What are the symptoms and management options for Ehlers-Danlos syndrome (EDS)?

Ehlers-Danlos Syndrome Symptoms and Management

Ehlers-Danlos Syndrome (EDS) is characterized by tissue fragility, joint hypermobility, and skin hyperextensibility, with hypermobile EDS (hEDS) being the most common subtype affecting 80-90% of EDS patients. 1

Key Symptoms of Ehlers-Danlos Syndrome

Musculoskeletal Symptoms

• Joint hypermobility (assessed using Beighton score ≥5)
• Joint pain and frequent dislocations
• Joint instability and subluxations
• Early-onset osteoarthritis
• Chronic musculoskeletal pain

Skin Manifestations

• Hyperextensible skin (soft or velvety texture)
• Poor wound healing with atrophic scarring
• Skin fragility with easy bruising
• Tissue fragility

Gastrointestinal Symptoms

• Disorders of gut-brain interaction (present in up to 98% of hEDS patients) 2
• Nausea, abdominal pain, vomiting
• Diarrhea, bloating, severe constipation
• Gastroparesis and dysmotility

Cardiovascular Manifestations

• Postural orthostatic tachycardia syndrome (POTS)
• Orthostatic intolerance
• Aortic abnormalities (especially in vascular EDS)
• Vascular fragility (primarily in vascular EDS)

Neurological Symptoms

• Headaches and migraines
• Fatigue
• Cognitive dysfunction ("brain fog")
• Dysautonomia

Other Common Symptoms

• Mast cell activation syndrome (MCAS)
• TMJ dysfunction
• Sleep disturbances
• Pelvic floor dysfunction

Diagnostic Approach

1. Joint Hypermobility Assessment:

   • Use Beighton scale to evaluate hypermobility (score ≥5 indicates generalized joint hypermobility) 1
   • Assess passive extension of little fingers, passive apposition of thumbs to forearm, hyperextension of elbows and knees, and forward flexion of trunk

2. Skin Examination:

   • Evaluate for hyperextensibility, soft texture, fragility, poor wound healing, atrophic scarring, and easy bruising 1

3. Family History:

   • Document family history of hypermobility and EDS-related symptoms

4. Genetic Testing:

   • Consider targeted genetic testing based on suspected EDS subtype
   • Note that hEDS currently has no genetic test available 1

Management Approach

Conservative Management

1. Physical and Occupational Therapy:

   • Gentle strengthening exercises to stabilize joints
   • Custom bracing for unstable joints
   • Manual therapy techniques
   • Patient education on proper joint positioning 1

2. Pain Management:

   • Avoid opioids for chronic pain due to high risk of addiction and limited efficacy 1
   • Consider neuromodulators (gabapentin, pregabalin) for neuropathic pain
   • Antispasmodics for muscle tension
   • Low-dose neuromodulators (e.g., mirtazapine) for pain with gastrointestinal symptoms 1

3. POTS Management:

   • Increase fluid and salt intake
   • Adapted exercise programs
   • Compression garments
   • Pharmacological treatments for volume expansion, heart rate control, and vasoconstriction 2, 1

4. MCAS Management:

   • Histamine receptor antagonists (H₁ and H₂ blockers)
   • Mast cell stabilizers (sodium cromoglycate, ketotifen)
   • Leukotriene receptor antagonists (montelukast)
   • Avoid triggers: certain foods, alcohol, strong smells, temperature changes, mechanical stimuli, emotional distress, specific medications 2, 1

5. Gastrointestinal Symptom Management:

   • Dietary modifications: gastroparesis diet (small particle foods), elimination diets (low FODMAP, gluten/dairy-free, low-histamine)
   • Nutritional counseling to avoid restrictive eating pitfalls 2
   • Consider testing for celiac disease and functional defecation disorders 1
   • Optimize oral nutrition and avoid unnecessary parenteral nutrition 1

6. Cardiovascular Management:

   • Regular cardiovascular follow-up, particularly for patients with aortic anomalies
   • Beta-blockers (e.g., celiprolol) may benefit vascular EDS patients 1
   • Baseline CT or MRI from head to pelvis for vascular EDS patients with annual surveillance imaging 1

Surgical Considerations

• Surgery should be considered only when:
  • Conservative measures fail
  • Progressive neurological deficits occur
  • Severe instability threatens spinal cord integrity
  • Quality of life is significantly impacted 1
• Surgical interventions for vascular complications require meticulous technique due to increased tissue fragility 1

Special Considerations

Pregnancy and Reproductive Health

• Complete vascular imaging before pregnancy in women with vascular EDS
• Shared decision-making regarding pregnancy risks in vascular EDS
• Most women with vascular EDS undergo cesarean delivery 1

TMJ Management

• Gentle TMJ exercises and manual therapy techniques
• Custom-made occlusal splint therapy for night-time use
• Regular follow-up TMJ evaluations every 3-6 months 1

Pitfalls and Caveats

1. Misdiagnosis: EDS is often misdiagnosed due to symptom overlap with other conditions and between EDS subtypes.

2. Medication Sensitivity: Patients may have increased sensitivity to medications due to autonomic dysfunction and MCAS.

3. Surgical Risks: Increased tissue fragility leads to higher surgical complications, including poor wound healing and vascular fragility.

4. Chronic Pain Management: Avoid opioid dependence by focusing on multimodal pain management strategies.

5. Psychological Impact: The chronic nature of EDS symptoms can lead to depression and anxiety, requiring appropriate mental health support.

6. Nutritional Concerns: Restrictive diets may lead to nutritional deficiencies if not properly monitored.

EDS requires a comprehensive approach to management with focus on symptom control and prevention of complications to improve quality of life and reduce morbidity.