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HLA-B*1502 Allele Associated With Carbamazepine-Induced Epidermal Necrolysis

HLA-B*1502 Allele Associated With Carbamazepine-Induced Epidermal Necrolysis Epidermal necrolysis (Stevens-Johnson syndrome [SJS] and toxic epidermal necrolysis [TEN]) is a rare, drug-induced, acute, and potentially life-threatening mucocutaneous reaction. Antiseizure medications are frequently implicated. Recently, a strong association was found between HLA-B*1502 and carbamazepine-induced epidermal necrolysis in the Han Chinese population.1 Rare reports recommend genotyping all Asian patients before initiating carbamazepine treatment.2 The present report describes an Asian teenage boy with HLA-B*1502 who developed TEN while being treated with carbamazepine. Report of a Case A 16-year-old Asian boy with a medical history significant only for refractory dystonia was seen in the emergency department for a 3-day history of a rapidly progressing eruption. The initiation of carbamazepine treatment for dystonia preceded the eruption by 1 week. He had no history of adverse drug reactions. Physical examination revealed erosions on the buccal mucosa and tongue with hemorrhagic crusted erosions on the lips. Examination of the skin showed coalescing macules, some of which were becoming vesiculobullous. Lesions were located on the face, trunk, and proximal extremities, with approximately 70% body surface area involved (Figure). A skin biopsy specimen from the right arm showed full-thickness epidermal necrosis, subepidermal clefting, necrotic keratinocytes, and a sparse perivascular lymphocytic infiltrate. A diagnosis of carbamazepine-induced TEN was made. He was treated with intravenous immunoglobulin at a dose of 1 g/kg/d, dressing changes, and ophthalmic ointments. Figure. View LargeDownload Patient's skin showed coalescing macules, some of which progressed to become vesiculobullous. Comment The incidence of SJS and TEN in Han Chinese patients has been shown to be significantly higher than among whites.3 Carbamazepine is the drug most implicated in this cutaneous drug reaction in Asians, accounting for nearly one-third of cases.1-3 Although the exact mechanism of this association is unclear, Chung et al1,4 first reported that HLA-B*1502 was strongly associated with carbamazepine-induced SJS and TEN in Han Chinese patients in 2004. The authors found that the HLA-B*1502 allele was present in 100% of patients with carbamazepine-induced SJS but in only 3% of carbamazepine-tolerant patients.1,4 There is increasing evidence to support that Han Chinese and other patients with an Asian ancestry who have the HLA-B*1502 allele are at a much increased risk for developing SJS and TEN when taking carbamazepine.5 The HLA-B*1502 allelic frequency in southeastern Asians has been estimated to be close to 10%, whereas it is probably less than 0.1% in whites, which explains the fewer incidences of carbamazepine-induced SJS in whites.2,4 After his hospital stay, our patient underwent HLA genotyping, which revealed the presence of HLA-B*1502. The high incidence of HLA-B*1502 in the Asian population has resulted in a recommendation by the US Food and Drug Administration for testing of all Asians before administration of carbamazepine.5 Unfortunately, this recommendation is not widely known. Given the high risk of mortality and morbidity from SJS and TEN, it is vital to be familiar with any measures that may decrease the incidence of these conditions, including genotyping. Our case highlights the importance of screening for the HLA-B*1502 allele as a risk factor for SJS and TEN drug hypersensitivity in Asian patients who are prescribed carbamazepine. Correspondence: Dr Haggstrom, Indiana University School of Medicine, Department of Dermatology, 550 N University Blvd, UH 3240, Indianapolis, IN 46220 (ahaggstr@iupui.edu) Financial Disclosure: None reported. References 1. Chung WHHung SIHong HS et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature 2004;428 (6982) 486PubMedGoogle ScholarCrossref 2. Lonjou CBorot NSekula P et al. RegiSCAR study group, A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics 2008;18 (2) 99- 107PubMedGoogle ScholarCrossref 3. Huang LYLiao WCChiou CCLou JPHu PKo FC Fatal toxic epidermal necrolysis induced by carbamazepine treatment in a patient who previously had carbamazepine-induced Stevens-Johnson syndrome. J Formos Med Assoc 2007;106 (12) 1032- 1037PubMedGoogle ScholarCrossref 4. Chung WHHung SIChen YT Human leukocyte antigens and drug hypersensitivity. Curr Opin Allergy Clin Immunol 2007;7 (4) 317- 323PubMedGoogle ScholarCrossref 5. Ferrell PB JrMcLeod HL Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics 2008;9 (10) 1543- 1546PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

HLA-B*1502 Allele Associated With Carbamazepine-Induced Epidermal Necrolysis

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Publisher
American Medical Association
Copyright
Copyright © 2010 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archdermatol.2010.364
Publisher site
See Article on Publisher Site

Abstract

Epidermal necrolysis (Stevens-Johnson syndrome [SJS] and toxic epidermal necrolysis [TEN]) is a rare, drug-induced, acute, and potentially life-threatening mucocutaneous reaction. Antiseizure medications are frequently implicated. Recently, a strong association was found between HLA-B*1502 and carbamazepine-induced epidermal necrolysis in the Han Chinese population.1 Rare reports recommend genotyping all Asian patients before initiating carbamazepine treatment.2 The present report describes an Asian teenage boy with HLA-B*1502 who developed TEN while being treated with carbamazepine. Report of a Case A 16-year-old Asian boy with a medical history significant only for refractory dystonia was seen in the emergency department for a 3-day history of a rapidly progressing eruption. The initiation of carbamazepine treatment for dystonia preceded the eruption by 1 week. He had no history of adverse drug reactions. Physical examination revealed erosions on the buccal mucosa and tongue with hemorrhagic crusted erosions on the lips. Examination of the skin showed coalescing macules, some of which were becoming vesiculobullous. Lesions were located on the face, trunk, and proximal extremities, with approximately 70% body surface area involved (Figure). A skin biopsy specimen from the right arm showed full-thickness epidermal necrosis, subepidermal clefting, necrotic keratinocytes, and a sparse perivascular lymphocytic infiltrate. A diagnosis of carbamazepine-induced TEN was made. He was treated with intravenous immunoglobulin at a dose of 1 g/kg/d, dressing changes, and ophthalmic ointments. Figure. View LargeDownload Patient's skin showed coalescing macules, some of which progressed to become vesiculobullous. Comment The incidence of SJS and TEN in Han Chinese patients has been shown to be significantly higher than among whites.3 Carbamazepine is the drug most implicated in this cutaneous drug reaction in Asians, accounting for nearly one-third of cases.1-3 Although the exact mechanism of this association is unclear, Chung et al1,4 first reported that HLA-B*1502 was strongly associated with carbamazepine-induced SJS and TEN in Han Chinese patients in 2004. The authors found that the HLA-B*1502 allele was present in 100% of patients with carbamazepine-induced SJS but in only 3% of carbamazepine-tolerant patients.1,4 There is increasing evidence to support that Han Chinese and other patients with an Asian ancestry who have the HLA-B*1502 allele are at a much increased risk for developing SJS and TEN when taking carbamazepine.5 The HLA-B*1502 allelic frequency in southeastern Asians has been estimated to be close to 10%, whereas it is probably less than 0.1% in whites, which explains the fewer incidences of carbamazepine-induced SJS in whites.2,4 After his hospital stay, our patient underwent HLA genotyping, which revealed the presence of HLA-B*1502. The high incidence of HLA-B*1502 in the Asian population has resulted in a recommendation by the US Food and Drug Administration for testing of all Asians before administration of carbamazepine.5 Unfortunately, this recommendation is not widely known. Given the high risk of mortality and morbidity from SJS and TEN, it is vital to be familiar with any measures that may decrease the incidence of these conditions, including genotyping. Our case highlights the importance of screening for the HLA-B*1502 allele as a risk factor for SJS and TEN drug hypersensitivity in Asian patients who are prescribed carbamazepine. Correspondence: Dr Haggstrom, Indiana University School of Medicine, Department of Dermatology, 550 N University Blvd, UH 3240, Indianapolis, IN 46220 (ahaggstr@iupui.edu) Financial Disclosure: None reported. References 1. Chung WHHung SIHong HS et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature 2004;428 (6982) 486PubMedGoogle ScholarCrossref 2. Lonjou CBorot NSekula P et al. RegiSCAR study group, A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics 2008;18 (2) 99- 107PubMedGoogle ScholarCrossref 3. Huang LYLiao WCChiou CCLou JPHu PKo FC Fatal toxic epidermal necrolysis induced by carbamazepine treatment in a patient who previously had carbamazepine-induced Stevens-Johnson syndrome. J Formos Med Assoc 2007;106 (12) 1032- 1037PubMedGoogle ScholarCrossref 4. Chung WHHung SIChen YT Human leukocyte antigens and drug hypersensitivity. Curr Opin Allergy Clin Immunol 2007;7 (4) 317- 323PubMedGoogle ScholarCrossref 5. Ferrell PB JrMcLeod HL Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics 2008;9 (10) 1543- 1546PubMedGoogle ScholarCrossref

Journal

Archives of DermatologyAmerican Medical Association

Published: Dec 20, 2010

Keywords: alleles,carbamazepine,epidermis,hla-b antigens

References

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