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

Abstract

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.

Case Report: Enfortumab Vedotin for Metastatic Urothelial Carcinoma: A Case Series on the Clinical and Histopathologic Spectrum of Adverse Cutaneous Reactions From Fatal Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis to Dermal Hypersensitivity Reaction

“…This is supported by the common occurrence of skin rash as an adverse event in trials evaluating other antibody-drug conjugates that incorporate MMAE, occurring in 31% of patients with classical Hodgkin lymphoma treated with brentuximab vedotin monotherapy, 44% of patients treated with glemutumumab vedotin, and 13–31% of patients treated with polatuzumab vedotin ( 10 ). Lastly, dermatologic toxicities from prior immune checkpoint inhibitor treatment cannot be entirely ruled out as delayed onset of SJS/TEN >8 weeks following exposure have been cited ( 11 , 12 ). The histomorphologic features exhibit interface dermatitis with dyskeratosis ( 3 ).…”

Stevens-Johnson syndrome/toxic epidermal necrolysis in patients treated with immune checkpoint inhibitors: A safety analysis of clinical trials and FDA pharmacovigilance database

“…In addition, ICIs were mostly used as later line therapy in the past years, the mortality rate due to SJS/TEN may decrease with the increasing use of ICIs in first line and adjuvant therapy setting. Therefore, a high index of suspicion is necessary to identify SJS/ TEN in its early stages in order to minimize the potential for both morbidity and mortality in patients using ICIs [7]. The mechanism of immune checkpoint inhibitor results to SJS/ TEN is not clear.…”

Nivolumab-associated Stevens-Johnson syndrome in a patient with lung cancer

“…Recently, Maloney et al [5] conducted a review of SJS-and TEN-like reactions to checkpoint inhibitors in which they collected 18 cases caused by nivolumab, pembrolizumab, atezolizumab, and ipilimumab, in which they estimated mortality at 60%. Also an extensive review of skin reactions caused by anti PD1 (pembrolizumab and nivolumab) consisted of 10 cases published in the literature and included SSJ, TEN, and erythema multiforme [8].…”

“…However, they can lead to lifethreatening severe cutaneous adverse reactions (SCARs) such as: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Fortunately, these severe cutaneous reactions are infrequent but a quick recognition of them can significantly decrease their mortality [5].…”