Diagnostic Testing More Common in Most Severe EB Types, Study Reports

Diagnostic testing in patients with epidermolysis bullosa (EB) is more frequent in the most severe disease types, according to a large study in North America. The findings also revealed a delay between showing signs at birth and clinical diagnosis in a subset of patients with recessive dystrophic EB (RDEB) and junctional EB (JEB).

The research, “Assessment of the Timing of Milestone Clinical Events in Patients With Epidermolysis Bullosa From North America,” was published in the journal JAMA Dermatology.

As it is a rare disease, having best practices for real-world care in EB — including its diagnosis, major clinical events, and outcomes — has been challenging. These outcomes, which scientists call milestone events, include when to place a gastrostomy tube for eating, or when to perform hand surgery to release contractures and pseudosyndactyly (mitten hand deformity).

If able to predict the timing of such interventions in people with different EB types, clinicians may better anticipate modifiable targets for intervention and collect more reliable information to counsel patients and their caregivers, the researchers posited.

The Epidermolysis Bullosa Clinical Research Consortium is a network of clinical research groups with 20 sites in the U.S. and Canada. Each site participates in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database (EBCCOD) to document well-described EB patients and to generate longitudinal data about EB’s course, complications, and treatment.

The team primarily intended to describe EB patients within EBCCOD, specifically looking at patient demographic information, clinical characteristics such as patient age at initial signs of EB and at clinical diagnosis, what diagnostic tests were performed, and milestone events for patients with RDEB — the most severe disease type.

Such an approach aims to find and fill gaps in EB diagnosis, and provide a summary of major interventions for EB patients and when they occur, researchers said. It also is intended to inform future longitudinal evaluations and to determine what characteristics may be linked with overall EB severity and/or disease progression.

The study included 644 patients (mean age 14.4 years) included in EBCCOD from Jan. 1, 2011, to June 30, 2017. Seventeen sites contributed with data.

Overall, 43.9% of patients had RDEB, 30.1% had EB simplex (EBS), 16.2% had dominant dystrophic EB (DDEB), and 9.8% had JEB. According to the investigators, the higher prevalence of RDEB is due to these patients’ more frequent contact with the medical system and their significant clinical needs requiring ongoing care.

During the study, 32 patients died. Of them, 19 had RDEB and a median age at death of 17.9 years; 12 had JEB and a median age at death of six months, and one had EBS.

Most patients had EB symptoms, such as skin blisters at birth, ranging from 38.1% to 71.4% depending on disease subtype. Those with RDEB had significantly higher incidence of aplasia cutis (absence of skin) at birth (60.2%) compared to the other disease types.

A clinical diagnosis was made at birth in 67% of patients with RDEB, 52.6% with DDEB, 47.3% with EBS, and 46.2% with JEB. Patients with JEB had the highest rate of confirmatory tests (81% of patients), followed by RDEB (77%), DDEB (68.3%), and EBS (51.5%). Nearly 33% of patients with RDEB and 53.8% of those with JEB had a delay between having signs at birth and clinical diagnosis of EB.

“The findings suggest that diagnostic testing for EB is more common for patients with severe phenotypes,” the scientists stated. “Understanding the course of major clinical events may enable improved counseling on prognosis and management of epidermolysis bullosa.”

When looking at specific confirmatory tests, both electron microscopy and immunofluorescence microscopy assessments were performed at younger ages than genetic analysis, which was the most common test for all patients (55.7%).

As for milestone clinical events specific to RDEB, 55.5% of patients had esophageal dilation at a median age of 6.6 years, 36.7% had a gastrostomy tube placement at 5.5 years, 21.9% had an initial hand surgery at 8.1 years, and 6.4% developed squamous cell carcinoma. Nineteen patients (6.7%) died, with the most common causes being respiratory failure (three cases), cardiac failure (three cases), neoplasm and renal failure (one each).

“This knowledge also aids clinicians in the initiation of counseling and planning at an optimal time, rather than overwhelming families with too much information at an initial visit,” the team said.