James F

Goh MSY

Mouhtouris E

Vogrin S

Chua KYL

Holmes NE

Awad A

Copaescu AM

De Luca JF

Zubrinich C

Gin D

Cleland H

Douglas A

Kern JS

Katelaris CH

Thien F

Barnes S

Yun J

Tong W

Smith WB

Carr A

Anderson T

Legg A

Bourke J

Mackay LK

Aung AK

Phillips EJ

Trubiano J

2022-08-17

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).

Centre for Antibiotic Allergy & Research, Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia Fiona.JAMES@austin.org.au.

Department of Dermatology, St Vincent's Hospital Melbourne Pty Ltd, Fitzroy, Victoria, Australia.

Department of Dermatology, Alfred Health, Melbourne, Victoria, Australia.

Centre for Antibiotic Allergy & Research, Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.

Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.

Allergy, Asthma & Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia.

School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia.

Department of Dermatology, Alfred Hospital, Melbourne, Victoria, Australia.

Victorian Adult Burns Service, Alfred Hospital, Melbourne, Victoria, Australia.

Infectious Diseases and Infection Control, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Dermatology Department, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Department of Immunology, Campbelltown Hospital, Campbelltown, New South Wales, Australia.

Eastern Health Clinical School, Monash University, Clayton, Victoria, Australia.

Department of Respiratory and Sleep Medicine, Eastern Health, Box Hill, Victoria, Australia.

Monash Lung Sleep Allergy and Immunology, Monash Health, Clayton, Victoria, Australia.

Immunology and Rheumatology, Nepean Hospital, Penrith, New South Wales, Australia.

HIV & Immunology, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia.

School of Clinical Medicine, St Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, UNSW, Sydney, New South Wales, Australia.

Clinical Immunology and Allergy, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Department of Infectious Diseases, Royal Hobart Hospital, Hobart, Tasmania, Australia.

Pharmacy Department, Royal Darwin Hospital, Casuarina, Northern Territory, Australia.

Department of Immunology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.

Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.

Department of General Medicine, Alfred Hospital, Melbourne, Victoria, Australia.

Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.

Departments of Medicine, Dermatology, Pathology, Microbiology, Immunology and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

BMJ Open. 2022 Aug 17;12(8):e055906. doi: 10.1136/bmjopen-2021-055906.

0000-0003-0469-5666

0000-0002-9183-5032

0000-0001-6541-5512

0000-0002-5111-6367

https://pubmed.ncbi.nlm.nih.gov/35977774/?otool=iaurydwlib

https://hdl.handle.net/10137/12252

12

Adolescent

Adult

Australia/epidemiology

*Eosinophilia/complications

Humans

Leukocytes, Mononuclear

Prospective Studies

Quality of Life

Registries

*Stevens-Johnson Syndrome/diagnosis/etiology/therapy

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

Clinical Trial Protocol

Journal Article

Publication