Increased mortality among African American patients with DRESS Syndrome compared to White patients

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but potentially fatal hypersensitivity drug reaction with 5 to 10% mortality.¹ DRESS syndrome outcomes and mortality vary based on the severity and extent of organ involvement, as well as sequelae of both the disease itself and any immunosuppressive treatment.¹ There is limited understanding of the demographic factors, for example racial differences, that impact patient outcomes in DRESS. Thus, this study aims to evaluate DRESS outcomes among different races.

This cross-sectional study identified 61 patients (52 White, 9 African American [AA]) with DRESS syndrome at a single academic institution (2012–2019). This study was approved by the institutional review board at the Ohio State University Wexner Medical Center; approval #2020H0276. Patient information including age, gender, body mass index (BMI), Charlson Comorbidity Index, Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) score, and poverty level was collected; patient poverty level was determined by Ohio postal code. Outcomes analyzed included length of stay (time before dermatology consult, after dermatology consult, and total), rehospitalization within 365 days, and death during hospitalization, or within 30 or 365 days of discharge. Shapiro-Wilk test was used to evaluate data for normality. Mann-Whitney and Student’s T-test were used to test for significance of continuous variables, while Fisher’s Exact test was used to test significance of categorical variables. Statistical significance was defined as p-value <0.05.

Age, gender, BMI, poverty level, Charlson Comorbidity Index, and RegiSCAR score were similar between the AA and White cohorts (p>0.05) (Table 1). Notably, a statistically significant difference in death within 30 days of discharge was found between AA and White patients (22% [n=2] versus 0% [n=0], respectively, p=0.02) (Table 2). Exact cause of death of the two AA patients was not specified in the electronic medical records because both were transferred to hospice care at another institution. One of the AA patients who died was a 79-year-old male with a BMI of 34 kg/m², Charlson Comorbidity score of 4, and RegiSCAR score of 4 with phenytoin as the culprit medication. The second AA patient who died was a 97-year-old female with a BMI of 20 kg/m², Charlson Comorbidity score of 1, and RegiSCAR score of 4 with ampicillin/sulbactam as the culprit medication. Other outcomes evaluated showed no significant difference between the cohorts. The two White patients’ deaths within 365 days of discharge were due to (1) terminal condition (steroid refractory acute graft vs. host disease associated with disseminated fungal infection and hepatic failure) and (2) unspecified.

Table 1.

Characteristics of DRESS patients

	White (n=52)	AA (n=9)	P-value
Age (years)	51.31	55.33	0.53
Gender, % male (n)	55.77 (29)	44.44 (4)	0.54
BMI (kg/m2)	30.46	29.22	0.72
Poverty quintile	2.75	3.38	0.32
Charlson score, % ≥3 (n)	23.08 (12)	33.33 (3)	0.52
RegiSCAR score	5	4.56	0.19

AA, African American; BMI, body mass index; RegiSCAR, Registry of Severe Cutaneous Adverse Reactions.

Means are shown.

Results considered significant at p<0.05.

Table 2.

Outcomes of DRESS syndrome among AA and White patients

	White (n=52)	AA (n=9)	P-value
LOS pre consult (days)	1.96	0.89	0.43
LOS post consult (days)	6.15	7.00	0.64
Total LOS (days)	8.11	7.89	0.83
Rehospitalization in 365 days, % (n)	34.62 (18)	44.44 (4)	0.71
Death during hospitalization, % (n)	0 (0)	0 (0)	1.00
Death in 30 days, % (n)	0 (0)	22.22 (2)	0.02 *
Death in 365 days, % (n)	3.85 (2)	0 (0)	1.00

AA: African American; LOS: length of stay.

Means are shown.

^*Significant at p<0.05

A closer look at the demographics of the two AA patients who died revealed that both were from the lowest poverty quintile, raising the question of whether social determinants of health may be contributing to the observed higher mortality.² The average poverty quintile of the AA patients who survived was 2.83. In both AA patients who died, the delay to diagnosis from rash onset was low (1–5 days). The average Charlson Comorbidity Index was 2.50 and 1.71 for the AA patients who died and survived, respectively. Thus, the differential mortality among African Americans seen in this study could potentially be influenced by systemic factors such as disparities in access to social or medical resources, more advanced disease, and/or comorbidities.

Interestingly, genetic factors have been suggested to play a role in developing specific severe cutaneous adverse reactions (SCARs).³ Black Americans have a higher risk for allopurinol-induced SCARs compared to White Americans⁴ and an additional reason is the higher prevalence of human leukocyte antigen (HLA)-B*5801 among Black Americans (2.6–6.4% versus <1–1.9%, respectively).⁵ While Black Americans had increased risk for developing this SCAR, they also had increased mortality.⁴ Additional risk alleles are in progress and may further explain worse outcomes in this population.

The limitations of this study include the small sample size and being conducted at a single institution. The results should be independently validated using larger, multi-institutional databases.

Our findings suggest greater short-term mortality among AA patients with DRESS syndrome compared to White patients. Future studies should seek to corroborate our findings and evaluate potential causes for the differences in race-specific survival of patients with DRESS syndrome.