Cutaneous autoimmune effects in the setting of therapeutic immune checkpoint inhibition for metastatic melanoma

Abstract

Therapeutic immune checkpoint blockade for metastatic melanoma has been associated with vitiligo, pruritus and morbilliform eruptions. Reports of other autoimmune skin disease in this setting are rare. We sought to expand the spectrum of cutaneous immune-mediated effects related to immune checkpoint inhibitor therapy. In this report, we describe two unusual cutaneous reactions related to checkpoint inhibitor therapy, namely bullous pemphigoid (BP) and dermatitis herpetiformis. The development of BP and dermatitis herpetiformis in the context of checkpoint inhibitor therapy is consistent with previous investigations supporting the importance of effector and regulatory T cells in the pathogenesis of these diseases.

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

“…Although this is the same pathomechanism believed to cause conventional BP, it is unclear how anti‐PD‐1/PD‐L1 immunotherapy facilitates this reaction. 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 .…”

“…To date, 22 cases of BP associated with PD‐1/PD‐L1 inhibitors have been reported in the literature . In contrast, BP associated with anti‐CTLA‐4 therapy has only been reported in two cases, suggesting this irAE is more specific to anti‐PD‐1/PD‐L1 therapy .…”

Immune Checkpoint Inhibition and the Prevalence of Autoimmune Disorders Among Patients With Lung and Renal Cancer

“…When considering that immune checkpoint inhibition is only approved in late stages of cancer, it is not clear whether the benefits of pursuing treatment in patients with autoimmune disease outweigh the risk of inducing worse irAEs. Several case reports have been published showing that while discontinuation of the ICI results in resolution of the irAE, long courses of medications specific to the autoimmune reaction may be needed to mitigate the effects of ICI therapy 11–13. In a large systematic review of 251 cases involving anti-CTLA-4 and anti-PD-1 agents, approximately 52% of treated patients discontinued ICI therapy due to the irAEs 11.…”

“…Death due to the irAEs occurred in 4.7% of patients. Cutaneous autoimmune reactions are commonly associated with ICI therapy, but a case report on 2 patients with metastatic melanoma illustrated that irAEs may not appear until long after initiation of therapy 13. An autopsy study presented an elderly patient with melanoma exhibiting a systemic inflammatory response that affected multiple organ sites ultimately resulting in the death of the patient 14…”

A review of bullous pemphigoid associated with PD‐1 and PD‐L1 inhibitors

“…19 The other patient improved with pembrolizumab cessa- Seven of the nine patients were treated with nivolumab 3 mg/kg every 2 weeks. 19 The other patient improved with pembrolizumab cessa- Seven of the nine patients were treated with nivolumab 3 mg/kg every 2 weeks.…”