Epidermal necrolysis in the context of immuno-oncologic medication as well as kinase inhibitors and biologics

Background: Stevens-Johnson syndrome and toxic epidermal necrolysis are severe, primarily drug-induced reactions of skin and mucosa. Since they differ in the extent of skin detachment but not in etiology, they are grouped together as epidermal necrolysis (EN). Due to nationwide registration, representative data are available at the German Center for the Documentation of Severe Skin Reactions (dZh). Here, an increasing number of case notifications in the context with new immuno-oncologic drugs, kinase inhibitors and biologics have been observed. Material and methods: Of 4,150 cases notifications between January 2003 and February 2019, 102 cases with exposure to these drug groups underwent systematic analysis, validation and causality assessment. Results: Two cases of EN to vemurafenib were confirmed and one case to afatinib and pembrolizumab, respectively. In 14 EN cases other drugs - predominantly allopurinol or cotrimoxazole - were the causative agent. Fourteen cases were EN-like reactions: six bullous lichenoid drug eruptions (DE) to pembrolizumab (2), obinutuzumab, nivolumab, rituximab, infliximab/nivolumab, and eight multiforme-like DE to rituximab (2), adalimumab, ramucirumab, bevacizumab, vemurafenib, sorafenib (2). Lichenoid DE were differentiated from EN through histopathology and by the protracted course of EN, multiforme-like DE by variable skin manifestations with only sparse epidermolysis or mucosal involvement. Conclusions: A correct diagnosis is highly relevant in terms of prognosis and use of these drugs in malignoma treatment. Re-exposure is contraindicated in EN, but possible in other DE after rigorous risk-benefit evaluation.