Validation of a genotyping technique for a surrogate marker of HLA-B58:01 for allopurinol-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in the Japanese population

Background UK guidelines for managing adults with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), published by the British Association of Dermatologists (BAD) in 2016, outline a set of audit standards. Aim To audit current management of SJS/TEN in adults against standards in the BAD guidelines. Methods BAD members were invited to submit data on five consecutive adults with SJS/TEN per department over an 8-week period in 2022. Results Thirty-nine (29%) dermatology centres in the UK participated and data for 147 adults with SJS/TEN were collected. Within 24 hours of the diagnosis being made or suspected, the following were documented: SCORTEN for 52% (76/147) of submitted cases, list of medications for 77% (113/147) and timelines for commencement/alterations of medications for 71% (104/147). Initial assessment was documented of the eyes by an ophthalmologist for 48% (71/147) of cases, mouth in 88% (130/147), genital skin in 70% (103/147) and the urinary tract in 63% (93/147). During the first 10 days after a suspected or confirmed diagnosis of SJS/TEN, daily assessments of the mouth were documented in 18% (26/147) of cases, eyes in 8% (12/147) and urinary tract and genital skin in 10% (14/147). Documentation regarding advice on i) avoidance of the culprit drug was present for 58% (76/130) and ii) requesting a MedicAlert® bracelet/amulet in 6% (9/147). Conclusion This audit suggests that a clinical review checklist might be needed to enable colleagues to maintain standards outlined in the guidelines, including documentation of SCORTEN, daily assessments of mucosal areas, and advice to avoid culprit drug(s) and request for a MedicAlert® bracelet/amulet.

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An Inexpensive and Quick Method for Genotyping of HLA Variants Included in the Spanish Pharmacogenomic Portfolio of National Health System

Taladriz-Sender,

Hernández-Osio,

Zapata-Cobo

et al. 2024

IJMS

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The possibility of using the same genotyping technology (TaqMan) for all the genetic tests included in the new Spanish pharmacogenomics portfolio should enable the application of a multigenotyping platform to obtain a whole pharmacogenomics profile. However, HLA-typing is usually performed with other technologies and needs to be adapted to TaqMan assays. Our aim was to establish a set of TaqMan assays for correct typing of HLA-A*31:01, HLA-B*15:02, HLA-B*57:01, and HLA-B*58:01. Therefore, we searched for and selected SNVs described in different populations as surrogate markers for these HLA alleles, designed TaqMan assays, and tested in a set of samples with known HLA-A and HLA-B. HLA-A*31:01 was correctly typed with a combination of rs1061235 and rs17179220 (PPV 100%, 95% CI 84.6–100-%; NPV 100%, 95% CI 96.5–100.0%), HLA-B*15:02 with rs10484555 (PPV 100%, 95% CI 69.2–100.0%; NPV 100%, 95% CI 96.8–100.0%) and rs144012689 (PPV 100%, 95% CI 69.2–100.0%; NPV 100%, 95% CI 96.8–100.0%), and HLA-B*57:01 with rs2395029 (PPV 99.5%, 95% CI 72.9–99.3%; NPV 99.5%, 95% CI 98.3–100.0%). HLA-B*58:01 was typed using two allele-specific TaqMan probes mixed with a ß-Globin reference and treated as a genotyping assay (PPV 100.0%, 95% CI 81.5–100.0%; NPV 100%, 95% CI 96.8–100.0%). In conclusion, we demonstrated a clinically useful way to type HLA-A and HLA-B alleles included in the Spanish pharmacogenomics portfolio using TaqMan assays.

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Validation of a genotyping technique for a surrogate marker of HLA-B58:01 for allopurinol-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in the Japanese population

Cited by 3 publications

References 40 publications

Anti-inflammatory and antipyretic analgesics and drugs used in gout

Anti-inflammatory and antipyretic analgesics and drugs used in gout

British Association of Dermatologists national clinical audit on the management of Stevens–Johnson syndrome/toxic epidermal necrolysis in adults

An Inexpensive and Quick Method for Genotyping of HLA Variants Included in the Spanish Pharmacogenomic Portfolio of National Health System

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