What is the primary management approach for patients with Ehlers-Danlos Syndrome (EDS)?

Management of Ehlers-Danlos Syndrome

The primary management approach for EDS requires distinguishing between vascular EDS (vEDS) and hypermobile EDS (hEDS), as vEDS demands aggressive cardiovascular surveillance with celiprolol therapy and annual vascular imaging to prevent life-threatening arterial complications, while hEDS focuses on symptomatic treatment with physical therapy, pain management, and gastrointestinal symptom control. 1, 2

Vascular EDS (Type IV) - The Life-Threatening Subtype

Diagnosis and Risk Stratification

• Genetic confirmation of COL3A1 pathogenic variants is mandatory for diagnosis—this is not optional 1
• Life expectancy averages only 51 years, with arterial complications occurring at 1.6 events per 5-year period 1
• Medium-sized arteries are most vulnerable to dissection, aneurysm, rupture, and arteriovenous fistulas, with complications starting in adolescence 1

Medical Management - Celiprolol First

• Start celiprolol (a beta-blocker with vasodilatory properties) after age 10 years to reduce vascular morbidity 1, 2
• This recommendation comes from two retrospective studies and one randomized open-label trial showing reduced arterial rupture risk 2, 3
• Maintain blood pressure in the normal range with aggressive hypertension treatment 1, 2

Surveillance Protocol

• Perform baseline imaging from head to pelvis using Doppler ultrasound, low-radiation CT, or cardiovascular MRI to evaluate the entire aorta and branching vessels 2, 3
• Conduct annual surveillance of the vascular tree, with frequency adapted individually for dilated or dissected segments 1, 3
• Never use invasive catheter angiography—fatal complications can occur from the procedure itself 3, 4

Surgical Considerations

• Acute unexplained pain requires urgent imaging to exclude arterial rupture 1
• Conservative management is preferred for acute arterial complications; surgery is reserved for vital risk only 1
• When surgery is unavoidable, use meticulous technique with pledgeted sutures for all anastomoses due to tissue fragility 2, 3
• Avoid procedures requiring organ inflation or perform with extreme caution 1

Pregnancy Risks

• Pregnancy carries significant risk of uterine and arterial rupture, though overall mortality may not differ from nulliparous vEDS women 1
• Engage patients in shared decision-making informed by vascular status and specific COL3A1 variant type 1

Hypermobile EDS - The Most Common Subtype

Diagnostic Requirements

• Beighton score ≥5/9 for joint hypermobility (passive fifth finger dorsiflexion >90°, thumb-to-forearm apposition, elbow hyperextension >10°, knee hyperextension >10°, forward bend with palms flat) 4
• Soft or velvety skin without fragility 4
• Mandatory genetic testing to exclude alternative diagnoses—26.4% of clinically diagnosed cases have different genetic conditions requiring different management 2, 4

Cardiovascular Surveillance

• Perform baseline echocardiogram, as 25-33% have aortic root dilatation 4
• Repeat echocardiography every 2-3 years until adult height is reached 2, 4
• If aortic root diameter exceeds 4.5 cm in adults or growth rate exceeds 0.5 cm/year, increase frequency to every 6 months 2, 4

Musculoskeletal Management

• Prescribe low-resistance exercise and physical therapy as the foundation of treatment 2, 4
• Occupational therapy and bracing show 70% improvement rates—the highest efficacy among treatment modalities 5
• Avoid high-impact activities that increase joint dislocation risk 6

Gastrointestinal Symptom Management

• Test for celiac disease in all patients with gastrointestinal symptoms, not just those with diarrhea, due to increased risk 2
• For nausea and vomiting: use antiemetics, prokinetics, and neuromodulators 2
• For constipation: prescribe laxatives, chloride channel activators, or guanylate cyclase-C receptor agonists 2
• For diarrhea: use antidiarrheal agents, bile acid sequestrants, or mixed opioid receptor agonists/antagonists 2
• In patients with postural orthostatic tachycardia syndrome (POTS) and chronic upper GI symptoms, evaluate gastric motor function after excluding structural disease 2

Pain Management Strategy

• Avoid opioid dependence—most hEDS patients have visceral hypersensitivity rather than true dysmotility, making opioids particularly problematic 4, 7
• Use nonsteroidal anti-inflammatory drugs, acetaminophen, and neuropathic modulators (though 47% report adverse effects with the latter) 5
• Implement cognitive-behavioral therapy for anxiety and stress management 2, 8
• Consider complementary/alternative treatments, which are the most commonly used modalities 5

Associated Conditions to Screen For

• POTS: treat with increased fluid and salt intake, exercise training, compression garments, and pharmacological agents for volume expansion if conservative measures fail 3
• Mast cell activation disorder 4
• Chronic urinary retention 4

Critical Pitfalls to Avoid

• Never perform invasive vascular procedures in vEDS without compelling vital indication—tissue fragility causes fatal complications 1, 3, 4
• Do not diagnose hEDS without genetic testing to exclude the 26.4% with alternative conditions 2, 4
• Avoid escalating to invasive nutrition support in hEDS with pain-predominant presentation 4
• Do not use endoscopic procedures with organ inflation in vEDS patients 2
• Never overlook the multidisciplinary team requirement: cardiology, vascular surgery, gastroenterology, genetics, physical medicine, and psychology specialists are all essential 2, 3