{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:25:04Z","timestamp":1790742304675,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T00:00:00Z","timestamp":1613865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health and Labor Sciences Research Grants (Research on Intractable Diseases) from the Ministry of Health, Labor and Welfare of Japan","award":["20FC1035"],"award-info":[{"award-number":["20FC1035"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Drug-induced hypersensitivity syndrome\/drug reaction with eosinophilia and systemic symptoms (DIHS\/DRESS) is a severe type of adverse drug eruption associated with multiorgan involvement and the reactivation of human herpesvirus 6, which arises after prolonged exposure to certain drugs. Typically, two waves of disease activity occur during the course of DIHS\/DRESS; however, some patients experience multiple waves of exacerbation and remission of the disease. Severe complications, some of which are related to cytomegalovirus reactivation, can be fatal. DIHS\/DRESS is distinct from other drug reactions, as it involves herpes virus reactivation and can lead to the subsequent development of autoimmune diseases. The association between herpesviruses and DIHS\/DRESS is now well established, and DIHS\/DRESS is considered to arise as a result of complex interactions between several herpesviruses and comprehensive immune responses, including drug-specific immune responses and antiviral immune responses, each of which may be mediated by distinct types of immune cells. It appears that both CD4 and CD8 T cells are involved in the pathogenesis of DIHS\/DRESS but play distinct roles. CD4 T cells mainly initiate drug allergies in response to drug antigens, and then herpesvirus-specific CD8 T cells that target virus-infected cells emerge, resulting in tissue damage. Regulatory T-cell dynamics are also suggested to contribute to the diverse symptoms of DIHS\/DRESS. However, the pathomechanisms of this complex disease remain largely unknown. In particular, how viral infections contribute to the pathogenesis of DIHS\/DRESS and why autoimmune sequelae arise in DIHS\/DRESS are yet to be elucidated. This review describes the clinical features of DIHS\/DRESS, including the associated complications and sequelae, and discusses recent advances in our understanding of the immunopathogenic mechanisms of DIHS\/DRESS.<\/jats:p>","DOI":"10.3390\/ijms22042147","type":"journal-article","created":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T22:04:15Z","timestamp":1613945055000},"page":"2147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Current Perspective Regarding the Immunopathogenesis of Drug-Induced Hypersensitivity Syndrome\/Drug Reaction with Eosinophilia and Systemic Symptoms (DIHS\/DRESS)"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2030-6969","authenticated-orcid":false,"given":"Fumi","family":"Miyagawa","sequence":"first","affiliation":[{"name":"Department of Dermatology, Nara Medical University School of Medicine, Nara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1971-9835","authenticated-orcid":false,"given":"Hideo","family":"Asada","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Nara Medical University School of Medicine, Nara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,21]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/j.1365-2133.2006.07704.x","article-title":"Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: Does a DRESS syndrome really exist?","volume":"156","author":"Kardaun","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/S1085-5629(96)80038-1","article-title":"Drug-induced pseudolymphoma and drug hypersensitivity syndrome (drug rash with eosinophilia and systemic symptoms: DRESS)","volume":"15","author":"Bocquet","year":"1996","journal-title":"Semin. Cutan. Med. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.alit.2019.03.006","article-title":"Drug-induced hypersensitivity syndrome (DiHS)\/drug reaction with eosinophilia and systemic symptoms (DRESS): An update in 2019","volume":"68","author":"Shiohara","year":"2019","journal-title":"Allergol. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6431694","DOI":"10.1155\/2018\/6431694","article-title":"An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity","volume":"2018","author":"Chen","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1016\/j.amjmed.2011.10.027","article-title":"Human herpesvirus 6 reactivation in drug-induced hypersensitivity syndrome and DRESS validation score","volume":"125","author":"Ushigome","year":"2012","journal-title":"Am. J. Med."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"1071","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":"ref_9","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/j.1365-2133.1997.tb03795.x","article-title":"Human herpesvirus 6 infection associated with anticonvulsant hypersensitivity syndrome and reactive haemophagocytic syndrome","volume":"137","author":"Descamps","year":"1997","journal-title":"Br. J. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1001\/archderm.134.9.1108","article-title":"Human Herpesvirus 6 Infection as a Risk Factor for the Development of Severe Drug-Induced Hypersensitivity Syndrome","volume":"134","author":"Suzuki","year":"1998","journal-title":"Arch. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1001\/archderm.134.9.1113","article-title":"Severe hypersensitivity syndrome due to sulfasala-zine associated with reactivation of human herpesvirus 6","volume":"134","author":"Tohyama","year":"1998","journal-title":"Arch. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e229","DOI":"10.1016\/j.jaad.2010.11.057","article-title":"A review of DRESS-associated myocarditis","volume":"66","author":"Bourgeois","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1001\/archdermatol.2009.195","article-title":"Cytomegalovirus disease during severe drug eruptions: Report of 2 cases and ret-rospective study of 18 patients with drug-induced hypersensitivity syndrome","volume":"145","author":"Asano","year":"2009","journal-title":"Arch. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.jaad.2018.08.052","article-title":"Drug-induced hypersensitivity syndrome\/drug reaction with eosinophilia and systemic symptoms severity score: A useful tool for assessing disease severity and predicting fatal cytomegalovirus disease","volume":"80","author":"Mizukawa","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/all.12602","article-title":"Human herpes virus reactivations and dynamic cytokine profiles in patients with cutaneous adverse drug reactions\u2014A prospective comparative study","volume":"70","author":"Chen","year":"2015","journal-title":"Allergy"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.jaad.2012.08.009","article-title":"Long-term sequelae of drug reaction with eosinophilia and systemic symptoms: A retrospective cohort study from Taiwan","volume":"68","author":"Chen","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/1346-8138.12770","article-title":"Sequelae in 145 patients with drug-induced hyper-sensitivity syndrome\/drug reaction with eosinophilia and systemic symptoms: Survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR)","volume":"42","author":"Kano","year":"2015","journal-title":"J. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1111\/j.1365-2133.2007.07784.x","article-title":"Sclerodermoid graft-versus-host disease-like lesions occurring after drug-induced hypersensi-tivity syndrome","volume":"156","author":"Kano","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e310","DOI":"10.1111\/1346-8138.14333","article-title":"Drug-induced hypersensitivity syndrome followed by chronic inflammatory demyelinating polyneuropathy","volume":"45","author":"Iinuma","year":"2018","journal-title":"J. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"bcr2018225528","DOI":"10.1136\/bcr-2018-225528","article-title":"Aggressive treatment in paediatric or young patients with drug-induced hyper-sensitivity syndrome (DiHS)\/drug reaction with eosinophilia and systemic symptoms (DRESS) is associated with future de-velopment of type III polyglandular autoimmune syndrome","volume":"2018","author":"Morita","year":"2018","journal-title":"BMJ Case Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1111\/bjd.18942","article-title":"The interferon-gamma-induced protein 10\/CXCR3 axis is associated with human herpesvirus-6 reactivation and the development of sequelae in drug reaction with eosinophilia and systemic symptoms","volume":"183","author":"Yang","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1111\/j.1398-9995.2004.00547.x","article-title":"The lymphocyte transformation test in the diagnosis of drug hypersensitivity","volume":"59","author":"Pichler","year":"2004","journal-title":"Allergy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1146\/annurev-med-050913-022745","article-title":"T Cell\u2013Mediated Hypersensitivity Reactions to Drugs","volume":"66","author":"Pavlos","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/eji.1830270602","article-title":"Penicilloyl peptides are recognized as T cell antigenic determi-nants in penicillin allergy","volume":"27","author":"Padovan","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1097\/00130832-200208000-00003","article-title":"Pharmacological interaction of drugs with antigen-specific immune receptors: The p-i concept","volume":"2","author":"Pichler","year":"2002","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1172\/JCI119505","article-title":"Direct, MHC-dependent presentation of the drug sulfameth-oxazole to human alphabeta T cell clones","volume":"100","author":"Schnyder","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1016\/j.jaci.2011.12.990","article-title":"Direct interaction between HLA-B and carbamazepine activates T cells in patients with Stevens-Johnson syndrome","volume":"129","author":"Wei","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2984","DOI":"10.4049\/jimmunol.1302306","article-title":"Oxypurinol Directly and Immediately Activates the Drug-Specific T Cells via the Preferential Use of HLA-B*58:01","volume":"192","author":"Yun","year":"2014","journal-title":"J. Immunol."},{"key":"ref_29","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_30","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_31","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_32","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0140-6736(02)08158-8","article-title":"Genetic variations in HLA-B region and hy-persensitivity reactions to abacavir","volume":"359","author":"Hetherington","year":"2002","journal-title":"Lancet"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/428486a","article-title":"Medical genetics: A marker for Stevens-Johnson syndrome","volume":"428","author":"Chung","year":"2004","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1073\/pnas.0409500102","article-title":"HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol","volume":"102","author":"Hung","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"612","DOI":"10.2340\/00015555-2925","article-title":"Up-regulation of Human Herpesvirus 6B-derived microRNAs in the Serum of Patients with Drug-induced Hypersensitivity Syndrome\/Drug Reaction with Eosinophilia and Systemic Symptoms","volume":"98","author":"Miyashita","year":"2018","journal-title":"Acta Derm. Venereol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1111\/j.1365-2133.2007.08167.x","article-title":"Association of human herpesvirus 6 re-activation with the flaring and severity of drug-induced hypersensitivity syndrome","volume":"157","author":"Tohyama","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1128\/JCM.00097-13","article-title":"Evidence for reactivation of human her-pesvirus 6 in generalized lymphadenopathy in a patient with drug-induced hypersensitivity syndrome","volume":"51","author":"Saraya","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"114","DOI":"10.2340\/00015555-2149","article-title":"Involvement of Human Herpesvirus 6 Infection in Renal Dysfunction Associated with DIHS\/DRESS","volume":"96","author":"Miyashita","year":"2016","journal-title":"Acta Derm. Venereol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.2169\/internalmedicine.55.6287","article-title":"Reactivation of Human Herpes Virus-6 in the Renal Tissue of a Patient with Drug-induced Hypersensitivity Syndrome\/Drug Rash with Eosinophilia and Systemic Symp-toms (DIHS\/DRESS)","volume":"55","author":"Hagiya","year":"2016","journal-title":"Int. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.jaip.2016.11.027","article-title":"Virus Reactivation in Drug Reaction with Eosinophilia and Systemic Symptoms (Dress) Results from a Strong Drug-Specific Immune Response","volume":"5","author":"Roujeau","year":"2017","journal-title":"J. Allergy Clin. Immunol. Pr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1046\/j.1365-2133.2003.05330.x","article-title":"Drug-induced hypersensitivity syn-drome associated with Epstein-Barr virus infection","volume":"148","author":"Descamps","year":"2003","journal-title":"Br. J. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1046\/j.1365-2133.2001.04239.x","article-title":"Anticonvulsant hypersensitivity syndrome associated with reactivation of cytomegalovirus","volume":"144","author":"Aihara","year":"2001","journal-title":"Br. J. Dermatol."},{"key":"ref_43","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 reac-tion in the same sequential order as in graft-versus-host disease","volume":"155","author":"Kano","year":"2006","journal-title":"Br. J. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1093\/cid\/ciw668","article-title":"Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials: Table 1","volume":"64","author":"Ljungman","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/337370a0","article-title":"Productive dual infection of human CD4+ T lymphocytes by HIV-1 and HHV-6","volume":"337","author":"Lusso","year":"1989","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1128\/jvi.63.7.3161-3163.1989","article-title":"Predominant CD4 T-lymphocyte tropism of human herpesvirus 6-related virus","volume":"63","author":"Takahashi","year":"1989","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1099\/0022-1317-72-6-1401","article-title":"Latent human herpesvirus 6 infection of human mono-cytes\/macrophages","volume":"72 Pt 6","author":"Kondo","year":"1991","journal-title":"J. Gen. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jdermsci.2016.05.001","article-title":"Preferential expression of CD134, an HHV-6 cel-lular 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_49","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1600-065X.2009.00766.x","article-title":"The significance of OX40 and OX40L to T-cell biology and immune disease","volume":"229","author":"Croft","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9096","DOI":"10.1073\/pnas.1305187110","article-title":"CD134 is a cellular receptor specific for human herpesvirus-6B entry","volume":"110","author":"Tang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/j.1365-2133.2009.09280.x","article-title":"Emergence of circulating monomyeloid precursors predicts reactivation of human herpesvirus-6 in drug-induced hypersensitivity syndrome","volume":"161","author":"Hashizume","year":"2009","journal-title":"Br. J. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/all.12138","article-title":"Skin recruitment of monomyeloid precursors involves human herpesvirus-6 reactivation in drug allergy","volume":"68","author":"Hashizume","year":"2013","journal-title":"Allergy"},{"key":"ref_53","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_54","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1111\/cea.13252","article-title":"Monocytes are involved in the balance be-tween regulatory T cells and Th17 cells in severe drug eruptions","volume":"48","author":"Ushigome","year":"2018","journal-title":"Clin. Exp. Allergy"},{"key":"ref_55","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 re-activation and hypogammaglobulinemia","volume":"140","author":"Kano","year":"2004","journal-title":"Arch Dermatol."},{"key":"ref_56","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_57","doi-asserted-by":"crossref","unstructured":"Kanatani, Y., Miyagawa, F., Ogawa, K., Arima, A., and Asada, H. (2020). Parallel changes in serum thymus and activation-regulated chemokine levels in response to flare-ups in drug-induced hypersensitivity syndrome. J. Dermatol., 47.","DOI":"10.1111\/1346-8138.15548"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.immuni.2008.04.020","article-title":"Human Leukocyte Antigen Class I-Restricted Activation of CD8+ T Cells Provides the Immunogenetic Basis of a Systemic Drug Hypersensitivity","volume":"28","author":"Chessman","year":"2008","journal-title":"Immunity"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1097\/00130832-200410000-00013","article-title":"The immunological and clinical spectrum of delayed drug-induced exanthems","volume":"4","author":"Lerch","year":"2004","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.4049\/jimmunol.157.3.1071","article-title":"Cross-reactivity of T cell lines and clones to be-ta-lactam antibiotics","volume":"157","author":"Zanni","year":"1996","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1016\/j.jaci.2011.08.013","article-title":"Shared and restricted T-cell receptor use is crucial for carbam-azepine-induced Stevens-Johnson syndrome","volume":"128","author":"Ko","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1080\/00015550410024094","article-title":"Drug-induced hypersensitivity syndrome associated with cytomegalovirus reactivation: Immu-nological characterization of pathogenic T cells","volume":"85","author":"Hashizume","year":"2005","journal-title":"Acta Derm. Venereol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1067\/mai.2003.1507","article-title":"Characterization of drug-specific T cells in lamotrigine hypersensitivity","volume":"111","author":"Naisbitt","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1124\/mol.63.3.732","article-title":"Hypersensitivity reactions to carbamazepine: Characterization of the specificity, phenotype, and cytokine profile of drug-specific T cell clones","volume":"63","author":"Naisbitt","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jdermsci.2015.11.002","article-title":"Reciprocal contribution of Th17 and regulatory T cells in severe drug allergy","volume":"81","author":"Hashizume","year":"2016","journal-title":"J. Dermatol. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/bjd.14839","article-title":"Drug-specific CD4(+) T-cell immune responses are responsible for antituberculosis drug-induced maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms syndrome","volume":"176","author":"Ye","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_67","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_68","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1046\/j.1365-2133.1998.02559.x","article-title":"Increased levels of interleukin 5 are associated with the generation of eosinophilia in drug-induced hypersensitivity syndrome","volume":"139","author":"Intrator","year":"1998","journal-title":"Br. J. Dermatol."},{"key":"ref_69","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_70","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/bjd.12948","article-title":"Elevated serum thymus and activa-tion-regulated chemokine (TARC\/CCL17) relates to reactivation of human herpesvirus 6 in drug reaction with eosinophilia and systemic symptoms (DRESS)\/drug-induced hypersensitivity syndrome (DIHS)","volume":"171","author":"Ogawa","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_71","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_72","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 symp-toms\/drug-induced hypersensitivity syndrome","volume":"178","author":"Miyagawa","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_73","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 Eosino-philia and Systemic Symptoms","volume":"233","author":"Teraki","year":"2017","journal-title":"Dermatology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"adv00102","DOI":"10.2340\/00015555-3465","article-title":"Correlation between Expression of CD134, a Human Herpesvirus 6 Cellular Receptor, on CD4+ T cells and Th2-type Immune Responses in Drug-induced Hypersensitivity Syn-drome\/Drug Reaction with Eosinophilia and Systemic Symptoms","volume":"100","author":"Miyagawa","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1182\/blood.V92.9.3338","article-title":"OX40 costimulation enhances interleukin-4 (IL-4) expression at priming and promotes the differentiation of naive human CD4(+) T cells into high IL-4-producing effectors","volume":"92","author":"Ohshima","year":"1998","journal-title":"Blood"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/2147\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:27:31Z","timestamp":1760160451000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/2147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,21]]},"references-count":75,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22042147"],"URL":"https:\/\/doi.org\/10.3390\/ijms22042147","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,21]]}}}