Vascular Ehlers-Danlos Syndrome

Introduction

• Vascular Ehlers-Danlos Syndrome (vEDS) is a genetic disorder transmitted as an autosomal dominant trait, caused by mutations in the COL3A1 gene coding for type III procollagen, according to the European Society of Cardiology 1

Diagnosis and Characteristics

• Vascular Ehlers-Danlos Syndrome is characterized by tissue fragility, which can manifest as arterial ruptures, and is associated with a high risk of vascular complications, as reported by the American Heart Association 2
• The Beighton scale is a key assessment tool for joint hypermobility, evaluating passive extension of little fingers, passive apposition of thumbs to forearm, hyperextension of elbows and knees, and forward flexion of trunk, as suggested by the American College of Cardiology 3
• The following table summarizes the Beighton scale:

• Skin examination should evaluate for hyperextensibility, soft or velvety texture, fragility and poor wound healing, atrophic scarring, and easy bruising, as suggested by the American College of Medical Genetics and Genomics 4, 5
• Targeted genetic testing based on suspected EDS subtype is recommended, with vascular EDS testing for the COL3A1 gene, and Loeys-Dietz syndrome testing for the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 genes 6, 2

Complications and Risks

• Aortic dissection can occur without prior dilatation in patients with Vascular Ehlers-Danlos Syndrome, and pregnancy significantly increases the risk of vascular rupture, as stated by the European Society of Cardiology 1
• Uterine rupture during pregnancy or labor is a significant risk in patients with Vascular Ehlers-Danlos Syndrome, and pregnancy is considered a contraindication due to this risk, as recommended by the European Society of Cardiology 1
• Valve prolapse is found in 43% of patients with EDS, and arterial tortuosity is also present in certain subtypes, as reported by the American Heart Association 2
• Vascular EDS can lead to life-threatening arterial ruptures, with median survival of only 48 years, emphasizing the importance of careful vascular assessment 2

Management and Treatment

• Surgical repair may be complicated by tissue fragility, hemorrhage, and poor wound healing in patients with Vascular Ehlers-Danlos Syndrome, as noted by the European Society of Cardiology 1
• Non-invasive imaging should be used whenever possible to minimize the risk of arterial injury in patients with vascular EDS, as recommended by the American Heart Association 7
• Avoid invasive diagnostic procedures, such as conventional angiography, which is contraindicated due to the high risk of complications in vascular EDS patients 7
• Beta-blockers like celiprolol may be beneficial for patients with vascular Ehlers-Danlos syndrome, but lack FDA approval, and consideration of starting beta blocker treatment after 10 years of age is recommended, as suggested by the European Heart Journal and supported by the American Heart Association 5, 8
• A comprehensive approach to EDS management, focusing on symptom control and prevention of complications, can improve quality of life and reduce morbidity in EDS patients, as suggested by the European Heart Journal and supported by the American College of Medical Genetics and Genomics 5, 8

Pregnancy and Reproductive Considerations

• Complete vascular imaging is essential before pregnancy in women with vEDS, and comprehensive CT imaging is crucial before any necessary surgical intervention due to the high risk of vascular complications, as recommended by the American College of Obstetricians and Gynecologists and supported by the European Heart Journal 5, 8
• Complex decision requiring shared decision-making is necessary for women with vascular EDS considering pregnancy, and most women with known vascular EDS undergo cesarean delivery, as suggested by the American College of Obstetricians and Gynecologists and supported by the American Heart Association 5, 9

Multidisciplinary Approach and Patient Education

• A multidisciplinary approach to management is recommended, with consideration of cardiovascular assessment, as aortic abnormalities are common, and recognition that hEDS has no genetic test available yet, diagnosis is clinical, as suggested by the European Heart Journal and supported by the American College of Medical Genetics and Genomics 5, 8
• Patient education on the disease and lifestyle modifications are essential components of management, as recommended by the Clinical Gastroenterology and Hepatology guidelines 10
• Regular cardiovascular follow-up, particularly for patients with aortic anomalies, is crucial, as suggested by the European Heart Journal and supported by the American College of Medical Genetics and Genomics 5, 8

Associated Conditions and Symptom Management

• Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by a heart rate increase of ≥30 beats/min within 10 minutes of upright posture, and symptoms of orthostatic intolerance for at least 6 months 10
• Mast Cell Activation Syndrome (MCAS) should be assessed for symptoms of mast cell activation, with testing targeted to patients with clinical manifestations 10
• Histamine receptor antagonists, mast cell stabilizers, and leukotriene receptor antagonists can help manage mast cell activation syndrome (MCAS) in EDS patients, as recommended by the Clinical Gastroenterology and Hepatology guidelines 10
• Neuromodulators, such as gabapentin and pregabalin, may be used to help manage pain in EDS patients, and antispasmodics, such as hyoscyamine and dicyclomine, may be used to manage muscle tension, with a strength of evidence rated as moderate, as suggested by the American Academy of Pain Medicine 10
• The American Society of Regional Anesthesia and Pain Medicine recommends avoiding opioids for chronic pain management in EDS patients, due to the high risk of addiction and limited efficacy, with a strength of evidence rated as high 10