Nivolumab-Induced Toxic Epidermal Necrolysis: Rare but Fatal Complication of Immune Checkpoint Inhibitor Therapy

Abstract

Toxic epidermal necrolysis (TEN) is a rare, but potentially fatal dermatological emergency most commonly caused by medication exposure. It is characterized by skin desquamation affecting over 30% of the body, and it remains a fatal condition with a high mortality rate. Nivolumab, an immune checkpoint inhibitor used in the treatment of various types of malignancies, has been linked to TEN. Nivolumab-induced TEN is a rare phenomenon with a low incidence rate in patients treated with a single-agent immune checkpoint inhibitor, but it has a high mortality rate that exceeds non-nivolumab-induced TEN. Nivolumab-induced TEN can present with many potential complications such as hemodynamic instability from excessive fluid loss, sepsis from bacterial superinfection, and disseminated intravascular coagulation. Due to its high mortality rate, prompt recognition of the condition, immediate withdrawal of the offending drug(s), vigorous skin care, multispecialty collaboration, and close monitoring of complications is needed. We present a case of nivolumab-induced TEN in an elderly male with a history of hepatocellular carcinoma who presented with acute-onset skin desquamation after nivolumab initiation.

Steven-Johnson Syndrome: A Rare but Serious Adverse Event of Nivolumab Use in a Patient With Metastatic Gastric Adenocarcinoma

“…Table 3 outlines baseline patient characteristics, latency onset, the clinical presentation of SJS/TEN, and outcome and management for each patient. Seven cases were SJS, while TEN was diagnosed in three cases [ 12 , 13 , 15 ], and one case was an SJS/TEN overlap in keeping with our reported patient [ 17 ].…”

“…An extensive review published by Maloney et al [4] identified a total of 18 patients with SJS/TEN following treatment with different anti-PD-1 agents (pembrolizumab, ipilimumab, nivolumab, and atezolizumab) [4]. We conducted a comprehensive search to identify nivolumab-induced SJS and/or TEN cases (either as a mono- therapy or combination therapy), which yielded 11 patients [12][13][14][15][16][17][18][19][20][21][22]. One patient was managed with dual therapy with ipilimumab, and one was treated with nivolumab after the failure of ipilimumab.…”

“…Furthermore, a recent meta-analysis has reported a beneficial role for cyclosporin (CsA) in SJS/TEN management, as CsA may block the cytotoxic T cells-induced epithelial cell injury [ 26 ]. TEN was associated with much worse mortality rates as all four patients with TEN died from polymicrobial sepsis and progression of the underlying malignancies [ 12 , 13 , 15 , 17 ].…”

Immune checkpoint inhibitor‐induced epidermal necrolysis: A narrative review evaluating demographics, clinical features, and culprit medications

“…In total, 95 cases of ICI‐induced SJS/TEN were identified from 55 peer‐reviewed publications, with 35 cases of SJS, two cases of SJS/TEN overlap, and 26 cases of TEN 7–63 (Figure 1a and Supporting Information Table S1). The precise nomination of the remaining 32 cases as SJS, SJS/TEN overlap or TEN was not specified by authors of the above publications.…”