Mathematical-structure based Morphological Classification of Skin Eruptions and Linking to the Pathophysiological State of Chronic Spontaneous Urticaria

Chronic spontaneous urticaria (CSU) is one of the most intractable human-specific skin diseases. However, as no experimental animal model exists, the mechanism underlying disease pathogenesis in vivo remains unclear, making the establishment of a curative treatment challenging. Here, using a novel approach combining mathematical modeling, in vitro experiments and clinical data analysis, we show that the pathological state of CSU patients can be inferred by geometric features of the skin eruptions. Based on our hierarchical mathematical modelling and the analysis of 105 CSU patient eruption pattern geometries, analyzed by six dermatologists, we demonstrate that the eruption patterns can be classified into five categories, each with distinct histamine, basophils, mast cells and coagulation factors network signatures. Furthermore, our network analysis revealed that tissue factor degradation/activation likely determines boundary/area pattern, and that the state of spontaneous histamine release from mast cells may contribute to divergence of the boundary pattern. Thus, our study not only demonstrates that pathological states of diseases can be defined by geometric features but will also facilitate more accurate decision-making to manage CSU in the clinical setting.