Clinical Pearls & Morning Reports
Published September 29, 2021
The presenting sign is vascular dissection, intestinal perforation, or organ rupture in 70% of patients with vascular Ehlers–Danlos syndrome. Read the NEJM Case Records of the Massachusetts General Hospital here.
Q: What causes the vascular form of Ehlers–Danlos syndrome?
A: Ehlers–Danlos syndrome is a rare autosomal dominant disorder, occurring in 1 in 50,000 to 200,000 patients. The vascular form of Ehlers–Danlos syndrome is caused by mutations in COL3A1. Approximately 50% of cases are associated with a de novo (i.e., not inherited) mutation; 2 to 5% of cases are associated with mosaicism, in which the mutation may be confined to one or more specific cell lines.
Q: What are some of the clinical features of vascular Ehlers–Danlos syndrome?
A: Approximately 15% of patients have intestinal perforation, usually in the sigmoid colon. Pneumothorax can be the presenting sign. A carotid–cavernous sinus fistula occurs in 10% of patients, resulting in sudden blurred vision and ocular pain and requiring rapid intervention to preserve the patient’s vision. Keratoconus, periodontal disease, and gingival recession are minor criteria. Dermatologic findings include skin fragility and poor wound healing. In rare cases, the spleen or liver may rupture.
A: Aggressive control of blood pressure and heart rate is a cornerstone of the medical management of vascular Ehlers–Danlos syndrome, and therefore, beta-adrenergic receptor antagonists are commonly used. Unfortunately, there is a paucity of peer-reviewed data suggesting a survival benefit associated with aggressive control. In general, elective surgeries should be avoided in patients with vascular Ehlers–Danlos syndrome; the risks and benefits of any surgery must be weighed carefully, with consideration of the best approach to the procedure. Since there are multiple reports of intestinal perforation associated with colonoscopy and there are no specific intestinal findings that predict bowel rupture, colonoscopy for cancer screening is generally not recommended unless there is a perceived high risk and strong family history of cancer. Lifestyle modifications are commonly recommended, although there is a paucity of scientific evidence regarding the effects of such strategies. Avoidance of activities that pose a risk of trauma to the arteries is sensible.
A: In patients with vascular Ehlers–Danlos syndrome, surveillance imaging is undertaken to identify early and asymptomatic arterial changes for consideration of preemptive repair. The challenge is that, given the unpredictable nature of the disorder, there is a risk of arterial dissection and rupture even after imaging shows normal arterial segments. However, patients are often reassured by regular surveillance and most clinicians recommend it, especially with the availability of advanced imaging techniques, including duplex ultrasonography and magnetic resonance arteriography, which avoid exposure to radiation and iodinated contrast material. It is prudent to perform imaging studies within 3 months after the index presentation; with control of the blood pressure and heart rate and in the absence of clinical symptoms, it is reasonable to decrease the frequency of imaging to semiannual and ultimately annual intervals.