Although conventional vaccines have generated major successes in the control of infectious diseases, several obstacles remain in their development against chronic diseases (HIV, tuberculosis), against which no current candidate vaccines yet ensure protection. The transcutaneous route of vaccine administration appears to be a promising approach of targeting vaccines toward antigen-presenting cells (APCs) and thus improving immune responses. We investigated the suitability of nanoparticles in this approach. We found a high density of Langerhans cells (LCs) around hair follicles that, when sorted, readily internalized all size particles. However, flow cytometry after transcutaneous application of 40, 750, or 1,500 nm nanoparticles on human skin samples revealed that only 40 nm particles entered epidermal LC. Fluorescence and laser scan microscopies, which were carried out to identify the penetration pathway of transcutaneously applied nanoparticles, revealed that only 40 nm particles deeply penetrate into vellus hair openings and through the follicular epithelium. We conclude that 40 nm nanoparticles, but not 750 or 1,500 nm nanoparticles, may be efficiently used to transcutaneously deliver vaccine compounds via the hair follicle into cutaneous APCs.

Twenty-six families with keratinopathic ichthyoses (epidermolytic ichthyosis, superficial epidermolytic ichthyosis or congenital reticular ichthyosiform erythroderma) were studied. Epidermolytic ichthyosis is caused by mutations in the genes KRT1 or KRT10, mutations in the gene KRT2 lead to superficial epidermolytic ichthyosis, and congenital reticular ichthyosiform erythroderma is caused by frameshift mutations in the genes KRT10 or KRT1, which lead to the phenomenon of revertant mosaicism. In this study mutations were found in KRT1, KRT2 and KRT10, including 8 mutations that are novel pathogenic variants. We report here the first case of a patient with congenital reticular ichthyosiform erythroderma carrying a mutation in KRT10 that does not lead to an arginine-rich reading frame. Novel clinical features found in patients with congenital reticular ichthyosiform erythroderma are described, such as mental retardation, spasticity, facial dysmorphisms, symblepharon and malposition of the 4th toe.

Proopiomelanocortin (POMC)-derived peptides and their receptors have been identified in many peripheral organs including the skin in which they exert a diversity of biological actions. We investigated the expression and potential role of the POMC system in human dermal papilla cells (DPCs), a specialized cutaneous mesenchymal cell type regulating hair follicle activity. In culture, these cells expressed POMC and displayed immunoreactivity for ACTH, alphaMSH, and beta-endorphin. Among the prohormone convertases (PCs) tested, only PC2, its chaperone 7B2, and furin convertase but not PC1 and paired basic amino acid cleaving enzyme 4 gene were detected. Human DPCs in vitro expressed both the melanocortin-1 receptor (MC-1R) and MC-4R, and immunoreactivity for these receptors was also present in cells of the human dermal papilla in situ. In contrast to the dermal papilla of agouti mice, agouti signaling protein, a natural and highly selective MC-1R and MC-4R antagonist, was undetectable in human DPCs. The MC-Rs detected in human DPCs were functionally active because alphaMSH increased intracellular cAMP and calcium. Preincubation of the cells with a synthetic peptide corresponding to the C-terminal domain of agouti signaling protein abrogated cAMP induction by alphaMSH. Furthermore, alphaMSH was capable of antagonizing the expression of intercellular adhesion molecule-1 induced by the proinflammatory cytokine interferon-gamma. Our data suggest a regulatory function of alphaMSH within the dermal papilla whose disruption may lead to deregulation of immune and inflammatory responses of the hair follicle, thereby possibly contributing to the development of inflammatory forms of alopecia.

Zusammenfassung Ichthyosen sind seltene genetische Hautkrankheiten, die den Kliniker vor mannigfache Herausforderungen stellen, insbesondere in Bezug auf das Stellen einer zutreffenden Diagnose und einer angemessenen therapeutischen Betreuung. Mit dieser Aktualisierung der deutschen Ichthyosis‐Leitlinie berücksichtigen wir jüngste diagnostische Fortschritte, die in die Konsensus‐Klassifikation von Sorèze mündeten und erarbeiten einen aktuellen Diagnose‐Algorithmus, der sowohl das klinische Bild als auch die Molekulargenetik dieser Erkrankungen berücksichtigt. Darüber hinaus wird der heutige Wissensstand bezüglich therapeutischer Ansätze wie psychosozialer Unterstützung, Balneotherapie, mechanischer Schuppenlösung, topischer Salbentherapie und Systemtherapie mit Retinoiden erläutert und es werden allgemeine Aspekte wie die Indikation für Physiotherapie, Ergotherapie oder die Notwendigkeit einer umfassenden genetischen Beratung diskutiert. Diese Aktualisierung der deutschen Ichthyosis‐Leitlinie wurde durch eine interdisziplinär besetzte Leitlinienkonferenz verabschiedet, an der Dermatologen, Kinderärzte, Humangenetiker und Naturwissenschaftler teilnahmen und in die die deutsche Patientenorganisation Selbsthilfe Ichthyose e. V. eingebunden war.