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

Fiona James; Michelle S Goh; Sara Vogrin; Irvin Ng; Abby P Douglas; Natasha E Holmes; Kyra Yl Chua; Joseph De Luca; Pooja Sharma; Celia Zubrinich; Ar K Aung; Douglas Gin; Belinda Lambros; Chris Baker; Peter Foley; Alvin H Chong; Francis Thien; Jie S Fok; John Su; Laura Scardamaglia; Andrew Awad; Steven Tong; Douglas Johnson; Jack Godsell; Alexis Arasu; Sara Barnes; Samar Ojaimi; Adrian Mar; James Yun; Nikhita Ange; Winnie W Y Tong; Andrew Carr; Jacqueline Loprete; Constance H Katelaris; Dana Slape; Karuna Keat; Timothy A West; Monique Lee; William Smith; Pravin Hissaria; Shireen Sidhu; Sonja Janson; Sudharsan Venkatesan; Jane Davies; Michael J Lane; Andrew M Redmond; Ivan Robertson; Amy Legg; Suran Fernando; Therese Boyle; Jamma Li; Elizabeth J Phillips; Heather Cleland; Johannes S Kern; Jason A Trubiano

doi:10.1016/j.waojou.2024.100936

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

World Allergy Organ J. 2024 Aug 5;17(8):100936. doi: 10.1016/j.waojou.2024.100936. eCollection 2024 Aug.

Authors

Fiona James^{1

2}, Michelle S Goh^{3

4

5

6

7}, Sara Vogrin^{1

2}, Irvin Ng¹, Abby P Douglas^{1

8}, Natasha E Holmes^{1

2}, Kyra Yl Chua^{1

2}, Joseph De Luca^{1

2}, Pooja Sharma⁶, Celia Zubrinich⁹, Ar K Aung¹⁰, Douglas Gin³, Belinda Lambros⁴, Chris Baker⁴, Peter Foley⁴, Alvin H Chong⁴, Francis Thien¹¹, Jie S Fok^{11

12}, John Su¹³, Laura Scardamaglia⁵, Andrew Awad^{2

5}, Steven Tong¹⁴, Douglas Johnson^{14

15}, Jack Godsell¹⁶, Alexis Arasu⁵, Sara Barnes^{12

17}, Samar Ojaimi^{12

17

18}, Adrian Mar¹⁹, James Yun²⁰, Nikhita Ange²⁰, Winnie W Y Tong²¹, Andrew Carr²¹, Jacqueline Loprete²¹, Constance H Katelaris²², Dana Slape²², Karuna Keat²², Timothy A West²², Monique Lee²², William Smith²³, Pravin Hissaria²³, Shireen Sidhu²⁴, Sonja Janson²⁵, Sudharsan Venkatesan²⁵, Jane Davies²⁵, Michael J Lane²⁶, Andrew M Redmond²⁶, Ivan Robertson²⁶, Amy Legg²⁷, Suran Fernando²⁸, Therese Boyle²⁸, Jamma Li²⁸, Elizabeth J Phillips^{29

30}, Heather Cleland³¹, Johannes S Kern^{3

5}, Jason A Trubiano^{1

2

4}

Affiliations

¹ Centre for Antibiotic Allergy and Research, Department of Infectious Diseases and Immunology, Austin Health, Victoria, Australia.
² Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Australia.
³ Department of Dermatology, Alfred Health and Monash University, Department of Medicine, Central Clinical School, Australia.
⁴ Department of Dermatology, St Vincent's Hospital Melbourne and the University of Melbourne, Australia.
⁵ Department of Dermatology, Royal Melbourne Hospital and Department of Medicine, University of Melbourne, Australia.
⁶ Department of Dermatology, Austin Health, Australia.
⁷ Department of Surgical Oncology (Dermatology), Peter MacCallum Cancer Centre, Melbourne, Australia.
⁸ National Centre for Infections in Cancer, Department of Infectious Diseases, Peter MacCallum Cancer Centre, Australia.
⁹ Department of Allergy, Asthma and Clinical Immunology, Alfred Health, Australia.
¹⁰ Department of General Medicine, Alfred Hospital and Monash University, School of Public Health and Preventive Medicine, Australia.
¹¹ Department of Respiratory Medicine, Eastern Health and Monash University, Australia.
¹² Department of Monash Lung Sleep Allergy and Immunology, Clinical Allergy and Immunology, Monash Health, Australia.
¹³ Department of Dermatology, Eastern Health, Australia.
¹⁴ Department of General Medicine and Infectious Diseases Royal Melbourne Hospital, Australia.
¹⁵ Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.
¹⁶ Department of Allergy and Immunology, Royal Melbourne Hospital, Australia.
¹⁷ Department of Medicine Monash University, Australia.
¹⁸ Monash Pathology, Monash Health, Australia.
¹⁹ Department of Dermatology, Monash Health, Australia.
²⁰ Department of Immunology, Nepean Hospital, NSW, Australia.
²¹ HIV & Immunology Unit, St Vincent's Hospital, Sydney and School of Clinical Medicine, UNSW Sydney, Australia.
²² Immunology/Allergy Unit, Campbelltown Hospital, NSW, Australia.
²³ Clinical Immunology and Allergy, Royal Adelaide Hospital, SA, Australia.
²⁴ Department of Dermatology, Royal Adelaide Hospital, SA, Australia.
²⁵ Department of Infectious Diseases, Royal Darwin Hospital, Tiwi, Northern Territory, Australia.
²⁶ Royal Brisbane and Women's Hospital, University of Queensland, Brisbane, Queensland, Australia.
²⁷ Department of Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
²⁸ Department of Clinical Immunology and Allergy, Royal North Shore Hospital, Sydney, Australia.
²⁹ Center for Drug Safety and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, USA.
³⁰ Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
³¹ Victorian Adult Burns Service (VABS), Alfred Hospital, Melbourne, Australia.

Abstract

Background: Severe 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.

Methods: Prospective 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.

Results: we 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%).

Conclusion: In 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 registration: ANZCTR ACTRN12619000241134. Registered 19 February 2019.

Keywords: Acute generalized exanthematous pustulosis; DRESS; Delayed hypersensitivity; Drug reaction with eosinophilia and systemic symptoms; Stevens-Johnson syndrome; T-cell mediated hypersensitivity; Toxic epidermal necrolysis.