Date of Award

January 2026

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Caroline A. Nelson

Abstract

Background/Scientific premise: Severe cutaneous adverse reactions (SCARs) are severe drug-induced skin eruptions, including Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP) and generalized bullous fixed drug eruption (GBFDE). Their psychological impact is increasingly recognized, with U.K. guidelines for SJS-TEN recommending psychological evaluation, and a continuing medical education review for DRESS recommending monitoring for anxiety, depression, and post-traumatic stress disorder (PTSD) for one year. However, monitoring for adverse psychosocial outcomes has not been standardized.

Research Aims: To characterize the existing literature on adverse psychosocial outcomes in SCAR survivors, to investigate the prevalence of adverse psychosocial outcomes of SCAR survivors at a single institution, and to develop a patient-reported outcome measure (PROM) to screen for adverse psychosocial outcomes in DRESS survivors.

Hypothesis or Question: What adverse psychosocial outcomes are survivors of SCARs at risk for and how should medical providers optimally screen for these outcomes?

Methods/approach: A three-pronged approach was utilized: a scoping review, a retrospective analysis, and a Delphi-based consensus exercise. For the scoping review, we searched MEDLINE, Embase, and PsycInfo for primary literature using terms related to SCARs and psychosocial outcomes. For the retrospective analysis, we assessed the electronic medical records of patients diagnosed with SCARs from 2012 to November 2024 at Yale New Haven Hospital who were >1 month post-discharge. Patient charts were reviewed for mental health disorders, including depression, anxiety, and post-traumatic stress disorder (PTSD), and other adverse psychosocial outcomes, including medication hesitancy and altered relationship with medical providers. For the Delphi-based consensus exercise, a modified Delphi method was used to assess statements related to adverse psychosocial outcomes. 13 international experts in DRESS were invited, and 12 experts representing the fields of dermatology, allergy and immunology, and infectious diseases agreed to participate in the consensus exercise, which took place from June to August 2025.

Results: In the scoping review, after screening 865 records, 24 studies were included. 88% focused on SJS-TEN and 21% addressed DRESS. 44-54% and 21-44% of SJS-TEN survivors and 36-63% and 50% of DRESS survivors screened positive for anxiety and depression, respectively, on the Hospital Anxiety and Depression Scale. 17-51% of SJS-TEN survivors and 50% of DRESS survivors had scores indicating PTSD using variations of the Impact of Events Scale. Quality of life, fear of medications, and altered relationships with medical providers were also frequently identified. In the retrospective analysis, 184 patients were included and all SCARs were represented, with 88 (48%) DRESS, 54 (29%) AGEP, 26 (14%) SJS-TEN, and 16 (9%) GBFDE cases. There was no statistically significant difference in mental health disorders across SCAR type. Psychosocial outcomes were most commonly documented by primary care physicians (n=15, 8%) and noted by dermatologists in 11 (6%) cases. The Delphi-based consensus study established the appropriateness of a 27-item PROM to screen for adverse psychosocial outcomes in DRESS survivors. MAP-DRESS (Monitoring for Adverse Psychosocial outcomes in DRESS survivors) is divided into two sections. The first section, relating to mental health outcomes, consists of the validated Hospital Anxiety and Depression Scale, the validated Primary Care PTSD Screen, and two items assessing past utilization of and current receptiveness to receiving mental health care. The second section, relating to other psychosocial outcomes, consists of six items assessing DRESS impact on quality of life (QOL), fear of medications, and relationships with medical providers. This PROM is intended for administration at both 3 and 6 months after an episode of DRESS.

Statement of scientific impact and relevance for communities of interest, including patients: This work highlights the needs for improved psychosocial support in SJS-TEN and DRESS survivors, as well as psychosocial outcome research in unexplored SCARs such as acute generalized exanthematous pustulosis and generalized bullous fixed drug eruption. Dermatologists are infrequently screening for adverse psychosocial outcomes of SCARs and there is a need for greater recognition of these psychosocial impacts and increased support for affected patients. The Delphi-based consensus of international experts yielded a novel 27-item PROM called MAP-DRESS which may be used to bridge this gap in survivors of DRESS. While further research is required to validate MAP-DRESS, the PROM can be incorporated into current clinical practice given the clear and pressing need for psychosocial evaluation in DRESS survivors and the absence of validated tools.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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