Keratin-associated epidermolysis bullosa simplex: phenotypes and challenges in clinical trials - a narrative review and systematic update.

Introduction: Clinical research on innovative therapies for the rare genodermatosis epidermolysis bullosa (EB) faces significant challenges, including small sample sizes, disease heterogeneity with intra- and inter-individual variability, limited understanding of pathogenic mechanisms and natural disease course, as well as the lack of patient-centred core outcomes. Moreover, existing tools and techniques to assess disease activity and dynamics are heterogeneous, inconsistent, and may fail to consider or inaccurately emphasize particularities of individual patients and distinct EB subtypes.

Methods: In order to exemplify the differences between keratin-associated subtypes of EB simplex (k-EBS), we summarized respective clinical characteristics in a narrative way.

Repurposing diacerein for the treatment of chronic wounds in recessive-dystrophic epidermolysis bullosa patients by modulating matrix metalloproteinase-9 expression.

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1, leading to loss or dysfunction of type-VII collagen (C7), a protein essential for skin stability. Clinically, patients suffer from severe skin blistering, chronic or recurrent wounds, and scarring, which predispose to early onset of aggressive squamous cell carcinoma. Previous studies showed that RDEB-keratinocytes (RDEB-KC) express high levels of matrix-metalloproteinase 9 (MMP-9), a molecule known to play a crucial role in wound chronification if dysregulated.

Facing the complex challenges of people with epidermolysis bullosa in Austria: a mixed methods study on burdens and helpful practices.

Background: With approximately 500 people affected in Austria, epidermolysis bullosa (EB) is a rare genetic skin disease reducing the quality of life of those affected and their relatives. The intensive efforts of the patient organisation DEBRA Austria during the last decades have led to a unique situation of those affected and their relatives, with increased support and broader knowledge about the disease in the general population. The aim of the study is to evaluate the current situation of patients and their relatives living in Austria, with a focus on burdens and helpful practices.

Translation, cultural adaptation and validation of the German Quality of Life in Epidermolysis Bullosa (QOLEB) questionnaire.

Epidermolysis bullosa (EB) is a rare disease characterised by skin fragility and a wide variety of symptoms. The Quality of Life in Epidermolysis Bullosa (QOLEB) score is an English 17-item EB-specific validated measurement tool with two dimensions: functioning and emotions. The aim of this cross-sectional study was to develop and validate a culturally adapted German QOLEB.

Recessive Dystrophic Epidermolysis bullosa due to Hemizygous 40 kb Deletion of COL7A1 and the Proximate PFKFB4 Gene Focusing on the Mutation c.425A>G Mimicking Homozygous Status.

Background: Dystrophic Epidermolysis bullosa (DEB) is a rare inherited mechanobullous disease characterised by the hyperfragility of the skin and mucous membranes. It is (typically) caused by (loss-of-function) mutations in the COL7A1 gene that impair the formation of collagen type VII, which represents the major constituent of anchoring fibrils within the basement membrane zone of epithelialised tissues. In a 4-year-old patient diagnosed with the clinical features of recessive DEB, genotyping via Next-Generation EB Panel Sequencing initially revealed the homozygosity of the maternal c.

Impact of low-dose calcipotriol ointment on wound healing, pruritus and pain in patients with dystrophic epidermolysis bullosa: A randomized, double-blind, placebo-controlled trial.

Background: Wound management is a critical factor when treating patients with the inherited skin fragility disease dystrophic epidermolysis bullosa (DEB). Due to genetic defects in structural proteins, skin and mucous epithelia are prone to blistering and chronic wounding upon minor trauma. Furthermore, these wounds are commonly associated with excessive pruritus and predispose to the development of life-threatening squamous cell carcinomas, underscoring the unmet need for new therapeutic options to improve wound healing in this patient cohort.

[Wound therapy with cold atmospheric plasma in severe recessive dystrophic epidermolysis bullosa : A pilot study].

Background: Cold atmospheric pressure plasma (CAP) has antimicrobial and wound-healing properties. Patients affected by severe autosomal recessive dystrophic epidermolysis bullosa (RDEB) suffer from widespread, difficult-to-treat wounds, which require complex wound management.

Objective: In a pilot project, we investigated over a period of 5 months the response and tolerability of a CAP wound therapy in a 21-year-old and a 28-year-old female patient with severe generalized RDEB and following cutaneous squamous cell cancer (cSSC) in the older patient.

Cells from discarded dressings differentiate chronic from acute wounds in patients with Epidermolysis Bullosa.

Impaired wound healing complicates a wide range of diseases and represents a major cost to healthcare systems. Here we describe the use of discarded wound dressings as a novel, cost effective, accessible, and non-invasive method of isolating viable human cells present at the site of skin wounds. By analyzing 133 discarded wound dressings from 51 patients with the inherited skin-blistering disease epidermolysis bullosa (EB), we show that large numbers of cells, often in excess of 100 million per day, continually infiltrate wound dressings.

Profiling trial burden and patients' attitudes to improve clinical research in epidermolysis bullosa.

Background: Epidermolysis bullosa (EB) comprises inherited mechanobullous dermatoses with considerable morbidity and mortality. While current treatments are symptomatic, a growing number of innovative therapeutic compounds are evaluated in clinical trials. Clinical research in rare diseases like EB, however, faces many challenges, including sample size requirements and recruitment failures.

Basal pharmacokinetic parameters of topically applied diacerein in pediatric patients with generalized severe epidermolysis bullosa simplex.

Generalized severe epidermolysis bullosa simplex (EBS-gen sev) is caused by mutations within either the KRT5 or KRT14 gene, phenotypically resulting in blistering and wounding of the skin and mucous membranes after minor mechanical friction. In a clinical phase 2/3 trial, diacerein has recently been shown to significantly reduce blister numbers upon topical application. In this study we addressed basic pharmacokinetic parameters of locally applied diacerein in vitro and in vivo.

Low-dose calcipotriol can elicit wound closure, anti-microbial, and anti-neoplastic effects in epidermolysis bullosa keratinocytes.

Recessive dystrophic epidermolysis bullosa (RDEB) patients suffer from chronic and repeatedly infected wounds predisposing them to the development of aggressive and life-threatening skin cancer in these areas. Vitamin D3 is an often neglected but critical factor for wound healing. Intact skin possesses the entire enzymatic machinery required to produce active 1-alpha,25-dihydroxyvitamin D3 (calcitriol), underscoring its significance to proper skin function.

Diacerein orphan drug development for epidermolysis bullosa simplex: A phase 2/3 randomized, placebo-controlled, double-blind clinical trial.

Background: Epidermolysis bullosa simplex (EBS) is a rare genetic, blistering skin disease for which there is no cure. Treatments that address the pathophysiology of EBS are needed.

Objective: Compare the impact of 1% diacerein cream with placebo in reducing the number of blisters in EBS.

S1 guidelines for the diagnosis and treatment of ichthyoses - update.

Ichthyoses are a group of rare genetic skin disorders that pose numerous clinical challenges, in particular with respect to the correct diagnosis and appropriate management. The present update of the German ichthyosis guidelines addresses recent diagnostic advances that have resulted in the Sorèze consensus classification. In this context, we provide an updated diagnostic algorithm, taking into account clinical features as well as the molecular genetic basis of these disorders.

Epidermolysis bullosa House Austria and Epidermolysis bullosa clinical network : Example of a centre of expertise implemented in a European reference network to face the burden of a rare disease.

Accurately addressing the diverse and complex issues of rare diseases (RD) in terms of prevention, recognition, diagnosis, treatment, care and research along key RD specificities, such as great heterogeneity, a limited number of patients, scarcity of relevant knowledge and expertise as well as enormous costs for patient care is a challenging task for healthcare providers and authorities that makes a supranational approach particularly feasible. The European Union has acknowledged RD matters by several initiatives, including efforts to implement national centres of expertise and European reference networks as well as a cross-border referral mechanism to foster access to expert services and to boost dissemination of clinical expertise and research activities. Exemplified by the EB House Austria, a centre of expertise for epidermolysis bullosa cross-linked with international reference partner institutions, this strategy proves its potential to be translated into optimized patient care and to meet the major medical, scientific, social and health-economic impact of RD.

Topical diacerein for epidermolysis bullosa: a randomized controlled pilot study.

Blistering in epidermolysis bullosa simplex type Dowling-Meara (EBS-DM) is associated with an inflammatory phenotype, which can be disrupted by diacerein in vitro. In this pilot study we hypothesized, that a topical formulation of diacerein 1% reduces blistering. Five patients initially applied diacerein underneath both armpits.

Diffuse cutaneous mastocytosis masquerading as epidermolysis bullosa.

A 10-month-old boy presented with a history of a generalized cutaneous bullous eruption since 3 months of age. Emesis, flush, pruritus, and fatigue had accompanied relapsing episodes of sometimes extensive blistering. Histopathology showed dense dermal infiltrates of mast cells on hematoxylin and eosin and corroborating immunohistochemical staining.

Herlitz junctional epidermolysis bullosa.

Junctional epidermolysis bullosa type Herlitz (JEB-H) is the autosomal recessively inherited, more severe variant of "lucidolytic" JEB. Characterized by generalized, extensive mucocutaneous blistering at birth and early lethality, this devastating condition is most often caused by homozygous null mutations in the genes LAMA3, LAMB3, or LAMC2, each encoding for 1 of the 3 chains of the heterotrimer laminin-332. The JEB-H subtype usually presents as a severe and clinically diverse variant of the EB group of mechanobullous genodermatoses.