Loss of FLG causes ichthyosis vulgaris. Reduced FLG expression compromises epidermal barrier function and is associated with atopic dermatitis, allergy, and asthma. The flaky tail mouse harbors two mutations that affect the skin barrier, Flg ft , resulting in hypomorphic FLG expression, and Tmem79 ma , inactivating TMEM79. Mice defective only for TMEM79 featured dermatitis and systemic atopy, but also Flg ft/ft BALB/c congenic mice developed eczema, high IgE, and spontaneous asthma, suggesting that FLG protects from atopy. In contrast, a targeted Flg-knockout mutation backcrossed to BALB/c did not result in dermatitis or atopy. To resolve this discrepancy, we generated FLG-deficient mice on pure BALB/c background by inactivating Flg in BALB/c embryos. These mice feature an ichthyosis phenotype, barrier defect, and facilitated percutaneous sensitization. However, they do not develop dermatitis or atopy. Whole-genome sequencing of the atopic Flg ft BALB/c congenics revealed that they were homozygous for the atopy-causing Tmem79 matted mutation. In summary, we show that FLG deficiency does not cause atopy in mice, in line with lack of atopic disease in a fraction of patients with ichthyosis vulgaris carrying two Flg null alleles. However, the absence of FLG likely promotes and modulates dermatitis caused by other genetic barrier defects.

Defects of filaggrin (FLG) compromise epidermal barrier function and represent an important known genetic risk factor for atopic dermatitis (AD), but also for systemic atopy, including allergic sensitization and asthma. The flaky tail mouse model, widely used to address mechanisms of atopy induction by barrier-defective skin, harbors two mutations that affect the skin barrier, the mutation Flgft, resulting in near-complete loss of FLG expression, and the matted mutation inactivating transmembrane protein 79 (Tmem79). Upon separation of the two mutant loci, which are closely linked on chromosome 3, mice defective only for Tmem79 featured pronounced dermatitis and systemic atopy. Upon extensive backcross to BALB/c, also Flgft/ft mice (assumed to be wild type for Tmem79), developed AD-like dermatitis and reproduced the human ‘atopic march’, with high IgE levels and spontaneous asthma, suggesting a key role for functional Flg in protection from atopy also in mice. In contrast, BALB/c mice congenic for a targeted Flg knock out mutation did not develop skin inflammation or atopy. To resolve this discrepancy, we generated Flg-deficient mice on a pure BALB/c background by inactivating the Flg gene in BALB/c embryos. These animals feature an ichthyosis phenotype, but do not develop spontaneous dermatitis or systemic atopy. We sequenced the genome of the atopic Flgft BALB/c congenics and discovered that they were unexpectedly homozygous for the atopy-causing Tmem79matted mutation. In summary, we show that Flg-deficiency does not cause atopy in mice. This finding is in line with lack of atopic disease in a fraction of Ichthyosis vulgaris patients carrying two FLG null alleles. However, absence of FLG may promote and modulate dermatitis caused by other genetic barrier defects, as skin inflammation in Tmem79ma/maFlgft/ft BALB/c congenics is qualitatively different compared to Tmem79ma/ma mice.

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BackgroundThe role and causality of the microbial ecosystem on the skin in relation to the development of hand eczema (HE) is still unknown.ObjectivesTo investigate the prevalence of different bacterial colonisations in HE patients and their association with the severity, symptoms and aetiology of the disease.MethodsIn a retrospective cohort study of 167 HE patients, bacterial swabs from lesional skin were collected for culturing. Patients were categorised according to bacterial colonisation, HE severity, HE symptoms and HE aetiology.ResultsThe majority of the patients were tested positive for Staphylococcus aureus (S. aureus) (n = 131, 78.4%) and/or commensal skin flora (CSF; n = 130, 77.8%), while other bacteria species were found only sporadically. Severe HE was significantly more prevalent in skin with S. aureus (odds ratio [OR]: 5.13, 95% confidence interval [CI]: 2.21–11.94) and less common in skin with CSF (OR: 0.20, 95% CI: 0.05–0.88). S. aureus colonisation was also associated with atopic HE aetiology (p < 0.001) and acute HE symptoms such as blisters, erosions and crusts (p = 0.003).ConclusionsThe main colonisation of HE patients is with S. aureus and is associated with disease severity, acute HE symptoms and atopic HE aetiology. CSF is associated with mild HE, which could result in new therapeutic approaches.

ZusammenfassungDas Pemphigoid gestationis (PG) ist eine seltene und chronische bullöse Autoimmundermatose, die vorwiegend in der 2. Schwangerschaftshälfte oder postpartal auftritt und durch Ausbildung großer, meist erheblich juckender, entzündlicher, erythematöser Infiltrate und Blasen gekennzeichnet ist. Außerhalb der Schwangerschaft wurde die Erkrankung in Assoziation mit trophoblastischen Tumoren (Chorionkarzinom, Blasenmole) beschrieben. Wir berichten über ein Pemphigoid gestationis bei einer 30-jährigen Patientin in der 33. Schwangerschaftswoche ihrer 2. Schwangerschaft. Nach der 1. Schwangerschaft zeigte sich anamnestisch die Erstmanifestation der Erkrankung mit selbstständiger Abheilung. Bei erneuter Exazerbation in der 2. Schwangerschaft erfolgte nach Diagnosestellung die Einleitung einer topischen und systemischen Prednisolontherapie, welche eine zügige Besserung erbrachte.