{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:25:16Z","timestamp":1793255116391,"version":"4.5.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u201387) 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2023.1134178","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T01:27:25Z","timestamp":1682645245000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome"],"prefix":"10.3389","volume":"14","author":[{"given":"Limor","family":"Rubin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aviv","family":"Talmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaarit","family":"Ribak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asa","family":"Kessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yossi","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal Keidar","family":"Haran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oded","family":"Shamriz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irit","family":"Adini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuval","family":"Tal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001655","article-title":"Acute liver Failure\/Injury related to drug reaction with eosinophilia and systemic symptoms: outcomes and prognostic factors","volume":"101","author":"Ichai","year":"2017","journal-title":"Transplantation"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2017.00179","article-title":"New insights into drug reaction with eosinophilia and systemic symptoms pathophysiology","volume":"4","author":"Musette","year":"2017","journal-title":"Front Med (Lausanne)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.3390\/ijms220311271127","article-title":"Drug reaction with eosinophilia and systemic symptoms: a complex interplay between drug, T cells, and herpesviridae","volume":"22","author":"Ganeshanandan","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12501","article-title":"Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. results from the prospective RegiSCAR study","volume":"169","author":"Kardaun","year":"2013","journal-title":"Br J Dermatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-018-00416-4","article-title":"Drug reaction with eosinophilia and systemic symptoms (DReSS): how far have we come","volume":"20","author":"Martinez-Cabriales","year":"2019","journal-title":"Am J Clin Dermatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/all.15283","article-title":"Targeting interleukin-5 with benralizumab: a novel treatment for drug rash with eosinophilia and systemic symptoms","volume":"77","author":"Maverakis","year":"2022","journal-title":"Allergy"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s40629-022-00224-7","article-title":"Treatment with IL5-\/IL-5 receptor antagonists in drug reaction with eosinophilia and systemic symptoms (DRESS)","author":"Gschwend","year":"2022","journal-title":"Allergo J Int"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2017.10.020","article-title":"Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome successfully treated with mepolizumab","volume":"6","author":"Ange","year":"2018","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2019-231355","article-title":"Mepolizumab rescue therapy for acute pneumonitis secondary to DRESS","volume":"12","author":"Thein","year":"2019","journal-title":"BMJ Case Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2021-242240e24224014\/7\/e242240","article-title":"Successful mepolizumab treatment for DRESS-induced refractory eosinophilic myocarditis and concurrent thyroiditis","volume":"14","author":"Truong","year":"2021","journal-title":"BMJ Case Rep"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1136\/bcr-2018-22646bcr2018226461","article-title":"DRESS syndrome-associated acute necrotizing eosinophilic myocarditis with giant cells","author":"Kowtoniuk","year":"2018","journal-title":"BMJ Case Rep"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1159\/000519471cro-0014-1548","article-title":"Successful treatment of imatinib-induced DRESS syndrome using reslizumab without cessation of imatinib: a case report","volume":"14","author":"Park","year":"2021","journal-title":"Case Rep Oncol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.jaip.2020.09.039","article-title":"Benralizumab for severe DRESS in two COVID-19 patients","volume":"9","author":"Schmid-Grendelmeier","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3529","DOI":"10.1016\/j.jaip.2021.06.047","article-title":"Benralizumab: a potential tailored treatment for life-threatening DRESS in the COVID-19 era","volume":"9","author":"Mesli","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2021.06.048","article-title":"Reply to \"Benralizumab: a potential tailored treatment for life-threatening DRESS in the COVID-19 era\"","volume":"9","author":"Lang","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-019-08775-4","article-title":"Targeted anti-IL-5 therapies and future therapeutics for hypereosinophilic syndrome and rare eosinophilic conditions","volume":"59","author":"Harish","year":"2020","journal-title":"Clin Rev Allergy Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2020.10.001","article-title":"The efficacy of off-label IL-5-modulating treatment in rare eosinophil-mediated diseases","volume":"70","author":"Shamriz","year":"2021","journal-title":"Allergol Int"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxp102dxp102","article-title":"IL-5- and eosinophil-mediated inflammation: from discovery to therapy","volume":"21","author":"Kouro","year":"2009","journal-title":"Int Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2015.02.005","article-title":"The betac receptor family - structural insights and their functional implications","volume":"74","author":"Broughton","year":"2015","journal-title":"Cytokine"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.148.4.dlt120002-c","article-title":"Poor benefit\/risk balance of intravenous immunoglobulins in DRESS","volume":"148","author":"Joly","year":"2012","journal-title":"Arch Dermatol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0733-7","article-title":"Targeted therapy guided by single-cell transcriptomic analysis in drug-induced hypersensitivity syndrome: a case report","volume":"26","author":"Kim","year":"2020","journal-title":"Nat Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2009.10.054","article-title":"Cyclophosphamide therapy for corticoresistant drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in a patient with severe kidney and eye involvement and Epstein-Barr virus reactivation","volume":"55","author":"Laban","year":"2010","journal-title":"Am J Kidney Dis"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2020.0048","article-title":"Evaluation of cyclosporine for the treatment of DRESS syndrome","volume":"156","author":"Nguyen","year":"2020","journal-title":"JAMA Dermatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/all.15056","article-title":"From DREAM to REALITI-a and beyond: mepolizumab for the treatment of eosinophil-driven diseases","volume":"77","author":"Pavord","year":"2022","journal-title":"Allergy"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1016\/j.jaip.2022.04.014","article-title":"Real-world effectiveness of reslizumab in patients with severe eosinophilic asthma - first initiators and switchers","volume":"10","author":"Hashimoto","year":"2022","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109131","article-title":"Efficacy and safety of treatment with benralizumab for eosinophilic asthma","volume":"111","author":"Zhu","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.18808","article-title":"Management and treatment outcome of DRESS patients in Europe: an international multicentre retrospective study of 141 cases","volume":"37","author":"Kridin","year":"2023","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.psym.2011.12.007","article-title":"The neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited","volume":"53","author":"Dubovsky","year":"2012","journal-title":"Psychosomatics"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11914-019-00498-x","article-title":"Glucocorticoid-induced osteoporosis: new insights into the pathophysiology and treatments","volume":"17","author":"Lane","year":"2019","journal-title":"Curr Osteoporos Rep"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.waojou.2022.100676100676","article-title":"Current and emerging biologic therapies targeting eosinophilic disorders","volume":"15","author":"Pitlick","year":"2022","journal-title":"World Allergy Organ J"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1134178\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T01:27:29Z","timestamp":1682645249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1134178\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,28]]},"references-count":30,"alternative-id":["10.3389\/fimmu.2023.1134178"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1134178","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,28]]},"article-number":"1134178"}}