TY - JOUR
T1 - Genetic variants associated with T cell–mediated cutaneous adverse drug reactions: A PRISMA-compliant systematic review—An EAACI position paper
AU - the Task Force “Genetic predictors of drug hypersensitivity” of the European Network on Drug Allergy (ENDA), European Academy of Allergy and Clinical Immunology (EAACI)
AU - Oussalah, Abderrahim
AU - Yip, Vincent
AU - Mayorga, Cristobalina
AU - Blanca, Miguel
AU - Barbaud, Annick
AU - Nakonechna, Alla
AU - Cernadas, Josefina
AU - Gotua, Maia
AU - Brockow, Knut
AU - Caubet, Jean-Christoph
AU - Bircher, Andreas
AU - Atanaskovic-Markovic, Marina
AU - Demoly, Pascal
AU - Kase-Tanno, Luciana
AU - Terreehorst, Ingrid
AU - Laguna, José Julio
AU - Romano, Antonino
AU - Guéant, Jean-Louis
AU - Pirmohamed, Munir
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell–mediated reactions classically occur more than 6 hours after drug administration and include life-threatening conditions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and hypersensitivity syndrome. Over the last 20 years, significant advances have been made in our understanding of the pathogenesis of DHRs with the identification of human leukocyte antigens as predisposing factors. This has led to the development of pharmacogenetic screening tests, such as HLA-B*57:01 in abacavir therapy, which has successfully reduced the incidence of abacavir hypersensitivity reactions. We have completed a PRISMA-compliant systematic review to identify genetic associations that have been reported in DHRs. In total, 105 studies (5554 cases and 123 548 controls) have been included in the review reporting genetic associations with carbamazepine (n = 31), other aromatic antiepileptic drugs (n = 24), abacavir (n = 11), nevirapine (n = 14), trimethoprim-sulfamethoxazole (n = 11), dapsone (n = 4), allopurinol (n = 10), and other drugs (n = 5). The most commonly reported genetic variants associated with DHRs are located in human leukocyte antigen genes and genes involved in drug metabolism pathways. Increasing our understanding of genetic variants that contribute to DHRs will allow us to improve diagnosis, develop new treatments, and predict and prevent DHRs in the future.
AB - Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell–mediated reactions classically occur more than 6 hours after drug administration and include life-threatening conditions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and hypersensitivity syndrome. Over the last 20 years, significant advances have been made in our understanding of the pathogenesis of DHRs with the identification of human leukocyte antigens as predisposing factors. This has led to the development of pharmacogenetic screening tests, such as HLA-B*57:01 in abacavir therapy, which has successfully reduced the incidence of abacavir hypersensitivity reactions. We have completed a PRISMA-compliant systematic review to identify genetic associations that have been reported in DHRs. In total, 105 studies (5554 cases and 123 548 controls) have been included in the review reporting genetic associations with carbamazepine (n = 31), other aromatic antiepileptic drugs (n = 24), abacavir (n = 11), nevirapine (n = 14), trimethoprim-sulfamethoxazole (n = 11), dapsone (n = 4), allopurinol (n = 10), and other drugs (n = 5). The most commonly reported genetic variants associated with DHRs are located in human leukocyte antigen genes and genes involved in drug metabolism pathways. Increasing our understanding of genetic variants that contribute to DHRs will allow us to improve diagnosis, develop new treatments, and predict and prevent DHRs in the future.
KW - T cell–mediated drug hypersensitivity reactions
KW - cutaneous adverse drug reactions
KW - genetic variants
KW - human leukocyte antigen genes
KW - systematic review
UR - http://www.scopus.com/inward/record.url?scp=85082812758&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/all.14174
DO - https://doi.org/10.1111/all.14174
M3 - Article
C2 - 31899808
SN - 0105-4538
VL - 75
SP - 1069
EP - 1098
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
IS - 5
ER -