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Epidermolysis bullosa (EB) is a rare genetic disorder manifesting with skin and mucosal membrane blistering in different degrees of severity.Epidemiological data from different countries have been published, but none are available from Germany.In this population-based cross-sectional study, people living with EB in Germany were identified using the following sources: academic hospitals, diagnostic laboratories and patient organization.Our study indicates an overall EB incidence of 45 per million live births in Germany. With 14.23 per million live births for junctional EB, the incidence is higher than in other countries, possibly reflecting the availability of early molecular genetic diagnostics in severely affected neonates. Dystrophic EB was assessed at 15.58 cases per million live births. The relatively low incidence found for EB simplex, 14.93 per million live births, could be explained by late or missed diagnosis, but also by 33% of cases remaining not otherwise specified. Using log-linear models, we estimated a prevalence of 54 per million for all EB types, 2.44 for junctional EB, 12.16 for dystrophic EB and 28.44 per million for EB simplex. These figures are comparable to previously reported data from other countries.Altogether, there are at least 2000 patients with EB in the German population. These results should support national policies and pharmaceutical companies in decision-making, allow more precise planning of drug development and clinical trials, and aid patient advocacy groups in their effort to improve quality of life of people with this orphan disease.

These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert-based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis.What's already known about this topic?Various symptomatic treatment options exist for congenital ichthyoses, but there are no European guidelines.What does this study add?These European guidelines for the management of congenital ichthyosis may help to improve outcomes and quality of life for patients.Linked Comment: Akiyama. Br J Dermatol 2019; 180:449-450. Plain language summary available online

Ichthyoses are genetically determined Mendelian disorders of cornification (MEDOC) that are characterized by universal scaling. Today we distinguish between non-syndromic and syndromic forms. Ichthyosis vulgaris is the most frequent type (prevalence 1:100) and is caused by autosomal semi-dominant filaggrin mutations. It is associated with a higher risk for the development of atopic diseases, such as atopic eczema and allergic rhinitis. Recessive X-linked ichthyosis (RXLI) occurs almost exclusively in boys; in Germany it has a prevalence of around 1:4,000. It is caused by steroid sulfatase deficiency and is often associated with further clinical problems, such as cryptorchidism (∼20%) or social communication deficits, such as attention deficit hyperactivity syndrome (40%) or autism (25%). Autosomal recessive congenital ichthyosis (ARCI) is genetically very heterogeneous and 8 different genes have been identified so far. The most frequent cause of ARCI is a transglutaminase 1 deficiency (prevalence 1:200, 000). Mutations in keratin genes are the cause of the keratinopathic ichthyoses, such as epidermolytic ichthyosis. They manifest at birth and often feature episodes of blistering. Most of these types are inherited as autosomal dominant traits, but autosomal recessive forms have also been described on occasion.

Background Ichthyosis vulgaris (IV) is caused by loss-of-function mutations in the profilaggrin (FLG) gene. Filaggrin drives complex interrelated functions, with strategic roles in establishing structural and chemical barrier function, hydration of the skin and maintaining epidermal homeostasis. Data on the effect of FLG mutations on epidermal barrier function in IV are very scarce. Objectives A primary aim of this study was to determine in vivo characteristics of epidermal permeability barrier function such as transepidermal water loss (TEWL), skin hydration and skin surface pH in homozygous or compound heterozygous (FLG−/−) and heterozygous (FLG+/−) subjects with IV. Methods We evaluated a cohort of 15 patients with IV, analysed epidermal ultrastructure and investigated epidermal barrier function by measurement of TEWL, skin surface pH and skin hydration. Mutations were screened by restriction enzyme analysis and/or complete sequencing. Ten patients were homozygous or compound heterozygous (FLG−/−), while five patients were heterozygous (FLG+/−). Twenty healthy individuals served as controls. Results In FLG−/− subjects, a moderate increase of TEWL from 5.41 ± 0.32–7.54 ± 0.90 g/m2h (P