What is the best approach to manage gastrointestinal symptoms such as early satiety, abdominal pain, bloating, nausea, and constipation in a patient with hypermobile Ehlers-Danlos Syndrome (hEDS)?

Management of GI Symptoms in a 26-Year-Old with hEDS

This patient's constellation of early satiety, abdominal pain, bloating, nausea, and constipation warrants initial treatment with dietary modifications, prokinetic agents for gastroparesis-like symptoms, and neuromodulators for pain, while screening for POTS and considering earlier gastric emptying studies given the high prevalence of autonomic dysfunction in hEDS. 1

Initial Diagnostic Approach

Rule Out Structural and Metabolic Causes

• Screen for hypothyroidism, celiac disease (elevated risk in hEDS), and diabetes 1, 2
• Assess postural vital signs to evaluate for POTS (heart rate increase ≥30 bpm within 10 minutes of standing) 1, 3
• Consider earlier gastric emptying testing (4-hour scintigraphy) given coexisting autonomic dysfunction risk in hEDS predisposes to gastroparesis 1

Evaluate for Pelvic Floor Dysfunction

• Given high prevalence in hEDS, consider anorectal manometry, balloon expulsion test, or defecography for the constipation component 1

First-Line Treatment Strategy

Dietary Interventions

• Implement small, frequent meals to reduce postprandial symptoms 3
• Trial a gastroparesis diet (low fat, low fiber, smaller portions) 2
• Consider supervised low FODMAP diet as second-line dietary therapy if initial measures fail 1, 3
• Ensure dietary interventions include nutritional counseling to prevent restrictive eating patterns 1, 2

Prokinetic Therapy for Early Satiety and Nausea

• Start metoclopramide 10 mg up to four times daily before meals for gastroparesis-like symptoms, after discussing extrapyramidal side effects 1, 4
• Add ondansetron 8 mg every 8-12 hours as needed for breakthrough nausea 1, 3
• Alternative prokinetics include erythromycin 125 mg before meals if metoclopramide is not tolerated 4

Constipation Management

• Initiate osmotic laxatives (PEG 3350) as first-line for constipation 3
• Add stimulant laxatives (bisacodyl) if osmotic agents insufficient 3
• Avoid loperamide given this patient's constipation 1

Pain Management

• Start tricyclic antidepressant (amitriptyline 10 mg at bedtime) as gut-brain neuromodulator, titrating slowly to 30-50 mg for abdominal pain 1, 2
• Alternative neuromodulators include gabapentin (titrate to 2400 mg daily in divided doses) or pregabalin (75-300 mg every 12 hours) 2
• Consider antispasmodics (hyoscyamine, dicyclomine, or peppermint oil) for cramping abdominal pain 2, 3
• Absolutely avoid opioids for chronic abdominal pain as they worsen GI dysmotility 1, 2, 3

POTS Management (If Confirmed)

Non-Pharmacologic Measures

• Increase fluid intake to 2-3 liters daily and salt intake to 10-12 grams daily 3
• Recommend compression garments for lower body to reduce venous pooling 3
• Initiate exercise training program (low-resistance, recumbent initially) 2, 3

Pharmacologic Options for Refractory POTS

• Fludrocortisone for volume expansion 3
• Low-dose propranolol for heart rate control 3
• Midodrine for significant orthostatic hypotension if conservative measures fail 3

Evaluation for Mast Cell Activation Syndrome

When to Consider MCAS Testing

• If patient reports flushing, urticaria, or multisystem symptoms beyond GI tract 1
• Obtain baseline serum tryptase and repeat 1-4 hours after symptom flare (diagnostic if increase of 20% above baseline plus 2 ng/mL) 1
• Limited evidence supports routine MCAS testing for isolated GI symptoms without systemic manifestations 1

MCAS Treatment (If Confirmed)

• H1 receptor antagonist (cetirizine) combined with H2 receptor antagonist (famotidine) 3
• Mast cell stabilizer (cromolyn sodium) for refractory cases 3
• Avoid triggers including certain foods, alcohol, strong smells, temperature changes 2, 3

Second-Line Considerations

If Symptoms Persist Despite Initial Management

• Consider small intestinal bacterial overgrowth (SIBO) testing with glucose breath test, as 39% of gastroparesis patients have SIBO 5
• SIBO treatment with rifaximin if positive, though evidence for routine testing in functional symptoms remains limited 6
• Evaluate for functional dyspepsia overlap and consider proton pump inhibitor trial 1, 2

Refractory Gastroparesis Options

• Referral for domperidone at centers with FDA permission 4
• Consider gastric electrical stimulation for intractable nausea/vomiting after failed medical therapy 1
• G-POEM at centers of excellence for severe gastric emptying delay 1

Critical Pitfalls to Avoid

• Never prescribe NSAIDs as they worsen GI symptoms in hEDS 2
• Do not use insoluble fiber (wheat bran) as it exacerbates bloating; use soluble fiber (ispaghula) starting at 3-4 g/day if needed 1
• Avoid opioid analgesics which worsen gastroparesis and constipation 1, 2, 3
• Do not implement restrictive diets without dietitian supervision to prevent malnutrition 1, 2
• Beighton scores may be overestimated by non-specialists; confirm hypermobility with experienced practitioner 7

Multidisciplinary Referrals

• Gastroenterology for motility testing and refractory symptoms 2
• Cardiology or autonomic specialist for confirmed POTS 3
• Allergy/immunology for suspected MCAS with systemic symptoms 1
• Pain management specialist for chronic pain 2
• Physical therapy for core strengthening and joint stability 2
• Psychology for cognitive behavioral therapy given high anxiety/depression comorbidity 2