Stevens-Johnson syndrome and toxic epidermal necrolysis-like reactions to checkpoint inhibitors: a systematic review

The use of checkpoint inhibitors for treatment of advanced malignancies is increasing. Rashes, pruritus, and more rarely, reactions resembling Stevens-Johnsons syndrome (SJS) or toxic epidermal necrolysis (TEN) may occur secondary to checkpoint inhibitors. To characterize existing literature on these reports, we queried the PubMed/MEDLINE database for cases of SJS or TEN associated with checkpoint inhibitors. We identified 18 cases of SJS or TEN-like reactions to checkpoint inhibitors in the literature. There were 12 cases of SJS-like rashes with median time to onset of 5.6 weeks (average of 8.9 weeks), of which five were delayed to week 8 or later from checkpoint inhibitor initiation. The five TEN-like reactions had a median time to onset of 4 weeks (average of 5.38 weeks), of which two were delayed to week 6 or later. SJS/TEN-like reactions to nivolumab (seven cases) had median onset time of 3 weeks, whereas five cases secondary to pembrolizumab had median onset time of 11 weeks. Seven cases in this study described prodromal rashes, which varied from localized papular rashes to generalized morbilliform rashes, prior to evolution into SJS or TEN-like patterns. SJS-like patterns generally improved well on systemic treatment/supportive care and no cases of death were identified, but mortality occurred in three of five patients with TEN-like reactions. Dermatologists should consider the possibility for unique features of SJS/TEN in response to checkpoint inhibitors. Additional studies will be necessary to further characterize SJS/TEN-like eruptions on checkpoint inhibitors and determine the optimal management of these cases.