What is the management approach for a patient with Ehlers-Danlos syndrome?

Management of Ehlers-Danlos Syndrome

Management of Ehlers-Danlos syndrome requires immediate determination of the EDS subtype through genetic testing, as vascular EDS (Type IV) demands specialized cardiovascular surveillance and celiprolol therapy to prevent catastrophic arterial rupture, while hypermobile EDS focuses on symptom-directed gastrointestinal management, physical rehabilitation, and psychological support—all coordinated through a multidisciplinary team. 1, 2

Critical First Step: Determine EDS Subtype

• Genetic testing is mandatory before initiating any management plan, as 26.4% of clinically diagnosed EDS cases have alternative genetic conditions requiring completely different treatment approaches 1
• For suspected vascular EDS, test for COL3A1 mutations immediately, as this subtype carries a median survival of only 48-51 years with arterial rupture as the leading cause of death 3
• Hypermobile EDS diagnosis requires 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

Immediate Cardiovascular Surveillance

• Obtain baseline noninvasive imaging from head to pelvis using Doppler ultrasound, CT, or MRI to evaluate the entire aorta and all arterial branches 2, 3
• Perform annual surveillance imaging for all vascular segments, as arterial dissection and rupture can occur at normal or minimally dilated diameters 3
• Never perform invasive catheterization or angiography, as these procedures can be fatal in vascular EDS patients 3

Medical Therapy

• Initiate celiprolol (beta-blocker with vasodilatory properties) as first-line treatment, which reduces vascular morbidity three-fold 1, 2, 3
• Implement aggressive blood pressure control to reduce rupture and arterial dissection risk 1
• Alternative beta-blockers with vasodilatory properties may be used when celiprolol is unavailable, though evidence is weaker 3
• Do not use ARBs, as there is no evidence supporting their use in vascular EDS (unlike Marfan syndrome) 3

Surgical Considerations

• Surgery carries extremely high risk due to tissue fragility, bleeding tendency, and poor wound healing 2, 3
• When surgery is unavoidable, use meticulous surgical technique with pledgeted sutures for all anastomoses 1, 2
• Prefer endovascular approaches and arterial embolization when possible, with decisions made by a Multidisciplinary Aortic Team 2
• Avoid prophylactic repair of unruptured aneurysms, as the role remains unclear and operative mortality is high 3

Pregnancy Management

• Pregnancy carries significant risks due to potential uterine rupture and vessel rupture during delivery 2
• Most women with known vascular EDS undergo cesarean delivery 2

Hypermobile EDS Management

Gastrointestinal Symptom Management

• Follow a symptom-based diagnostic strategy similar to disorders of gut-brain interaction (DGBI) in the general population, with limited noninvasive testing 4
• Consider celiac disease testing earlier in the diagnostic evaluation for patients reporting various GI symptoms, not just diarrhea 4, 1
• For chronic upper GI symptoms with comorbid POTS, perform timely diagnostic testing of gastric motor functions (gastric emptying and/or accommodation) after excluding anatomical diseases 4, 1
• Test for functional defecation disorders with anorectal manometry, balloon expulsion test, or defecography in patients with incomplete evacuation, given high prevalence of pelvic floor dysfunction 4

Specific GI Treatments

• For nausea/vomiting: Use antiemetics (ondansetron, promethazine, prochlorperazine, aprepitant) and prokinetics (metoclopramide, domperidone, erythromycin, prucalopride) 4, 1
• For abdominal pain: Consider acid-suppressive drugs (PPIs, H2 antagonists), antispasmodics (hyoscyamine, dicyclomine, peppermint oil), and neuromodulators (tricyclic antidepressants, SSRIs, SNRIs, pregabalin, gabapentin) 4, 1
• For constipation: Use laxatives, chloride channel activators, and guanylate cyclase-C receptor agonists 1
• For diarrhea: Use antidiarrheal agents, bile acid sequestrants, and mixed opioid receptor agonists/antagonists 1
• Absolutely avoid opiates for chronic pain management, especially in patients with gastrointestinal manifestations 4, 2

Mast Cell Activation Syndrome (MCAS) Evaluation

• Consider testing for mast cell disorders in patients with hypermobile EDS and DGBI who present with episodic symptoms suggesting generalized mast cell disorder 4
• If MCAS is suspected, obtain serum tryptase levels at baseline and 1-4 hours following symptom flares 4
• Refer to an allergy specialist or mast cell disease research center if MCAS is supported by clinical and/or laboratory features 4

POTS Management

• Increase fluid and salt intake as first-line conservative measures 2
• Implement exercise training programs and compression garments 2
• For patients not responding to conservative measures, consider pharmacological treatments for volume expansion, heart rate control, and vasoconstriction 2

Musculoskeletal and Pain Management

• Implement low-resistance exercise and physical therapy for musculoskeletal management 1
• Use a multidisciplinary approach including physiotherapy, occupational therapy, and cognitive behavioral therapy 5, 6
• Optimize daily medications with neuromodulators rather than opioids 6
• Provide pain education, self-management sessions including cognitive behavioral therapy, graded exercises, coping strategies, and relaxation techniques 6

Psychological Support

• Provide brain-gut behavioral therapies due to increased rates of anxiety and psychological distress in patients with hypermobility 4, 1
• Address kinesiophobia, panic, and anxiety disorders that increase the burden of pain 6

Classical and Other EDS Subtypes

Cardiovascular Surveillance

• Obtain baseline echocardiogram to evaluate for aortic root dilatation 1, 3
• If aortic root is normal, repeat echocardiogram every 2-3 years until adult height is reached 1, 3
• If aortic root diameter is >4.5 cm in adults or growth rate is >0.5 cm/year, perform echocardiography every 6 months 1, 3
• If aortic root diameter is <4.5 cm in adults and growth rate is <0.5 cm/year, perform annual echocardiogram 3

Multidisciplinary Team Coordination

• Assemble a team including cardiologists, vascular surgeons, gastroenterologists, geneticists, and physical medicine and rehabilitation specialists 1, 2
• Centralize care at centers of excellence whenever feasible, particularly for vascular EDS 3
• Ensure regular follow-up with the multidisciplinary team for all EDS subtypes 2

Critical Pitfalls to Avoid

• Never perform invasive diagnostic procedures in vascular EDS patients due to risk of fatal complications 2, 3
• Never use opioids for chronic pain management, especially with gastrointestinal manifestations 4, 2
• Never delay imaging for acute unexplained pain in vascular EDS, as arterial rupture is time-sensitive 3
• Never assume low complication rates for endoscopic procedures in vascular EDS, though they appear safe in hypermobile EDS 1
• Never use local anesthetics cautiously based on outdated concerns—the caution that EDS patients are resistant to local anesthetics is unwarranted 6