Drug Reaction with Eosinophilia and Systemic Symptoms: Medication Adherence and Quality of Life in Survivors

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse reaction (SCAR) associated with multiorgan involvement and mortality rates of up to 10%.¹ The majority of DRESS patients are hospitalized, many in intensive care.² DRESS survivors may have residual physical and/or mental health problems.^3,4 Prior studies have assessed health-related quality of life (HRQoL) in patients with SCAR using the Short Formulary-36, Euro Quality of Life-5 Dimensions, and tools from psychiatry and dermatology; however, studies were small and did not focus on DRESS.^5,6 In this study, we aimed to characterize medication adherence and HRQoL following DRESS utilizing a large population of survivors from Mass General Brigham, a large northeastern United States health care system.

We applied rule-based approaches to identify cases of DRESS occurring January 1, 1980, to January 15, 2023 by searching allergy list, problem list, billing/encounters, medical history, and clinical note data. The rules considered ICD codes (ICD-9 codes 693.0, E947.9, 288.3 and ICD-10 codes D72.12, T50.905A), keywords, and information identified via natural language processing. We then conducted manual chart review to validate the rule-identified cases. Each case was first screened by a clinician to rule out unlikely cases. The possible cases were then reviewed by trained research fellows to confirm whether the cases were DRESS diagnosed by a specialist (i.e., dermatology and/or allergy/immunology).⁷ DRESS survivors, with acute DRESS between 2009 and 2022, received study invitations by electronic message invitation. Consented patients completed questionnaires including the Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q), which prior to use, was professionally bidirectionally translated and adapted for content and face validity guided by experts in survey science, allergy-immunology, and dermatology.⁸ Chi-square tests compared responder and non-responder demographic characteristics in the unweighted total sample and medication adherence and HRQoL in responders. To account for selection bias in the sample of DRESS survivors who completed questionnaires, the primary analyses used a propensity-based weight that was calculated as the inverse of a multivariable logistic regression-based predicted probability predicting completion of the survey (n=65) in the total sample (n=256). We also assessed whether those with higher Registry of Severe Cutaneous Reactions scores (≥4, probable or definite DRESS) reported differential medication compliance or HRQoL.

Of 256 invited DRESS survivors, 65 (25%) completed the HRQoL questionnaire and 60 (23%) completed the medication adherence questionnaire from December 22, 2021 to May 22, 2023. The respondents (mean age 46 [SD 16.3] years, 69% female, 79% White, 8% Black, 8% Asian, 60% RegiSCAR score ≥4) had DRESS a mean of 5 [SD 2.5] years prior to questionnaire completion (see Table E1 in the Online Repository). Mean age was older in non-responders than responders (51 vs 46, p=0.046), but race (p=0.35), sex (p=0.08), RegiSCAR score (p=0.69), and year of SCAR (p=0.53) did not differ by questionnaire response status. Having vancomycin as the implicated drug for DRESS was associated with responding to the survey (40% vs 28%, p ≤ 0.001).

In the propensity-weighted analysis, DRESS survivors report medication non-adherence, including not taking medications (21%), taking less of medications (20%), and stopping medications due to side effects (18%, Table I). DRESS survivors report fear of receiving a drug to which they are allergic in an emergency (73%, Table II); those with RegiSCAR scores ≥4 more commonly reported fear (90%, p=0.051). DRESS survivors reported a desire that, for every illness, certainty that there is a drug available which can be safely taken (71%). A majority of DRESS survivors (59%) would like the opinion of an allergist before taking drugs prescribed by other specialists. DRESS survivors report fear (59%; 76% RegiSCAR score ≥4), anxiety (48%; 56% RegiSCAR score ≥4), and distress (48%; 55% RegiSCAR score ≥4) because of their problem with adverse drug reactions. DRESS survivors report the problem of drug reactions affects their life (56%; 73% RegiSCAR score ≥4) with some giving up recreational opportunities (12%; 18% RegiSCAR score ≥4). DRESS survivors report finding every disease more limiting because of their inability to take certain drugs (43%) and even a minor illness becoming a problem (44%).

Table I.

Pooled weighted responses to medication adherence^a,b

	n (%)	%
Self-reported medication adherence responses	Anyc	Daily	> 5 times	1 to 5 times
How often do you decide not to take your medication?	13 (21)	2	2	16
How often do you decide to take less of your medication?	12 (20)	2	<1	17
How often do you stop taking your medicine because you feel sick due to side effects of the medicine?	11 (18)	0	0	18

^a60 patients reported taking medications, RegiSCAR ≥ 4 (n=23, 90%) and RegiSCAR < 4 (n=37, 96%) (p=0.39).

^bPoint estimates for percentages and chi-square test statistics reflect propensity-based weighted data.

^c“Any” signifies to any degree affirmation. Values may not add due to rounding.

Table II.

Pooled weighted responses to Drug-Related Hypersensitivity Quality of Life (DrHy-Q) 15-Item Scale questionnaire^a

	n (%)	%
Self-reported DrHy-Q responses	Anyb	Extremely	Very	Moderately	Slightly
I am afraid that in an emergency I might be given a drug I am allergic to.c	50 (73)	19	11	14	29
For every illness, I would like to be certain that there is a drug available that I may safely take.	49 (71)	19	14	18	20
I would like the opinion of an allergist before I take drugs prescribed by other specialists.	42 (59)	11	10	10	28
I feel afraid because of my problem with medications.	40 (59)	13	8	16	22
The problem of drug reactions affects my life.d	38 (56)	14	4	9	30
I worry every time I have to take a drug, even if it’s not the one that caused an allergic reaction.	36 (50)	11	8	3	29
The idea of taking a drug makes me feel anxious.	34 (47)	11	5	4	27
I feel anxious because of my problem of drug reactions.	35 (48)	11	6	4	27
I find every disease more limiting than other people do because I cannot take certain drugs.	30 (43)	10	5	8	20
Even a minor illness becomes a problem for me.	30 (44)	6	7	6	24
The fact that I can’t safely take drugs makes me feel different from others.	29 (41)	11	3	7	19
I’m afraid of not being able to get treatment for pain.e,f	25 (41)	8	7	9	18
I feel distressed because of my problem with adverse drug reactions.	31 (48)	10	2	4	31
I feel down or depressed because of my problem with drug reactions	16 (24)	8	3	4	9
I’ve given up recreational opportunities (sports, holidays, trips…) because of my problem with drug reactions.e	10 (12)	1	6	3	3

^aPoint estimates for percentages and chi-square test statistics reflect propensity-based weighted data.

^b“Any” signifies to any degree affirmation. Values may not add due to rounding.

^c“Any” fear was slightly more common in RegiSCAR ≥ 4 (90% vs 63%; p=0.051).

^dResponses were different according to RegiSCAR with RegiSCAR ≥ 4 (severity: 9%, 4%, 22%, 37%; any: 73%) vs RegiSCAR <4 (severity: 17%, 3%, 1%, 26%; any: 47%) (severity: p=0.01; any: χ²₁ = 3.0, p=0.08).

^en=1 missing respondent on this specific item.

^f“Any” fear of not being able to get treatment for pain was more common in RegiSCAR <4 (22% vs 52%; p=0.03).

This large study of DRESS survivors in the United States identified substantial problems with medication adherence and HRQoL associated with DRESS survivorship. A recent study suggested that DRESS survivors experience anxiety, depression, and post-traumatic stress disorder.³ Similarly, another study identified psychological complications and decreased HRQoL associated with survivorship after another SCAR, Stevens-Johnson Syndrome/toxic epidermal necrolysis.⁶ In our study, more than 1 in 5 DRESS survivors reported problems with medication adherence, and DrHy-Q responses indicate fears, anxiety, and worry about taking medications. Drug allergy-specific HRQoL was often worse for participants with RegiSCAR ≥ 4, suggesting a possible relationship between certainty and severity of DRESS and HRQoL sequelae. As many models of health care are adapting to include a more patient-centered approach, so too should the care for those affected by DRESS.

Participants had acute DRESS episodes with diverse clinical presentations and causative agents. Although findings may not be broadly representative, we used propensity score methods to account for non-responder bias. Limitations include a lack of comparison group for medication adherence and DrHy-Q scores outside of the DRESS study population. RegiSCAR criteria were calculated retrospectively from electronic health records and prior studies, including one in our US health system, have shown that retrospective assessment of RegiSCAR can be incomplete or result in lower scores.² Lastly, the DrHy-Q has not yet been fully validated in English.

DRESS survivors report persistent problems with medications. Sequelae include fears, anxiety, and worry related to recurrence and taking medications. Increased recognition of long-term DRESS-associated morbidity and efforts to improve the emotional wellbeing of DRESS survivors is needed.

Clinical Implications:

DRESS survivors report substantial problems with medication adherence and health-related quality of life. Increased recognition of long-term DRESS-associated morbidity and efforts to improve the emotional wellbeing of DRESS survivors is needed.