How should increased inflammation, particularly in the gastrointestinal system, be managed in individuals with Hypermobile Ehlers-Danlos Syndrome (hEDS)?

Management of Inflammation in Hypermobile Ehlers-Danlos Syndrome (hEDS)

Inflammation in hEDS should be managed through targeted physical therapy and symptom-specific treatments rather than traditional anti-inflammatory approaches, as hEDS joint pain stems from joint instability and connective tissue abnormalities rather than inflammatory processes. 1

Understanding Inflammation in hEDS

Pathophysiology

• hEDS is characterized by joint hypermobility, skin abnormalities, and chronic pain
• Joint pain in hEDS stems from joint instability and connective tissue abnormalities, not from inflammatory or degenerative joint disease processes 1
• GI symptoms in hEDS are multifactorial and may include:
  • Connective tissue laxity effects
  • Autonomic dysfunction
  • Visceral hypersensitivity
  • Potential myofibroblast-like phenotype with inflammatory characteristics 2

Gastrointestinal Manifestations

• GI symptoms are common in hEDS, affecting approximately 57.5% of patients 3
• Common GI symptoms include:
  • Abdominal pain (56.1%)
  • Nausea (42.3%)
  • Constipation (38.6%)
  • Heartburn (37.6%)
  • IBS-like symptoms (27.5%) 3

Diagnostic Approach for Inflammation

Biomarker Assessment

• For patients with GI symptoms suggesting inflammatory bowel disease, fecal calprotectin can help distinguish between inflammatory and non-inflammatory conditions 4
  • Fecal calprotectin >150 mg/g suggests active inflammation
  • CRP >5 mg/L may indicate systemic inflammation

Endoscopic Evaluation

• For patients with moderate to severe GI symptoms and elevated inflammatory markers (fecal calprotectin >150 mg/g or CRP >5 mg/L), endoscopic assessment may be warranted to rule in active inflammation 4
• For patients with mild symptoms and normal inflammatory markers, endoscopic assessment is still suggested before empiric treatment adjustment 4

Treatment Approach

Physical Therapy (First-Line)

• Low-resistance exercise to improve joint stability by increasing muscle tone 1
• Focus on proprioception and core strengthening
• Avoid high-impact activities that may worsen joint instability

Pain Management

• Consult with pain management specialist focusing on central pain mechanisms 1
• Consider non-opioid analgesics for breakthrough pain
• Avoid NSAIDs for long-term use due to potential GI side effects

GI Symptom Management

• For reflux symptoms: Proton pump inhibitors (most commonly used medication in 38% of hEDS patients) 3
• For constipation: Appropriate laxatives (used in 23% of hEDS patients) 3
• For diarrhea: Consider bile acid sequestrants if bile salt malabsorption is suspected

For Confirmed Inflammatory Conditions

• If inflammatory bowel disease is confirmed through endoscopy and biomarkers:
  • For mild-to-moderate ulcerative colitis: Consider mesalamine (oral or topical depending on disease location) 4
  • For moderate-to-severe inflammation with elevated inflammatory markers: Consider dexamethasone during inflammatory phase 4

Special Considerations

Surgical Intervention

• Surgery should be delayed when possible in favor of conservative management 1
• Only 2.9% of hEDS patients with GI symptoms undergo colectomy and 4% undergo small bowel surgery 3
• Consider evaluation for abdominal compression syndromes in patients with persistent abdominal pain 5

Multidisciplinary Approach

• Coordinate care between:
  • Gastroenterologist
  • Physical therapist
  • Pain specialist
  • Geneticist (for diagnostic confirmation)
  • Autonomic specialist (if POTS is present)

Monitoring and Follow-up

• Regular assessment of inflammatory markers if inflammatory condition is confirmed
• Interval biomarker assessment every 2-4 months for patients being treated for active inflammatory symptoms 4
• After symptom resolution and normalization of biomarkers, endoscopic evaluation should be performed 6-12 months after treatment initiation 4

Pitfalls to Avoid

• Misattributing all symptoms to hEDS without ruling out concurrent inflammatory conditions
• Overuse of anti-inflammatory medications for pain that stems from joint instability rather than inflammation
• Failing to consider the role of autonomic dysfunction in symptom presentation
• Overlooking the potential for abdominal compression syndromes, which may require surgical intervention 5