Milestone events in recessive dystrophic epidermolysis bullosa: findings from a prospective register study
Evaluation of antipruritic effects of serlopitant, a neurokinin 1 receptor antagonist, in patients with epidermolysis bullosa: A phase 2 randomized controlled trial
1 July 2024
Developing the Prospective Epidermolysis Bullosa Longitudinal Evaluation Study (PEBLES) to explore natural history and identify endpoints for the rare disease recessive dystrophic epidermolysis bullosa
1 July 2024
Evaluation of antipruritic effects of serlopitant, a neurokinin 1 receptor antagonist, in patients with epidermolysis bullosa: A phase 2 randomized controlled trial
1 July 2024
Developing the Prospective Epidermolysis Bullosa Longitudinal Evaluation Study (PEBLES) to explore natural history and identify endpoints for the rare disease recessive dystrophic epidermolysis bullosa
1 July 2024

British Journal of Dermatology, Volume 191, Issue Supplement_1, July 2024, Page i49, https://doi.org/10.1093/bjd/ljae090.101

P074 Milestone events in recessive dystrophic epidermolysis bullosa: findings from a prospective register study

Authors:

Jemima Mellerio, 1,2 Elizabeth Pillay,1 Kathryn Sollesta,1 Konstantin Thiel,3 Georg Zimmermann,3 John McGrath,2 Anna Martinez4 and Eunice Jeffs1

Affiliation:

  1. St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK;
  2. Genetic Skin Disease Group, King’s College London, London, UK;
  3. University Hospital of the Paracelsus Medical University Salzburg, Salzburg, Austria;
  4. Department of Dermatology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

Abstract:

All forms of the genetic skin fragility disorder recessive dystrophic epidermolysis bullosa (RDEB) are characterized by mucocutaneous blistering healing with scarring, although subtype severity, distribution and associated features correlate to the underlying collagen VII genotype. Understanding the natural history of each distinct subtype is key to prognostication and clinical management, and for determining meaningful endpoints relevant for clinical trials of emerging RDEB therapies. The Prospective Epidermolysis Bullosa Longitudinal Evaluation Study (PEBLES), a prospective register study, explores the natural history of different RDEB subtypes across all ages in patients attending two national EB reference centres. Data were collected over a 1–9-year period to evaluate frequency and age of onset, or first milestone RDEB events: dysphagia, oesophageal dilatation (OD), gastrostomy tube (GT) placement, hand surgery, cutaneous squamous cell carcinoma (SCC), cardiomyopathy and death. The study included 62 participants with different RDEB subtypes: severe (RDEB-S), n = 26; intermediate (RDEB-I), n = 22; inversa (RDEB-Inv), n = 9; pruriginosa (RDEB-Pru), n = 4; and pretibial (RDEB-PT), n = 1. Dysphagia was experienced by 85% of participants, including all with RDEB-S and RDEB-Inv. Frequencies in RDEB-I and RDEB-Pru were lower, at 73% and 50%, respectively. The median age of onset of dysphagia was 2.6 years [interquartile range (IQR) 1.3–5.9] in RDEB-S but later in other subtypes (9.0 years in RDEB-Inv, 10.9 years in RDEB-I, 20.8 years in RDEB-Pru). Similarly, the proportion of participants having at least one OD was greatest in RDEB-S (92%) and RDEB-Inv (89%), compared with RDEB-I (50%) and RDEB-Pru (0%). Initial OD was performed earlier in RDEB-S (8.3 years, IQR 4.3–21.8) compared with RDEB-I (42.9 years) and RDEB-Inv (23.4 years). In RDEB-S, 46% of participants had GT placement, compared with RDEB-I (5%), RDEB-Inv (11%) and RDEB-Pru (0%). First GT was cited earliest in RDEB-S at 6.4 years (IQR 4.8–9.8). Hand contracture surgery was only reported in RDEB-S (58%) and RDEB-I (27%). First surgery occurred earlier in RDEB-S, at 13.1 years (IQR 6.5–19.7), compared with RDEB-I, at 19.6 years (IQR 18.3–23.3). SCC occurred in 21% of all participants, most frequently in RDEB-S (35%) and at an earlier age, 27.8 years (IQR 24.9–33.6), compared with fifth-decade onset in RDEB-I and RDEB-Pru. Cardiomyopathy occurred infrequently, in just one participant with RDEB-S (4%) and one with RDEB-I (5%) participant, both in the third decade. One patient with RDEB-I and six with RDEB-S died during the study period, at age 61.2 years and median 36.0 years (IQR 28.2–37.6), respectively. Our results demonstrate that milestone events are frequent in RDEB, particularly RDEB-S, with earlier age of onset. Most previous EB studies analysed all RDEB subtypes as a group, losing this important distinction. Our study provides important insights for natural history by RDEB subtype, with implications for prognostication, monitoring and treatment planning. Limitations include relative under-representation of less common RDEB subtypes and extremely rare complications such as cardiomyopathy.

Keywords:

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