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      Pembrolizumab-Induced Toxic Epidermal Necrolysis

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          Abstract

          Immunotherapy has nowadays become part of the mainstay of treatment for several cancers. In this report, we present a case of toxic epidermal necrolysis (TEN) occurring as a relatively rare complication of pembrolizumab, which is a humanized monoclonal anti-programmed cell death-1 (anti-PD1) IgG4 antibody that targets tumours expressing PDL-1. In our case, this monoclonal antibody (MAB) was being used for the treatment of metastatic non-small cell lung cancer, before being withheld because of this potentially life-threatening reaction. There are no guidelines on the optimal management of TEN, with varying reports on the efficacy on steroids, intravenous immunoglobulin (IVIG), and cyclosporin. In this report, we describe a case of TEN following the second dose of three-weekly pembrolizumab in a 50-year-old man, comparing it to four similar cases reported in the literature. It is important that oncologists are aware of this potentially life-threatening adverse reaction of pembrolizumab, as early recognition and treatment of TEN are essential to improve clinical outcome.

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          SCORTEN: a severity-of-illness score for toxic epidermal necrolysis.

          The mortality of toxic epidermal necrolysis is about 30%. Our purpose was to develop and validate a specific severity-of-illness score for cases of toxic epidermal necrolysis admitted to a specialized unit and to compare it with the Simplified Acute Physiology Score and a burn scoring system. A sample of 165 patients was used to develop the toxic epidermal necrolysis-specific severity-of-illness score and evaluate the other scores, a sample of 75 for validation. Model development used logistic regression equations that were translated into probability of hospital mortality; validation used measures of calibration and discrimination. We identified seven independent risk factors for death and constituted the toxic epidermal necrolysis-specific severity-of-illness score: age above 40 y, malignancy, tachycardia above 120 per min, initial percentage of epidermal detachment above 10%, serum urea above 10 mmol per liter, serum glucose above 14 mmol per liter, and bicarbonate below 20 mmol per liter. For each toxic epidermal necrolysis-specific severity-of-illness score point the odds ratio was 3.45 (confidence interval 2.26-5.25). Probability of death was: P(death) = elogit/1 + elogit with logit = -4.448 + 1.237 (toxic epidermal nec-rolysis-specific severity-of-illness score). Calibration demonstrated excellent agreement between expected (19. 6%) and actual (20%) mortality; discrimination was also excellent with a receiver operating characteristic area of 82%. The Simplified Acute Physiology Score and the burn score were also associated with mortality. The discriminatory powers were poorer (receiver operating characteristic area: 72 and 75%) and calibration of the Simplified Acute Physiology Score indicated a poor agreement between expected (9.1%) and actual (26.7%) mortality. This study demonstrates that the risk of death of toxic epidermal necrolysis patients can be accurately predicted by the toxic epidermal necrolysis-specific severity-of-illness score. The Simplified Acute Physiology Score and burn score appear to be less adequate.
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            Pembrolizumab Cutaneous Adverse Events and Their Association With Disease Progression.

            Immunomodulatory anticancer drugs, such as the anti-programmed death-1 drug pembrolizumab, have shown promising results in trials, and more patients will receive such treatments. Little is known about cutaneous adverse events (AEs) caused by these drugs and their possible correlation with treatment response.
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              Cytotoxic Cutaneous Adverse Drug Reactions during Anti-PD-1 Therapy

              Immunotherapy has experienced impressive progress in cancer treatment. Antibodies against PD-1 improved survival in different types of cancer including melanoma. They are generally well tolerated. However, skin toxicities including pruritus, rashes, and vitiligo are reported. Although frequent, they have not been characterized further yet. In this analysis, we aimed to systematically assess and characterize the adverse cutaneous reactions observed in patients with melanoma treated with anti-PD-1 antibodies.
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                Author and article information

                Journal
                Case Rep Oncol
                Case Rep Oncol
                CRO
                Case Reports in Oncology
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                1662-6575
                Sep-Dec 2022
                3 October 2022
                3 October 2022
                : 15
                : 3
                : 887-893
                Affiliations
                [1] aDepartment of Medicine, Mater Dei Hospital, Msida, Malta
                [2] bDepartment of Oncology, Sir Anthony Mamo Oncology Centre, Msida, Malta
                [3] cDepartment of Pathology, Mater Dei Hospital, Msida, Malta
                [4] dDepartment of Dermatology, Mater Dei Hospital, Msida, Malta
                Author notes
                Article
                cro-0015-0887
                10.1159/000526931
                9941788
                36825108
                82bdca47-2699-421f-9c8b-979409f8a5af
                Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 2 August 2022
                : 30 August 2022
                : 2022
                Page count
                Figures: 3, Tables: 1, References: 12, Pages: 7
                Funding
                The submission and publishing of this case report is not sponsored, and the authors have no funding sources to declare.
                Categories
                Case Report

                Oncology & Radiotherapy
                pembrolizumab,toxic epidermal necrolysis,steroids,intravenous immuoglobulin,cyclosporin,non-small cell lung cancer,immunotherapy

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