What is the mechanism by which Ehlers-Danlos Syndrome (EDS) causes chest pain?

Mechanisms of Chest Pain in Ehlers-Danlos Syndrome

Chest pain in Ehlers-Danlos Syndrome (EDS) primarily occurs due to vascular fragility, arterial dissection, and musculoskeletal instability, requiring prompt evaluation to rule out life-threatening complications.

Vascular Mechanisms

Arterial Fragility and Dissection

• The vascular form of EDS (Type IV) is characterized by fragility of medium and large arteries, leading to:

  • Spontaneous arterial dissections, including coronary and aortic dissections 1
  • Arterial ruptures that can affect thoracic vessels 1
  • Arteriovenous fistulas that may develop in chest vasculature 1

• Coronary artery involvement:

  • Spontaneous coronary artery dissection can occur, even affecting all three coronary arteries simultaneously 2
  • These dissections can present as acute chest pain mimicking acute coronary syndrome

Aortic Complications

• Aortic dissection occurs in approximately 10% of vascular EDS patients 1
• Both Type A and Type B aortic dissections can present with severe chest or back pain 1
• Unlike other connective tissue disorders, aortic aneurysms may not be present before dissection or rupture 1

Musculoskeletal Mechanisms

Costochondral and Thoracic Instability

• Joint hypermobility in EDS affects the costochondral junctions and sternoclavicular joints
• Subluxation or dislocation of these joints can cause acute chest pain
• Costochondritis-like symptoms are common due to ligamentous laxity 1

Thoracic Spine Involvement

• Spinal instability, particularly in the thoracic region, can refer pain to the chest wall
• Vertebral subluxations may compress intercostal nerves, causing neuropathic chest pain

Pulmonary Mechanisms

• Spontaneous pneumothorax can occur due to tissue fragility
• When present, pneumothorax typically causes:
  • Sudden-onset, sharp chest pain
  • Pain that worsens with inspiration
  • Unilateral decreased or absent breath sounds 1

Gastrointestinal Mechanisms

• Esophageal dysfunction can present as chest pain that mimics cardiac symptoms
• Esophageal rupture, though rare, is a life-threatening complication that presents with severe chest pain 1
• Distinguishing features include pain that worsens with swallowing or after meals

Diagnostic Approach for Chest Pain in EDS Patients

1. Initial assessment:

   • 12-lead ECG within 10 minutes of presentation to rule out acute coronary syndrome 1
   • Focused cardiovascular examination to identify complications 1
   • Assessment for pulse differentials (suggesting aortic dissection) 1

2. Imaging considerations:

   • For suspected vascular complications: CT angiography or MRI of the chest
   • For suspected pneumothorax: Chest radiography 1
   • Non-invasive vascular imaging is preferred over invasive techniques due to tissue fragility 1

Management Considerations

• Vascular EDS patients require aggressive blood pressure control to reduce risk of dissection 1
• Celiprolol (a beta-blocker with vasodilatory properties) has shown benefit in reducing vascular events 1
• Surgical repair of vascular complications requires special techniques due to tissue fragility 1
• Tissue handling during procedures must be extremely careful, with pledgeted sutures for anastomoses 1

Important Caveats and Pitfalls

• Do not dismiss chest pain in EDS patients as musculoskeletal without thorough evaluation
• Vascular complications can occur without preceding aneurysm formation, unlike in other connective tissue disorders 1
• Invasive procedures carry higher risks in EDS patients due to tissue fragility 1
• Median survival in vascular EDS is only 48 years, with arterial rupture accounting for most deaths 3
• Complications are rare during infancy but occur in up to 25% of affected persons before age 20 and 80% before age 40 3

Genetic Basis

• Vascular EDS is caused by pathogenic variants in the COL3A1 gene, which encodes type III collagen 1
• Diagnosis is confirmed through genetic testing identifying COL3A1 mutations 1
• The severity of vascular manifestations depends on the specific genetic variant, with null variants having somewhat better outcomes 1

Understanding these mechanisms is essential for appropriate evaluation and management of chest pain in EDS patients, as early recognition of serious vascular complications can be life-saving.