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Background: Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss‐of‐function mutations of these genes constitute a risk factor for atopic dermatitis and eczema‐related asthma. Furthermore, both FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation. Methods: By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double‐deficient (FlgHrnr−/−) mouse model lacking both genes including the intergenomic sequence. Results: Neonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans. Structurally, FlgHrnr−/− mice displayed a markedly reduced granular layer and a condensed cornified layer. Functionally, FlgHrnr−/− mice showed permeability abnormalities and metabolic aberrations regarding the production of natural moisturizing factors (NMFs) in the stratum corneum. Surprisingly, although the immune system revealed no aberrations under steady‐state conditions, FlgHrnr−/− mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels eliciting allergic reactions. Conclusions: Together, our FlgHrnr−/− mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions. [ABSTRACT FROM AUTHOR]

Background: Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss-of-function mutations of these genes constitute a risk factor for atopic dermatitis and eczema-related asthma. Furthermore, both FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation., Methods: By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double-deficient (FlgHrnr -/- ) mouse model lacking both genes including the intergenomic sequence., Results: Neonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans. Structurally, FlgHrnr -/- mice displayed a markedly reduced granular layer and a condensed cornified layer. Functionally, FlgHrnr -/- mice showed permeability abnormalities and metabolic aberrations regarding the production of natural moisturizing factors (NMFs) in the stratum corneum. Surprisingly, although the immune system revealed no aberrations under steady-state conditions, FlgHrnr -/- mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels eliciting allergic reactions., Conclusions: Together, our FlgHrnr -/- mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background and Objectives: Reflectance confocal microscopy (RCM) may be a useful method for accurate, rapid, and noninvasive bedside diagnosis of vesiculobullous skin diseases (VSD). The main outcome measure of this study was a descriptive statistical analysis of RCM features associated with selected group of VSD., Patients and Methods: Single-center, observational study at a university-based dermatology department. Forty skin lesions in 24 patients with bullous pemphigoid (BP), varicella zoster virus infection (VZI), or allergic contact dermatitis (ACD) were assessed., Results: Patients with BP, VZI, and ACD were assessed for the presence of a large spectrum of RCM features, among others including histopathological correlates for spongiosis, vesicles/blisters, epidermal necrosis, pleomorphic ballooned keratinocytes, and inflammatory infiltrate. The three conditions showed distinct patterns of occurrence with respect to these RCM features. Using a multivariate regression model, we identified sets of morphologic features in BP (vesicles/blisters at the dermoepidermal junction, inflammatory infiltrate within blisters and basal epidermal layers, spongiosis in basal epidermal layers), VZI (acantholysis in the stratum spinosum, epidermal necrosis, pleomorphic ballooned keratinocytes, multinucleated giant cells), and ACD (microvesicles, spongiosis, and prominent inflammatory infiltrate in the stratum granulosum/spinosum)., Conclusions: RCM seems to be a useful tool in the evaluation and differentiation of a selected group of VSD, and offers a good correlation with histopathological findings., (© 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Hintergrund Und Zielvorgaben: Konfokale Laserscanmikroskopie (Reflectance confocal microscopy; RCM) kann eine nützliche Methode für die genaue, schnelle und nicht-invasive Diagnose für vesikullobullöse Hauterkrankungen (VSD) am Krankenbett sein. Das primäre Ergebnis dieser Studie war eine deskriptive statistische Analyse von RCM-Merkmalen, die mit einer ausgewählten Gruppe an VSD einhergehen., Patienten Und Methoden: Monozentrische Beobachtungsstudie an einer Universitätsklinik für Dermatologie. Vierzig Hautläsionen bei 24 Patienten mit bullösem Pemphigoid (BP), Infektion mit Varizella Zoster (VZI) oder allergischer Kontaktdermatitis (ACD) wurden ausgewertet., Ergebnisse: Patienten mit BP, VZI und ACD wurden auf die Anwesenheit eines großen Spektrums an RCM-Merkmalen hin untersucht, darunter die histopathologische Korrelation von Spongiose, Vesikel/Hautblasen, epidermaler Nekrose, pleomorphen, ballonierte Keratinozyten und entzündlichen Infiltraten. Die drei Erkrankungen zeigten spezifische Muster für Auftreten dieser RCM-Merkmale. Wir identifizierten mit Hilfe einer multivariaten Regressionsanalyse einen Satz morphologischer Merkmale bei BP (Vesikel/Hautblasen an der dermoepidermalen Junktionszone, entzündliche Infiltrate in Hautblasen und basalen Epidermisschichten, Spongiose in basalen Epidermisschichten), VZI (Akantholyse im Stratum spinosum, epidermale Nekrose, pleomorphe, ballonierte Keratinozyten, multinukleäre Riesenzellen) und ACD (Mikrovesikel, Spongiose und auffällige entzündliche Infiltrate im Stratum granulosum/spinosum)., Schlussfolgerungen: RCM scheint ein nützliches Werkzeug bei der Analyse und der Unterscheidung einer ausgewählten Gruppe von VSDs zu sein und bietet eine gute Korrelation mit histopathologischen Untersuchungsergebnissen., (© 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)