What are the treatment options for Ehlers-Danlos syndrome (EDS)?

Ehlers-Danlos Syndrome Treatment

Treatment for Ehlers-Danlos syndrome must be tailored to the specific subtype, with vascular EDS requiring celiprolol and intensive vascular surveillance to prevent life-threatening complications, while hypermobile EDS centers on physical therapy and avoidance of opioids. 1

Vascular EDS (Type IV) - Life-Threatening Subtype

Medical Management

• Celiprolol (a beta-blocker with vasodilatory properties) should be considered as the primary pharmacologic treatment to reduce vascular morbidity, though it lacks FDA approval in the United States 2, 1
• Maintain optimal blood pressure control to reduce arterial stress 1
• ARBs have no proven benefit in vascular EDS and should not be used as a substitute for celiprolol 1

Vascular Surveillance Protocol

• Perform baseline imaging (MRI or CT) from head to pelvis to evaluate the entire aorta and all arterial branches at initial diagnosis 1, 3
• Implement annual surveillance imaging of any dilated or dissected segments 1, 3
• When initial studies are normal, continue imaging every 2 years 1
• Use only non-invasive imaging modalities (Doppler ultrasound, CT, or MRI) 2, 3

Critical Surgical Considerations

• Surgical intervention is indicated only for rapid arterial aneurysm growth or acute dissection - no diameter thresholds exist for prophylactic surgery 1
• When surgery is unavoidable, use meticulous tissue handling and pledgeted sutures for all anastomoses due to extreme tissue fragility 3
• Never perform invasive diagnostic procedures (including catheter angiography) due to risk of fatal complications 1, 3

Pregnancy Management

• Pregnancy carries significant risk of uterine rupture and vessel rupture during delivery 3
• Most women with known vascular EDS undergo cesarean delivery 3

Hypermobile EDS - Most Common Subtype

Physical Medicine (Cornerstone of Treatment)

• Physical therapy with low-resistance exercise to increase muscle tone and improve joint stability is the primary treatment, combined with myofascial release techniques 1
• Occupational therapy and bracing show 70% improvement rates and are highly effective 4

Cardiovascular Screening

• Perform baseline echocardiogram to evaluate for aortic root dilation, which occurs in 25-33% of hypermobile EDS patients 1

Gastrointestinal Management

• Treat prominent GI symptoms based on specific manifestations and abnormal function test results (up to 98% of patients have GI involvement) 1
• Consider special diets (gastroparesis diet, elimination diets) with mandatory nutritional counseling to prevent restrictive eating 1
• Never prescribe opioids for chronic pain management, especially with GI manifestations 1, 5

Autonomic Dysfunction (POTS)

• Increase fluid and salt intake as first-line treatment 1
• Implement exercise training programs 1
• Use compression garments 1
• Consider pharmacological treatments for volume expansion, heart rate control, and vasoconstriction only if conservative measures fail 3

Mast Cell Activation Syndrome (MCAS)

• When MCAS is suspected, treat with histamine receptor antagonists and/or mast cell stabilizers 1
• Test for MCAS only if patient presents with episodic multisystem symptoms involving ≥2 physiological systems 6

Psychological Support

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

Pain Management Across All Subtypes

• Neuropathic modulators can be used but are poorly tolerated, with 47% of patients reporting adverse effects 4
• Nonsteroidal anti-inflammatory drugs may be considered for acute pain 4
• Complementary/alternative treatments are the most commonly used modalities (used by 88% of patients in one study) 4
• Opioids should be avoided due to risk of opioid use disorder and lack of efficacy in connective tissue-related pain 1, 5

Multidisciplinary Team Approach

• All EDS subtypes require regular follow-up with a multidisciplinary team including medical geneticists, cardiologists, gastroenterologists, physical medicine specialists, and pain management specialists 1, 3
• Patients with known or suspected EDS should be evaluated in a center with experience in caring for this patient group 2

Critical Pitfalls to Avoid

• Never use invasive diagnostic procedures in vascular EDS patients - this can cause fatal complications 1, 3
• Never prescribe opioids for chronic pain management in EDS patients, particularly those with GI manifestations 1, 5
• Recognize that vessels may rupture or dissect in vascular EDS even without significant dilation - surveillance must be comprehensive 1
• Neuropathic modulators have high adverse effect rates (47%) and should be used cautiously 4