Changes in Psychological Burden and Quality of Life During In Vivo Diagnostic Evaluation for Immediate Drug Hypersensitivity: A Prospective Stepwise Study

Background/Objective: The psychological impact of in vivo diagnostic procedures remains poorly understood. We assessed changes in psychological distress and drug hypersensitivity-related quality of life (QoL) throughout a diagnostic evaluation for suspected immediate drug hypersensitivity reactions (IDHRs) and aimed to identify predictors of persistent psychological burden. Methods: This single-center prospective observational longitudinal study included 100 consecutive adults undergoing evaluation for suspected IDHRs. Psychological distress and QoL were assessed using the Depression Anxiety Stress Scale-21 (DASS-21) and the Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q). Assessments were performed before and after each diagnostic phase, including skin tests (STs), placebo, and drug provocation tests (DPTs). Results: The mean age was 44.2 ± 12.5 years, and women comprised 72% of the cohort. Depression, anxiety, stress, and DrHy-Q scores significantly decreased after ST, placebo, and DPT compared with baseline measurements. Across diagnostic stages, depression, anxiety, stress, and DrHy-Q scores were significantly lower during the DPT phase than during the ST and placebo phase in both pre-test and post-test measurements (p < 0.01 for pairwise comparisons). The number of prior HSRs showed a weak but significant positive correlation with DrHy-Q scores. In multivariable linear regression analysis, the number of prior HSRs was the only independent predictor of post-DPT DrHy-Q scores (β = 3.43, 95% CI 1.36–5.50, p = 0.001). Patients who avoided the provoked drug despite a negative DPT had higher DPT-post depression, anxiety, stress, and DrHy-Q scores. Conclusions: Psychological burden progressively decreased over the course of the stepwise diagnostic evaluation for suspected IDHRs, although patients with repeated reactions may benefit from additional support.