Ultrastructural scoring of skin biopsies for diagnosis of vascular Ehlers–Danlos syndrome

• Published in: Virchows Archiv : an international journal of pathology Vol. 460; no. 6; pp. 637 - 649
• Main Authors: Ong, Kim-Thanh, Plauchu, Henri, Peyrol, Simone, Roux, Elisabeth, Errazuriz, Elisabeth, Van Kien, Philippe Khau, Arbeille, Brigitte, Gaulier, Alain, Georgescou, Gabriela, Collignon, Patrick, Germain, Dominique P., Gaveau, Marie-Noëlle, Perdu, Jérôme, Laurent, Stéphane, Bruneval, Patrick, Boutouyrie, Pierre
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.06.2012; Springer; Springer Nature B.V
• Subjects: Biological and medical sciences; Biopsy; Collagen Type III - genetics; Collagen Type III - ultrastructure; Ehlers-Danlos Syndrome - diagnosis; Ehlers-Danlos Syndrome - genetics; Ehlers-Danlos Syndrome - pathology; Humans; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Medicine; Medicine & Public Health; Original Article; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Regression analysis; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin - ultrastructure; Blinded study; Score; Ultrastructure; Case–control; Skin biopsy; Diagnosis; Vascular Ehlers–Danlos syndrome; Fibroblast; Skin disease; Ehlers-Danlos syndrome; Elastic tissue disease; Diseases of the osteoarticular system; Case control study; Genetic disease; Case-control; Anatomic pathology; Biopsy; Blood vessel; Vascular Ehlers-Danlos syndrome; Systemic disease; Skin; Circulatory system
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-012-1233-z

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.