title: Fever, rash, and systemic symptoms: understanding the role of virus and HLA in severe cutaneous drug allergy.
abstract: Drug hypersensitivity syndromes such as abacavir hypersensitivity and the severe cutaneous adverse drug reactions have been associated with significant short- and long-term morbidity and mortality. More recently, these immunologically mediated and previously unpredictable diseases have been shown to be associated with primarily class I but also class II HLA alleles. The case of the association of HLA-B*57:01 and abacavir hypersensitivity has created a translational roadmap for how this knowledge can be used in the clinic to prevent severe reactions. Although many hurdles exist to the widespread translation of such HLA screening approaches, our understanding of how drugs interact with the major histocompatibility complex has contributed to the discovery of new models that have provided considerable insights into the immunopathogenesis of severe cutaneous adverse drug reactions and other T-cell-mediated drug hypersensitivity syndromes. Future translation of this knowledge will facilitate the development of preclinical toxicity screening to significantly improve efficacy and safety of drug development and design.
authors.affiliation: Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pavlos
authors.affiliation: Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia; Vanderbilt University School of Medicine, Nashville, Tenn.
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, College of Medicine, Gainsville, Fla.
authors.forename: David
authors.initials: D
authors.lastname: Ostrov
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, College of Medicine, Gainsville, Fla.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Pompeu
authors.affiliation: Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia; Vanderbilt University School of Medicine, Nashville, Tenn. Electronic address: elizabeth.j.phillips@vanderbilt.edu.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Phillips
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects*; D003587:Cytomegalovirus / Q000276:immunology / Q000472:pathogenicity; D015224:Dideoxynucleosides / Q000009:adverse effects; D063926:Drug Hypersensitivity Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology / Q000628:therapy / Q000821:virology; D005076:Exanthema / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology / Q000628:therapy / Q000821:virology; D005260:Female; D005334:Fever / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology / Q000628:therapy / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology / Q000472:pathogenicity; D014645:Herpesvirus 3, Human / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D011379:Prognosis; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D012307:Risk Factors; D012720:Severity of Illness Index; D012882:Skin Tests; D013262:Stevens-Johnson Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology / Q000628:therapy / Q000821:virology; D014775:Virus Activation; D014780:Viruses / Q000276:immunology* / Q000472:pathogenicity; D000099227:Abacavir
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D015224:Dideoxynucleosides; D006680:HLA Antigens; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir
keywords: ABC; ADR; AGEP; Abacavir; Acute generalized exanthematous pustulosis; Adverse drug reaction; CBZ; CMV; CTL; Carbamazepine; Cytomegalovirus; Cytotoxic lymphocyte; DIHS; DRESS; DRESS-DIHS-HSS; Drug reaction with eosinophilia and systemic symptoms; Drug-induced hypersensitivity syndrome; EBV; Epstein-Barr Virus; HHV; HLA; HSR; HSS; Human herpesvirus; Human leukocyte antigen; Hypersensitivity reaction; Hypersensitivity syndrome; INF-γ; Interferon gamma; NSAID; Nonsteroidal anti-inflammatory drug; Orally; PBMC; Peripheral blood mononuclear cell; SCAR; SJS; SJS-TEN; Severe cutaneous adverse drug reaction; Steven-Johnson syndrome; T-cell receptor; TCR; TEN; Toxic epidermal necrolysis; Twice a day; Viral reactivation; bid; po