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Understanding the modifiers of growth in generalised junctional and dystrophic epidermolysis bullosa. (Reimer 1)

Project lead Dr. Antonia Reimer
Organisation University of Freiburg Medical Center, Freiburg, GERMANY
Project budget EUR 90,616.00 + 12 months time only extension
Start date / Duration 01. Apr 2018 / 48 months
Funder(s) / Co-Funder(s) DEBRA Austria, MSAP/EBEP Recommended
Research area EB genetics, epigenetics & biology

Project details

Short lay summary

Although Epidermolysis bullosa (EB) is primarily a skin disease, it may often affect multiple organs. Individuals suffering from generalised dystrophic (DEB) and junctional EB (JEB),  may show reduced growth and anaemia as a result of impaired nutrition. However, the extent to which growth retardation is solely the product of specific genetic defects or whether other factors can also modify its course remains unsubstantiated. This project will investigate the “natural history” of generalised JEB and dystrophic EB by following a large, clinically and molecularly well-characterised group of patients. Its purpose is to correlate data on weight and height development with nutritional parameters, the profile of inflammatory molecules in serum, and the bacterial species that populate wounds. It will include data from the clinic as well as genetic and molecular biology laboratory analysis of serum samples and skin swabs. Some of the data are already available (retrospective study), but some will be collected during this project (prospective study). This study is expected to contribute to the assessment of the impact of nutrition, anaemia, chronic inflammation, the extent of skin affection, and the microbiome on growth. The expected results could improve the care for children with EB, as they would help clinicians in prognosis. By deepening our understanding of the biology and genetics of EB, it could also help in the development of new therapies.

Scientific summary

Impaired growth is a common extracutaneous manifestation of epidermolysis bullosa (EB). Our project will identify growth determinants in patients with generalised dystrophic and junctional EB. The study is based on a large, clinically and molecularly well-characterised cohort. We will combine retrospective and prospective studies of weight and height development with parameters of nutrition, inflammation and the microbiome. The new knowledge of disease-modifying factors and natural history will help to reduce disease burden and to develop new strategies to treat EB. This knowledge will also facilitate patient stratification to new therapies developed from the understanding of EB’s biology and genetics.

Strategic relevance

This project will generate EB-specific growth charts for body weight, height and body mass index (BMI). These charts can serve as a valuable prognostic tool in assessing the development of children with EB, help identify distinct disease modifiers and allow for improved care. They can also aid in planning interventions and dosage of medications. Furthermore, this natural history study of EB may facilitate patient stratification for new therapies.

What did this project achieve?

  • With the help of this grant, the research group has presented growth patterns of children with RDEB and JEB in the largest cohort described so far. These can be a valuable resource in both clinical care and trials. The group has furthermore provided guide values for laboratory parameters in this cohort, e.g., for hemoglobin, CRP, and vitamin D.
  • The research group's genotype-phenotype correlations in EB simplex identified five different kinds of plantar keratoderma (PK): focal, focal at sites of mechanical pressure, progressive from focal to diffuse, diffuse, and diffuse with striate aspect and scleroderma-like fingers. These PK types correlated in part with the genotype, e.g., focal plantar keratoderma with PLEC mutations; diffuse keratoderma with striatal aspect with helix-initiation or -termination peptides in KRT5 or in a helix-initiation peptide in KRT14. PK was found in 75.8% of patients beginning at a mean age of 4.3 years. Both focal and diffuse PK were observed, and 60% of adults with localized and severe EBS were preobese or obese, with ~30% of patients reporting severely reduced mobility. The presence of PK, especially diffuse PK, correlated significantly with local infections, obesity, pain and requirement of a wheelchair. These results highlight the potential impact of EBS, which is often referred to as a “mild” EB, and the importance of proactive counselling also regarding mobility, nutrition, and choice of profession.
  • The project's data on microbiome characteristics in children with RDEB have added to the sparse literature in this field. The researchers have shown that changes of oral and enteral microbiome are (surprisingly) minimal, while changes in the skin microbiome start early. The data emphasize the therapeutic importance of reducing wound burden and S. aureus while promoting the expansion of commensals. Topical strategies include antibiotics and antiseptics, and one should consider not to only apply these to wounds but also to unwounded RDEB skin, for example through baths. Probiotic therapies or strategies using commensal microorganisms might additionally be helpful, and potential candidates should be carefully tested in pilot trials, for which we hope that our data will form a base and rationale.


natural history
chronic Inflammation
University of Freiburg
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