported cases of PD‐1/PD‐L1 inhibitor‐induced BP, the majority were controlled with topical and/or oral steroids alone . This is a therapeutic challenge due to the necessity of balancing the effects of immunosuppressive medications in a patient with advanced melanoma, who was previously successful on nivolumab and without alternative options.…”

Bullous pemphigoid associated with nivolumab, a programmed cell death 1 protein inhibitor

“…1,2 To our knowledge, there are only six previously reported cases of nivolumab-induced BP, as well as six associated with pembrolizumab, in which the onset ranged from 3 weeks to 21 months after initiating treatment with the PD-1 inhibitor for metastatic melanoma, metastatic squamous cell carcinoma (SCC) of the head and neck, metastatic or recurrent non-small-cell lung cancer (NSCLC), and metastatic urothelial carcinoma. [1][2][3][4][5][6] The pathophysiological mechanism remains unclear, but one hypothesis posits that these agents may alter the regulation of T cells that target collagen XVII/BP180, which is expressed at the dermalepidermal junction and the surface of various tumour cells, including those of malignant melanoma, SCC of the skin and NSCLC, in addition to the normal urothelial surface. 1,7 The association of BP with checkpoint inhibitors that block the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), such as ipilimumab and tremelimumab, has not been clearly established.…”

“…[1][2][3][4][5][6] In one case, the patient safely restarted nivolumab treatment while on a steroid-sparing agent, but in another case, rechallenge with nivolumab resulted in the development of BP, requiring cessation of the PD-1 inhibitor for clearance. 2,3 Recognizing that these drugs provide a remarkable improvement in our ability to manage advanced cancers, we can anticipate more widespread use and must learn to recognize their unique side-effects. Thus, we wish to highlight this little-known class effect of PD-1 inhibitors and recommend prompt referral to a dermatologist for suspicious signs and symptoms.…”