Carbamazepine hypersensitivity syndrome triggered by a human herpes virus reactivation in a genetically predisposed patient.
A case of severe hypersensitivity syndrome, triggered by carbamazepine in the presence of a concomitant active human herpes virus (HHV) 6 and 7 infection is described. To further understand the molecular mechanism of this adverse reaction, analyses of the genetic variants of human leukocyte antigen (HLA) and of the epoxide hydrolase gene (EPHX1), previously associated with carbamazepine hypersensitivity, were performed. A lymphocyte transformation test (LTT) was conducted in order to detect drug-specific lymphocytes. In the hypersensitive patient, 2 genetic factors previously associated with intolerance to carbamazepine were detected: the allele HLA-A*3101 and homozygosity for the variant allele of SNP rs1051740 in EPHX1. Drug-specific lymphocytes could be detected by LTT when the HHV was active (positive PCR for viral DNA and increased anti-HHV 6 IgG titer), but not when it was no longer active. In conclusion, we document a case of severe carbamazepine hypersensitivity triggered by viral reactivation in a patient presenting the interaction of 2 unfavorable genetic factors.
Calligaris
Lorenzo
L
IRCCS Burlo Garofolo, Pediatric Clinic, University of Trieste, Trieste IT-34127, Italy.
Stocco
Gabriele
G
De Iudicibus
Sara
S
Marino
Sara
S
Decorti
Giuliana
G
Barbi
Egidio
E
Carrozzi
Marco
M
Marchetti
Federico
F
Bartoli
Fiora
F
Ventura
Alessandro
A
D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects*; D002478:Cells, Cultured; D002648:Child; D004342:Drug Hypersensitivity / Q000235:genetics / Q000821:virology*; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics; D006566:Herpesviridae Infections / Q000150:complications*; D015654:Herpesvirus 6, Human; D016199:Herpesvirus 7, Human; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D013577:Syndrome; D014775:Virus Activation / Q000235:genetics / Q000276:immunology
D000927:Anticonvulsants; D015234:HLA-A Antigens; C506273:HLA-A*31:01 antigen; D002220:Carbamazepine; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human