. 2022 Aug 17;12(8):e055906.

doi: 10.1136/bmjopen-2021-055906.

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

Fiona James¹, Michelle S Y Goh^{2

3}, Effie Mouhtouris⁴, Sara Vogrin⁵, Kyra Y L Chua⁴, Natasha E Holmes^{4

5}, Andrew Awad⁴, Ana-Maria Copaescu⁴, Joseph F De Luca⁴, Celia Zubrinich^{6

7}, Douglas Gin⁸, Heather Cleland⁹, Abby Douglas¹⁰, Johannes S Kern^{5

11}, Constance H Katelaris¹², Francis Thien^{13

14}, Sara Barnes¹⁵, James Yun¹⁶, Winnie Tong^{17

18}, William B Smith¹⁹, Andrew Carr¹⁷, Tara Anderson²⁰, Amy Legg²¹, Jack Bourke²², Laura K Mackay²³, Ar Kar Aung²⁴, Elizabeth J Phillips^{25

26}, Jason Trubiano^{4

5

27}

Affiliations

¹ Centre for Antibiotic Allergy & Research, Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia Fiona.JAMES@austin.org.au.
² Department of Dermatology, St Vincent's Hospital Melbourne Pty Ltd, Fitzroy, Victoria, Australia.
³ Department of Dermatology, Alfred Health, Melbourne, Victoria, Australia.
⁴ Centre for Antibiotic Allergy & Research, Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.
⁵ Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
⁶ Allergy, Asthma & Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia.
⁷ School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia.
⁸ Department of Dermatology, Alfred Hospital, Melbourne, Victoria, Australia.
⁹ Victorian Adult Burns Service, Alfred Hospital, Melbourne, Victoria, Australia.
¹⁰ Infectious Diseases and Infection Control, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
¹¹ Dermatology Department, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
¹² Department of Immunology, Campbelltown Hospital, Campbelltown, New South Wales, Australia.
¹³ Eastern Health Clinical School, Monash University, Clayton, Victoria, Australia.
¹⁴ Department of Respiratory and Sleep Medicine, Eastern Health, Box Hill, Victoria, Australia.
¹⁵ Monash Lung Sleep Allergy and Immunology, Monash Health, Clayton, Victoria, Australia.
¹⁶ Immunology and Rheumatology, Nepean Hospital, Penrith, New South Wales, Australia.
¹⁷ HIV & Immunology, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia.
¹⁸ School of Clinical Medicine, St Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, UNSW, Sydney, New South Wales, Australia.
¹⁹ Clinical Immunology and Allergy, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
²⁰ Department of Infectious Diseases, Royal Hobart Hospital, Hobart, Tasmania, Australia.
²¹ Pharmacy Department, Royal Darwin Hospital, Casuarina, Northern Territory, Australia.
²² Department of Immunology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.
²³ Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
²⁴ Department of General Medicine, Alfred Hospital, Melbourne, Victoria, Australia.
²⁵ Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
²⁶ Departments of Medicine, Dermatology, Pathology, Microbiology, Immunology and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁷ National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

PMID: 35977774
PMCID: PMC9389100
DOI: 10.1136/bmjopen-2021-055906

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

Fiona James et al. BMJ Open. 2022.

. 2022 Aug 17;12(8):e055906.

doi: 10.1136/bmjopen-2021-055906.

Authors

Affiliations

¹ Centre for Antibiotic Allergy & Research, Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia Fiona.JAMES@austin.org.au.
² Department of Dermatology, St Vincent's Hospital Melbourne Pty Ltd, Fitzroy, Victoria, Australia.
³ Department of Dermatology, Alfred Health, Melbourne, Victoria, Australia.
⁴ Centre for Antibiotic Allergy & Research, Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.
⁵ Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
⁶ Allergy, Asthma & Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia.
⁷ School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia.
⁸ Department of Dermatology, Alfred Hospital, Melbourne, Victoria, Australia.
⁹ Victorian Adult Burns Service, Alfred Hospital, Melbourne, Victoria, Australia.
¹⁰ Infectious Diseases and Infection Control, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
¹¹ Dermatology Department, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
¹² Department of Immunology, Campbelltown Hospital, Campbelltown, New South Wales, Australia.
¹³ Eastern Health Clinical School, Monash University, Clayton, Victoria, Australia.
¹⁴ Department of Respiratory and Sleep Medicine, Eastern Health, Box Hill, Victoria, Australia.
¹⁵ Monash Lung Sleep Allergy and Immunology, Monash Health, Clayton, Victoria, Australia.
¹⁶ Immunology and Rheumatology, Nepean Hospital, Penrith, New South Wales, Australia.
¹⁷ HIV & Immunology, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia.
¹⁸ School of Clinical Medicine, St Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, UNSW, Sydney, New South Wales, Australia.
¹⁹ Clinical Immunology and Allergy, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
²⁰ Department of Infectious Diseases, Royal Hobart Hospital, Hobart, Tasmania, Australia.
²¹ Pharmacy Department, Royal Darwin Hospital, Casuarina, Northern Territory, Australia.
²² Department of Immunology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.
²³ Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
²⁴ Department of General Medicine, Alfred Hospital, Melbourne, Victoria, Australia.
²⁵ Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
²⁶ Departments of Medicine, Dermatology, Pathology, Microbiology, Immunology and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁷ National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

PMID: 35977774
PMCID: PMC9389100
DOI: 10.1136/bmjopen-2021-055906

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).

Keywords: Adverse events; CLINICAL PHARMACOLOGY; Dermatological epidemiology; EPIDEMIOLOGY; IMMUNOLOGY; PREVENTIVE MEDICINE.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

**Figure 1**
Overview of Australasian Registry of Severe Cutaneous Adverse Reactions study design (adapted from Eldridge *et al*25). SCAR, severe cutaneous adverse reactions.

See this image and copyright information in PMC

Cited by

The Australasian Registry for Severe Cutaneous Adverse Reactions (AUS-SCAR) - Providing a roadmap for closing the diagnostic, patient, and healthcare gaps for a group of rare drug eruptions.
James F, Goh MS, Vogrin S, Ng I, Douglas AP, Holmes NE, Chua KY, De Luca J, Sharma P, Zubrinich C, Aung AK, Gin D, Lambros B, Baker C, Foley P, Chong AH, Thien F, Fok JS, Su J, Scardamaglia L, Awad A, Tong S, Johnson D, Godsell J, Arasu A, Barnes S, Ojaimi S, Mar A, Yun J, Ange N, Tong WWY, Carr A, Loprete J, Katelaris CH, Slape D, Keat K, West TA, Lee M, Smith W, Hissaria P, Sidhu S, Janson S, Venkatesan S, Davies J, Lane MJ, Redmond AM, Robertson I, Legg A, Fernando S, Boyle T, Li J, Phillips EJ, Cleland H, Kern JS, Trubiano JA. James F, et al. World Allergy Organ J. 2024 Aug 5;17(8):100936. doi: 10.1016/j.waojou.2024.100936. eCollection 2024 Aug. World Allergy Organ J. 2024. PMID: 39211425 Free PMC article.
Drug-induced Stevens Johnson syndrome and toxic epidermal necrolysis: Interpreting the systematic reviews on immunomodulatory therapies.
Thong BY. Thong BY. Asia Pac Allergy. 2023 Jun;13(2):72-76. doi: 10.5415/apallergy.0000000000000101. Epub 2023 Jun 6. Asia Pac Allergy. 2023. PMID: 37388817 Free PMC article. Review.

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ANZCTR/ACTRN12619000241134

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

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

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