International Archives of Allergy and Immunology
Novel Insights from Clinical Practice
Carbamazepine Hypersensitivity Syndrome Triggered by a Human Herpes Virus Reactivation in a Genetically Predisposed PatientCalligaris L.a · Stocco G.a, c · De Iudicibus S.a, c · Marino S.a, c · Decorti G.c · Barbi E.a · Carrozzi M.a · Marchetti F.a · Bartoli F.b · Ventura A.a, baIRCCS Burlo Garofolo, Pediatric Clinic, and Departments of bReproductive and Developmental Sciences, and cLife Sciences, University of Trieste, Trieste, Italy
|
|
Log in to MyKarger to check if you already have access to this content.
KAB
Buy a Karger Article Bundle (KAB) and profit from a discount!
If you would like to redeem your KAB credit, please log in.
Save over 20% compared to the individual article price.
Article / Publication Details
Received: July 18, 2008
Accepted: September 30, 2008
Published online: January 06, 2009
Issue release date: May 2009
Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 0
ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)
For additional information: https://www.karger.com/IAA
Abstract
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by LTT when the HHV was active (positive PCR for viral DNA and increased anti-HHV 6 IgG titer), but not when it was no longer active.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.
© 2009 S. Karger AG, Basel
Related Articles:
References
- Naisbitt DJ, Britschgi M, Wong G, Farrell J, Depta JP, Chadwick DW, Pichler WJ, Pirmohamed M, Park BK: Hypersensitivity reactions to carbamazepine: characterization of the specificity, phenotype, and cytokine profile of drug-specific T cell clones. Mol Pharmacol 2003;63:732–741.
- Gerber BO, Pichler WJ: Cellular mechanisms of T cell mediated drug hypersensitivity. Curr Opin Immunol 2004;16:732–737.
- Pichler WJ, Tilch J: The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy 2004;59:809–820.
- Svensson CK, Cowen EW, Gaspari AA: Cutaneous drug reactions. Pharmacol Rev 2001;53:357–379.
- Levy M: Role of viral infections in the induction of adverse drug reactions. Drug Saf 1997;16:1–8.
- Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JY, Chen YT: Medical genetics: a marker for Stevens-Johnson syndrome. Nature 2004;428:486.
- Lonjou C, Thomas L, Borot N, Ledger N, de Toma C, LeLouet H, Graf E, Schumacher M, Hovnanian A, Mockenhaupt M, Roujeau JC: A marker for Stevens-Johnson syndrome: ethnicity matters. Pharmacogenomics J 2006;6:265–268.
- Lonjou C, Borot N, Sekula P, Ledger N, Thomas L, Halevy S, Naldi L, Bouwes-Bavinck JN, Sidoroff A, de Toma C, Schumacher M, Roujeau JC, Hovnanian A, Mockenhaupt M: A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics 2008;18:99–107.
- Green VJ, Pirmohamed M, Kitteringham NR, Gaedigk A, Grant DM, Boxer M, Burchell B, Park BK: Genetic analysis of microsomal epoxide hydrolase in patients with carbamazepine hypersensitivity. Biochem Pharmacol 1995;50:1353–1359.
- Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, Jagel-Guedes E, Rugina S, Kozyrev O, Cid JF, Hay P, Nolan D, Hughes S, Hughes A, Ryan S, Fitch N, Thorborn D, Benbow A: HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 2008;358:568–579.
- The International HapMap Consortium: The international HapMap project. Nature 2003;426:789–796.
- Hung SI, Chung WH, Jee SH, Chen WC, Chang YT, Lee WR, Hu SL, Wu MT, Chen GS, Wong TW, Hsiao PF, Chen WH, Shih HY, Fang WH, Wei CY, Lou YH, Huang YL, Lin JJ, Chen YT: Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics 2006;16:297–306.
- Smith CA, Harrison DJ: Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema. Lancet 1997;350:630–633.
- Nyfeler B, Pichler WJ: The lymphocyte transformation test for the diagnosis of drug allergy: sensitivity and specificity. Clin Exp Allergy 1997;27:175–181.
- Oskay T, Karademir A, Erturk OI: Association of anticonvulsant hypersensitivity syndrome with herpesvirus 6, 7. Epilepsy Res 2006;70:27–40.
- Mitani N, Aihara M, Yamakawa Y, Yamada M, Itoh N, Mizuki N, Ikezawa Z: Drug-induced hypersensitivity syndrome due to cyanamide associated with multiple reactivation of human herpesviruses. J Med Virol 2005;75:430–434.
- Yagami A, Yoshikawa T, Asano Y, Koie S, Shiohara T, Matsunaga K: Drug-induced hypersensitivity syndrome due to mexiletine hydrochloride associated with reactivation of human herpesvirus 7. Dermatology 2006;213:341–344.
- Lusso P: HHV-6 and the immune system: mechanisms of immunomodulation and viral escape. J Clin Virol 2006;37(suppl 1):S4–S10.
- Kano Y, Inaoka M, Shiohara T: Association between anticonvulsant hypersensitivity syndrome and human herpesvirus 6 reactivation and hypogammaglobulinemia. Arch Dermatol 2004;140:183–188.
- Patsalos PN, Perucca E: Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs. Lancet Neurol 2003;2:347–356.
- Vittorio CC, Muglia JJ: Anticonvulsant hypersensitivity syndrome. Arch Intern Med 1995;155:2285–2290.
- Klotz U: The role of pharmacogenetics in the metabolism of antiepileptic drugs: pharmacokinetic and therapeutic implications. Clin Pharmacokinet 2007;46:271–279.
- Alfirevic A, Mills T, Harrington P, Pinel T, Sherwood J, Jawaid A, Smith JC, March RE, Barratt BJ, Chadwick DW, Kevin Park B, Pirmohamed M: Serious carbamazepine-induced hypersensitivity reactions associated with the hsp70 gene cluster. Pharmacogenet Genomics 2006;16:287–296.
- Gourraud PA, Feolo M, Hoffman D, Helmberg W, Cambon-Thomsen A: The DBMHC microsatellite portal: a public resource for the storage and display of MHC microsatellite information. Tissue Antigens 2006;67:395–401.
- Ingelman-Sundberg M: Pharmacogenomic biomarkers for prediction of severe adverse drug reactions. N Engl J Med 2008;358:637–639.
Article / Publication Details
Received: July 18, 2008
Accepted: September 30, 2008
Published online: January 06, 2009
Issue release date: May 2009
Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 0
ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)
For additional information: https://www.karger.com/IAA
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Get Permission
PubMed ID
