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

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

Journal

Journal of the American Academy of Dermatology
ISSN: 1097-6787
Titre abrégé: J Am Acad Dermatol
Pays: United States
ID NLM: 7907132

Informations de publication

Date de publication:
05 2022
Historique:
received: 03 09 2020
revised: 03 06 2021
accepted: 09 09 2021
pubmed: 12 10 2021
medline: 20 4 2022
entrez: 11 10 2021
Statut: ppublish

Résumé

Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling. To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB. 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. 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%). Retrospective design. 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.

Sections du résumé

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.

Identifiants

pubmed: 34634382
pii: S0190-9622(21)02584-6
doi: 10.1016/j.jaad.2021.09.065
pii:
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1063-1071

Subventions

Organisme : NCATS NIH HHS
ID : UL1 TR002535
Pays : United States

Informations de copyright

Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of interest Dr Bruckner serves as an investigator for Fibrocell, Phoenix Tissue Repair, PROQR/Wings, and Castle Creek and on an ad hoc advisory board for Castle Creek. Dr Pope receives research funding from the EB Research Foundation. Dr Paller serves as an investigator for Castle Creek and Lenus Pharmaceuticals and has been a consultant with honorarium for Abeona. Dr Levy serves on the advisory board for Cassiopea, Regeneron; as an investigator for Fibrocell/Castle Creek, Galderma, Janssen, Pfizer; on the Data Safety and Monitoring Board for Novan; and as a section editor for UpToDate. Dr Lucky serves as an investigator for Lenus Pharmaceuticals and Castle Creek and on the scientific advisory board for EBRP (EB Research Partnership) and Abeona. Dr Glick serves as an investigator for Lenus Pharmaceuticals. Authors Phillips, Augsburger, and Peoples and Drs Huang, Kaplan, Khuu, Tang, Lara-Corrales, Wiss, Levin, Morel, Hook, Eichenfield, McCuaig, Powell, Castelo-Soccio, Price, Schachner, Browning, Jahnke, Shwayder, and Bayliss have no conflicts of interest to declare.

Auteurs

Gregory Scott Phillips (GS)

Department of Dermatology, State University of New York Downstate Health Sciences University, Brooklyn, New York.

Amy Huang (A)

Department of Dermatology, State University of New York Downstate Health Sciences University, Brooklyn, New York.

Bret D Augsburger (BD)

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Laura Kaplan (L)

Department of Dermatology, State University of New York Downstate Health Sciences University, Brooklyn, New York.

Kathleen Peoples (K)

Children's Hospital Colorado, Aurora, Colorado.

Anna L Bruckner (AL)

Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado.

Phuong Khuu (P)

Department of Dermatology, Stanford University School of Medicine, Stanford, California.

Jean Y Tang (JY)

Department of Dermatology, Stanford University School of Medicine, Stanford, California.

Irene Lara-Corrales (I)

Section of Dermatology, Division of Paediatric Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.

Elena Pope (E)

Section of Dermatology, Division of Paediatric Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.

Karen Wiss (K)

Departments of Dermatology and Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts.

Laura E Levin (LE)

Department of Dermatology, Columbia Irving Medical Center, New York, New York.

Kimberly D Morel (KD)

Department of Dermatology, Columbia Irving Medical Center, New York, New York; Department of Pediatrics, Columbia Irving Medical Center, New York, New York.

Kristen P Hook (KP)

Department of Dermatology, University of Minnesota Medical School, Minneapolis, Minnesota.

Amy S Paller (AS)

Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Lawrence F Eichenfield (LF)

Departments of Dermatology and Pediatrics, University of California San Diego, San Diego, California.

Catherine C McCuaig (CC)

Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada.

Julie Powell (J)

Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada.

Leslie Castelo-Soccio (L)

Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Moise L Levy (ML)

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.

Harper N Price (HN)

Department of Dermatology, Phoenix Children's Hospital, Phoenix, Arizona.

Lawrence A Schachner (LA)

Department of Dermatology, University of Miami Miller School of Medicine, Miami, Florida.

John C Browning (JC)

Department of Pediatric Dermatology, Children's Hospital San Antonio, San Antonio, Texas.

Marla Jahnke (M)

Department of Dermatology, Henry Ford Hospital, Detroit, Michigan.

Tor Shwayder (T)

Department of Dermatology, Henry Ford Hospital, Detroit, Michigan.

Susan Bayliss (S)

Division of Dermatology, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri.

Anne W Lucky (AW)

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Sharon A Glick (SA)

Department of Dermatology, State University of New York Downstate Health Sciences University, Brooklyn, New York. Electronic address: sharon.glick@downstate.edu.

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