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Drug reaction with eosinophilia and systemic symptoms (DRESS) is associated with commonly prescribed drugs, carries significant morbidity and mortality, and is frequently encountered by Allergists and Immunologists in clinical practice. METHODS: We reviewed the publicly available FDA adverse event reporting system (FAERS) database from 1999-2019 for reports that specifically contained the term ''drug reaction with eosinophilia and systemic symptoms.'' We sorted reports by generic drug names, number and sex of cases, median age of cases, and reported deaths. RESULTS: The search term for ''DRESS'' was reported from 2003from onwards. From 2003from -2019,293 (0.09%) of 16,693,661 adverse drug events reported in FAERS were reported as DRESS. The overall median reported age of DRESS was 51 years with a distribution of 47% female and 43% male. The top 5 drugs associated with DRESS were allopurinol, vancomycin, lamotrigine, carbamazepine, and trimethoprim-sulfamethoxazole. These accounted for 7398 (48.4%) reported cases and 56% of reported deaths. There were significantly more females than males affected by lamotrigine DRESS (63%), p<0.0005. Death was reported in 1057 (6.9%) cases overall, at a median age of 61, and was highest with allopurinol (235/2020 (11.6%)). Increasing reports of DRESS for all reported agents were observed over time. CONCLUSIONS: Currently, five drugs account for almost 50% of DRESS cases. Importantly, allopurinol, vancomycin, and carbamazepine account for one-third of reported cases and 40% of deaths and have actionable HLA risk factors suggesting a need for heightened awareness and risk stratification strategies to improve prevention and early diagnosis of DRESS.

Prof.RATIONALE: Vancomycin is recognized to be associated with ''allergy labels'' (VAL) in the electronic health record; however, clinical distribution and knowledge of host predisposition across distinct clinical phenotypes are lacking. METHODS: BioVu, a DNA Biobank paired with a deidentified EHR was used to review VAL. We included subjects with multiethnicity genotyping array (MegaEx) typing with HLA ABC DR DQ DP imputed by SNP2HLA. We interrogated specific VAL phenotypes for HLA associations, concurrent allergy labels, and outcomes compared with age, sex, race and disease matched vancomycin tolerant controls (conditional logistical analyses, R version 4.0.3) Bonferroni controlled for multiple comparisons. Where VAL phenotype sample size >100 , we performed MegaEx genome wide association studies (GWAS). RESULTS: 1020/3076236 (0.33%) BioVu MegaEx VAL patients were identified (non-IgE mediated reactions (Redman) type reactions (42%), nephrotoxicity (6.2%) cytopenias, and potential hypersensitivity reactions (15.7%). Those with Redman-type reactions were younger 40 IQR [23, 61] vs. 55 IQR [40, 67], p<0.0005. HLA-A*32:01, previously associated with vancomycin DRESS, was equally represented across the entire VAL group (67/1017 (6.59%) and BioVu MegaEx population 5634/94179 (5.98%)), but was less common in VAL nephrotoxicity group (1/42 (2.38%), driven by higher prevalence of African Americans in vancomycin-piperacillin tazobactam nephrotoxicity group (4/77 (5.2%) vs. 12/587 (2.0%) European-Americans, p50.08.). Cluster and network analyses from HLA and MegaEx data identified significant phenotype-genotype relationships. CONCLUSIONS: VAL are complex and heterogeneous clinical phenotypes that can be defined by epidemiological and genetic differences. Non-IgE mediated reactions, the most common, remain a permanent part of the EHR despite their modifiability.