What are the diagnostic criteria and management options for Ehlers-Danlos Syndrome (EDS)?

Diagnostic Criteria and Management of Ehlers-Danlos Syndrome (EDS)

The diagnosis of Ehlers-Danlos Syndrome requires a systematic clinical evaluation using the established Beighton scale for joint hypermobility (score ≥5), assessment of skin characteristics, and cardiovascular evaluation, followed by targeted genetic testing for specific subtypes except hypermobile EDS which remains a clinical diagnosis. 1

Diagnostic Criteria by EDS Subtype

Hypermobile EDS (hEDS)

• Major Diagnostic Criteria 2:

  1. Joint hypermobility with Beighton score ≥5/9:
     • Passive dorsiflexion of each fifth finger >90° (1 point each)
     • Passive apposition of each thumb to flexor surface of forearm (1 point each)
     • Hyperextension of each elbow >10° (1 point each)
     • Hyperextension of each knee >10° (1 point each)
     • Placing palms flat on floor with knees extended (1 point)
  2. Soft/velvety skin with normal or slightly increased extensibility
  3. Absence of skin/soft tissue fragility suggestive of other EDS subtypes

• Minor Diagnostic Criteria 2:

  • Autosomal dominant family history with similar features
  • Recurrent joint dislocations or subluxations
  • Chronic joint/limb pain
  • Easy bruising
  • Functional bowel disorders
  • Neurally mediated hypotension or POTS
  • High, narrow palate
  • Dental crowding

Vascular EDS (vEDS)

• Requires identification of a pathogenic COL3A1 variant 2
• Clinical features include:
  • Thin skin with visible veins
  • Characteristic facial features
  • Arterial dissections, aneurysms, ruptures
  • Arteriovenous fistulas
  • Hollow organ rupture (intestinal, uterine)

Diagnostic Workup

1. Clinical Evaluation:

   • Complete joint hypermobility assessment using Beighton scale
   • Skin examination for hyperextensibility, texture, scarring
   • Family history evaluation

2. Cardiovascular Assessment 2, 1:

   • Echocardiogram to evaluate aortic root dimensions
   • Assessment for mitral valve prolapse
   • Evaluation for aortic dilatation

3. Genetic Testing 1:

   • Target testing based on clinical presentation
   • COL3A1 sequencing for suspected vascular EDS
   • No specific genetic test available for hypermobile EDS

4. Additional Testing:

   • Bone density scan (DXA) for suspected osteoporosis 2
   • MRI or CT imaging for vascular assessment in suspected vEDS 2

Management Approach

Cardiovascular Management

• Monitoring 2:

  • Regular echocardiograms based on findings
  • For normal aortic root: repeat every 2-3 years until adult height reached
  • For aortic root dilation: every 6 months if diameter >4.5 cm or growth rate >0.5 cm/year

• Intervention 2:

  • Consider surgical repair if aortic measurements >4.5 cm, growth rate >1 cm/year, or progressive aortic regurgitation
  • For vEDS, surgical decisions must be individualized due to tissue fragility

Musculoskeletal Management 2, 1

• Low-resistance exercise to improve joint stability through increased muscle tone
• Physical therapy for myofascial release
• Pain management specialist involvement for chronic pain
• Calcium and vitamin D supplementation
• DXA scan for height loss >1 inch

Gastrointestinal Management 2

• Proton pump inhibitors, H-2 blockers, or sucralfate for gastritis and reflux
• Promotility agents for delayed gastric emptying
• Antispasmodics, antidiarrheals, and laxatives for irritable bowel symptoms

Special Considerations for vEDS 2

• Education about lifestyle modification to minimize injury risk
• Maintaining blood pressure in normal range
• Annual surveillance of vascular tree by ultrasound, CT, or MRI
• Consideration of celiprolol (beta blocker with vasodilatory properties)
• Extreme caution with invasive procedures due to vascular fragility

Pregnancy Considerations

• Women with vEDS have increased risk of uterine and vessel rupture during delivery 2
• Cesarean delivery is common for known vEDS patients 2
• Close monitoring required throughout pregnancy

Common Pitfalls and Caveats

• Misdiagnosis: EDS is often misdiagnosed due to symptom overlap with other connective tissue disorders 3, 4
• Delayed Diagnosis: Poor knowledge within medical community can lead to diagnostic delays 2
• Surgical Risks: Tissue fragility in vEDS significantly increases surgical complications 2
• Overdiagnosis: While hEDS is frequently suspected due to chronic pain symptoms, true prevalence is estimated at only 1/10,000 4
• Incomplete Evaluation: Failure to perform echocardiographic monitoring and bone density assessment can miss important complications 5

By following this systematic approach to diagnosis and management, clinicians can improve outcomes for patients with this complex connective tissue disorder.