Asymptomatic hyperuricaemia and allopurinol induced toxic epidermal necrolysis.

Auböck, Josef; Fritsch, P.

doi:10.1136/bmj.290.6486.1969

Cited by 38 publications

(16 citation statements)

References 11 publications

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“…Even though rare, the mortality rate can be as high as 26% (4,5). SJS͞TEN is characterized by a rapidly developing blistering exanthema of macules and target-like lesions accompanied by mucosal involvement and skin detachment.…”

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confidence: 99%

HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol

Hung

Chung

Liou

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

1,118

810

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Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis. The adverse events are unpredictable and carry significant morbidity and mortality. To identify genetic markers for allopurinol–SCAR, we carried out a case-control association study. We enrolled 51 patients with allopurinol–SCAR and 228 control individuals (135 allopurinol-tolerant subjects and 93 healthy subjects from the general population), and genotyped for 823 SNPs in genes related to drug metabolism and immune response. The initial screen revealed strong association between allopurinol–SCAR and SNPs in the MHC region, including BAT3 (encoding HLA-B associated transcript 3), MSH5 (mutS homolog 5), and MICB (MHC class I polypeptide-related sequence B) ( P < 10 –7 ). We then determined the alleles of HLA loci A, B, C, and DRB1. The HLA-B*5801 allele was present in all (100%) 51 patients with allopurinol–SCAR, but only in 20 (15%) of 135 tolerant patients [odds ratio 580.3 (95% confidence interval, 34.4–9780.9); corrected P value = 4.7 × 10 –24 ] and in 19 (20%) of 93 of healthy subjects [393.51 (23.23–6665.26); corrected P value = 8.1 × 10 –18 ]. HLA alleles A*3303, Cw*0302, and DRB1*0301 were in linkage disequilibrium and formed an extended haplotype with HLA-B*5801. Our results indicated that allopurinol–SCAR is strongly associated with a genetic predisposition in Han Chinese. In particular, HLA-B*5801 allele is an important genetic risk factor for this life-threatening condition.

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confidence: 99%

HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol

Hung

Chung

Liou

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

1,118

810

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“…1 Allopurinol has been implicated repeatedly in lifethreatening severe adverse drug reactions including hypersensitivity syndrome, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). 2,3 SJS and TEN are rare, life-threatening, bullous cutaneous diseases generally considered as immune-mediated reactions to drugs. These severe cutaneous adverse reactions (SCAR) are characterized by epidermal necrosis, extensive detachment of the epidermis, erosions of mucous membranes and severe constitutional symptoms.…”

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confidence: 99%

Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel

Halevy

Ghislain

Mockenhaupt

et al. 2008

Journal of the American Academy of Dermatology

420

312

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“…5 Once SCARs occur, the mortality rate increases to 25% in cases related to allopurinol, which is higher than those of other drugs. 6,7 Therefore, physicians have to pay more attention to recognize and prevent the development of SCARs when they prescribe allopurinol. 8 Chronic renal insufficiency (CRI) is a well-known risk factor for allopurinolinduced SCARs and is an underlying disease that needs an allopurinol prescription for the related hyperuricemia.…”

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confidence: 99%

An effective strategy to prevent allopurinol-induced hypersensitivity by HLA typing

Jung

Park

et al. 2015

Genetics in Medicine

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Purpose: This study was conducted to evaluate the usefulness of human leukocyte antigen (HLA) typing in preventing allopurinolinduced severe cutaneous adverse reactions (SCARs) through the application of an allopurinol tolerance induction protocol or prescription of other alternative medications in high-risk patients.Methods: HLA typing was performed in patients with chronic renal insufficiency who needed allopurinol. HLA-B*58:01-negative patients were prescribed the usual dose of allopurinol. For HLA-B*58:01-positive patients, administration of either allopurinol based on a 28-day tolerance induction protocol or alternative medications was initiated. Hypersensitivity reactions were surveyed for 90 days and compared with the result of a previous retrospective cohort study.

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Asymptomatic hyperuricaemia and allopurinol induced toxic epidermal necrolysis.

Cited by 38 publications

References 11 publications

HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol

HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol

Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel

An effective strategy to prevent allopurinol-induced hypersensitivity by HLA typing

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