2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:Tb58,Carriage of HLA-B*58:01 has been shown to be associated with allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) in many populations globally; however, there is a critical need to investigate whether this is generalizable to populations of mixed ancestry, such as those in the US. To assess the association of human leukocyte antigen (HLA) class I and II in a cohort of US patients who received a diagnosis of allopurinol-induced SJS/TEN or DRESS compared with allopurinol-tolerant and population control participants. This genetic association study included consenting individuals who had specialist-adjudicated allopurinol-induced SJS/TEN or DRESS (collectively allopurinol-induced severe cutaneous adverse reactions [SCARs]) between January 1, 2015, and December 31, 2024. HLA carriage in these individuals was compared with allopurinol-tolerant and population control participants identified through the Vanderbilt University Medical Center biobank, which includes 94 489 individuals with imputed HLA class I and II typing from genotyping array data. Data were analyzed from January 2025 to August 2025. The main outcome measure was the association of HLA class I and II alleles with allopurinol-induced SCARs. HLA class I and II conditional logistic regression case-control analyses were performed between patients with allopurinol-induced SCARs and both population control and allopurinol-tolerant control participants matched on age, sex, and self-identified race. Odds ratios (ORs) and 95% CIs were reported, with Bonferroni-corrected P < .05. This genetic association study used conditional logistic regression analyses and included 16 patients with allopurinol-induced SCAR (mean [SD] age, 61.1 [12.6] years; 9 female patients [56.25%] and 7 male patients [43.75%]) and 160 allopurinol-tolerant control participants matched 10:1. Two HLA class I alleles were found to be independently associated with increased risk of allopurinol-induced SCAR: HLA-B*58:01 (OR, 28.0 [95% CI, 8.6-100.6]) and HLA-A*34:02 (OR, 20.6 [95% CI, 3.3-131.1]). No HLA class II alleles meeting the Bonferroni-corrected P < .05 level of significance were identified. These findings suggest that although HLA-B*58:01 was found to be associated with allopurinol-induced SCARs, generalizing findings from previous studies, the allele was absent in more than one-third of the patient cohort and is therefore an incomplete indicator of risk. Importantly, in the US allopurinol-induced SCAR cohort, HLA-A*34:02 was found to be a second independent genetic risk factor for allopurinol-induced SCARs. These findings underscore the need to conduct population-based studies that both reproduce known and uncover novel HLA associations to reduce harm through contributions to screening, risk stratification, and diagnosis.31:T1098, Importance Carriage of HLA-B*58:01 has been shown to be associated with allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) in many populations globally; however, there is a critical need to investigate whether this is generalizable to populations of mixed ancestry, such as those in the US. Objective To assess the association of human leukocyte antigen (HLA) class I and II in a cohort of US patients who received a diagnosis of allopurinol-induced SJS/TEN or DRESS compared with allopurinol-tolerant and population control participants. Design, Setting, and Participants This genetic association study included consenting individuals who had specialist-adjudicated allopurinol-induced SJS/TEN or DRESS (collectively allopurinol-induced severe cutaneous adverse reactions [SCARs]) between January 1, 2015, and December 31, 2024. HLA carriage in these individuals was compared with allopurinol-tolerant and population control participants identified through the Vanderbilt University Medical Center biobank, which includes 94 489 individuals with imputed HLA class I and II typing from genotyping array data. Data were analyzed from January 2025 to August 2025. Main Outcomes and Measures The main outcome measure was the association of HLA class I and II alleles with allopurinol-induced SCARs. HLA class I and II conditional logistic regression case-control analyses were performed between patients with allopurinol-induced SCARs and both population control and allopurinol-tolerant control participants matched on age, sex, and self-identified race. Odds ratios (ORs) and 95% CIs were reported, with Bonferroni-corrected P &lt; .05. Results This genetic association study used conditional logistic regression analyses and included 16 patients with allopurinol-induced SCAR (mean [SD] age, 61.1 [12.6] years; 9 female patients [56.25%] and 7 male patients [43.75%]) and 160 allopurinol-tolerant control participants matched 10:1. Two HLA class I alleles were found to be independently associated with increased risk of allopurinol-induced SCAR: HLA-B*58:01 (OR, 28.0 [95% CI, 8.6-100.6]) and HLA-A*34:02 (OR, 20.6 [95% CI, 3.3-131.1]). No HLA class II alleles meeting the Bonferroni-corrected P &lt; .05 level of significance were identified. Conclusions and Relevance These findings suggest that although HLA-B*58:01 was found to be associated with allopurinol-induced SCARs, generalizing findings from previous studies, the allele was absent in more than one-third of the patient cohort and is therefore an incomplete indicator of risk. Importantly, in the US allopurinol-induced SCAR cohort, HLA-A*34:02 was found to be a second independent genetic risk factor for allopurinol-induced SCARs. These findings underscore the need to conduct population-based studies that both reproduce known and uncover novel HLA associations to reduce harm through contributions to screening, risk stratification, and diagnosis. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Drug Reaction With Eosinophilia and Systemic Symptoms: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Drug Reaction With Eosinophilia and Systemic Symptoms (condition). Clinician-written summaries and actionable practice insights. 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Two HLA class I alleles were found to be independently associated with increased risk of allopurinol-induced SCAR: HLA-B*58:01 (OR, 28.0 [95% CI, 8.6-100.6]) and HLA-A*34:02 (OR, 20.6 [95% CI, 3.3-131.1]). No HLA class II alleles meeting the Bonferroni-corrected P < .05 level of significance were identified.","abstract":"$30","keywords":[],"pubmed_id":"41160012","conclusions":"","publication_date":"2025-10-29T00:00:00"},"crossref":{"DOI":"10.1001/jamadermatol.2025.4240","URL":"https://doi.org/10.1001/jamadermatol.2025.4240","ISSN":["2168-6068"],"link":[{"URL":"https://jamanetwork.com/journals/jamadermatology/articlepdf/2840445/jamadermatology_campbell_2025_br_250010_1765313940.3825.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"1258","type":"journal-article","issue":"12","score":1,"title":["HLA-B*58:01 and Risk of Allopurinol-Induced Severe Cutaneous Adverse Reactions in the US"],"author":[{"given":"Chelsea N.","family":"Campbell","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Center for Drug Safety and 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Study","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.4240","tag_type":"warning","value":"Case count is very small (n=16), yielding wide CIs around effect estimates.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.4240","tag_type":"warning","value":"Controls relied on imputed HLA data from a single biobank, which may affect allele-calling accuracy.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.4240","tag_type":"warning","value":"Population-control sample size and matching details are not provided in the excerpt.","value_numeric":null}],"summaries":{"what_studied":"A US genetic case-control study (2015-2024) assessed whether HLA class I/II alleles are associated with allopurinol-induced severe cutaneous adverse reactions (SJS/TEN or DRESS) by comparing 16 adjudicated cases with matched allopurinol-tolerant and population controls.","key_result":"Two HLA class I alleles showed independent associations with allopurinol-induced SCAR: HLA-B*58:01 (OR 28.0, 95% CI 8.6-100.6) and HLA-A*34:02 (OR 20.6, 95% CI 3.3-131.1); no class II allele met Bonferroni-corrected significance. HLA-B*58:01 was absent in more than one-third of cases, indicating incomplete sensitivity.","limitations":"Very small case sample (n=16) with wide confidence intervals. Controls from a single biobank used imputed HLA typing, which may reduce allele-calling accuracy.","practice_takeaway":"HLA-B*58:01 remains a strong risk marker for allopurinol-induced SCAR in US patients, but testing alone will miss many at-risk patients. HLA-A*34:02 emerged as a second independent risk allele and warrants replication before informing routine screening."}},{"doi":"10.1001/jamadermatol.2022.4519","pmid":"36630118","title":"Drug Reaction With Eosinophilia and Systemic Symptoms","journal_title":"JAMA Dermatology","journal_issn":"2168-6068","published_at":"2023-01-12T00:00:00.000Z","url":"https://doi.org/10.1001/jamadermatol.2022.4519","source_score":62,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2023-02-03","doi":"10.1001/jamadermatol.2022.4519","days":"30","issn":"2168-6068","rank":"2","field":"Clinical Medicine","score":"62","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1001/jamadermatol.2022.4519","title":"Drug Reaction With Eosinophilia and Systemic Symptoms.","journal":"JAMA dermatology","methods":"","results":"","abstract":"This Patient Page describes the symptoms, diagnosis, and treatment of drug reaction with eosinophilia and systemic symptoms.","keywords":[],"pubmed_id":"36630118","conclusions":"","publication_date":"2023-01-12T00:00:00"},"crossref":{"DOI":"10.1001/jamadermatol.2022.4519","URL":"https://doi.org/10.1001/jamadermatol.2022.4519","ISSN":["2168-6068"],"link":[{"URL":"https://jamanetwork.com/journals/jamadermatology/articlepdf/2800235/jamadermatology_krantz_2023_pg_220004_1677862975.67056.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"348","type":"journal-article","issue":"3","score":1,"title":["Drug Reaction With Eosinophilia and Systemic Symptoms"],"author":[{"given":"Matthew S.","family":"Krantz","sequence":"first","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}]},{"given":"Elizabeth J.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}]}],"issued":{"date-parts":[[2023,3,1]]},"member":"10","prefix":"10.1001","source":"Crossref","volume":"159","created":{"date-time":"2023-01-11T16:04:39Z","timestamp":1673453079000,"date-parts":[[2023,1,11]]},"indexed":{"date-time":"2025-09-13T15:59:33Z","timestamp":1757779173748,"date-parts":[[2025,9,13]]},"subject":[],"abstract":"This Patient Page describes the symptoms, diagnosis, and treatment of drug reaction with eosinophilia and systemic symptoms.","language":"en","relation":{},"resource":{"primary":{"URL":"https://jamanetwork.com/journals/jamadermatology/fullarticle/2800235"}},"subtitle":[],"deposited":{"date-time":"2023-03-15T15:12:26Z","timestamp":1678893146000,"date-parts":[[2023,3,15]]},"issn-type":[{"type":"print","value":"2168-6068"}],"published":{"date-parts":[[2023,3,1]]},"publisher":"American Medical Association (AMA)","reference":null,"short-title":[],"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3,1]]}},"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["JAMA Dermatology"],"published-print":{"date-parts":[[2023,3,1]]},"reference-count":0,"published-online":null,"references-count":0,"short-container-title":["JAMA Dermatol"],"is-referenced-by-count":8},"unpaywall":{"doi":"10.1001/jamadermatol.2022.4519","is_oa":true,"title":"Drug Reaction With Eosinophilia and Systemic Symptoms","updated":"2025-06-20T04:27:11+00:00","published_date":"2023-01-11","best_oa_location":{"url":"https://jamanetwork.com/journals/jamadermatology/articlepdf/2800235/jamadermatology_krantz_2023_pg_220004_1677862975.67056.pdf","pmh_id":null,"url_for_pdf":"https://jamanetwork.com/journals/jamadermatology/articlepdf/2800235/jamadermatology_krantz_2023_pg_220004_1677862975.67056.pdf","url_for_landing_page":"https://doi.org/10.1001/jamadermatol.2022.4519"}}},"created_at":"2025-09-22T14:20:55.574Z","updated_at":"2025-09-22T14:20:55.574Z","tags":[{"paper_doi":"10.1001/jamadermatol.2022.4519","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2022.4519","tag_type":"condition","value":"Drug Reaction With Eosinophilia and Systemic Symptoms","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2022.4519","tag_type":"study_design","value":"Editorial","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2022.4519","tag_type":"warning","value":"Study design label is approximate because the article is not a traditional study.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2022.4519","tag_type":"warning","value":"This is a patient education page, not a research study; no outcomes, comparators, or sample size are provided.","value_numeric":null}],"summaries":{"what_studied":"A patient education page outlining the symptoms, diagnosis, and treatment of drug reaction with eosinophilia and systemic symptoms (DRESS).","limitations":"This is a patient education page, not original research or a clinical study.","practice_takeaway":"Use this as a concise resource to counsel patients on DRESS symptoms, diagnostic approach, and treatment options."}}],"initialOffset":2,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Drug Reaction With Eosinophilia and Systemic Symptoms"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Drug Reaction With Eosinophilia and Systemic Symptoms"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Drug Reaction With Eosinophilia and Systemic Symptoms"}}}]]

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