Distinguishing DRESS syndrome from drug rash and eosinophilia: Beyond RegiSCAR criteria.

Background: Diagnosing drug reaction with eosinophilia and systemic symptoms (DRESS) can be challenging.

Objectives: We sought to identify clinical and laboratory features outside of the Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria that distinguish patients with probable DRESS (RegiSCAR ≥ 4) from those with drug rash and eosinophilia (DRE).

Methods: Using international coding classifications of drug-induced fever, generalized skin eruption due to medications, and eosinophilia, a retrospective audit from 2008 to 2023 of hospitalized patients was performed.

Results: Forty-four cases of DRESS were compared to 80 cases of DRE. In addition to the RegiSCAR distinguishing factors for DRESS were longer drug latency before symptom onset (median 21 vs 5 days,  < .001) and higher alanine transaminase levels (increase by a factor of 2.49 [95% confidence interval, 1.56, 4.00;  = .009]). Follow-up (mean 5.67 years) revealed a low rate of statewide drug alert reporting (29.6%) and drug allergy testing in DRESS (20.5%). Inadvertent reexposure to a culprit or structurally related drug resulted in recurrent DRESS in 3 patients (7.5%), and tolerance of structurally related drugs occurred in 8 patients (17.5%).

Conclusion: In this large study evaluating DRE patients whose disease does not meet the RegiSCAR criteria for DRESS, we found that additional factors outside the RegiSCAR criteria may help clinicians differentiate DRESS, which is critical for optimal and timely patient management. Our study also highlights the need for development of local protocols to ensure appropriate allergy labeling and testing are performed to prevent recurrent DRESS.