HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms

Katherine C. Konvinse, Jason A. Trubiano, Rebecca Pavlos, Ian James, Christian M. Shaffer, Cosmin A. Bejan, Ryan J. Schutte, David A. Ostrov, Mark A. Pilkinton, Misha Rosenbach, Jeffrey P. Zwerner, Kristina B. Williams, Jack Bourke, Patricia Martinez, Francois Rwandamuriye, Abha Chopra, Mark Watson, Alec J. Redwood, Katie D. White, Simon A. Mallal & 1 others Elizabeth J. Phillips

    Research output: Contribution to journalArticle

    7 Citations (Scopus)

    Abstract

    Background: Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy, affecting future treatment choices. Variations in HLA class I in particular have been associated with serious T cell-mediated adverse drug reactions, which has led to preventive screening strategies for some drugs.

    Objective: We sought to determine whether variation in the HLA region is associated with vancomycin-induced DRESS.

    Methods: Probable vancomycin-induced DRESS cases were matched 1:2 with tolerant control subjects based on sex, race, and age by using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by means of conditional logistic regression. An extended sample set from BioVU was used to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele.

    Results: Twenty-three subjects met the inclusion criteria for vancomycin-associated DRESS. Nineteen (82.6%) of 23 cases carried HLA-A*32:01 compared with 0 (0%) of 46 of the matched vancomycin-tolerant control subjects (P = 1 x 10(-8)) and 6.3% of the BioVU population (n = 54,249, P = 2 x 10(-16)). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01-positive group indicated that 19.2% had DRESS and did so within 4 weeks.

    Conclusions: HLA-A*32:01 is strongly associated with vancomycin-induced DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug, and preserve future treatment options with coadministered antibiotics.

    Original languageEnglish
    Pages (from-to)183-192
    Number of pages10
    JournalJournal of Allergy and Clinical Immunology
    Volume144
    Issue number1
    DOIs
    Publication statusPublished - Jul 2019

    Cite this

    Konvinse, K. C., Trubiano, J. A., Pavlos, R., James, I., Shaffer, C. M., Bejan, C. A., ... Phillips, E. J. (2019). HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms. Journal of Allergy and Clinical Immunology, 144(1), 183-192. https://doi.org/10.1016/j.jaci.2019.01.045
    Konvinse, Katherine C. ; Trubiano, Jason A. ; Pavlos, Rebecca ; James, Ian ; Shaffer, Christian M. ; Bejan, Cosmin A. ; Schutte, Ryan J. ; Ostrov, David A. ; Pilkinton, Mark A. ; Rosenbach, Misha ; Zwerner, Jeffrey P. ; Williams, Kristina B. ; Bourke, Jack ; Martinez, Patricia ; Rwandamuriye, Francois ; Chopra, Abha ; Watson, Mark ; Redwood, Alec J. ; White, Katie D. ; Mallal, Simon A. ; Phillips, Elizabeth J. / HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms. In: Journal of Allergy and Clinical Immunology. 2019 ; Vol. 144, No. 1. pp. 183-192.
    @article{f8ac67b423c74536af1f6573215a03a6,
    title = "HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms",
    abstract = "Background: Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy, affecting future treatment choices. Variations in HLA class I in particular have been associated with serious T cell-mediated adverse drug reactions, which has led to preventive screening strategies for some drugs.Objective: We sought to determine whether variation in the HLA region is associated with vancomycin-induced DRESS.Methods: Probable vancomycin-induced DRESS cases were matched 1:2 with tolerant control subjects based on sex, race, and age by using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by means of conditional logistic regression. An extended sample set from BioVU was used to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele.Results: Twenty-three subjects met the inclusion criteria for vancomycin-associated DRESS. Nineteen (82.6{\%}) of 23 cases carried HLA-A*32:01 compared with 0 (0{\%}) of 46 of the matched vancomycin-tolerant control subjects (P = 1 x 10(-8)) and 6.3{\%} of the BioVU population (n = 54,249, P = 2 x 10(-16)). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01-positive group indicated that 19.2{\%} had DRESS and did so within 4 weeks.Conclusions: HLA-A*32:01 is strongly associated with vancomycin-induced DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug, and preserve future treatment options with coadministered antibiotics.",
    keywords = "Vancomycin, drug reaction with eosinophilia and systemic symptoms, human leukocyte antigen, antibiotic allergy, delayed hypersensitivity, T-cell hypersensitivity, HYPERSENSITIVITY, HLA, HLA-B-ASTERISK-5701",
    author = "Konvinse, {Katherine C.} and Trubiano, {Jason A.} and Rebecca Pavlos and Ian James and Shaffer, {Christian M.} and Bejan, {Cosmin A.} and Schutte, {Ryan J.} and Ostrov, {David A.} and Pilkinton, {Mark A.} and Misha Rosenbach and Zwerner, {Jeffrey P.} and Williams, {Kristina B.} and Jack Bourke and Patricia Martinez and Francois Rwandamuriye and Abha Chopra and Mark Watson and Redwood, {Alec J.} and White, {Katie D.} and Mallal, {Simon A.} and Phillips, {Elizabeth J.}",
    year = "2019",
    month = "7",
    doi = "10.1016/j.jaci.2019.01.045",
    language = "English",
    volume = "144",
    pages = "183--192",
    journal = "The Journal of Allergy and Clinical Immunology",
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    publisher = "Elsevier - Mosby",
    number = "1",

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    Konvinse, KC, Trubiano, JA, Pavlos, R, James, I, Shaffer, CM, Bejan, CA, Schutte, RJ, Ostrov, DA, Pilkinton, MA, Rosenbach, M, Zwerner, JP, Williams, KB, Bourke, J, Martinez, P, Rwandamuriye, F, Chopra, A, Watson, M, Redwood, AJ, White, KD, Mallal, SA & Phillips, EJ 2019, 'HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms' Journal of Allergy and Clinical Immunology, vol. 144, no. 1, pp. 183-192. https://doi.org/10.1016/j.jaci.2019.01.045

    HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms. / Konvinse, Katherine C.; Trubiano, Jason A.; Pavlos, Rebecca; James, Ian; Shaffer, Christian M.; Bejan, Cosmin A.; Schutte, Ryan J.; Ostrov, David A.; Pilkinton, Mark A.; Rosenbach, Misha; Zwerner, Jeffrey P.; Williams, Kristina B.; Bourke, Jack; Martinez, Patricia; Rwandamuriye, Francois; Chopra, Abha; Watson, Mark; Redwood, Alec J.; White, Katie D.; Mallal, Simon A.; Phillips, Elizabeth J.

    In: Journal of Allergy and Clinical Immunology, Vol. 144, No. 1, 07.2019, p. 183-192.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms

    AU - Konvinse, Katherine C.

    AU - Trubiano, Jason A.

    AU - Pavlos, Rebecca

    AU - James, Ian

    AU - Shaffer, Christian M.

    AU - Bejan, Cosmin A.

    AU - Schutte, Ryan J.

    AU - Ostrov, David A.

    AU - Pilkinton, Mark A.

    AU - Rosenbach, Misha

    AU - Zwerner, Jeffrey P.

    AU - Williams, Kristina B.

    AU - Bourke, Jack

    AU - Martinez, Patricia

    AU - Rwandamuriye, Francois

    AU - Chopra, Abha

    AU - Watson, Mark

    AU - Redwood, Alec J.

    AU - White, Katie D.

    AU - Mallal, Simon A.

    AU - Phillips, Elizabeth J.

    PY - 2019/7

    Y1 - 2019/7

    N2 - Background: Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy, affecting future treatment choices. Variations in HLA class I in particular have been associated with serious T cell-mediated adverse drug reactions, which has led to preventive screening strategies for some drugs.Objective: We sought to determine whether variation in the HLA region is associated with vancomycin-induced DRESS.Methods: Probable vancomycin-induced DRESS cases were matched 1:2 with tolerant control subjects based on sex, race, and age by using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by means of conditional logistic regression. An extended sample set from BioVU was used to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele.Results: Twenty-three subjects met the inclusion criteria for vancomycin-associated DRESS. Nineteen (82.6%) of 23 cases carried HLA-A*32:01 compared with 0 (0%) of 46 of the matched vancomycin-tolerant control subjects (P = 1 x 10(-8)) and 6.3% of the BioVU population (n = 54,249, P = 2 x 10(-16)). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01-positive group indicated that 19.2% had DRESS and did so within 4 weeks.Conclusions: HLA-A*32:01 is strongly associated with vancomycin-induced DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug, and preserve future treatment options with coadministered antibiotics.

    AB - Background: Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy, affecting future treatment choices. Variations in HLA class I in particular have been associated with serious T cell-mediated adverse drug reactions, which has led to preventive screening strategies for some drugs.Objective: We sought to determine whether variation in the HLA region is associated with vancomycin-induced DRESS.Methods: Probable vancomycin-induced DRESS cases were matched 1:2 with tolerant control subjects based on sex, race, and age by using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by means of conditional logistic regression. An extended sample set from BioVU was used to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele.Results: Twenty-three subjects met the inclusion criteria for vancomycin-associated DRESS. Nineteen (82.6%) of 23 cases carried HLA-A*32:01 compared with 0 (0%) of 46 of the matched vancomycin-tolerant control subjects (P = 1 x 10(-8)) and 6.3% of the BioVU population (n = 54,249, P = 2 x 10(-16)). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01-positive group indicated that 19.2% had DRESS and did so within 4 weeks.Conclusions: HLA-A*32:01 is strongly associated with vancomycin-induced DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug, and preserve future treatment options with coadministered antibiotics.

    KW - Vancomycin

    KW - drug reaction with eosinophilia and systemic symptoms

    KW - human leukocyte antigen

    KW - antibiotic allergy

    KW - delayed hypersensitivity

    KW - T-cell hypersensitivity

    KW - HYPERSENSITIVITY

    KW - HLA

    KW - HLA-B-ASTERISK-5701

    U2 - 10.1016/j.jaci.2019.01.045

    DO - 10.1016/j.jaci.2019.01.045

    M3 - Article

    VL - 144

    SP - 183

    EP - 192

    JO - The Journal of Allergy and Clinical Immunology

    JF - The Journal of Allergy and Clinical Immunology

    SN - 0091-6749

    IS - 1

    ER -