title: Ultrastructural scoring of skin biopsies for diagnosis of vascular Ehlers-Danlos syndrome.
abstract: Vascular Ehlers-Danlos syndrome (vEDS) results from a mutation in the gene encoding alpha-1, type III pro-collagen (COL3A1) and confers fragility to skin, ligament and vascular tissue. We tested the value of skin biopsy for diagnosis of vEDS through an ultrastructure scoring procedure. Study design was a multicentric, case-control, blinded trial consisting of two phases: phase 1 was to identify an ultra-structure score providing the best discriminative value for vEDS and phase 2 was to replicate this result in a different population. We enrolled 103 patients, 66 cases defined through the revised nosology for Ehlers-Danlos syndromes and 37 control subjects selected from patients referred for other pathologies. Ultrastructure of extracellular matrix was read by three to five experienced pathologists blinded for diagnosis. We used the receiver operating curves and logistic regression analysis for ranking ultrastructure scores. We created a detailed description of lesions observed in vEDS patients with 27 items (coded 0 or 1). In the phase 1 (17 cases and 20 controls), abnormal fibroblast shape, presence of lysosomes in the fibroblast and abnormal basal lamina were found to be independent discriminative items. Addition of these three items (defining an ultrastructure score) had the best diagnosis value (area under the curve (AUC) = 0.96). In the phase 2 (49 cases, 17 controls), ultrastructure score provided odds ratio of 9.76 (95 % CI 2.91-32.78), and AUC of 0.90. The ultrastructure score of skin biopsy has predictive value for the diagnosis of vEDS. Presence of two or more signs (either abnormal fibroblast, presence of lysosomes in the fibroblast or abnormal basal lamina) is very evocative of vEDS.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Inserm U970, Université Paris Descartes, Paris, France.
authors.forename: Kim-Thanh
authors.initials: KT
authors.lastname: Ong
authors.forename: Henri
authors.initials: H
authors.lastname: Plauchu
authors.forename: Simone
authors.initials: S
authors.lastname: Peyrol
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Roux
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Errazuriz
authors.forename: Philippe
authors.initials: P
authors.lastname: Khau Van Kien
authors.forename: Brigitte
authors.initials: B
authors.lastname: Arbeille
authors.forename: Alain
authors.initials: A
authors.lastname: Gaulier
authors.forename: Gabriela
authors.initials: G
authors.lastname: Georgescou
authors.forename: Patrick
authors.initials: P
authors.lastname: Collignon
authors.forename: Dominique P
authors.initials: DP
authors.lastname: Germain
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Gaveau
authors.forename: Jérôme
authors.initials: J
authors.lastname: Perdu
authors.forename: Stéphane
authors.initials: S
authors.lastname: Laurent
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Pierre
authors.initials: P
authors.lastname: Boutouyrie
mesh_terms: D001706:Biopsy; D024061:Collagen Type III / Q000235:genetics* / Q000648:ultrastructure; D004535:Ehlers-Danlos Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D012867:Skin / Q000648:ultrastructure*
chemical_list: C439971:COL3A1 protein, human; D024061:Collagen Type III