Speaker
Description
Chronic spontaneous urticaria (CSU) is an immune-mediated skin disease characterized by red, itchy eruptions of various shapes, known as wheals. Second-generation H1 antihistamines are a mainstay of treatment, but treatment responses vary widely among patients, with approximately 30% remaining symptomatic despite conventional therapy. On the other hand, the results of our previous studies suggest that CSU can be classified into five distinct types of wheal morphology, which corresponds well to clinical observations, and new, more effective targeted therapies could be developed based on these endotypes. To address this, we studied the effectiveness of antihistamines across these endotypes. We first evaluated the severity of CSU and efficacy of antihistamines in silico using three key measures: wheal area, itching severity, and wheal expansion dynamics. Our results showed that even though we assumed the same intensity of H1 histamine receptor suppression, the overall effectiveness to reduce the symptom varied depending on the endotypes. Furthermore, we found a key pathological network associated with antihistamine efficacy, which enables the proposal of new targeted immune drugs for the treatment of CSU. Our study demonstrates that mathematical and morphological endotyping of CSU can uncover hidden therapeutic determinants and pave the way for next-generation targeting critical components in the mechanism of individual patients.
