Phenobarbital‐induced severe cutaneous adverse drug reactions are associated with CYP2C19*2 in Thai children

Manuyakorn, Wiparat; Siripool, Khanitha; Kamchaisatian, Wasu; Pakakasama, Samart; Visudtibhan, Anannit; Vilaiyuk, Soamarat; Rujirawat, Thidarat; Benjaponpitak, Suwat

doi:10.1111/pai.12058

Cited by 54 publications

(47 citation statements)

References 20 publications

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“…A majority etiology of this study was drug-induced causes, which is consistent with most other earlier studies [4][5][6][7][8]. However, the most prevalent drug group found in this study was antiepileptics, rather than antibiotics, in contrasts with a previous study in Thai children [4].…”

Section: Discussioncontrasting

confidence: 57%

Stevens-Johnson Syndrome and toxic epidermal necrolysis in children: a retrospective study at Srinagarind Hospital, Khon Kaen, Thailand 1992–2012

Paipool

Sriboonnark

2015

Asian Biomedicine

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Background: Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening skin conditions with an etiology of drug exposure or infections. Objectives: To determine the cause, treatments, complications, and outcomes of SJS/TEN in children admitted to Srinagrind Hospital during 1992−2012. Methods: Retrospective chart review. A diagnosis of SJS and TEN was confirmed by pediatric dermatologists. Results: A total of 38 patients was recorded. They consisted 31 (82%) SJS patients and 7 (18%) TEN patients. Mean age 6.6 years (range 1 to 14 years). Male to female was 1.1:1. Most cases (30 or 79%) were caused by drug exposure. Three cases (8%) by infection, and 5 cases (13%) were of unknown cause. The antiepileptic drug group was the most common cause. Systemic corticosteroids were used in 33 cases (87%). Intravenous immunoglobulin was used in one TEN patient (3%). There were 18 cases (47%) with acute complications. Ocular complications (7 cases, 39%), septicemia (4 cases, 22%), and secondary skin infections (3 cases, 17%) were the most common. Mean difference in length of hospital stay between those with and without acute complications was 12.3 days (P < 0.01, 95% CI 5.9-18.6). Ocular complications were the only long-term complications at 1-year follow up, and included symblepharon, corneal pannus, and dry eyes. Two patients (5%), both having cases of TEN, died. Conclusions: Antiepileptic drugs were the most common causes of SJS/TEN in our study. Good ophthalmologic care of the prevalent acute eye complications in these patients is needed to prevent long-term ophthalmic complications.

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Section: Discussioncontrasting

confidence: 57%

Stevens-Johnson Syndrome and toxic epidermal necrolysis in children: a retrospective study at Srinagarind Hospital, Khon Kaen, Thailand 1992–2012

Paipool

Sriboonnark

2015

Asian Biomedicine

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“…It should be noted that the negative finding for the association between the HLA-B*15:02 and phenytoin-related SCAR (OR = 1.4, 95% CI = 0.43-5.1, P = 0.53) was also reported in a small case-control study carried out in Thai patients (i.e. 17 phenytoin-related SCAR patients and 40 phenytoin-tolerant controls) [29]. The present findings suggest that as the increased risk of phenytoin-related SJS/TEN in the presence of the HLA-B*15:02 was not statistically significant in a Thai population, the HLA-B*15:02 allele may not be a valid genetic marker for the prediction of SJS/TEN-related to phenytoin in this population.…”

Section: Discussionmentioning

confidence: 77%

Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population

Tassaneeyakul

Prabmeechai

Sukasem

et al. 2016

Pharmacogenetics and Genomics

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“…20 Polymorphisms in the CYP2C19 gene that encode an isoform of cytochrome P450 may increase the risk of SJS/TEN following the administration of phenobarbital, phenytoin, or carbamazepine. 38 Moreover, some patients with STS/NET have a low N-acetylation capacity, which predisposes them to serious adverse skin reactions. 39 Many cases of SJS/TEN are clearly linked to medications; however, approximately 20---25% of cases and probably an even higher proportion in paediatric patients cannot be clearly attributed to a drug.…”

Section: Introductionmentioning

confidence: 99%

Severe delayed skin reactions related to drugs in the paediatric age group: A review of the subject by way of three cases (Stevens–Johnson syndrome, toxic epidermal necrolysis and DRESS)

Belver

Michavila

Bobolea

et al. 2016

Allergologia et Immunopathologia

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Severe delayed drug-induced skin reactions in children are not common but potentially serious. This article describes aspects concerning the etiology, pathogenesis and clinical manifestations of these processes; it presents three paediatric cases, namely STS (Steven Johnson Syndrome), TEN (toxic epidermal necrolysis), probably related to amoxicillin/clavulanate and ibuprofen and DRESS (a drug reaction with eosinophilia and systemic symptoms) secondary to phenytoin; and in relation to them, the diagnosis and the treatment of these processes are discussed and reviewed. The AGEP (acute generalised exanthematous pustulosis) is also reviewed. The aetiological diagnosis of severe non-immediate reactions is difficult, and the value of current allergological testing is not well defined in these cases. Diagnosis is based on clinical history, the empirical risk of drugs to trigger SJS/TEN or DRESS, and the in vivo and in vitro testing of the suspect drug. Skin biopsy confirms that the clinical diagnosis and delayed hypersensitivity tests, especially the patch test and the lymphoblastic transformation test (LTT), may be important to confirm the aetiological diagnosis, in our cases emphasising the latter. These diseases can be life threatening (especially DRESS and TEN) and/or have a high rate of major complications or sequelae (SJS/TEN). The three cases described progressed well without sequelae. All were treated with corticosteroids, which is the most currently accepted treatment although the effect has not been clearly demonstrated.

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Phenobarbital‐induced severe cutaneous adverse drug reactions are associated with CYP2C19*2 in Thai children

Abstract: CYP2C19*2 variant may play a role in the genetic predisposition of SCARs from phenobarbital.

Cited by 54 publications

References 20 publications

Stevens-Johnson Syndrome and toxic epidermal necrolysis in children: a retrospective study at Srinagarind Hospital, Khon Kaen, Thailand 1992–2012

Stevens-Johnson Syndrome and toxic epidermal necrolysis in children: a retrospective study at Srinagarind Hospital, Khon Kaen, Thailand 1992–2012

Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population

Severe delayed skin reactions related to drugs in the paediatric age group: A review of the subject by way of three cases (Stevens–Johnson syndrome, toxic epidermal necrolysis and DRESS)

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