CRTh2 and Aspirin/NSAID Intolerance in Chronic Spontaneous Urticaria

A significant fraction of patients with chronic spontaneous urticaria (CSU) develop Aspirin/NSAID intolerance during clinical disease, leading to the avoidance of such medications even when indicated for cardiac disease prevention. Reduced surface expression of the PGD2 receptor, CRTh2, is observed on basophils and eosinophils in CSU subjects. We compared clinical and cellular features in CSU subjects with and without Aspirin/NSAID intolerance. We recruited adult CSU subjects (n=18). We obtained detailed histories, complete blood counts, and disease activity surveys from all subjects. We examined basal expression of CRTH2 via flow cytometry. Basophils and eosinophils were gated using scatter and specific markers. Data are reported as Median Net MFI (± SEM), and were analyzed using Mann-Whitney Test. 5/18 patients reported histories of Aspirin/NSAID intolerance. CSU patients with Aspirin/NSAID intolerance showed lower median UAS7 scores (16.5 ± 12.06 vs 25.5 ± 10.96) and subcomponent hives scores (7. ± 8.112 vs 15.5 ± 6.453). The median MFI (± SEM) for basophil CRTh2 expression trended lower in CSU patients in Aspirin/NSAID intolerance (171.9 ± 81.21 vs 245.4 ± 80.11). Eosinophil CRTh2 and PGD2-induced eosinophil shape change were similar. There was no correlation between CRTh2 expression, CBC eosinophil percentage, and UAS7 scores. CSU subjects with self-reported histories of Aspirin/NSAID intolerance had lower UAS7 scores. CRTh2 expression trended lower on basophils from CSU subjects with Aspirin/NSAID intolerance. Levels of eosinophil CRTh2 expression were similar. These findings suggest that functional differences may exist in the CRTh2 pathway in a subset of CSU subjects with Aspirin/NSAID intolerance.