What is the recommended management plan for individuals with Ehlers-Danlos syndrome (EDS)?

Management of Ehlers-Danlos Syndrome

Management of EDS requires immediate genetic testing to determine the specific subtype, as vascular EDS (vEDS) demands aggressive vascular surveillance and celiprolol therapy to prevent life-threatening arterial rupture, while hypermobile EDS (hEDS) focuses on physical therapy and symptom management without the same mortality risk. 1, 2

Diagnostic Workup

Essential Initial Testing

• Genetic testing is mandatory before finalizing any EDS diagnosis, as 26.4% of clinically diagnosed cases have alternative genetic conditions requiring completely different management 1
• For vEDS specifically, identification of a causal COL3A1 variant is required for diagnosis 3, 4
• Physical examination must document Beighton score (≥5/9 indicates hypermobility), skin characteristics (soft/velvety texture), and tissue fragility 1
• Obtain three-generation pedigree focusing on joint hypermobility, sudden deaths, and arterial events 1

Baseline Imaging Requirements

• Echocardiogram is required for all EDS patients to evaluate aortic root dilatation, which occurs in 25-33% of classic and hypermobile types 1
• For vEDS, baseline imaging from head to pelvis using non-invasive methods (Doppler ultrasound, CT, or MRI) is essential to evaluate the entire aorta and branches 1, 2, 4

Management by EDS Subtype

Vascular EDS (Type IV) - High Mortality Risk

Medical Management:

• Start celiprolol (beta-blocker with vasodilatory properties) after age 10 years to reduce vascular morbidity by three-fold 3, 2, 5
• Maintain blood pressure in normal range with aggressive hypertension treatment 3, 4, 6
• Life expectancy averages 51 years, with recurrence rate of 1.6 vascular events per 5-year period 3

Surveillance Protocol:

• Annual vascular surveillance of entire arterial tree using non-invasive imaging only 3, 1, 2
• Imaging intervals can be extended after demonstrating stability 4
• Never use invasive diagnostic procedures (including catheter angiography) due to fatal complication risk 1, 2, 4

Emergency Management:

• Acute unexplained pain requires urgent non-invasive imaging to exclude arterial rupture 3
• Conservative approach is preferred for vascular complications unless life-threatening 7
• If surgery is unavoidable, use meticulous tissue handling with pledgeted sutures for anastomoses 2
• Endovascular therapy with coil embolization may be considered for ruptured pseudoaneurysms 5

Pregnancy Considerations:

• Pregnancy carries significant risk of uterine and vessel rupture during delivery 2
• Most women with vEDS undergo cesarean delivery 2

Hypermobile EDS - Focus on Quality of Life

Musculoskeletal Management:

• Low-resistance exercise and physical therapy are the cornerstone of treatment 1
• Occupational therapy and bracing show 70% improvement rate, making them the most effective interventions 8

Cardiovascular Surveillance:

• Echocardiogram every 2-3 years until adult height is reached 1
• Repeat if cardiovascular symptoms develop or major physical activity increase is planned 1
• If aortic root diameter >4.5 cm in adults or growth rate >0.5 cm/year, perform echocardiogram every 6 months 1

Gastrointestinal Management:

• Treat prominent GI symptoms based on abnormal function test results 2, 4
• For gastritis/reflux: proton pump inhibitors, H2-blockers, or sucralfate 1
• For delayed gastric emptying: promotility agents 1
• Most hEDS patients have visceral hypersensitivity rather than true dysmotility—do not escalate to invasive nutrition support or parenteral nutrition except in life-threatening malnutrition 1, 4
• Consider gastroparesis diet and elimination diets with nutritional counseling 2

Associated Conditions Screening:

• Screen for postural orthostatic tachycardia syndrome (POTS), mast cell activation disorder, and chronic urinary retention 1
• For POTS: increase fluid and salt intake, exercise training, compression garments 2
• If conservative measures fail for POTS, consider pharmacological treatments for volume expansion, heart rate control, and vasoconstriction 2

Pain Management:

• Neuropathic modulators can be considered but are poorly tolerated (47% report adverse effects) 8
• Avoid opioid dependence for chronic pain, particularly problematic in patients with gastrointestinal manifestations 1, 4, 8
• Brain-gut behavioral therapies are recommended due to increased anxiety and psychological distress 2, 4

Critical Pitfalls to Avoid

• Never diagnose hEDS without genetic testing to exclude alternative diagnoses that require different management 1
• Never perform invasive vascular procedures in vEDS patients due to fatal complication risk—use non-invasive imaging exclusively 1, 2
• Never use opioids as primary chronic pain management, especially with GI manifestations 1, 4
• Never escalate to parenteral nutrition in hEDS with pain-predominant presentation without evidence of true intestinal failure 1, 4
• Avoid invasive diagnostic procedures in childhood that might be mistaken for coagulation disorders 7

Multidisciplinary Care Structure

• Management requires specialists in cardiology, gastroenterology, physical medicine, and genetics 2
• Patients should be evaluated at centers with experience in connective tissue disorders 4, 5, 6
• Create individualized emergency care plans ("vascular EDS passport") with diagnosis and management plan for use when traveling 6
• Regular follow-up with multidisciplinary team is essential for all EDS subtypes 2, 4