Novel insights into the epidemiology of epidermolysis bullosa (EB) from the Dutch EB Registry: EB more common than previously assumed?

Abstract

Background: Epidermolysis bullosa (EB) is a heterogeneous group of rare and incurable genetic disorders characterized by fragility of the skin and mucosae, resulting in blisters and erosions. Several epidemiological studies in other populations have been carried out, reporting varying and sometimes inconclusive figures, highlighting the need for standardized epidemiological analyses in well-characterized cohorts.

Objectives: To evaluate the epidemiological data on EB in the Netherlands, extracted from the molecularly well-characterized cohort in the Dutch EB Registry.

Methods: In this observational study all EB-patients that were based in the Netherlands and captured in the Dutch EB Registry between 1988 and 2018 were included. The epidemiological outcomes were based on complete diagnostic data (clinical features, immunofluorescence, electron microscopy and mutation analysis), with longitudinal follow-up.

Results: A total of 464 EB-patients (287 families) were included. The incidence and point-prevalence of EB in the Netherlands were 41.3 per million live births and 22.4 per million population, respectively. EB Simplex (EBS), Junctional EB (JEB), Dystrophic EB (DEB) and Kindler EB were diagnosed in 45.7%, 18.8%, 34.7% and 0.9% of the EB-patients, respectively, with an incidence and point-prevalence of 17.5 and 11.9 (EBS), 9.3 and 2.1 (JEB), 14.1 and 8.3 (DEB), 0.5 and 0.2 (Kindler EB). In 90.5% of the EB-patients the diagnosis was genetically confirmed. During the investigated time period 73 EB-patients died, 72.6% of whom as a direct consequence of their EB.

Conclusion: The epidemiological outcomes of EB in the Netherlands are high, attributed to a high detection rate in a well-organized set-up, indicating that EB might be more common than previously assumed. These epidemiological data help to understand the extensive need for (specialized) medical care of EB-patients and is invaluable for the design and execution of therapeutic trials. This study emphasizes the importance of thorough reporting systems and registries worldwide.

Figure 1

Epidemiological outcomes of each major type of Epidermolysis Bullosa in the Netherlands for the time period 1988–2018,n = 490. (a) Annual point‐prevalence (per million population) of each major type of EB. (b) Annual incidence rates (per million live births). Based on the Dutch Epidermolysis Bullosa Registry (Dutch‐EB‐Reg). DEB, dystrophic epidermolysis bullosa; EB, epidermolysis bullosa; EBS, epidermolysis bullosa simplex; JEB, junctional epidermolysis bullosa.

Figure 2

Distribution of the major types and genes involved in patients with Epidermolysis Bullosa in the Dutch Epidermolysis Bullosa Registry for the time period 1988–2018, n = 464. (a) The total distribution and genes involved in the major EB types in the cohort of the Dutch Epidermolysis Bullosa Registry (Dutch‐EB‐Reg). (b) The total distribution of the 14 genes involved in the Dutch Epidermolysis Bullosa Registry (Dutch‐EB‐Reg). Patients without mutation analysis performed were classified as ‘No DNA’; patients in which no pathogenic mutation(s) could be found with mutation analysis were genetically classified as ‘Unsolved’.