Diagnosis and management of vascular Ehlers-Danlos syndrome: Experience of the UK national diagnostic service, Sheffield

Abstract

The UK National Diagnostic Service for Ehlers-Danlos Syndromes (EDS) was established in 2009 for the rare types of EDS. Vascular EDS (vEDS) is an inherited connective tissue disorder caused by pathogenic variants in the COL3A1 gene. Associated tissue fragility affects multiple organ systems, increasing the risk of blood vessel dissection and rupture, with potentially fatal consequences. The diagnosis of vEDS has improved with advances in genetic testing, however this is most often suspected following an acute event. We provide data on the clinical features of vEDS for 180 patients (full cohort) seen in our service with confirmed molecular diagnoses. Increased awareness of this rare condition will prompt genetic testing essential to confirm the diagnosis. Outcomes are improved by early diagnosis followed by appropriate management. Fragile connective tissues make invasive procedures potentially dangerous, particularly in an emergency setting. Lifestyle advice from a young age can help acceptance and understanding of the diagnosis and inform choices. There is currently limited evidence for the use of drug therapy to reduce vascular events. We report on the incidence of vascular events in 126 patients (statistical analysis cohort) in our care and the use of medication. Our retrospective data showed that those patients on a long-term angiotensin II receptor blocker and/or beta-blocker had fewer vascular events than those not on cardiac medication who received the same lifestyle and emergency care advice.

Fig. 1. Study identification, inclusion and exclusion flow chart for the statistical analysis cohort.

Group I = glycine substitutions within the triple helix, Group II = splice site variants and in frame deletions and duplications, Group III = variants causing haploinsufficiency [5]. Those age under 15 excluded to allow comparison with previous cohort [10]. (PM = post mortem).

Fig. 2. Survival Graphs.

a Overall patient survival. Patient survival was 99.1% at year 1, 90.5% at year 5, and 88.2% at year 10 of follow-up. Overall patient survival was 88.2% (95% confidence interval [CI]: 76.6–94.2%) after 10 years of follow-up. b Survival according to the type of COL3A1 pathogenic variant. Patient survival did not significantly differ between groups of pathogenic variants (Group I: 85.3% [95% CI: 69.7–93.3%] vs. Group II: 92.3% [95% CI: 56.7–98.9%] vs. Group III: 100%). Log-rank (Group I vs. Group II vs. Group III) p = 0.499. c Survival by treatment group. Survival at the end of follow-up was 93.3% for those on BB&ARB [95% CI: 79.49–97.93%] and 42.67% for those on no treatment [95% CI: 69.80–76.14%]. d Treated vs untreated. Survival at 5 years was 42.67% for those not on treatment [95% CI: 6.98–76.14%] and 96.53% for those on medication [95% CI: 89.35% to 98.9%]. e Groups I and II combining treatment types. Survival for those on BB/ARB/BB&ARB was 98.72% at 1 year, 96.89% at 5 years, and 93.95% at 10 years.

Fig. 2. Survival Graphs.

a Overall patient survival. Patient survival was 99.1% at year 1, 90.5% at year 5, and 88.2% at year 10 of follow-up. Overall patient survival was 88.2% (95% confidence interval [CI]: 76.6–94.2%) after 10 years of follow-up. b Survival according to the type of COL3A1 pathogenic variant. Patient survival did not significantly differ between groups of pathogenic variants (Group I: 85.3% [95% CI: 69.7–93.3%] vs. Group II: 92.3% [95% CI: 56.7–98.9%] vs. Group III: 100%). Log-rank (Group I vs. Group II vs. Group III) p = 0.499. c Survival by treatment group. Survival at the end of follow-up was 93.3% for those on BB&ARB [95% CI: 79.49–97.93%] and 42.67% for those on no treatment [95% CI: 69.80–76.14%]. d Treated vs untreated. Survival at 5 years was 42.67% for those not on treatment [95% CI: 6.98–76.14%] and 96.53% for those on medication [95% CI: 89.35% to 98.9%]. e Groups I and II combining treatment types. Survival for those on BB/ARB/BB&ARB was 98.72% at 1 year, 96.89% at 5 years, and 93.95% at 10 years.