Why do individuals with Hypermobile Spectrum Disorder (HSD)/hypermobile Ehlers-Danlos Syndrome (hEDS) experience diarrhea and gastric dumping?

Gastrointestinal Symptoms in HSD/hEDS: Diarrhea and Gastric Dumping

Individuals with Hypermobile Spectrum Disorder (HSD) and hypermobile Ehlers-Danlos Syndrome (hEDS) experience diarrhea and gastric dumping primarily due to autonomic dysfunction (POTS) and/or mast cell activation syndrome (MCAS), which frequently coexist with these connective tissue disorders. 1

Pathophysiological Mechanisms

Autonomic Dysfunction (POTS)

• Postural orthostatic tachycardia syndrome (POTS) is highly prevalent in HSD/hEDS patients
• Affects gastric motility and emptying, leading to:
  • Abnormally rapid gastric emptying (gastric dumping)
  • Altered gut transit time
  • Splanchnic vasodilation after meals
• Testing for POTS should be considered in patients with refractory GI symptoms who report orthostatic intolerance 1

Mast Cell Activation Syndrome (MCAS)

• Frequently co-occurs with HSD/hEDS
• Causes episodic symptoms affecting multiple systems, including GI tract
• Mast cell mediators can trigger:
  • Abdominal cramping
  • Diarrhea
  • Nausea and vomiting
  • Altered gut motility 1

Connective Tissue Abnormalities

• Inherent tissue laxity affects GI tract structure and function
• May contribute to altered gut motility and transit time
• Higher prevalence of pelvic floor dysfunction, especially rectal hyposensitivity 1, 2

Diagnostic Evaluation

Initial Assessment

• Screen for POTS using postural vital signs (symptomatic increase in heart rate ≥30 beats/min with 10 minutes of standing) 1
• Consider MCAS if episodic symptoms affect multiple physiological systems (GI, cutaneous, cardiac, respiratory) 1
• Test for celiac disease earlier in diagnostic workup (higher prevalence in HSD/hEDS) 1

Specialized Testing

• For upper GI symptoms with POTS: Consider gastric emptying studies 1
• For lower GI symptoms: Consider anorectal manometry, balloon expulsion test, or defecography 1, 2
• If MCAS suspected: Serum tryptase levels at baseline and 1-4 hours after symptom flares (increase of 20% above baseline plus 2 ng/mL indicates mast cell activation) 1

Management Approach

Treating Diarrhea

• Antidiarrheals (loperamide)
• Bile acid sequestrants (cholestyramine, colestipol, colesevelam) if bile acid malabsorption suspected
• 5-HT3 receptor antagonists (alosetron, ondansetron)
• Avoid opioids for pain management as they can worsen GI symptoms long-term 1

Managing Gastric Dumping

• Dietary modifications:
  • Small, frequent meals
  • Low carbohydrate content
  • Adequate protein and fat
  • Avoid liquids with meals
• Consider acarbose for post-prandial hypoglycemia 3

POTS Management

• Increase fluid and salt intake
• Exercise training program
• Compression garments
• For refractory cases: Consider pharmacological treatments for volume expansion, heart rate control, and vasoconstriction 1

MCAS Management

• Histamine receptor antagonists (H1 and H2 blockers)
• Mast cell stabilizers
• Avoid triggers:
  • Certain foods
  • Alcohol
  • Strong smells
  • Temperature changes
  • Mechanical stimuli
  • Emotional distress
  • Medications like opioids and NSAIDs 1

Dietary Considerations

• Consider specialized diets:
  • Small particle diet (gastroparesis diet)
  • Low FODMAP diet for IBS-like symptoms
  • Low-histamine diet if MCAS suspected
• Ensure proper nutritional counseling to avoid restrictive eating patterns 1

Important Caveats and Pitfalls

1. Diagnostic challenges: HSD/hEDS patients often have multiple overlapping conditions that contribute to GI symptoms
2. Medication caution: Avoid opioids for pain management as they can worsen GI symptoms
3. Misdiagnosis risk: Symptoms may be misattributed to functional GI disorders without recognizing the underlying connective tissue disorder
4. Limited evidence: Few clinical trials specifically guide management of GI symptoms in HSD/hEDS
5. Hydrogen breath testing: Low yield in HSD/hEDS patients for diagnosing SIBO (none tested positive in one study) 4

The management of GI symptoms in HSD/hEDS requires a systematic approach addressing the underlying autonomic dysfunction, mast cell activation, and connective tissue abnormalities that contribute to diarrhea and gastric dumping.