Milestone Events by Recessive Dystrophic Epidermolysis Bullosa Subtype Identified

Jemima E. Mellerio, MD

Credit: MellerioDermatology.com

New findings highlight both the frequency and prevalence of notable milestone events by recessive dystrophic epidermolysis bullosa (RDEB) subtype, specifically noting occurrences of cutaneous squamous cell carcinoma (SCC) and dysphagia.¹

The findings were the result of research authored by Jemima E. Mellerio, MD, from St. John’s Institute of Dermatology at the Guy’s and St Thomas’ NHS Foundation Trust in London, alongside a team of investigators. Mellerio and colleagues sought to examine the age of onset and the prevalence among patients of milestone events based on RDEB subtypes.

Mellerio et al. highlighted the lack of robust information available regarding the onset and progress of RDEB-related complications in those with the condition.² Despite this fact, they added that prior research tended not to include details by subtype.

“Here, we present the PEBLES findings for age and frequency of milestone events by RDEB subtype, specifically onset of dysphagia, first oesophageal dilatation (OD), first gastrostomy tube placement, first hand surgery for contracture release, first SCC, onset of cardiomyopathy and death,” Mellerio and colleagues wrote.¹

PEBLES Study and Findings on RDEB Patient Subtypes

The investigative team established the PEBLES study in 2014, with the prospective registry design being used for the purposes of tracking the natural progression of RDEB among patients. The team recruited subjects from 2 major EB treatment centers located in London.

At the time of enrollment in the analysis, the investigators conducted their initial assessments, performing follow-up evaluations every 6 months for children who were under the age of 10 and annually for subjects aged 10 years and older. The investigators’ assessments updated prior data, with a comprehensive review of EB-associated and non-EB-associated health complications as well as information on such factors as quality of life, costs of healthcare, and laboratory and imaging data.

The research team confirmed participants’ RDEB diagnoses through the use of genetic testing and/or skin biopsies. In their assessment of specific RDEB subtypes, they used clinical features for their determinations.

The team specifically assessed the aforementioned milestone events across the various RDEB subtypes between November 2014 - November 2022. The frequency of these events was also noted by the investigators, with most milestones highlighted retrospectively during the initial review.

Overall, the investigative team found that dysphagia had been seen among 89% of the 62 trial participants, including all individuals with the severe subtype (RDEB-S) and those with the inversa (RDEB-Inv) subtype. Another highly prevalent event was esophageal obstruction, impacting 69% of study subjects, with rates of 92% in those with RDEB-S and 89% of those with RDEB-Inv.

Participants with RDEB-S had a median age of esophageal obstruction, onset of dysphagia, and gastrostomy tube placement within the first decade of life. Among those diagnosed with RDEB-S, almost all of the resulting events were shown by the research team to be more frequent and to have taken place at a younger age. The exception to this was cardiomyopathy.

When looking at dysphagia and esophageal obstruction, the frequent and early development of these conditions among those diagnosed with RDEB-Inv indicates that such symptoms may serve as early indicators of the RDEB subtype prior to the condition’s characteristic skin involvement in flexural areas is observed.

The analysis further demonstrated that cutaneous SCC was observed among 35% of trial subjects with RDEB-S, and there was a median age at the time of first diagnosis of 27.8 years. It was noted that 7 individuals lost their lives over the 10-year study timeframe, with 6 of these subjects having RDEB-S.

In this subgroup, the median age of death in this group was 36 years. The team noted that causes included metastatic SCC, sepsis, and complications connected to refeeding syndrome.

“This study provides a comprehensive review of key milestone events in different subtypes of RDEB across all ages,” they wrote. “It highlights the prevalence and timing of important complications which have a direct bearing on an individual’s clinical course throughout life. The cumulative data mean that it is possible to prognosticate about anticipated complications and events relevant to individuals living with EB and to their healthcare teams.”¹

References

1. ^{Jemima E Mellerio, Elizabeth I Pillay, Kathryn Sollesta, Konstantin E Thiel, Georg Zimmerman, John A McGrath, Anna E Martinez, Eunice Jeffs, Milestone events in recessive dystrophic epidermolysis bullosa (RDEB): findings of the PEBLES Study, Clinical and Experimental Dermatology, 2025;, llaf009, https://doi.org/10.1093/ced/llaf009.}
2. ^{Fine JD, Mellerio JE. Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part II. Other organs. J Am Acad Dermatol. 2009; 61:387-402.}