James A Feinstein1,2,3, Purevsuren Jambal4, Kathleen Peoples3, Anne W Lucky5, Phuong Khuu6, Jean Y Tang6, Irene Lara-Corrales7, Elena Pope7, Karen Wiss8, Kristen P Hook9, Laura E Levin10, Kimberly D Morel10,11, Amy S Paller12,13,14, Catherine C McCuaig15, Julie Powell15, Lawrence F Eichenfield16,17,18, Harper Price19, Moise L Levy20,21,22, Lawrence A Schachner23, John C Browning24, Susan Bayliss25, Marla Jahnke26, Tor Shwayder26, Sharon A Glick27, Anna L Bruckner1,3,4,28. 1. Department of Pediatrics, University of Colorado School of Medicine, Aurora. 2. Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado, Aurora. 3. Children's Hospital Colorado, Aurora. 4. Department of Dermatology, University of Colorado School of Medicine, Aurora. 5. Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 6. Department of Dermatology, Stanford University School of Medicine, Stanford, California. 7. Section of Dermatology, Division of Paediatric Medicine, Hospital for Sick Children, Toronto, Ontario, Canada. 8. Division of Dermatology, Department of Medicine, University of Massachusetts Medical School, Worcester. 9. Department of Dermatology, University of Minnesota Medical School, Minneapolis. 10. Department of Dermatology, Columbia Irving Medical Center, New York, New York. 11. Department of Pediatrics, Columbia Irving Medical Center, New York, New York. 12. Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 13. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 14. Department of Dermatology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois. 15. CHU Sainte-Justine, University of Montreal, Montreal, Quebec, Canada. 16. Department of Dermatology, University of California San Diego, San Diego. 17. Department of Pediatrics, University of California San Diego, San Diego. 18. Department of Pediatric and Adolescent Dermatology, Rady Children's Hospital, San Diego, California. 19. Department of Dermatology, Phoenix Children's Hospital, Phoenix, Arizona. 20. Departments of Internal Medicine, Dell Medical School, University of Texas, Austin. 21. Departments of Pediatrics, Dell Medical School, University of Texas, Austin. 22. Department of Pediatric Dermatology, Dell Children's Medical Center, Austin, Texas. 23. Department of Dermatology, University of Miami Miller School of Medicine, Miami, Florida. 24. Department of Pediatric Dermatology, Children's Hospital San Antonio, San Antonio, Texas. 25. Division of Dermatology, Department of Medicine, Washington University in St Louis, St Louis, Missouri. 26. Department of Dermatology, Henry Ford Hospital, Detroit, Michigan. 27. Department of Dermatology, State University of New York Downstate Medical Center, Brooklyn. 28. Associate Editor.
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.
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.
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