HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis

Abstract

HLA-A*31:01 was reported to be associated with carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCAR), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We conducted an international study using consensus diagnosis criteria to enroll a total of 93 patients with CBZ-SCAR from Europe or Asia. We found that HLA-A*31:01 showed a significant association with CBZ-DRESS in Europeans (P<0.001; odds ratio (OR) (95% confidence interval (CI))=57.6 (11.0-340)), and the strong association was also found in Chinese (P<0.001; OR (95% CI)=23.0 (4.2-125)). However, HLA-A*31:01 had no association with CBZ-SJS/TEN in neither Chinese nor Europeans. By comparison, HLA-B*15:02 showed a strong association with CBZ-SJS/TEN in Chinese (P<0.001, OR (95% CI)=58.1 (17.6-192)). A meta-analysis of this and other published studies confirmed that in all populations, HLA-A*31:01 had an extremely strong association with CBZ-DRESS (P<0.001, a pooled OR (95% CI)=13.2 (8.4-20.8)), but a much weaker association with CBZ-SJS/TEN (P=0.01, OR (95% CI)=3.94 (1.4-11.5)). Our data revealed that HLA-A*31:01 is a specific predictor for CBZ-DRESS but not for CBZ-SJS/TEN. More studies are needed to investigate the genetic determinant of CBZ-SJS/TEN in Europeans. Considering the potential clinical utility, the cost-effectiveness of the combined HLA-A*31:01 and HLA-B*15:02 genetic test to prevent CBZ-SCAR in Chinese needs further investigation.

Lamotrigine Associated DRESS Syndrome – a Case Report

“…Th e liver is the most commonly involved organ in DRESS syndrome, and hepatitits, present also in our patient, occurs in about 80% of all cases (19,20,21). Th e degree of hepatitis is related to the interval between the onset of the syndrome and the discontinuation of the off ending drug.…”

“…Aromatic anticonvulsants (phenytoin, phenobarbital, carbamazepine) and sulphonamides are the most common causative drugs, but a variety (18,(20)(21)(22)(23)(24)(25)(26)(27). Lamotrigine [6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine] is an antiepileptic drug, used in the management of a broad range of seizures in adults and children which is not an aromatic antiepileptic, thus being structurally and pharmacologically unrelated to other antiepileptic medications e.g.…”

Cutaneous drug reactions to antiepileptic drugs and relation with HLA alleles in the Turkish population

“…The statistical significance was defined as P < 0.05. (15). The authors found that HLA-A*31:01 had a sensitivity of 70% and a specificity of 96% as a predictor for CBZ-DRESS in Europeans, yet had a sensitivity of 50% and a specificity of 96% in Chinese.…”

Evolving models of the immunopathogenesis of T cell–mediated drug allergy: The role of host, pathogens, and drug response

“…[74][75][76][77][78] This association, however, was not consistently seen in subsequent studies many of which also reported a range of phenotypic variation among the carbamazepine induced IM-ADR observed. 77,[79][80][81] Work to more precisely define these associations and the structural basis for these interactions is ongoing.…”