A retrospective analysis of diagnostic testing in a large North American cohort of patients with epidermolysis bullosa

Gregory Scott Phillips; Amy Huang; Bret D Augsburger; Laura Kaplan; Kathleen Peoples; Anna L Bruckner; Phuong Khuu; Jean Y Tang; Irene Lara-Corrales; Elena Pope; Karen Wiss; Laura E Levin; Kimberly D Morel; Kristen P Hook; Amy S Paller; Lawrence F Eichenfield; Catherine C McCuaig; Julie Powell; Leslie Castelo-Soccio; Moise L Levy; Harper N Price; Lawrence A Schachner; John C Browning; Marla Jahnke; Tor Shwayder; Susan Bayliss; Anne W Lucky; Sharon A Glick

doi:10.1016/j.jaad.2021.09.065

A retrospective analysis of diagnostic testing in a large North American cohort of patients with epidermolysis bullosa

J Am Acad Dermatol. 2022 May;86(5):1063-1071. doi: 10.1016/j.jaad.2021.09.065. Epub 2021 Oct 8.

Authors

Gregory Scott Phillips¹, Amy Huang¹, Bret D Augsburger², Laura Kaplan¹, Kathleen Peoples³, Anna L Bruckner⁴, Phuong Khuu⁵, Jean Y Tang⁵, Irene Lara-Corrales⁶, Elena Pope⁶, Karen Wiss⁷, Laura E Levin⁸, Kimberly D Morel⁹, Kristen P Hook¹⁰, Amy S Paller¹¹, Lawrence F Eichenfield¹², Catherine C McCuaig¹³, Julie Powell¹³, Leslie Castelo-Soccio¹⁴, Moise L Levy¹⁵, Harper N Price¹⁶, Lawrence A Schachner¹⁷, John C Browning¹⁸, Marla Jahnke¹⁹, Tor Shwayder¹⁹, Susan Bayliss²⁰, Anne W Lucky², Sharon A Glick²¹

Affiliations

¹ Department of Dermatology, State University of New York Downstate Health Sciences University, Brooklyn, New York.
² Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
³ Children's Hospital Colorado, Aurora, Colorado.
⁴ Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado.
⁵ Department of Dermatology, Stanford University School of Medicine, Stanford, California.
⁶ Section of Dermatology, Division of Paediatric Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.
⁷ Departments of Dermatology and Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts.
⁸ Department of Dermatology, Columbia Irving Medical Center, New York, New York.
⁹ Department of Dermatology, Columbia Irving Medical Center, New York, New York; Department of Pediatrics, Columbia Irving Medical Center, New York, New York.
¹⁰ Department of Dermatology, University of Minnesota Medical School, Minneapolis, Minnesota.
¹¹ Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
¹² Departments of Dermatology and Pediatrics, University of California San Diego, San Diego, California.
¹³ Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada.
¹⁴ Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
¹⁵ Pediatric/Adolescent Dermatology, Dell Children's Medical Center, University of Texas, Austin, Texas; Departments of Pediatrics and Medicine (Dermatology), Dell Medical School, University of Texas, Austin, Texas.
¹⁶ Department of Dermatology, Phoenix Children's Hospital, Phoenix, Arizona.
¹⁷ Department of Dermatology, University of Miami Miller School of Medicine, Miami, Florida.
¹⁸ Department of Pediatric Dermatology, Children's Hospital San Antonio, San Antonio, Texas.
¹⁹ Department of Dermatology, Henry Ford Hospital, Detroit, Michigan.
²⁰ Division of Dermatology, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri.
²¹ Department of Dermatology, State University of New York Downstate Health Sciences University, Brooklyn, New York. Electronic address: sharon.glick@downstate.edu.

PMID: 34634382
DOI: 10.1016/j.jaad.2021.09.065

Abstract

Background: Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling.

Objective: To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB.

Methods: A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal.

Results: A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P < .001). The likelihood of undergoing genetic analysis was greater for junctional EB and recessive dystrophic EB, and the same for dominant dystrophic EB as compared with EB simplex. TEM results in 163 patients were equivocal (55%), concordant (42%), and discordant (3%). IFM results in 185 patients were equivocal (54%), concordant (42%), and discordant (4%).

Limitations: Retrospective design.

Conclusions: Diagnostic testing has shifted in favor of genetic analysis. TEM and IFM frequently offer equivocal findings when compared to the specificity afforded by genetic analysis.

Keywords: diagnostic concordance; diagnostic testing; electron microscopy; epidermolysis bullosa; genetic analysis; genetics; immunofluorescence mapping; laboratory testing; next-generation sequencing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Epidermolysis Bullosa Dystrophica* / diagnosis
Epidermolysis Bullosa Simplex* / diagnosis
Epidermolysis Bullosa* / diagnosis
Epidermolysis Bullosa* / genetics
Epidermolysis Bullosa, Junctional*
Fluorescent Antibody Technique
Humans
North America
Retrospective Studies