What are the treatment options for a patient with Ehlers-Danlos Syndrome (EDS)?

Treatment of Ehlers-Danlos Syndrome

Treatment for EDS must be tailored to the specific subtype, with vascular EDS requiring celiprolol and intensive vascular surveillance, while hypermobile EDS centers on physical/occupational therapy, pain management without opioids, and treatment of comorbid POTS and MCAS. 1

Immediate Subtype Determination

Before initiating treatment, you must determine the EDS subtype as management differs dramatically:

• Vascular EDS (Type IV): Life-threatening subtype requiring urgent genetic testing (COL3A1) and specialized vascular care 1
• Hypermobile EDS: Most common (80-90% of cases), managed primarily with rehabilitation and symptom control 2
• Classical EDS: Requires genetic confirmation (COL5A1/COL5A2) and focuses on skin/joint protection 1

Vascular EDS (Type IV) - High-Risk Management

Pharmacological Treatment

• Celiprolol (beta-blocker with vasodilatory properties) is the recommended medication to reduce vascular morbidity, though it lacks FDA approval in the US 1
• Maintain blood pressure in normal range with aggressive antihypertensive therapy 1

Vascular Surveillance Protocol

• Baseline imaging from head to pelvis using Doppler ultrasound, CT, or MRI to evaluate the entire aorta and branch vessels 1
• Annual surveillance imaging for any dilated or dissected aortic/arterial segments 1
• Noninvasive imaging is mandatory—invasive catheter angiography has caused fatal complications 1

Surgical Considerations

• Surgery carries extremely high mortality risk due to arterial fragility and bleeding 1
• When unavoidable, use pledgeted sutures for all anastomoses and minimize tissue trauma 1
• Requires multidisciplinary team with vascular surgery on standby 1

Critical Pitfall

Never perform invasive vascular imaging in vascular EDS patients—fatal complications have been reported 1

Hypermobile EDS - Comprehensive Symptom Management

First-Line Physical Rehabilitation

Occupational therapy and bracing are the most effective treatments, with 70% of patients reporting improvement 3

• Physical therapy focusing on muscle strengthening, proprioception training, and joint stabilization 3, 4
• Occupational therapy for activity modification and adaptive strategies 3
• Bracing/compression garments for joint support 3
• Multidisciplinary rehabilitation combining physical and cognitive-behavioral therapy shows significant improvements in daily activities, muscle strength, and reduction of kinesiophobia 4

Pain Management Strategy

Avoid opioids as first-line therapy despite their reported efficacy, due to high dependence risk and worsening of GI symptoms 1, 3

Recommended Analgesic Hierarchy:

1. NSAIDs and acetaminophen (most commonly used by 70-92% of patients) 3, 5
2. Neuropathic modulators (gabapentin, pregabalin) for neuropathic pain components, though 47% report adverse effects 3
3. Topical agents for localized pain 1
4. Muscle relaxants for muscle spasm 3

Complementary therapies are used by 56% of EDS patients, particularly those with higher pain levels, and should be discussed collaboratively 5

Gastrointestinal Manifestations (Affect up to 98% of hEDS Patients)

Medical management should focus on treating the most prominent GI symptoms and abnormal GI function test results 2

Diagnostic Workup:

• Gastric emptying studies for chronic upper GI symptoms after excluding structural disease 2
• Anorectal manometry, balloon expulsion test, or defecography for incomplete evacuation symptoms due to high prevalence of pelvic floor dysfunction 2
• Celiac disease testing should be performed earlier in hEDS patients with any GI symptoms, not just diarrhea 2

Dietary Interventions:

• Gastroparesis diet (small particle diet) for delayed gastric emptying 2
• Elimination diets (low-FODMAP, gluten-free, dairy-free, low-histamine) with appropriate nutritional counseling to avoid restrictive eating patterns 2
• Nutritional support to prevent malnutrition 2

POTS Management (Comorbid in Many hEDS Patients)

Treatment begins with conservative measures before pharmacological intervention 2

Conservative Management:

• Increase fluid intake (2-3 liters daily) and salt intake (10-12 grams daily) 2
• Exercise training (recumbent exercises initially, progressing to upright) 2
• Compression garments (waist-high, 30-40 mmHg) 2

Pharmacological Treatment (if conservative measures fail):

• Volume expansion agents (fludrocortisone) 2
• Heart rate control (beta-blockers, ivabradine) 2
• Vasoconstrictors (midodrine) 2
• Requires integrated care from cardiology and neurology 2

Mast Cell Activation Syndrome (MCAS) Management

Only treat MCAS if diagnosis is supported through clinical features and/or laboratory evidence (baseline serum tryptase increases of 20% plus 2 ng/mL during flares) 2

Treatment Approach:

• Histamine receptor antagonists (H1 and H2 blockers) 2
• Mast cell stabilizers (cromolyn sodium, ketotifen) 2
• Trigger avoidance: certain foods, alcohol, strong smells, temperature changes, mechanical stimuli, emotional distress, specific medications (opioids, NSAIDs, iodinated contrast) 2
• Refer to allergy specialist or mast cell disease research center for additional testing 2

Psychological Support

Brain-gut behavioral therapies are recommended due to increased rates of anxiety and psychological distress in hypermobility patients 1

• Cognitive-behavioral therapy for pain management and kinesiophobia 4
• Psychological support for chronic pain coping strategies 6

Multidisciplinary Team Coordination

A multidisciplinary approach involving specialists in cardiology, gastroenterology, physical medicine, and genetics is essential 1

Core Team Members:

• Medical genetics for definitive diagnosis and classification 1
• Cardiology for cardiovascular surveillance and POTS management 1
• Gastroenterology for GI symptom management 2
• Physical medicine and rehabilitation for pain and functional optimization 1
• Pain specialists for complex pain management 2
• Allergy/immunology for MCAS evaluation 2

Regular follow-up with the multidisciplinary team is recommended for all EDS subtypes 1

Pregnancy Considerations

Pregnancy in vascular EDS carries significant risks due to potential uterine rupture and vessel rupture during delivery 1

• Most women with known vascular EDS undergo cesarean delivery 1
• Requires high-risk obstetric care with multidisciplinary involvement 1

Critical Pitfalls to Avoid

• Never use parenteral nutrition in hEDS patients except in life-threatening malnutrition extremis, as it reinforces maladaptive behaviors and increases infection risk 2
• Avoid long-term opioid therapy due to opioid bowel dysfunction that may mimic CIPO and worsen GI symptoms 2
• Do not perform routine MCAS testing in all hEDS patients with isolated GI symptoms—only test those with episodic multisystem symptoms 2
• Avoid invasive procedures in vascular EDS due to fatal complication risk 1

Treatment Efficacy Evidence

Based on a retrospective cohort of 98 EDS patients, occupational therapy and bracing showed the highest efficacy (70% improvement), while neuropathic modulators were least well tolerated (47% adverse effects) 3. Physical therapy and complementary therapies were most commonly used (88-92% of patients), with marijuana and opioids rated as most efficacious by users (10-24% rating as extremely helpful), though opioids should be avoided due to long-term complications 3, 5.

Pain in EDS is common (highly prevalent), severe, and associated with moderate to severe functional impairment in daily life, making pain management a prominent aspect of symptomatic treatment 7. Pain severity correlates with hypermobility degree, dislocations, and previous surgery 7.