BI12 Systematic review of checkpoint inhibitor-induced epidermal necrolysis: a clinical entity distinct from ‘classic’ Stevens–Johnson syndrome/toxic epidermal necrolysis

Abstract The use of immune checkpoint inhibitors in the treatment of cancer has transformed the prognosis and outcomes for patients with cancer. However, immune checkpoint inhibitor epidermal necrolysis (ICI-EN), a cutaneous immune-related adverse event, is associated with a high burden of morbidity and significant mortality. ICI-EN is clinically similar to ‘classic’ Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) but with distinctive distinguishing phenotypic features. As with SJS/TEN, the time to diagnosis and initiation of treatment are crucial in the management of ICI-EN. It is therefore important for dermatologists and oncologists to recognize the unique and idiosyncratic features of ICI-EN. To try to define these distinctions we performed a comprehensive review of the up-to-date literature. We reviewed all articles from 1 July 2019 to 1 March 2024 on the PubMed and MEDLINE database that contained original reports of ICI adverse events. We identified 39 patients who developed ICI-induced SJS/TEN following treatment with either pembrolizumab, nivolumab, atezolizumab or nivolumab–ipilimumab combination. Fifteen cases were diagnosed with SJS and 24 cases with TEN (including five patients with SJS/TEN overlap). The average time between drug initiation and reaction (latency) was 92 days (median 28). Overall, 69% (27 of 39) of the patients developed an inflammatory dermatosis prior to blistering. These dermatoses included eruptions with exanthematous, eczematous, lichenoid, psoriasiform or urticarial features. The mean length of prebullous dermatosis was 67 days (median 25). Although 29 of 39 cases documented mucosal involvement, they described lower-intensity mucosal inflammation than that which occurs in SJS/TEN. Lip crusting, when present, did not correlate with oral mucositis. Patients showed a positive response to corticosteroids, with 50% also receiving intravenous immunoglobulin. Three patients were successfully rechallenged with an ICI. Of these, one was given concurrent steroid and one a different class of ICI, without a further reaction. Six of the 39 patients died from ICI-EN (mortality rate 15%). All deaths occurred in patients with epidermal detachment of > 30% body surface area; no other features appeared to influence mortality, including ICI type, latency or length of prebullous phase. This review of recently published cases reinforces the concept that ICI-EN, although resembling SJS/TEN, possesses unique and idiosyncratic features. There is a need for a greater understanding of the clinical and immunological phenotype of ICI-EN, particularly the prebullous phase, to aid with prophylaxis and management.

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