Epidermal Anti-Programmed Cell Death-Ligand 1 Expression in TEN Associated with Nivolumab Therapy

Abstract

Background

Nivolumab is an anti-programmed cell death receptor-1 (PD-1) antibody used in the treatment of metastatic or unresectable melanoma. Cutaneous reactions are the most common adverse events reported with these agents and are rarely severe or life-threatening.

Methods

Case report describing the clinicopathological findings of a patient with a fatal toxic epidermal necrolysis (TEN) eruption associated with use of nivolumab for treatment of metastatic melanoma.

Results

The patient developed a pruritic, morbiliform eruption, which slowly progressed over 3 months to a tender, exfoliative dermatosis. Histology initially demonstrated interface dermatitis and subsequently revealed full thickness epidermal necrosis. The diagnosis of TEN was made. From initial biopsy to TEN presentation, there was an increase in the number of CD8+ lymphocytes within the dermal-epidermal junction and programmed death ligand 1 (PD-L1) expression increased in both lymphocytes and keratinocytes. Despite treatment with infliximab, high dose steroids, and intravenous immunoglobulin, the patient expired.

Conclusions

Herein we describe what we believe is the 2^nd case of TEN associated with anti-PD1 therapy reported in the literature. Increased expression of PD-L1 by immunohistochemistry was observed as the eruption progressed to TEN. Early diagnosis and treatment is necessary in these fatal TEN reactions secondary to the anti-PD-1 antibody therapies.

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