What are the diagnosis and management approaches for Ehler Danlos syndrome?

Diagnosis and Management of Ehlers-Danlos Syndrome

Ehlers-Danlos syndrome (EDS) requires systematic diagnosis based on specific clinical criteria and genetic testing, with management focused on surveillance, physical therapy, pain control, and careful surgical planning to reduce morbidity and mortality risks, particularly for vascular complications.

Diagnosis

Clinical Assessment

• Utilize the Beighton scale to evaluate joint hypermobility (score ≥5 indicates hypermobility) 1
• Assess for diagnostic criteria:
  • Major criteria: Joint hypermobility, soft/velvety skin, absence of skin/soft tissue fragility suggestive of other EDS subtypes 1
  • Minor criteria: Autosomal dominant family history, recurrent joint dislocations, chronic joint/limb pain, easy bruising, functional bowel disorders, neurally mediated hypotension or POTS, high narrow palate, dental crowding 1

Laboratory Testing

• Genetic testing should be targeted based on clinical features:
  • For vascular EDS: COL3A1 gene sequencing 1
  • Laboratory diagnosis may include:
    1. Demonstration of structurally abnormal collagen type III by fibroblasts
    2. Identification of mutations in specific genes (e.g., COL3A1)
    3. Linkage analysis with intragenic polymorphic markers 2

Classification

• The 2017 International Classification recognizes 13 subtypes of EDS 3
• Hypermobile EDS remains a clinical diagnosis without specific genetic markers 1

Management

Cardiovascular Monitoring and Management

• For patients with normal aortic root: Echocardiogram every 2-3 years until adult height is reached 1
• For patients with aortic root dilation: More frequent monitoring every 6 months if diameter >4.5 cm or growth rate >0.5 cm/year 1
• For vascular EDS:
  • Annual surveillance of vascular tree by ultrasound, CT, or MRI 1
  • Consider celiprolol (beta blocker with vasodilatory properties) 2, 1
  • Avoid invasive procedures when possible due to vascular fragility 2
  • Surgical repair may be considered if aortic measurements exceed 4.5 cm or if growth rate >1 cm/year 1

Musculoskeletal Management

• Low-resistance exercise to improve joint stability 1
• Physical therapy for myofascial release 1
• Occupational therapy and bracing (70% of patients report improvement) 4
• Prefer bracing over surgery when possible 1

Pain Management

• Involve pain management specialists for chronic pain 1
• Neuropathic modulators may be used but are least well tolerated (47% of patients report adverse effects) 4
• NSAIDs and acetaminophen for pain control 4

Gastrointestinal Management

• Proton pump inhibitors, H-2 blockers, or sucralfate for gastritis and reflux 1
• Promotility agents for delayed gastric emptying 1

Nutritional Support

• Vitamin C supplementation as a cofactor for collagen cross-linking 1
• Calcium and vitamin D supplementation 1
• Low-impact weight-bearing exercise 1
• DXA scan for height loss >1 inch 1

Surgical Considerations

• Inform surgeons about EDS diagnosis before any procedure 5
• For vascular repair, prefer simple procedures over complex techniques 5
• Use pledgeted sutures and careful tissue handling 1
• Extended postoperative surveillance with close medical follow-up and serial CT scans 5

Pregnancy Management

• High-risk monitoring throughout pregnancy, especially for vascular EDS 1
• Cesarean delivery often recommended for vascular EDS patients due to increased risk of uterine and vessel rupture 1

Special Considerations for Vascular EDS

• Affects 1 in 50,000 to 100,000 individuals 2
• Caused by pathogenic variants in COL3A1 gene 2
• High risk of spontaneous aortic and arterial dissections, aneurysms, and rupture at young ages 2
• Aorta and arterial branches may rupture even without significant dilation 2
• Education about lifestyle modification to minimize injury risk 1
• Maintain blood pressure in normal range 1
• Avoid invasive procedures when possible 2
• Surgical repair carries increased risk due to vascular fragility 2

Monitoring Algorithm

1. Initial evaluation:

   • Complete joint hypermobility evaluation using Beighton scale
   • Skin examination
   • Family history documentation
   • Baseline echocardiogram
   • For suspected vascular EDS: full vascular imaging (MRI or CT from head to pelvis)

2. Follow-up monitoring:

   • Standard EDS: Echocardiogram every 2-3 years if normal
   • Vascular EDS or aortic dilation: Echocardiogram every 6 months and annual vascular imaging
   • Monitor for joint dislocations, pain, gastrointestinal symptoms

3. Intervention thresholds:

   • Consider surgical repair if aortic measurements >4.5 cm
   • Intervene if growth rate >1 cm/year
   • Address progressive aortic regurgitation

Remember that EDS is not a uniform diagnosis among patients, and a combination of several different treatments is usually needed for optimal symptom control and to reduce morbidity and mortality risks 4.