How to monitor and manage aneurysm risk in patients with Ehlers-Danlos syndrome (EDS), a genetic disorder characterized by joint hypermobility, skin hyperextensibility, and tissue fragility?

Monitoring Aneurysm Risk in Ehlers-Danlos Syndrome

Immediate Priority: Determine EDS Subtype

All patients with EDS require immediate genetic testing to distinguish vascular EDS (Type IV) from other subtypes, as this fundamentally changes monitoring intensity and prognosis—vascular EDS carries a median survival of only 48-51 years with arterial rupture as the leading cause of death. 1

• Genetic confirmation of COL3A1 mutations is mandatory for vascular EDS diagnosis, as 26.4% of clinically diagnosed EDS cases have alternative genetic conditions requiring different management strategies. 1, 2
• Vascular EDS patients face catastrophic risk of spontaneous arterial dissection and rupture even at normal or minimally dilated aortic diameters, unlike other EDS subtypes. 3, 1

Baseline Imaging Protocol

For confirmed or suspected vascular EDS, obtain baseline imaging from head to pelvis using noninvasive methods (CT or MRI) to evaluate the entire aorta and all arterial branches. 3, 1, 2

• Never perform invasive catheterization or angiography in vascular EDS patients—this can be fatal. 1, 4, 5
• Noninvasive vascular imaging using Doppler ultrasound, CT, or MRI is strongly preferred over any invasive procedures. 2, 5
• Baseline imaging identifies pre-existing aneurysms or dissections that require closer monitoring. 2

Surveillance Imaging Schedule by EDS Subtype

For Vascular EDS (Type IV):

Annual surveillance imaging is required for all vascular segments, with imaging every 2 years acceptable only when initial imaging is completely normal. 3, 2

• Any dilated or dissected aortic or arterial segments require annual surveillance at minimum. 3, 2
• The recurrence rate is 1.6 vascular events per 5-year period, necessitating lifelong vigilance. 1

For Hypermobile and Classical EDS:

Obtain baseline echocardiogram to evaluate for aortic root dilatation, then follow a risk-stratified protocol. 3

• If aortic root is normal: Repeat echocardiogram every 2-3 years until adult height is reached. 3
• If no dilatation is present after reaching adult height: Repeat echocardiogram only if cardiovascular symptoms develop or when major increase in physical activity is planned. 3
• If aortic root diameter is >4.5 cm in adults OR rate of increase is >0.5 cm/year: Echocardiogram every 6 months. 3
• If aortic root diameter is <4.5 cm in adults AND rate of increase is <0.5 cm/year: Annual echocardiogram. 3

Medical Management

Initiate celiprolol (beta-blocker with vasodilatory properties) for vascular EDS patients, as this reduces vascular morbidity three-fold. 1, 2

• While celiprolol lacks FDA approval in the US, it has the strongest evidence for benefit in vascular EDS. 3, 2
• Alternative beta-blockers with vasodilatory properties may be prescribed when celiprolol is unavailable. 3
• No evidence supports ARB use in vascular EDS, unlike Marfan syndrome. 3
• Aggressive blood pressure control is essential for all vascular EDS patients. 1

Critical Clinical Pitfalls to Avoid

Never delay imaging for acute unexplained pain in vascular EDS patients—arterial rupture is time-sensitive and can occur without warning. 1

• Avoid all invasive diagnostic procedures including arterial lines and central venous catheters, as these carry risk of fatal vascular complications. 1, 2, 4
• Do not assume normal aortic diameter provides safety in vascular EDS—dissection and rupture occur at normal or minimally dilated diameters. 3, 1
• Classical EDS (COL5A1/COL5A2 mutations) can also present with arterial complications in 4.5% of cases, though typically involving medium-sized vessels. 6

Multidisciplinary Care Coordination

All EDS patients with vascular risk require management coordination between cardiology, vascular surgery, and genetics, with centralization of care at centers of excellence whenever feasible. 1, 2

• Surgical interventions in vascular EDS carry extremely high risk due to tissue fragility, bleeding tendency, and poor wound healing. 3, 1, 2
• When surgery is necessary, meticulous technique with pledgeted sutures is mandatory to prevent tissue tearing. 1, 2
• Endovascular techniques and arterial embolization may be preferred over open surgery depending on individual circumstances. 3, 2