New Data on the Features of Skin Barrier in Hidradenitis Suppurativa

Abstract

Hidradenitis suppurativa (HS) is a Th1/17-driven inflammatory skin disease of the apocrine gland-rich (AGR) skin regions, where keratinocytes seem to be the crucial drivers of the initial pathogenic steps. However, the possible role of permeability barrier alteration in activating keratinocytes during HS development has not been clarified. We compared the major permeability barrier elements of non-lesional HS (HS-NL; n = 10) and lesional HS (HS-L; n = 10) skin with healthy AGR regions (n = 10) via RT-qPCR and immunohistochemistry. Stratum corneum components related to cornified envelope formation, corneocyte desquamation and (corneo)desmosome organization were analyzed along with tight junction molecules and barrier alarmins. The permeability barrier function was also investigated with transepidermal water loss (TEWL) measurements (n = 16). Junction structures were also visualized using confocal microscopy. At the gene level, none of the investigated molecules were significantly altered in HS-NL skin, while 11 molecules changed significantly in HS-L skin versus control. At the protein level, the investigated molecules were similarly expressed in HS-NL and AGR skin. In HS-L skin, only slight changes were detected; however, differences did not show a unidirectional alteration, as KRT1 and KLK5 were detected in decreased levels, and KLK7, KRT6 and DSG1 in increased levels. No significant differences in TEWL or the expression of junction structures were assessed. Our findings suggest that the permeability barrier is not significantly damaged in HS skin and permeability barrier alterations are not the driver factors of keratinocyte activation in this disease.

S2k-Leitlinie zur Therapie der Hidradenitis suppurativa/Acne inversa (ICD-10-Code: L73.2)

“…Der natürliche Erkrankungsverlauf in unterschiedlichen Schweregraden und die begleitenden Provokationsfaktoren sind inzwischen teilweise bekannt. Vieles spricht dafür, dass die primären Veränderungen weder, wie ursprünglich vermutet, die apokrinen Drüsen [59] noch die Hautbarriere [60], sondern den terminalen Haartalgdrüsenapparat betreffen [26,27]. Die zwei Säulen der HS/ AI-Pathogenese sollen eine abnormale Differenzierung der Keratinozyten des Haartalgdrüsenapparats und eine massive begleitende Entzündung sein [27,28,61,62].…”