Assessment of the Timing of Milestone Clinical Events in Patients With Epidermolysis Bullosa From North America

Abstract

IMPORTANCE Children with epidermolysis bullosa (EB) comprise a rare population with high morbidity and mortality. An improved understanding of the clinical trajectory of patients with EB, including age at time of clinical diagnosis and major clinical events, is needed to refine best practices and improve quality of life and clinical outcomes for patients with EB. OBJECTIVES To describe demographics, clinical characteristics, milestone diagnostic and clinical events (such as initial esophageal dilation), and outcomes in patients with EB using the Epidermolysis Bullosa Clinical Characterization and Outcomes Database and to determine what characteristics may be associated with overall EB severity and/or disease progression. DESIGN, SETTING, AND PARTICIPANTS This cohort study included data on patients with EB who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2011, to June 30, 2017; 17 participating EB centers in the United States and Canada contributed data to this study. EXPOSURES Type of EB, including recessive dystrophic epidermolysis bullosa (RDEB), junctional epidermolysis bullosa (JEB), dominant dystrophic epidermolysis bullosa (DDEB), and epidermolysis bullosa simplex (EBS). MAIN OUTCOMES AND MEASURES Demographic information, clinical characteristics (including age at onset of signs of EB and subsequent clinical diagnosis), types of diagnostic testing performed, and milestone clinical events for patients with RDEB. RESULTS Of 644 enrolled patients from 17 sites included in this study, 323 were male (50.2%), with a mean (SD) age of 14.4 (11.7) years; 283 (43.9%) had RDEB, 194 (30.1%) had EBS, 104 (16.2%) had DDEB, and 63 (9.8%) had JEB. Signs of disease were present at birth in 202 patients with RDEB (71.4%), 39 with JEB (61.9%), 60 with DDEB (57.7%), and 74 with EBS (38.1%). For those with signs of disease at birth, a clinical diagnosis was made at the time of birth in 135 patients with RDEB (67.0%), 31 with DDEB (52.6%), 35 with EBS, (47.3%) and 18 with JEB (46.2%). Patients with JEB had the highest rate of any confirmatory testing (51 of 63 [81.0%]), followed by RDEB (218 of 283 [77.0%]), DDEB (71 of 104 [68.3%]), and EBS (100 of 194 [51.5%]). For all types of EB, both electron microscopy and immunofluorescence microscopy were performed at younger ages than genetic analysis. Among 283 patients with RDEB, 157 (55.5%) had esophageal dilation, 104 (36.7%) had gastrostomy tube placement, 62 (21.9%) had hand surgery, 18 (6.4%) developed squamous cell carcinoma, and 19 (6.7%) died. CONCLUSIONS AND RELEVANCE The findings suggest that diagnostic testing for EB is more common for patients with severe phenotypes. Earlier diagnostic testing may enable improved characterizations of patients so that appropriate counseling and clinical care may be offered, especially pertaining to milestone events for those with RDEB.

Natural history of growth and anaemia in children with epidermolysis bullosa: a retrospective cohort study*

“…Children with JEB‐generalized severe were excluded as the course has been described before 12‐13. Bodyweight and height measurements, ethnicity and laboratory results, and the milestone clinical events:14 oesophageal stenosis (indicated by medical history and/or imaging), oesophageal dilatation, gastrostomy insertion and death were retrieved from patient records. Laboratory parameters were grouped into nutrition (total protein, albumin, vitamin D, zinc and selenium), anaemia (haemoglobin, reticulocytes, ferritin, transferrin, saturation of transferrin and iron level), and inflammation [leucocytes, C‐reactive protein (CRP), IgA, IgG, IgM] and thyroid‐stimulating hormone (TSH).…”

Clinical practice guidelines for laboratory diagnosis of epidermolysis bullosa

“…Although genetic testing can make a definite diagnosis and its turnaround time is progressively shortening, IFM can provide the diagnosis within hours, thus ensuring appropriate neonatal management. While this will undoubtedly change in the coming years, IFM still remains the first method of choice …”

Intravenous allogeneic umbilical cord blood–derived mesenchymal stem cell therapy in recessive dystrophic epidermolysis bullosa patients

“…Recessive dystrophic EB (RDEB) is caused by mutations in COL7A1 , which encodes type VII collagen (C7), the main constituent of anchoring fibrils at the dermoepidermal junction (DEJ). RDEB is one of the most severe forms of EB; it is characterized by recurrent blistering, chronic wounds, disabling scarring in the skin, and mucosa and internal organ dysfunctions, leading to substantial morbidity and mortality ( 2 – 4 ). Currently, there is no cure for this severe subtype of EB; however, novel therapeutic strategies have been developed in the fields of gene and cell therapies ( 5 – 15 ).…”