What is the management approach for Ehlers-Danlos disease?

Management of Ehlers-Danlos Syndrome

Management of Ehlers-Danlos syndrome requires immediate subtype identification through genetic testing, with vascular EDS demanding celiprolol therapy and annual vascular surveillance, while hypermobile EDS centers on physical therapy, symptom-directed gastrointestinal management, and avoidance of opioids. 1, 2, 3

Initial Diagnostic Approach

Genetic testing is mandatory for definitive diagnosis, particularly identifying COL3A1 variants in vascular EDS, which is the most life-threatening subtype with average life expectancy of 51 years. 4, 3 The European Society of Cardiology notes that 26.4% of clinically diagnosed cases have alternative genetic conditions requiring different management, making molecular confirmation essential. 1

For hypermobile EDS, apply rigorous diagnostic criteria including a Beighton score ≥5/9 for joint hypermobility, soft skin without fragility, and mandatory exclusion of alternative diagnoses through genetic testing. 1

Vascular EDS (Type IV) Management

Medical Treatment

Celiprolol is the first-line pharmacologic treatment for vascular EDS, demonstrating reduction in arterial rupture in both retrospective studies and an open randomized trial, though it lacks FDA approval in the United States. 4, 1, 2, 3 Start celiprolol after 10 years of age, which is considered reasonable by expert consensus. 4

Maintain aggressive blood pressure control in the normal range to reduce risk of rupture and arterial dissection. 4, 1, 2 ARBs have no proven benefit in vascular EDS and should not be used as substitutes for celiprolol. 3

Surveillance Protocol

Perform baseline imaging from head to pelvis using Doppler ultrasound, low-radiation CT angiography, or cardiovascular magnetic resonance to evaluate the entire aorta and arterial branches. 4, 1, 2, 3

Annual surveillance imaging is required for any dilated or dissected segments, with imaging every 2 years when initial studies are normal. 2, 3 The European Society of Cardiology recommends that frequency of follow-up should be adapted individually based on findings. 4

Critical Safety Measures

Never perform invasive diagnostic procedures in vascular EDS patients due to risk of fatal complications—use non-invasive imaging exclusively. 2, 3 Diagnostic catheter angiography carries unacceptable risks in these patients. 2

Recognize that vessels may rupture or dissect even without significant dilation, making diameter-based thresholds unreliable. 2, 3 Surgical intervention is indicated only for rapid arterial aneurysm growth or acute dissection, as no diameter thresholds exist for prophylactic surgery. 3

Surgical Considerations

When surgery is unavoidable, use meticulous surgical technique with careful tissue handling to prevent wound dehiscence and pledgeted sutures for all anastomoses in vascular procedures. 4, 1, 2 Consider endovascular therapy with coil embolization for ruptured pseudoaneurysms, visceral aneurysms, and arteriovenous fistulas. 5

Pregnancy in vascular EDS carries significant risks due to potential uterine rupture and vessel rupture during delivery, with most women undergoing cesarean delivery. 2

Hypermobile EDS Management

Musculoskeletal Treatment

Physical therapy with low-resistance exercise to increase muscle tone and improve joint stability is the cornerstone of treatment for hypermobile EDS. 1, 3 Combine with myofascial release techniques to address chronic musculoskeletal pain. 3

Cardiovascular Monitoring

Perform baseline echocardiogram to evaluate for aortic root dilation. 1, 3 Repeat echocardiography every 2-3 years until adult height is reached and when cardiovascular symptoms develop or significant increases in physical activity are planned. 1

For aortic root dilatation, perform echocardiography every 6 months if the diameter is >4.5 cm in adults or the growth rate is >0.5 cm/year. 1

Gastrointestinal Management

Treat prominent GI symptoms based on specific manifestations and abnormal function test results. 1, 2, 3 Consider celiac disease testing in patients with hypermobile EDS who report gastrointestinal symptoms, not limited to those with diarrhea, due to increased risk. 1

For patients with comorbid postural orthostatic tachycardia syndrome (POTS) and chronic upper GI symptoms, evaluate gastric motor function with tests such as gastric emptying and accommodation after excluding anatomical and structural diseases. 1, 2

Specific symptom-directed therapies include:

• Antiemetics, prokinetics, and neuromodulators for nausea, vomiting, and abdominal pain 1
• Laxatives, chloride channel activators, and guanylate cyclase-C receptor agonists for constipation 1
• Antidiarrheal agents, bile acid sequestrants, and mixed opioid receptor agonists/antagonists for diarrhea 1

Special diets including gastroparesis diet and elimination diets may be considered with mandatory nutritional counseling to prevent restrictive eating patterns. 2, 3

POTS Management

First-line treatment for POTS includes increasing fluid and salt intake, exercise training, and compression garments. 2, 3 For patients who don't respond to conservative measures, consider pharmacological treatments for volume expansion, heart rate control, and vasoconstriction. 2

Psychological Support

Implement cognitive-behavioral therapies and brain-gut behavioral therapies due to increased rates of anxiety and psychological distress in patients with hypermobility. 1, 2, 3

Multidisciplinary Team Approach

All EDS subtypes require regular follow-up with a multidisciplinary team including cardiologists, vascular surgeons, gastroenterologists, geneticists, physical medicine and rehabilitation specialists, and pain management specialists. 1, 2, 3, 6 This coordinated approach should integrate support from nursing care, rehabilitation, psychology, and nutrition to facilitate transition from an illness-defined life to a more normalized life. 6

Critical Pitfalls to Avoid

Never prescribe opioids for chronic pain management in EDS patients, especially those with gastrointestinal manifestations. 2, 3 Despite weak evidence for alternative pain control methods, lack of safer alternatives necessitates the conservative multidisciplinary approach. 7

Endoscopic procedures do not appear to have increased complication rates in adults with hypermobile EDS, but are contraindicated in individuals with vascular EDS. 1

Acute, unexplained pain requires urgent imaging to exclude arterial rupture in vascular EDS patients. 4 The rate of recurrence of organic complications in patients with vascular EDS is 1.6 events per 5 year period, requiring constant vigilance. 4