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Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome
BACKGROUND: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe hypersensitivity reaction. Up-to-date treatment is based on withdrawal of medication, supportive care, and immunosuppression using high-dose corticosteroid (CS) therapy. However, evidence-based...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175640/ https://www.ncbi.nlm.nih.gov/pubmed/37187735 http://dx.doi.org/10.3389/fimmu.2023.1134178 |
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author | Rubin, Limor Talmon, Aviv Ribak, Yaarit Kessler, Asa Martin, Yossi Haran, Tal Keidar Shamriz, Oded Adini, Irit Tal, Yuval |
author_facet | Rubin, Limor Talmon, Aviv Ribak, Yaarit Kessler, Asa Martin, Yossi Haran, Tal Keidar Shamriz, Oded Adini, Irit Tal, Yuval |
author_sort | Rubin, Limor |
collection | PubMed |
description | BACKGROUND: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe hypersensitivity reaction. Up-to-date treatment is based on withdrawal of medication, supportive care, and immunosuppression using high-dose corticosteroid (CS) therapy. However, evidence-based data are lacking regarding second-line therapy for steroid-resistant or steroid-dependent patients. OBJECTIVES: We hypothesize that the interleukin (IL)-5 axis plays a critical role in the pathophysiology of DRESS; hence, inhibition of this signaling pathway could offer a potential therapy for steroid-dependent and/or steroid-resistant cases, and it may offer an alternative to CS therapy in certain patients more prone to CS toxicity. METHODS: Herein, we collected worldwide data on DRESS cases treated with biological agents targeting the IL-5 axis. We reviewed all cases indexed in PubMed up to October 2022 and performed a total analysis including our center experience with two additional novel cases. RESULTS: A review of the literature yielded 14 patients with DRESS who were treated with biological agents targeting the IL-5 axis as well as our two new cases. Reported patients are characterized by a female-to-male ratio of 1:1 and a mean age of 51.8 (17–87) years. The DRESS-inducing drugs, as expected from the prospective RegiSCAR study, were mostly antibiotics (7/16), as follows: vancomycin, trimethoprim-sulfamethoxazole, ciprofloxacin, piperacillin-tazobactam, and cefepime. DRESS patients were treated with anti-IL-5 agents (mepolizumab and reslizumab) or anti-IL-5 receptor (IL-5R) biologics (benralizumab). All patients have clinically improved under anti-IL-5/IL-5R biologics. Multiple doses of mepolizumab were needed to achieve clinical resolution, whereas a single dose of benralizumab was often sufficient. Relapse was noted in one patient receiving benralizumab treatment. One patient receiving benralizumab had a fatal outcome, although mortality was probably related to massive bleeding and cardiac arrest due to coronavirus disease 2019 (COVID-19) infection. CONCLUSION: Current treatment guidelines for DRESS are based on case reports and expert opinion. Understanding the central role of eosinophils in DRESS pathogenicity emphasizes the need for future implementation of IL-5 axis blockade as steroid-sparing agents, potential therapy to steroid-resistant cases, and perhaps an alternative to CS treatment in certain DRESS patients more prone to CS toxicity. |
format | Online Article Text |
id | pubmed-10175640 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101756402023-05-13 Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome Rubin, Limor Talmon, Aviv Ribak, Yaarit Kessler, Asa Martin, Yossi Haran, Tal Keidar Shamriz, Oded Adini, Irit Tal, Yuval Front Immunol Immunology BACKGROUND: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe hypersensitivity reaction. Up-to-date treatment is based on withdrawal of medication, supportive care, and immunosuppression using high-dose corticosteroid (CS) therapy. However, evidence-based data are lacking regarding second-line therapy for steroid-resistant or steroid-dependent patients. OBJECTIVES: We hypothesize that the interleukin (IL)-5 axis plays a critical role in the pathophysiology of DRESS; hence, inhibition of this signaling pathway could offer a potential therapy for steroid-dependent and/or steroid-resistant cases, and it may offer an alternative to CS therapy in certain patients more prone to CS toxicity. METHODS: Herein, we collected worldwide data on DRESS cases treated with biological agents targeting the IL-5 axis. We reviewed all cases indexed in PubMed up to October 2022 and performed a total analysis including our center experience with two additional novel cases. RESULTS: A review of the literature yielded 14 patients with DRESS who were treated with biological agents targeting the IL-5 axis as well as our two new cases. Reported patients are characterized by a female-to-male ratio of 1:1 and a mean age of 51.8 (17–87) years. The DRESS-inducing drugs, as expected from the prospective RegiSCAR study, were mostly antibiotics (7/16), as follows: vancomycin, trimethoprim-sulfamethoxazole, ciprofloxacin, piperacillin-tazobactam, and cefepime. DRESS patients were treated with anti-IL-5 agents (mepolizumab and reslizumab) or anti-IL-5 receptor (IL-5R) biologics (benralizumab). All patients have clinically improved under anti-IL-5/IL-5R biologics. Multiple doses of mepolizumab were needed to achieve clinical resolution, whereas a single dose of benralizumab was often sufficient. Relapse was noted in one patient receiving benralizumab treatment. One patient receiving benralizumab had a fatal outcome, although mortality was probably related to massive bleeding and cardiac arrest due to coronavirus disease 2019 (COVID-19) infection. CONCLUSION: Current treatment guidelines for DRESS are based on case reports and expert opinion. Understanding the central role of eosinophils in DRESS pathogenicity emphasizes the need for future implementation of IL-5 axis blockade as steroid-sparing agents, potential therapy to steroid-resistant cases, and perhaps an alternative to CS treatment in certain DRESS patients more prone to CS toxicity. Frontiers Media S.A. 2023-04-28 /pmc/articles/PMC10175640/ /pubmed/37187735 http://dx.doi.org/10.3389/fimmu.2023.1134178 Text en Copyright © 2023 Rubin, Talmon, Ribak, Kessler, Martin, Haran, Shamriz, Adini and Tal https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Rubin, Limor Talmon, Aviv Ribak, Yaarit Kessler, Asa Martin, Yossi Haran, Tal Keidar Shamriz, Oded Adini, Irit Tal, Yuval Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome |
title | Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome |
title_full | Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome |
title_fullStr | Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome |
title_full_unstemmed | Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome |
title_short | Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome |
title_sort | novel targeted inhibition of the il-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175640/ https://www.ncbi.nlm.nih.gov/pubmed/37187735 http://dx.doi.org/10.3389/fimmu.2023.1134178 |
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