Do HLA-A markers predict skin-reactions from aromatic antiepileptic drugs in a Norwegian population? A case control study

Shirzadi, Maryam; Thorstensen, Ketil; Helde, Grethe; Moen, Torolf; Brodtkorb, Eylert

doi:10.1016/j.eplepsyres.2015.09.011

Cited by 15 publications

(8 citation statements)

References 22 publications

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“…The established associations of HLA-B*15:02 and HLA-A*24:02 with various cADRs induced by aromatic AEDs were not noted in our study population. [9,[22][23][24] This could be due to lower prevalence of HLA-B*15:02 in the Indian population (2-4%) vis a vis in the Han Chinese (8%) [25,26]. However, we did find that HLA-A*24 had a higher AF in CBZ-induced MPE compared to tolerant controls (p = 0.06).…”

Section: Discussionmentioning

confidence: 81%

Association of cutaneous adverse drug reactions due to antiepileptic drugs with HLA alleles in a North Indian population

Ihtisham

Ramanujam

Srivastava

et al. 2019

Seizure

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Aromatic antiepileptic drugs (AEDs) are frequently implicated in cutaneous adverse drug reactions (cADRs), a few of which are associated with certain human leukocyte antigen (HLA) alleles in some populations. We aimed to find HLA-associations with AED-related cADRs among North Indians. Methods: North Indian subjects with cADR due to an AED, and those who were AED-tolerant were recruited as cases and controls, respectively. Genotyping for HLA-A, B and DRB1 were performed. Statistical analysis to compare carrier-rates and allele-frequencies between cases and controls (and healthy population, where necessary), was done for HLA-alleles occurring more than twice in either group. Results: 120 cases {11 -Lamotrigine (LTG), 14 -Valproic acid (VPA), 8 -Levetiracetam (LEV), 35 -Carbamazepine (CBZ) and 52 -Phenytoin (PHT)}, and 250 controls were recruited. Presence of HLA-A*31:01 and HLA-B*51:01 were found to increase the risk of Maculopapular exanthema (MPE) due to CBZ and PHT (

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Section: Discussionmentioning

confidence: 81%

Association of cutaneous adverse drug reactions due to antiepileptic drugs with HLA alleles in a North Indian population

Ihtisham

Ramanujam

Srivastava

et al. 2019

Seizure

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“…The association between HLA and CBZ-SJS/TEN is generally ethnically specific such as HLA-B*15:02 in populations in south China and southeast Asia, with sensitivities varying from 69.6% (the present study) to 100%, 12–17,20 and HLA-A*31:01 in white 29 and Japanese populations. 35 Notably, the specificity of HLA-B*15:02 for CBZ-SJS/TEN appears to correlate with phenotype severity. 36 In Taiwanese cases with CBZ-SJS/TEN with >5% skin detachment, the HLA-B*15:02 carrier rate was as high as 100%, whereas in more common cases with <5% skin detachment, this rate varied from 80.0% to 87.7%; HLA-A*31:01 was also demonstrated to be a risk factor for MPE in Taiwanese populations.…”

Section: Discussionmentioning

confidence: 99%

HLA-A*24:02 as a common risk factor for antiepileptic drug–induced cutaneous adverse reactions

Shi¹,

Min²,

Zhou³

et al. 2017

Neurology

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Objective:To investigate the involvement of human leukocyte antigen (HLA) loci in aromatic antiepileptic drug–induced cutaneous adverse reactions.Methods:A case-control study was performed to detect HLA loci involved in aromatic antiepileptic drug–induced Stevens-Johnson syndrome in a southern Han Chinese population. Between January 1, 2006, and December 31, 2015, 91 cases of Stevens-Johnson syndrome induced by aromatic antiepileptic drugs and 322 matched drug-tolerant controls were enrolled from 8 centers. Important genotypes were replicated in cases with maculopapular eruption and in the meta-analyses of data from other populations. Sequence-based typing determined the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genotypes.Results:HLA-B*15:02 was confirmed as strongly associated with carbamazepine-induced Stevens-Johnson syndrome (p = 5.63 × 10−15). In addition, HLA-A*24:02 was associated significantly with Stevens-Johnson syndrome induced by the aromatic antiepileptic drugs as a group (p = 1.02 × 10−5) and by individual drugs (carbamazepine p = 0.015, lamotrigine p = 0.005, phenytoin p = 0.027). Logistic regression analysis revealed a multiplicative interaction between HLA-B*15:02 and HLA-A*24:02. Positivity for HLA-A*24:02 and/or HLA-B*15:02 showed a sensitivity of 72.5% and a specificity of 69.0%. The presence of HLA-A*24:02 in cases with maculopapular exanthema was also significantly higher than in controls (p = 0.023). Meta-analysis of data from Japan, Korea, Malaysia, Mexico, Norway, and China revealed a similar association.Conclusions:HLA-A*24:02 is a common genetic risk factor for cutaneous adverse reactions induced by aromatic antiepileptic drugs in the southern Han Chinese and possibly other ethnic populations. Pretreatment screening is recommended for people in southern China.

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“…The association between HLA-A*31:01 and CBZ hypersensitivity was not detected in a population from Norway. 26 There were 48 cases of CBZ hypersensitivity in this study, but nearly all patients (43/48 [89.6%]) were diagnosed with MPE according to the phenotype standardization for immunemediated drug-induced skin injury guidance. 27 A major issue with MPE is that causality determination is more difficult as many other factors including concomitant viral infections can cause mild cutaneous eruptions.…”

Section: Hla-a*31:01 and Cbz Hypersensitivitymentioning

confidence: 81%

“… 7 A subsequent study detected an association with HSS but not SJS, 22 whereas the most recent study in a Norwegian population was unable to detect any association between HLA-A*31:01 and CBZ-induced MPE. 26 The discrepancies in the studies are most likely to be due to a combination of small sample sizes, incorrect classification/diagnosis of cases and difficulty in determining causality particularly in milder cases. It is important to note that diagnosis of CBZ hypersensitivity reactions is complex because many patients are prescribed multiple medications preceding a reaction with diverse clinical presentations and variable times to onset of hypersensitivity, and the difficulty in excluding other nondrug etiologies.…”

Section: Hla-a*31:01 and Cbz Hypersensitivitymentioning

confidence: 99%

The <em>HLA-A*31:01</em> allele: influence on carbamazepine treatment

Yip

Pirmohamed²

2017

PGPM

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Carbamazepine (CBZ) is an effective anticonvulsant that can sometimes cause hypersensitivity reactions that vary in frequency and severity. Strong associations have been reported between specific human leukocyte antigen (HLA) alleles and susceptibility to CBZ hypersensitivity reactions. Screening for HLA-B*15:02 is mandated in patients from South East Asia because of a strong association with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). HLA-A*31:01 predisposes to multiple phenotypes of CBZ hypersensitivity including maculopapular exanthema, hypersensitivity syndrome, and SJS/TEN in a range of populations including Europeans, Japanese, South Koreans and Han Chinese, although the effect size varies between the different phenotypes and populations. Between 47 Caucasians and 67 Japanese patients would need to be tested for HLA-A*31:01 in order to avoid a single case of CBZ hypersensitivity. A cost-effectiveness study has demonstrated that HLA-A*31:01 screening would be cost-effective. Patient preference assessment has also revealed that patients prefer pharmacogenetic screening and prescription of alternative anticonvulsants compared to current standard of practice without pharmacogenetic testing. For patients who test positive for HLA-A*31:01, alternative treatments are available. When alternatives have failed or are unavailable, HLA-A*31:01 testing can alert clinicians to 1) patients who are at increased risk of CBZ hypersensitivity who can then be targeted for more intensive monitoring and 2) increase diagnostic certainty in cases where hypersensitivity has already occurred, so patients can be advised to avoid structurally related drugs in the future. On the basis of the current evidence, we would favor screening all patients for HLA-A*31:01 and HLA-B*15:02 prior to starting CBZ therapy.

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Do HLA-A markers predict skin-reactions from aromatic antiepileptic drugs in a Norwegian population? A case control study

Cited by 15 publications

References 22 publications

Association of cutaneous adverse drug reactions due to antiepileptic drugs with HLA alleles in a North Indian population

Association of cutaneous adverse drug reactions due to antiepileptic drugs with HLA alleles in a North Indian population

HLA-A*24:02 as a common risk factor for antiepileptic drug–induced cutaneous adverse reactions

The <em>HLA-A*31:01</em> allele: influence on carbamazepine treatment

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