Supplementary Material for: Histamine Iontophoresis as in vivo Model to Study Human Skin Inflammation with Minimal Barrier Impairment: Pilot Study Results of Application of the Model to a Sensitive Skin Panel

<p><b><i>Background/Aims:</i></b> Histamine iontophoresis is known to elicit itch and a wheal-and-flare reaction; however, its impact on the skin barrier and underlying compartments has not been thoroughly evaluated yet. The primary objective of this study was to characterize that using immunohistochemistry, biophysical measurements, and image analysis, and secondly, to explore whether skin reactions to this model differ in sensitive skin (SS). <b><i>Methods:</i></b> Eighteen healthy subjects, <i>n</i> = 9 with SS and <i>n</i> = 9 with non-sensitive skin (NSS), were included based on a perception-based questionnaire. Histamine iontophoresis was performed on the buttock, and skin reactions were evaluated up to 72 h after stimulation. <b><i>Results:</i></b> The wheal-and-flare peaked at 30 min; after 8 h, no clinical signs were visible. No signs of disruption of the stratum corneum, as well as no increase in the number of Ki67-positive cells emerged, whereas fewer tryptase-positive mast cells and increased epidermal thickness were observed at 1 and 72 h, respectively. SS subjects showed higher perception of itch compared to NSS subjects. <b><i>Conclusion:</i></b> Histamine iontophoresis is a well-standardized in vivo model to quantitatively study the early stages of cutaneous inflammation with minimal impact on the skin barrier. In line with previous studies, it highlighted increased sensory perceptions in SS.</p>