Ehlers-Danlos Syndrome: Diagnosis and Treatment
Diagnosis
Genetic testing is essential for definitive diagnosis, particularly identifying COL3A1 variants in vascular EDS, which is the most life-threatening subtype. 1, 2
Diagnostic Approach by Subtype
Vascular EDS (Type IV):
- Confirm diagnosis through COL3A1 genetic testing 1, 2
- Perform baseline imaging (MRI or CT) from head to pelvis to evaluate the entire aorta and arterial branches 3, 1
- Look for characteristic facial features (acrogeria), translucent skin with visible subcutaneous vessels, and easy bruising 4
Hypermobile EDS:
- Medical geneticists provide primary diagnosis and classification 5
- Rheumatologists evaluate joint hypermobility using the Beighton scale 5
- Assess for gastrointestinal manifestations, cardiovascular abnormalities (aortic root dilation), and autonomic dysfunction (POTS) 5, 2
Treatment of Vascular EDS
Surveillance and Medical Management
For vascular EDS, implement annual surveillance imaging of dilated or dissected segments, with imaging every 2 years when initial studies are normal. 3, 1
Medical therapy:
- Celiprolol (beta-blocker with vasodilatory properties) is recommended to reduce vascular morbidity, though it lacks FDA approval in the US 3, 1, 2
- Alternative beta-blockers with vasodilatory properties may be prescribed when celiprolol is unavailable 3
- Maintain optimal blood pressure control 2
- ARBs have no proven benefit in vascular EDS 3
Critical Precautions
Avoid invasive diagnostic procedures due to risk of fatal complications—use non-invasive imaging exclusively. 1, 2
- Diagnostic catheter angiography carries significantly increased risks 1
- Educate patients on lifestyle modifications and avoidance of high-risk activities 3
Surgical Considerations
Surgical intervention is indicated only for rapid arterial aneurysm growth or acute dissection, as no diameter thresholds exist for prophylactic surgery. 3
- Surgery requires meticulous technique with careful tissue handling and pledgeted sutures for anastomoses 1
- Decisions must involve a Multidisciplinary Aortic Team with shared decision-making 3, 1
- Consider endovascular therapy and arterial embolization based on individual circumstances 3, 1
- Vascular fragility increases bleeding complications significantly 3, 1
Pregnancy Management
Most women with vascular EDS undergo cesarean delivery due to risks of uterine and vessel rupture. 1
Treatment of Hypermobile EDS
Musculoskeletal Management
Physical therapy with low-resistance exercise to increase muscle tone and improve joint stability is the cornerstone of treatment, combined with myofascial release techniques. 5
- Delay orthopedic surgery in favor of physical therapy and bracing, as surgical outcomes are inferior compared to non-EDS patients 5
- Use bracing for joint stabilization—occupational therapy and bracing show 70% improvement rates 5, 6
- Vitamin C supplementation may improve hypermobility as it aids collagen cross-linking 5
Pain Management
Use neuropathic modulators (tricyclic antidepressants, SSRIs, SNRIs, pregabalin, gabapentin) as first-line pharmacologic agents for chronic pain. 5
- Avoid opioids for chronic or abdominal pain management 5, 2
- Consider antispasmodics (hyoscyamine, dicyclomine, peppermint oil) for abdominal pain 5
- Engage a pain management specialist for patients with chronic pain 5
- Note that neuropathic modulators have a 47% adverse effect rate 6
Cardiovascular Monitoring
Perform baseline echocardiogram to evaluate for aortic root dilation. 5
- If aortic root is normal: repeat echocardiogram every 2-3 years until adult height is reached 5
- If aortic root is dilated: increase monitoring frequency based on diameter and rate of progression 5
Gastrointestinal Management
Treat prominent GI symptoms based on specific manifestations and abnormal function test results. 1, 5
- For gastritis/reflux: proton pump inhibitors, H-2 blockers, or sucralfate 5
- For delayed gastric emptying: promotility agents 5
- For irritable bowel symptoms: antispasmodics, antidiarrheals, and laxatives as needed 5
- Test for celiac disease in patients with GI symptoms, as risk is elevated 5
- Consider diagnostic testing of gastric motor functions in patients with comorbid POTS and chronic upper GI symptoms 1
Dietary Interventions
Special diets (gastroparesis diet, elimination diets) may be considered with mandatory nutritional counseling to prevent restrictive eating. 1, 5
Autonomic Dysfunction (POTS)
For POTS, increase fluid and salt intake, implement exercise training, and use compression garments as first-line treatment. 1, 5
- For inadequate response to conservative measures: use pharmacological treatments for volume expansion, heart rate control, and vasoconstriction 1, 5
Mast Cell Activation Syndrome
When MCAS is suspected, treat with histamine receptor antagonists and/or mast cell stabilizers. 5
- Advise avoidance of triggers: certain foods, alcohol, strong smells, temperature changes, and specific medications 5
Bone Health
- Encourage calcium and vitamin D supplementation 5
- Recommend low-impact weight-bearing exercise 5
- Consider DXA scan for height loss greater than one inch 5
Psychological Support
Implement brain-gut behavioral therapies due to increased rates of anxiety and psychological distress in patients with hypermobility. 1, 2
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, 5, 2
Critical Pitfalls to Avoid
- Never use invasive diagnostic procedures in vascular EDS patients 1, 2
- Never prescribe opioids for chronic pain management, especially with GI manifestations 5, 2
- Never use parenteral nutrition in hypermobile EDS except for life-threatening malnutrition 2
- Never perform isolated aortic root replacement in vascular EDS—replace the entire ascending aorta 3
- Recognize that vessels may rupture or dissect in vascular EDS even without significant dilation 3, 1