Is there a link between Ehlers-Danlos (EDS) hypermobility type, Sjögren's syndrome, and Takotsubo syndrome?

Relationship Between Ehlers-Danlos Hypermobility Type, Sjögren's Syndrome, and Takotsubo Syndrome

There is a potential link between Ehlers-Danlos hypermobility type (hEDS), Sjögren's syndrome, and Takotsubo syndrome through shared mechanisms of autonomic dysfunction and immune dysregulation, though direct causative relationships are not firmly established in current guidelines.

Underlying Connections

Autonomic Dysfunction as a Common Thread

• hEDS is frequently associated with autonomic dysfunction, particularly postural orthostatic tachycardia syndrome (POTS) 1, 2
• Autonomic dysfunction can affect cardiovascular regulation, potentially contributing to Takotsubo syndrome (stress cardiomyopathy)
• The 2025 AGA Clinical Practice Update recognizes that patients with hEDS commonly experience dysautonomia that affects multiple organ systems 1

Immune System Dysregulation

• hEDS is associated with mast cell activation syndrome (MCAS) 1, 2
• Sjögren's syndrome is an autoimmune condition with potential overlap with connective tissue disorders
• Both conditions involve immune system dysregulation that could potentially contribute to cardiovascular events like Takotsubo syndrome

Specific Relationships

hEDS and Autonomic/Immune Dysfunction

• The 2025 AGA guidelines highlight that patients with hEDS frequently have comorbid POTS and MCAS 1
• These patients often require integrated care from multiple specialties including cardiology and neurology 1
• Mast cell activation can cause multisystemic symptoms affecting the cardiovascular system 1

hEDS and Sjögren's Syndrome

• While not directly addressed in the guidelines, both conditions involve connective tissue and immune system abnormalities
• Patients with hEDS have higher rates of autoimmune conditions, which may include Sjögren's syndrome
• The multisystemic nature of both conditions suggests potential overlap in pathophysiology

Connection to Takotsubo Syndrome

• Takotsubo syndrome (stress cardiomyopathy) involves temporary weakening of the heart muscle
• The autonomic dysfunction seen in hEDS could potentially trigger or contribute to Takotsubo events
• Emotional or physical stress, which can trigger Takotsubo syndrome, may have heightened effects in patients with dysautonomia

Clinical Implications

Assessment Recommendations

• Patients with hEDS should be evaluated for signs of POTS using postural vital signs 1
• Consider referral for autonomic function testing including tilt table testing 1
• When MCAS is suspected, diagnostic testing with serum tryptase levels collected at baseline and during symptomatic periods 1

Management Considerations

• Patients with coexisting conditions may benefit from:
  • Increased fluid and salt intake, adapted exercise programs, compression garments for POTS 2
  • Histamine receptor antagonists and mast cell stabilizers for MCAS 1, 2
  • Avoidance of triggers such as certain foods, alcohol, strong smells, temperature changes 1

Important Caveats

Diagnostic Challenges

• hEDS diagnosis is clinical with no genetic test currently available 2, 3
• Takotsubo syndrome may be underdiagnosed in patients with hEDS due to overlapping symptoms
• The prevalence of hEDS is estimated to be approximately 1/10,000, making it a rare condition that is frequently suspected but less commonly confirmed 4

Treatment Considerations

• Endovascular procedures in patients with connective tissue disorders like EDS carry increased risks 1
• Non-invasive imaging should be used whenever possible in these patients 1
• A multidisciplinary approach involving cardiology, rheumatology, and neurology is essential for managing these complex patients 2

While these three conditions can coexist and share some pathophysiological mechanisms, current guidelines do not definitively establish a direct causative relationship between them. Management should focus on addressing the autonomic dysfunction and immune dysregulation that may underlie all three conditions.