Dataset Information

Study protocol: Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR).

ABSTRACT:

Introduction

Severe cutaneous adverse reactions (SCAR) are a group of T cell-mediated hypersensitivities associated with significant morbidity, mortality and hospital costs. Clinical phenotypes include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP). In this Australasian, multicentre, prospective registry, we plan to examine the clinical presentation, drug causality, genomic predictors, potential diagnostic approaches, treatments and long-term outcomes of SCAR in Australia and New Zealand.

Methods and analysis

Adult and adolescent patients with SCAR including SJS, TEN, DRESS, AGEP and another T cell-mediated hypersensitivity, generalised bullous fixed drug eruption, will be prospectively recruited. A waiver of consent has been granted for some sites to retrospectively include cases which result in early mortality. DNA will be collected for all prospective cases. Blood, blister fluid and skin biopsy sampling is optional and subject to patient consent and site capacity. To develop culprit drug identification and prevention, genomic testing will be performed to confirm human leukocyte antigen (HLA) type and ex vivo testing will be performed via interferon-γ release enzyme linked immunospot assay using collected peripheral blood mononuclear cells. The long-term outcomes of SCAR will be investigated with a 12-month quality of life survey and examination of prescribing and mortality data.

Ethics and dissemination

This study was reviewed and approved by the Austin Health Human Research Ethics Committee (HREC/50791/Austin-19). Results will be published in peer-reviewed journals and presented at relevant conferences.

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12619000241134).

SUBMITTER: James F

PROVIDER: S-EPMC9389100 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Study protocol: Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR).

James Fiona F Goh Michelle S Y MSY Mouhtouris Effie E Vogrin Sara S Chua Kyra Y L KYL Holmes Natasha E NE Awad Andrew A Copaescu Ana-Maria AM De Luca Joseph F JF Zubrinich Celia C Gin Douglas D Cleland Heather H Douglas Abby A Kern Johannes S JS Katelaris Constance H CH Thien Francis F Barnes Sara S Yun James J Tong Winnie W Smith William B WB Carr Andrew A Anderson Tara T Legg Amy A Bourke Jack J Mackay Laura K LK Aung Ar Kar AK Phillips Elizabeth J EJ Trubiano Jason J

BMJ open 20220817 8

<h4>Introduction</h4>Severe cutaneous adverse reactions (SCAR) are a group of T cell-mediated hypersensitivities associated with significant morbidity, mortality and hospital costs. Clinical phenotypes include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP). In this Australasian, multicentre, prospective registry, we plan to examine the clinical presentation, drug ...[more]

PMID: 35977774

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Project description:BackgroundSevere cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR.MethodsProspective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites.Resultswe report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%).ConclusionIn the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality.Trial registrationANZCTR ACTRN12619000241134. Registered 19 February 2019.

Project description:PurposeSevere cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) to antiepileptic drug (AED), are rare, but result in significant morbidity and mortality. We investigated the major culprit drugs, clinical characteristics, and clinical course and outcomes of AED-induced SCARs using a nationwide registry in Korea.MethodsA total of 161 patients with AED-induced SCARs from 28 referral hospitals were analyzed. The causative AEDs, clinical characteristics, organ involvements, details of treatment, and outcomes were evaluated. We compared the clinical and laboratory parameters between SJS/TEN and DRESS according to the leading causative drugs. We further determined risk factors for prolonged hospitalization in AED-induced SCARs.ResultsCarbamazepine and lamotrigine were the most common culprit drugs causing SCARs. Valproic acid and levetiracetam also emerged as the major causative agents. The disease duration and hospital stay in carbamazepine-induced SJS/TEN were shorter than those in other AEDs (P< 0.05, respectively). In younger patients, lamotrigine caused higher incidences of DRESS than other drugs (P= 0.045). Carbamazepine, the most common culprit drug for SCARs, was associated with a favorable outcome related with prolonged hospitalization in SJS (odds ratio, 0.12; 95% confidence interval, 0.02-0.63, P= 0.12), and thrombocytopenia was found to be a risk factor for prolonged hospitalization in DRESS.ConclusionThis was the first large-scale epidemiological study of AED-induced SCARs in Korea. Valproic acid and levetiracetam were the significant emerging AEDs causing SCARs in addition to the well-known offending AEDs such as carbamazepine and lamotrigine. Carbamazepine was associated with reduced hospitalization, but thrombocytopenia was a risk factor for prolonged hospitalization. Our results suggest that the clinical characteristics and clinical courses of AED-induced SCARs might vary according to the individual AEDs.

Project description:PurposeNonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry.MethodsA retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids.ResultsA total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals.ConclusionsThe present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.

Dataset Information

Study protocol: Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR).

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Publications

Study protocol: Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR).

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