Identifying Culprit Drugs in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

1. Physicians are more likely to over-label patients as allergic to non-culprit drugs, in comparison to missing possible culprit drugs for Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN).

2. Using a systematized unbiased approach, in addition to diagnostic tests, could improve culprit SJS/TEN drug identification.

Evidence Rating Level: 2 (Good)

Study Rundown: Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a delayed-type hypersensitivity reaction and severe mucocutaneous desquamative disease with no clear treatment, distinguished by the extent of epidermis body surface area (BSA) that is detached (i.e., SJS = less than 10%, SJS/TEN = overlap of 10%-30%, and TEN = greater than 30%). SJS/TEN is most commonly drug-induced, and thus identification and discontinuation of culprit drugs are essential to preventing the disease. Therefore, this retrospective cohort study had three main focuses: (1) to evaluate patient allergy list outcomes, (2) to investigate the current approaches to identifying culprit drugs, and (3) to identify potential methods to improve culprit drug discovery. This descriptive analysis found that physicians rely on commonly allergy-evoking drugs and the timing of exposure when adding an allergy to a patient’s list. The Algorithm for Drug Casulaity for Epidermyly Necrolysis found that more drugs were mislabelled as allergens compared to the number of culprit drugs missing from patients’ allergy lists. This study recommends incorporating a systematized unbiased approach and diagnostic tests to optimize the accuracy of patients’ allergy lists. This study is limited by the retrospective approach, and thus only explicitly recorded medical cases were included. Additionally, as this study spanned 2000 to 2018, many cases predated research advancements. Lastly, although the data from this study is from two USA tertiary care centres with several consult physicians, the results may not be generalizable to the entire USA and beyond.

Click to read the study in JAMA Dermatology

Relevant Reading: ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson syndrome and toxic epidermal necrolysis: comparison with case-control analysis

In-Depth [retrospective cohort]: This retrospective cohort study was undertaken at the Brigham and Women’s Hospital and Massachusetts General Hospital from 2000 to 2018. Pathology database searches were conducted to identify cases using the terms SJS, TEN, and SJS/TEN. Three steps were taken to confirm case inclusion: (1) diagnosed clinically by a board-certified dermatologist, (2) pathology confirmed disease at the time of disease, and (3) another board-certified dermatologist specialized in SJS/TEN retrospectively reviewed the case. Inclusion criteria included patients with clinical and histological SJS/TEN overlap and TEN cases with 10% or greater total BSA blistering/detachment. Erythema multiforme, Mycoplasma pneumoniae mucositis, and a history of hematopoietic cell transplant were excluded. The main outcome of this study was descriptively analyzing potential drug culprits to SJS/TEN by examing patient allergies and the approach physicians use to create patient allergy lists. The following patient medical record data were extracted: sex, age at diagnosis, race, ethnicity, comorbidities, concurrent infection, prodromal symptoms, heart rate, BSA blistered/soughed, mucosal involvement, intubation, reduced liver and kidney function before SJS/TEN, systemic treatment, burn treatment, all medications within 3 months of SJS/TEN onset, and drug allergies. In total, 48 patients (29 women [60.4%]; 4 Asian [8.3%], 6 Black [12.5%], 5 Hispanic [10.4%], and 25 White [52.1%] individuals; median age, 40 years [range, 1-82 years]) were included, with a mean (SD) number of drugs taken at SJS/TEN onset of 6.5 (4.7). 17 patients were labelled as allergic to one culprit drug, whereas, 104 drugs were added to the allergy list across all the patients. When labelling a patient as allergic to a drug, physicians relied heavily on commonly allergy-evoking drugs and the timing of exposure. When using the Algorithm for Drug Casulaity for Epidermyly Necrolysis, 9 drugs were found to be missed, and 43 drugs were found to be mislabeled as allergens. Lastly, physicians rarely considered infection a culprit, and the human leukocyte antigen testing could have affected at least 20 cases. Overall this study demonstrates physicians’ susceptibility to over-labelling patient allergens, although possible culprit drugs were less commonly missed. One potential recommendation from this study is to incorporate a systematized unbiased approach in addition to diagnostic tests.

Image: PD

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