{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:03:28Z","timestamp":1790622208380,"version":"4.1.0"},"reference-count":88,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,23]],"date-time":"2021-01-23T00:00:00Z","timestamp":1611360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug induced hypersensitivity (DiHS) syndrome is a severe delayed hypersensitivity reaction with potentially fatal consequences. Whilst recognised as T cell-mediated, our understanding of the immunopathogenesis of this syndrome remains incomplete. Here, we discuss models of DRESS, including the role of human leukocyte antigen (HLA) and how observations derived from new molecular techniques adopted in key studies have informed our mechanism-based understanding of the central role of Herpesviridae reactivation and heterologous immunity in these disorders.<\/jats:p>","DOI":"10.3390\/ijms22031127","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T02:07:00Z","timestamp":1611540420000},"page":"1127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Drug Reaction with Eosinophilia and Systemic Symptoms: A Complex Interplay between Drug, T Cells, and Herpesviridae"],"prefix":"10.3390","volume":"22","author":[{"given":"Luckshman","family":"Ganeshanandan","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology, Sir Charles Gairdner Hospital, Perth, WA 6009, Australia"},{"name":"PathWest Laboratory Medicine WA, Queen Elizabeth II Medical Centre, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Lucas","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Sir Charles Gairdner Hospital, Perth, WA 6009, Australia"},{"name":"PathWest Laboratory Medicine WA, Queen Elizabeth II Medical Centre, Perth, WA 6009, Australia"},{"name":"Faculty of Health and Medical Sciences, UWA Medical School, University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hakkarainen, K.M., Hedna, K., Petzold, M., and H\u00e4gg, S. (2012). Percentage of patients with preventable adverse drug reactions and preventability of adverse drug reactions\u2014A meta-analysis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033236"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1345\/aph.1L037","article-title":"Hospital admissions associated with adverse drug reactions: A systematic review of prospective observational studies","volume":"42","author":"Kongkaew","year":"2008","journal-title":"Ann. Pharmacother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1001\/jama.279.15.1200","article-title":"Incidence of Adverse Drug Reactions in Hospitalized PatientsA Meta-analysis of Prospective Studies","volume":"279","author":"Lazarou","year":"1998","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1136\/bmj.329.7456.15","article-title":"Adverse drug reactions as cause of admission to hospital: Prospective analysis of 18 820 patients","volume":"329","author":"Pirmohamed","year":"2004","journal-title":"BMJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1345\/aph.10094","article-title":"Clinical and economic impact of adverse drug reactions in hospitalized patients","volume":"34","author":"Suh","year":"2000","journal-title":"Ann. Pharmacother."},{"key":"ref_6","unstructured":"Davies, D.M. (1977). Textbook of Adverse Drug Reactions, Oxford University Press."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/S0140-6736(00)02799-9","article-title":"Adverse drug reactions: Definitions, diagnosis, and management","volume":"356","author":"Edwards","year":"2000","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.2217\/pgs.12.108","article-title":"HLA and pharmacogenetics of drug hypersensitivity","volume":"13","author":"Pavlos","year":"2012","journal-title":"Pharmacogenomics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1212\/WNL.49.2.542","article-title":"Risk of serious cutaneous disorders after initiation of use of phenytoin, carbamazepine, or sodium valproate: A record linkage study","volume":"49","author":"Tennis","year":"1997","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1111\/j.1528-1157.1999.tb00807.x","article-title":"Lamotrigine-associated rash: Risk\/benefit considerations in adults and children","volume":"40","author":"Guberman","year":"1999","journal-title":"Epilepsia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.jaad.2013.11.053","article-title":"Comments on: DRESS syndrome","volume":"71","author":"Kardaun","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"46ra62","DOI":"10.1126\/scitranslmed.3001116","article-title":"Drug reaction with eosinophilia and systemic symptoms (DRESS): A multiorgan antiviral T cell response","volume":"2","author":"Picard","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1111\/j.1365-2133.2007.07807.x","article-title":"The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations","volume":"156","author":"Shiohara","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/sj.bjp.0704074","article-title":"Antigenicity and immunogenicity of sulphamethoxazole: Demonstration of metabolism-dependent haptenation and T-cell proliferation in vivo","volume":"133","author":"Naisbitt","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0300-483X(00)00397-8","article-title":"Metabolic activation in drug allergies","volume":"158","author":"Park","year":"2001","journal-title":"Toxicology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1034\/j.1398-9995.2002.02161.x","article-title":"Pathogenesis of drug-induced exanthems","volume":"57","author":"Pichler","year":"2002","journal-title":"Allergy"},{"key":"ref_17","first-page":"12","article-title":"Hypersensitivity reactions to \u03b2-lactams: Relevance of hapten-protein conjugates","volume":"25","author":"Ariza","year":"2015","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1124\/jpet.111.190900","article-title":"Characterization of the antigen specificity of T-cell clones from piperacillin-hypersensitive patients with cystic fibrosis","volume":"341","author":"Monshi","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1097\/WOX.0b013e3181778282","article-title":"The p-i Concept: Pharmacological Interaction of Drugs With Immune Receptors","volume":"1","author":"Pichler","year":"2008","journal-title":"World Allergy Organ J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2174\/1573395510666140407212357","article-title":"Interaction of Small Molecules with Specific Immune Receptors: The p-i Concept and its Consequences","volume":"10","author":"Pichler","year":"2014","journal-title":"Curr. Immunol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1172\/JCI119505","article-title":"Direct, MHC-dependent presentation of the drug sulfamethoxazole to human alphabeta T cell clones","volume":"100","author":"Schnyder","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/nature11147","article-title":"Immune self-reactivity triggered by drug-modified HLA-peptide repertoire","volume":"486","author":"Illing","year":"2012","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9959","DOI":"10.1073\/pnas.1207934109","article-title":"Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire","volume":"109","author":"Ostrov","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1345\/aph.1E202","article-title":"Updated clinical risk factor analysis of suspected hypersensitivity reactions to abacavir","volume":"38","author":"Cutrell","year":"2004","journal-title":"Ann. Pharmacother."},{"key":"ref_25","first-page":"222","article-title":"A near-fatal hypersensitivity reaction to abacavir: Case report and literature review","volume":"11","author":"Shapiro","year":"2001","journal-title":"AIDS Read."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1002\/eji.201142159","article-title":"Avidity determines T-cell reactivity in abacavir hypersensitivity","volume":"42","author":"Adam","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Adam, J., Wuillemin, N., Watkins, S., Jamin, H., Eriksson, K.K., Villiger, P., Fontana, S., Pichler, W.J., and Yerly, D. (2014). Abacavir induced T cell reactivity from drug na\u00efve individuals shares features of allo-immune responses. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095339"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10523","DOI":"10.1038\/s41598-019-47001-1","article-title":"The Role of Conformational Dynamics in Abacavir-Induced Hypersensitivity Syndrome","volume":"9","author":"Fodor","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0140-6736(02)08158-8","article-title":"Genetic variations in HLA-B region and hypersensitivity reactions to abacavir","volume":"359","author":"Hetherington","year":"2002","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0140-6736(02)07873-X","article-title":"Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir","volume":"359","author":"Mallal","year":"2002","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1086\/529382","article-title":"High Sensitivity of Human Leukocyte Antigen-B*5701 as a Marker for Immunologically Confirmed Abacavir Hypersensitivity in White and Black Patients","volume":"46","author":"Saag","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s00228-011-1009-4","article-title":"Strong association between HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in mainland Han Chinese patients","volume":"67","author":"Zhang","year":"2011","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jaci.2019.01.045","article-title":"HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms","volume":"144","author":"Konvinse","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1093\/hmg\/ddq537","article-title":"Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population","volume":"20","author":"Takeshi","year":"2011","journal-title":"Human Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Agrawal, B. (2019). Heterologous Immunity: Role in Natural and Vaccine-Induced Resistance to Infections. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02631"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nri820","article-title":"No one is naive: The significance of heterologous T-cell immunity","volume":"2","author":"Welsh","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.0105-2896.2010.00897.x","article-title":"Heterologous immunity between viruses","volume":"235","author":"Welsh","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jaci.2015.05.050","article-title":"Evolving models of the immunopathogenesis of T cell-mediated drug allergy: The role of host, pathogens, and drug response","volume":"136","author":"White","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3146","DOI":"10.1182\/blood-2009-07-234906","article-title":"Allo-HLA reactivity of virus-specific memory T cells is common","volume":"115","author":"Amir","year":"2010","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1097\/TP.0b013e318207944c","article-title":"Tissue Specificity of Cross-Reactive Allogeneic Responses by EBV EBNA3A-Specific Memory T Cells","volume":"91","author":"Roelen","year":"2011","journal-title":"Transplantation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1097\/00007890-199707150-00034","article-title":"Tissue-specific Characteristics of Cytotoxic Grafit-infiltrating T Cells during Renal Allograft Rejection1","volume":"64","author":"Deckers","year":"1997","journal-title":"Transplantation"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.jaci.2019.05.009","article-title":"Virus-specific T-cell clonotypes might contribute to drug hypersensitivity reactions through heterologous immunity","volume":"144","author":"Almeida","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lucas, A., Lucas, M., Strhyn, A., Keane, N.M., McKinnon, E., Pavlos, R., Moran, E.M., Meyer-Pannwitt, V., Gaudieri, S., and D\u2019Orsogna, L. (2015). Abacavir-reactive memory T cells are present in drug na\u00efve individuals. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117160"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1084\/jem.20050882","article-title":"Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects","volume":"202","author":"Sylwester","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1006\/viro.2000.0697","article-title":"Direct measurement of CD4+ and CD8+ T-cell responses to CMV in HIV-1-infected subjects","volume":"279","author":"Komanduri","year":"2001","journal-title":"Virology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.humimm.2004.02.014","article-title":"CD8(+) T-cell immunity to cytomegalovirus","volume":"65","author":"Moss","year":"2004","journal-title":"Hum. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cell.2007.01.048","article-title":"How a Single T Cell Receptor Recognizes Both Self and Foreign MHC","volume":"129","author":"Colf","year":"2007","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1111\/j.1365-2133.2006.07332.x","article-title":"Reactivation of human herpesvirus (HHV) family members other than HHV-6 in drug-induced hypersensitivity syndrome","volume":"155","author":"Seishima","year":"2006","journal-title":"Br. J. Dermatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1111\/j.1365-2133.2007.08167.x","article-title":"Association of human herpesvirus 6 reactivation with the flaring and severity of drug-induced hypersensitivity syndrome","volume":"157","author":"Tohyama","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1365-2133.2006.07238.x","article-title":"Several herpesviruses can reactivate in a severe drug-induced multiorgan reaction in the same sequential order as in graft-versus-host disease","volume":"155","author":"Kano","year":"2006","journal-title":"Br. J. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2332\/allergolint.55.1","article-title":"Drug-induced hypersensitivity syndrome (DIHS): A reaction induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses","volume":"55","author":"Shiohara","year":"2006","journal-title":"Allergol. Int."},{"key":"ref_52","first-page":"301","article-title":"Association of human herpesvirus 6 infection with drug reaction with eosinophilia and systemic symptoms","volume":"137","author":"Descamps","year":"2001","journal-title":"Arch. Dermatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9913","DOI":"10.1038\/srep09913","article-title":"Association of CD8(+) T lymphocyte repertoire spreading with the severity of DRESS syndrome","volume":"5","author":"Niu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1126\/science.2876520","article-title":"Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders","volume":"234","author":"Salahuddin","year":"1986","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2340\/00015555-2791","article-title":"Predominant Contribution of CD4 T Cells to Human Herpesvirus 6 (HHV-6) Load in the Peripheral Blood of Patients with Drug-induced Hypersensitivity Syndrome and Persistent HHV-6 Infection","volume":"98","author":"Miyagawa","year":"2018","journal-title":"Acta Derm. Venereol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41525-018-0064-5","article-title":"HHV-6 encoded small non-coding RNAs define an intermediate and early stage in viral reactivation","volume":"3","author":"Prusty","year":"2018","journal-title":"npj Genom. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8071","DOI":"10.4049\/jimmunol.0804002","article-title":"Defective regulatory T cells in patients with severe drug eruptions: Timing of the dysfunction is associated with the pathological phenotype and outcome","volume":"182","author":"Takahashi","year":"2009","journal-title":"J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1016\/j.lfs.2005.01.003","article-title":"Carbamazepine is an inhibitor of histone deacetylases","volume":"76","author":"Beutler","year":"2005","journal-title":"Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"36734","DOI":"10.1074\/jbc.M101287200","article-title":"Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen","volume":"276","author":"Phiel","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"236","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":"ref_61","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jdermsci.2016.05.001","article-title":"Preferential expression of CD134, an HHV-6 cellular receptor, on CD4T cells in drug-induced hypersensitivity syndrome (DIHS)\/drug reaction with eosinophilia and systemic symptoms (DRESS)","volume":"83","author":"Miyagawa","year":"2016","journal-title":"J. Dermatol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5163129","DOI":"10.1155\/2018\/5163129","article-title":"Recent Advances in Drug-Induced Hypersensitivity Syndrome\/Drug Reaction with Eosinophilia and Systemic Symptoms","volume":"2018","author":"Watanabe","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"10149","DOI":"10.1128\/JVI.75.21.10149-10160.2001","article-title":"The R3 Region, One of Three Major Repetitive Regions of Human Herpesvirus 6, Is a Strong Enhancer of Immediate-Early Gene U95","volume":"75","author":"Takemoto","year":"2001","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"S123","DOI":"10.1016\/S1386-6532(02)00088-4","article-title":"A model for reactivation of CMV from latency","volume":"25","author":"Hummel","year":"2002","journal-title":"J. Clin. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jdermsci.2014.01.007","article-title":"TNF-\u03b1 as a useful predictor of human herpesvirus-6 reactivation and indicator of the disease process in drug-induced hypersensitivity syndrome (DIHS)\/drug reaction with eosinophilia and systemic symptoms (DRESS)","volume":"74","author":"Uno","year":"2014","journal-title":"J. Dermatol. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jdermsci.2013.07.003","article-title":"Occupational trichloroethylene hypersensitivity syndrome: Human herpesvirus 6 reactivation and rash phenotypes","volume":"72","author":"Kamijima","year":"2013","journal-title":"J. Dermatol. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1111\/cea.13252","article-title":"Monocytes are involved in the balance between regulatory T cells and Th17 cells in severe drug eruptions","volume":"48","author":"Ushigome","year":"2018","journal-title":"Clin. Exp. Allergy"},{"key":"ref_68","first-page":"139","article-title":"Drug reaction with eosinophilia and systemic symptoms (DRESS): Incidence, pathogenesis and management","volume":"16","author":"Shiohara","year":"2017","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1399-3038.2012.01268.x","article-title":"The association between DRESS and the diminished numbers of peripheral B lymphocytes and natural killer cells","volume":"23","author":"Yazicioglu","year":"2012","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jaad.2006.02.050","article-title":"Hypogammaglobulinemia as an early sign of drug-induced hypersensitivity syndrome","volume":"55","author":"Kano","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1001\/archderm.140.2.183","article-title":"Association between anticonvulsant hypersensitivity syndrome and human herpesvirus 6 reactivation and hypogammaglobulinemia","volume":"140","author":"Kano","year":"2004","journal-title":"Arch. Dermatol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Omenetti, S., and Pizarro, T.T. (2015). The Treg\/Th17 Axis: A Dynamic Balance Regulated by the Gut Microbiome. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00639"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"17675","DOI":"10.1038\/s41598-019-53240-z","article-title":"IL-23 induces regulatory T cell plasticity with implications for inflammatory skin diseases","volume":"9","author":"Kannan","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jdermsci.2012.10.002","article-title":"Identification of thymus and activation-regulated chemokine (TARC\/CCL17) as a potential marker for early indication of disease and prediction of disease activity in drug-induced hypersensitivity syndrome (DIHS)\/drug rash with eosinophilia and systemic symptoms (DRESS)","volume":"69","author":"Ogawa","year":"2013","journal-title":"J. Dermatol. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/S0167-5699(98)01346-2","article-title":"Chemokines and chemokine receptors in T-cell priming and Th1\/Th2-mediated responses","volume":"19","author":"Sallusto","year":"1998","journal-title":"Immunol. Today"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1084\/jem.194.6.847","article-title":"Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells","volume":"194","author":"Iellem","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.alit.2016.06.003","article-title":"Serum TARC levels are strongly correlated with blood eosinophil count in patients with drug eruptions","volume":"66","author":"Kaneko","year":"2017","journal-title":"Allergol. Int."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1111\/bjd.16132","article-title":"Serum thymus and activation-regulated chemokine is associated with the severity of drug reaction with eosinophilia and systemic symptoms\/drug-induced hypersensitivity syndrome","volume":"178","author":"Miyagawa","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1684\/ejd.2014.2477","article-title":"Differential expression profile of Th1\/Th2-associated chemokines characterizes Stevens-Johnson syndrome\/toxic epidermal necrolysis (SJS\/TEN) and drug-induced hypersensitivity syndrome\/drug reaction with eosinophilia and systemic symptoms (DIHS\/DRESS) as distinct entities","volume":"25","author":"Miyagawa","year":"2015","journal-title":"Eur. J. Dermatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.alit.2017.06.001","article-title":"The thymus and activation-regulated chemokine (TARC) level in serum at an early stage of a drug eruption is a prognostic biomarker of severity of systemic inflammation","volume":"67","author":"Chinuki","year":"2018","journal-title":"Allergol. Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1159\/000475546","article-title":"Skin-Homing IL-13-Producing T Cells Expand in the Circulation of Patients with Drug Rash with Eosinophilia and Systemic Symptoms","volume":"233","author":"Teraki","year":"2017","journal-title":"Dermatology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1016\/j.jid.2018.10.048","article-title":"Increased Type 2 Innate Lymphoid Cells in Patients with Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome","volume":"139","author":"Tsai","year":"2019","journal-title":"J. Investig. Dermatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.5415\/apallergy.2020.10.e2","article-title":"Altered T cell and monocyte subsets in prolonged immune reconstitution inflammatory syndrome related with DRESS (drug reaction with eosinophilia and systemic symptoms)","volume":"10","author":"Kang","year":"2020","journal-title":"Asia Pac. Allergy"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1059","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":"ref_85","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.jdcr.2019.07.004","article-title":"Drug-induced hypersensitivity syndrome with myocardial involvement treated with tofacitinib","volume":"5","author":"Damsky","year":"2019","journal-title":"JAAD Case Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/1346-8138.14776","article-title":"Drug-induced hypersensitivity syndrome\/drug reaction with eosinophilia and systemic symptoms due to lamotrigine differs from that due to other drugs","volume":"46","author":"Tashiro","year":"2019","journal-title":"J. Dermatol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Hammond, C.L., Roztocil, E., Phipps, R.P., Feldon, S.E., and Woeller, C.F. (2019). Proton pump inhibitors attenuate myofibroblast formation associated with thyroid eye disease through the aryl hydrocarbon receptor. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222779"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Rochman, M., Xie, Y.M., Mack, L., Caldwell, J.M., Klingler, A.M., Osswald, G.A., Azouz, N.P., and Rothenberg, M.E. (2020). Broad Transcriptional Response of the Human Esophageal Epithelium to Proton Pump Inhibitors. J. Allergy Clin. Immunol., in press.","DOI":"10.1016\/j.jaci.2020.09.039"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1127\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:14:34Z","timestamp":1760159674000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,23]]},"references-count":88,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22031127"],"URL":"https:\/\/doi.org\/10.3390\/ijms22031127","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,23]]}}}