What is the treatment approach for patients with Ehlers-Danlos Syndromes (EDS)?

Treatment Approach for Ehlers-Danlos Syndrome: Hypermobile vs Classical Subtypes

The treatment strategies for hypermobile EDS (hEDS) and classical EDS (cEDS) differ fundamentally from vascular EDS, with hEDS/cEDS focusing on conservative multidisciplinary management centered on physical therapy and symptom control, while avoiding the aggressive vascular surveillance and surgical precautions required for vascular EDS. 1, 2

Hypermobile EDS (hEDS) Treatment Algorithm

First-Line Physical 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 1
• Occupational therapy and bracing show the highest efficacy, with 70% of patients reporting improvement 3
• Implement compression garments for joint stabilization and orthostatic symptoms 4

Gastrointestinal Symptom Management

• Treat prominent GI symptoms based on specific manifestations and abnormal GI function test results, following the same approach as disorders of gut-brain interaction in the general population 4
• Consider special diets including gastroparesis diet (small particle diet) and elimination diets (low fermentable carbohydrates, gluten-free, dairy-free, low-histamine) with mandatory nutritional counseling to prevent restrictive eating 4
• Perform diagnostic testing of gastric motor functions (gastric emptying, accommodation) in patients with chronic upper GI symptoms after excluding structural diseases 4
• Test for celiac disease earlier in the diagnostic evaluation, not just in those with diarrhea 4

Autonomic Dysfunction (POTS) Management

• Increase fluid and salt intake, implement exercise training, and use compression garments as first-line treatment 4
• For patients not responding to conservative measures, consider pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from cardiology and neurology 4

Mast Cell Activation Syndrome (MCAS) Management

• When MCAS is suspected, treat with histamine receptor antagonists and/or mast cell stabilizers 4
• Avoid triggers including certain foods, alcohol, strong smells, temperature changes, mechanical stimuli (friction), emotional distress, pollen, mold, opioids, NSAIDs, and iodinated contrast 4

Psychological Support

• Implement brain-gut behavioral therapies due to increased rates of anxiety and psychological distress in patients with hypermobility 1, 2

Baseline Cardiac Evaluation

• Perform baseline echocardiogram to evaluate for aortic root dilation 1

Classical EDS (cEDS) Treatment Approach

Classical EDS shares many treatment principles with hEDS, focusing on:

• Physical therapy for joint stabilization 3, 5
• Wound care protocols due to tissue fragility and delayed healing 6, 7
• Avoidance of activities with high risk of tissue trauma 7
• Multidisciplinary follow-up similar to hEDS 1, 2

Critical Differences from Vascular EDS

Unlike vascular EDS, hEDS and cEDS do NOT require:

• Annual vascular surveillance imaging 1, 2
• Celiprolol therapy 1, 2
• Avoidance of invasive diagnostic procedures 1, 2
• Extreme surgical precautions with pledgeted sutures 2

Pain Management Strategy

Preferred Modalities

• Neuropathic modulators (though 47% report adverse effects, requiring careful titration) 3
• NSAIDs if no contraindications 8
• Acetaminophen 3
• Complementary/alternative treatments (most commonly used, n=88 in one cohort) 3

Critical Pitfall: Never prescribe opioids for chronic pain management, especially with GI manifestations, due to high risk of dependence and worsening gastrointestinal symptoms 1, 2, 9

Multidisciplinary Team Structure

All EDS subtypes require regular follow-up with: 1, 2

• Medical geneticists for definitive diagnosis and genetic counseling
• Physical medicine specialists for rehabilitation
• Gastroenterologists for GI manifestations (particularly in hEDS)
• Cardiologists for baseline cardiac assessment
• Pain management specialists using non-opioid modalities
• Nutritionists for dietary interventions

Diagnostic Testing for hEDS Comorbidities

• Anorectal manometry, balloon expulsion test, or defecography for incomplete evacuation symptoms given high prevalence of pelvic floor dysfunction and rectal hyposensitivity 4
• Serum tryptase levels at baseline and 1-4 hours following symptom flares for MCAS evaluation (increases of 20% above baseline plus 2 ng/mL indicate mast cell activation) 4
• Referral to allergy specialist or mast cell disease research center for additional testing (urinary N-methylhistamine, leukotriene E4, 11b-prostaglandin F2) if MCAS diagnosis is supported 4

Evidence Quality Note

The evidence for individual treatment components in hEDS and cEDS is weak, with most recommendations based on expert consensus and observational data rather than randomized controlled trials 5. However, the conservative multidisciplinary approach remains the standard of care due to lack of alternative effective therapies and the need to avoid surgical interventions with their accompanying morbidity risks 5, 9.