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

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but can cause immune-related adverse events (irAEs). Severe cutaneous irAEs, including epidermal necrolysis, are rare but potentially life-threatening. There is limited understanding of the clinical features and management of ICI-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), so we aimed to analyze 95 cases of ICI-induced SJS/TEN (35 cases of SJS, 26 cases of TEN, two cases of SJS/TEN overlap, and 32 cases of unspecified) to increase knowledge of this condition among oncologists and dermatologists. We conducted a comprehensive search of PubMed for all relevant case reports published until the end of December 2022, and collected data on patient demographics, cancer type, ICI regimen, time to onset of SJS/TEN, clinical presentation, management strategies, and outcomes. PD-1 inhibitors were the most common ICIs associated with SJS/TEN (58.9%), followed by the combination of PD-1 and CTLA-4 inhibitors (11.6%), and PD-L1 inhibitors (6.3%). Lung cancer and melanoma were the most frequent malignancies treated (35.8% and 25.4%, respectively). SJS/TEN occurred most frequently within the first 4 weeks (51.7%), and corticosteroid monotherapy was the most commonly chosen systemic treatment (56.4%). The overall mortality rate of ICI-induced SJS/TEN was 30.8%. Our findings highlight the frequency and severity of ICI-induced SJS/TEN and the urgent need for predictive molecular biomarkers aimed at preventive measures and early intervention.

Automated summary

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but they can also lead to immune-related adverse events (irAEs), including severe cutaneous reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). This study analyzed 95 cases of ICI-induced SJS/TEN and found that PD-1 inhibitors were most commonly associated with these reactions. SJS/TEN typically occurred within the first 4 weeks of treatment, and corticosteroid monotherapy was the most frequently chosen treatment approach. The overall mortality rate of ICI-induced SJS/TEN was high.