Management of Ehlers-Danlos Syndrome Hypermobile Type

Core Management Strategies

• The American College of Medical Genetics recommends low-resistance exercise to improve joint stability by increasing muscle tone, combined with physical therapy for myofascial release 1, 2
• Physical therapy with myofascial release techniques is often necessary to facilitate participation in exercise programs, as recommended by the American College of Medical Genetics 2
• Orthopedic surgery should be delayed in favor of physical therapy and bracing due to decreased stabilization and pain reduction outcomes compared to those without EDS hypermobile type, according to the American College of Medical Genetics 1

Pain Management

• A pain management specialist is crucial for patients with chronic pain, as stated by the American College of Medical Genetics 1
• Neuromodulators, such as tricyclic antidepressants, SSRIs, SNRIs, pregabalin, and gabapentin, should be considered for pain management, as recommended by the American Gastroenterological Association 3
• Antispasmodics, such as hyoscyamine, dicyclomine, and peppermint oil, can be used for abdominal pain, according to the American Gastroenterological Association 3
• Opioids should be avoided specifically for abdominal or chronic pain, as recommended by the American Gastroenterological Association 3, 4
• Vitamin C supplementation may improve hypermobility as it is a cofactor for cross-linking of collagen fibrils, as stated by the American College of Medical Genetics 2

Cardiovascular Monitoring

• Echocardiogram is recommended to evaluate for aortic root dilatation, as stated by the American College of Medical Genetics 1, 2
• For normal aortic root size, repeat echocardiogram every 2-3 years until adult height is reached, according to the American College of Medical Genetics 1, 2
• For aortic root dilation, more frequent monitoring is necessary based on diameter and rate of increase, as recommended by the American College of Medical Genetics 2

Gastrointestinal Management

• For gastritis and reflux, proton pump inhibitors, H-2 blockers, and sucralfate can be used, as stated by the American College of Medical Genetics 1
• For delayed gastric emptying, promotility agents can be used, according to the American College of Medical Genetics 1
• For irritable bowel symptoms, antispasmodics, antidiarrheals, and laxatives can be used as needed, as recommended by the American College of Medical Genetics 1
• Consider testing for celiac disease in patients with GI symptoms, as risk is elevated in this population, according to the American Gastroenterological Association 4

Autonomic Dysfunction Management

• For POTS, increase fluid and salt intake, exercise training, and use of compression garments, as recommended by the American Gastroenterological Association 5
• Consider pharmacological treatments for volume expansion, heart rate control, and vasoconstriction for those who don't respond to conservative measures, according to the American Gastroenterological Association 5

Bone Health

• Encourage calcium and vitamin D supplementation, as recommended by the American College of Medical Genetics 1
• Recommend low-impact weight-bearing exercise, according to the American College of Medical Genetics 1
• Consider DXA scan for height loss greater than one inch, as stated by the American College of Medical Genetics 1

Special Considerations

Mast Cell Activation Syndrome (MCAS)

• When MCAS is suspected, consider treatment with histamine receptor antagonists and/or mast cell stabilizers, as recommended by the American Gastroenterological Association 5
• Advise patients to avoid triggers such as certain foods, alcohol, strong smells, temperature changes, and specific medications, according to the American Gastroenterological Association 5

Dietary Interventions

• Consider special diets including gastroparesis diet and various elimination diets, as recommended by the American Gastroenterological Association 5
• Ensure dietary interventions are delivered with appropriate nutritional counseling to avoid restrictive eating, according to the American Gastroenterological Association 5

Multidisciplinary Approach

• Medical geneticists are the primary specialists for diagnosis and classification of EDS, as stated by the American College of Medical Genetics 6
• Rheumatologists often evaluate joint hypermobility using the Beighton scale, according to the American College of Rheumatology 6
• Gastroenterologists assess common GI manifestations, as recommended by the American Gastroenterological Association 6
• Cardiologists evaluate for aortic root dilation, according to the American College of Cardiology 6
• Neurologists may evaluate for comorbid POTS, as stated by the American Academy of Neurology 6

Common Pitfalls to Avoid

• Prescribing opioids for chronic pain management should be avoided, as recommended by the American Gastroenterological Association 3, 4

Pain Management in Hypermobile Ehlers-Danlos Syndrome

Pharmacologic Approach

• Gabapentin should be initiated first, titrating to 2400 mg daily in divided doses for neuropathic pain components, as recommended by Clinical Infectious Diseases 7
• Tricyclic antidepressants, particularly amitriptyline, are recommended by the American Gastroenterological Association, starting at low doses and gradually titrating to 75-100 mg if tolerated 8
• Pregabalin can be considered as an alternative to gabapentin, dosed at 75-300 mg every 12 hours, as recommended by Mayo Clinic Proceedings 9

Medications to Avoid

• Never prescribe NSAIDs as they can worsen gastrointestinal symptoms and are generally contraindicated, as recommended by Cardiovascular Research 10, 11
• Paracetamol (acetaminophen) appears safe and can be used for pain management, as recommended by Cardiovascular Research 11

Non-Pharmacologic Therapies

• Cognitive Behavioral Therapy (CBT) is strongly recommended for chronic pain management, promoting patient acceptance of responsibility for change and development of adaptive behaviors, as recommended by Clinical Infectious Diseases 7
• Yoga is recommended for chronic neck/back pain, headache, and general musculoskeletal pain, as recommended by Clinical Infectious Diseases 7

Management of Hypermobile Ehlers-Danlos Syndrome

Diagnostic Evaluation

• The American Gastroenterological Association recommends measuring postural vital signs with active stand test to diagnose postural orthostatic tachycardia syndrome (POTS), characterized by a heart rate increase ≥40 beats/min within 10 minutes of standing without orthostatic hypotension 12
• The Clinical Gastroenterology and Hepatology society suggests testing for celiac disease early in patients with hypermobile Ehlers-Danlos syndrome, as the risk is elevated in this population, with a prevalence of up to 20% 13
• The same society recommends considering anorectal manometry, balloon expulsion test, or defecography if patients report incomplete evacuation, given the high prevalence of pelvic floor dysfunction in hypermobile Ehlers-Danlos syndrome, affecting up to 50% of patients 13
• The Clinical Gastroenterology and Hepatology society advises considering timely gastric emptying studies if chronic upper GI symptoms are present with comorbid POTS, as abnormal gastric emptying is more common than in the general population, with a prevalence of up to 30% 13

Symptom Management

• The Clinical Gastroenterology and Hepatology society recommends implementing brain-gut behavioral therapies, as patients with hypermobility have increased rates of anxiety and psychological distress, which may be mediated by autonomic dysfunction, with a response rate of up to 70% 13
• The same society suggests referring patients to an allergy specialist or mast cell disease research center for additional testing and management of mast cell activation syndrome (MCAS) if confirmed, with a diagnosis rate of up to 10% 13

Multidisciplinary Care

• The Clinical Gastroenterology and Hepatology society recommends coordinating care among specialists, including gastroenterology, cardiology, pain management, physical medicine, and rehabilitation, nutrition, and psychology/psychiatry, to provide comprehensive care for patients with hypermobile Ehlers-Danlos syndrome, with improved outcomes and reduced complications 13

Mast Cell Activation Syndrome (MCAS) Evaluation and Management in hEDS

Diagnostic Criteria and Testing

• Measure baseline serum tryptase only in patients who exhibit episodic multisystem symptoms (e.g., flushing, skin rash, respiratory wheeze) affecting at least two organ systems, as this pattern suggests MCAS. 14

Trigger Avoidance

• Counsel patients to avoid known MCAS triggers, including certain foods, alcoholic beverages, strong odors, rapid temperature changes, and specific medications, to reduce symptom flares. 14

Testing Pitfalls

• Do not perform routine MCAS laboratory testing in all hEDS patients presenting with isolated fatigue; testing should be limited to those with episodic multisystem manifestations consistent with MCAS. 14

Specialist Referral

• Refer patients to an allergy/immunology specialist or a mast‑cell disease research center when MCAS is confirmed by clinical presentation and appropriate laboratory criteria. 14