What is the initial management for a 16-year-old female with Hypermobile Ehlers-Danlos Syndrome (hEDS) and multisystem symptoms?

Initial Management of Hypermobile EDS in a 16-Year-Old Female with Multisystem Symptoms

Begin with low-resistance exercise combined with physical therapy for myofascial release to improve joint stability, while simultaneously screening for and managing the most common comorbidities: gastrointestinal dysfunction, postural orthostatic tachycardia syndrome (POTS), and mast cell activation syndrome (MCAS). 1

Immediate Core Interventions

Musculoskeletal Management

• Start low-resistance exercise immediately to increase muscle tone and improve joint stability, as this is the cornerstone of hEDS management 1
• Physical therapy with myofascial release techniques must be initiated first, as it facilitates participation in the exercise program 1
• Delay any orthopedic surgery in favor of physical therapy and bracing, as surgical outcomes for stabilization and pain reduction are significantly worse in hEDS patients compared to those without the condition 1

Pain Management Strategy

• Establish care with a pain management specialist immediately for chronic pain, as this is crucial for long-term management 1
• Start gabapentin first, titrating to 2400 mg daily in divided doses for neuropathic pain components 1
• Consider tricyclic antidepressants (amitriptyline starting at low doses, gradually titrating to 75-100 mg if tolerated) as an alternative or adjunct 1
• Never prescribe opioids for chronic pain management in hEDS, particularly when GI manifestations are present, as they worsen outcomes and increase complications 2, 1
• Acetaminophen is safe and can be used for pain management 1
• Avoid NSAIDs entirely, as they worsen gastrointestinal symptoms and are generally contraindicated 1

Essential Screening and Diagnostic Workup

Cardiovascular Assessment

• Obtain echocardiogram immediately to evaluate for aortic root dilatation, as this occurs in 25-33% of hypermobile EDS patients 1, 3
• If aortic root size is normal, repeat echocardiogram every 2-3 years until adult height is reached 1
• If aortic root dilation is present, more frequent monitoring is necessary based on diameter and rate of increase 1

Autonomic Dysfunction Screening (POTS)

• Measure postural vital signs with active stand test: heart rate increase ≥40 beats/min (for adolescents 12-19 years) within 10 minutes of standing without orthostatic hypotension 3, 4
• If POTS is confirmed, immediately increase fluid intake to 2-3 liters daily and salt intake to 10-12 grams daily 2
• Apply lower body compression garments during upright activities to reduce venous pooling 2
• Consider referral for tilt table testing if symptoms persist despite conservative measures 3

Gastrointestinal Evaluation

• Test for celiac disease early, as risk is elevated in this population and should not be limited to patients with diarrhea alone 4, 1
• Consider anorectal manometry, balloon expulsion test, or defecography if she reports incomplete evacuation, given the high prevalence of pelvic floor dysfunction in hEDS 4, 3
• If chronic upper GI symptoms are present with comorbid POTS, consider timely gastric emptying studies, as abnormal gastric emptying is more common than in the general population 4

Mast Cell Activation Syndrome (MCAS) Screening

• Only test for MCAS if she presents with episodic multisystem symptoms involving ≥2 physiological systems (flushing, urticaria, wheezing, multisystem symptoms) 4, 3
• If MCAS is suspected, obtain baseline serum tryptase level 4
• During symptom flares, collect serum tryptase 1-4 hours after symptom onset; increases of 20% above baseline plus 2 ng/mL are diagnostic 4
• Do not perform MCAS testing for isolated GI symptoms without evidence of multisystem involvement 2, 3

Symptom-Specific Management

Gastrointestinal Symptoms

• For gastritis and reflux: use proton pump inhibitors, H2 receptor antagonists (famotidine 20mg twice daily), or sucralfate 1
• For nausea/vomiting: use antiemetics (ondansetron, promethazine, prochlorperazine) and prokinetics (metoclopramide 5-10mg three times daily before meals) 4, 2
• For abdominal pain: use antispasmodics (hyoscyamine, dicyclomine, peppermint oil) 4, 1
• For delayed gastric emptying: implement gastroparesis diet with small, frequent meals that are low in fat and fiber 2
• For irritable bowel symptoms: use antispasmodics, antidiarrheals, and laxatives as needed 1
• All dietary interventions must include nutritional counseling to prevent restrictive eating patterns and avoidant/restrictive food intake disorder (ARFID) 2

MCAS Treatment (if confirmed)

• Start H1 receptor antagonist (cetirizine 10mg daily) combined with H2 receptor antagonist (famotidine 20mg twice daily) 2
• Advise avoidance of triggers including certain foods, alcohol, strong smells, temperature changes, and specific medications 1
• Refer to allergy specialist or mast cell disease research center for additional testing and management 4

Psychological Support

• Implement brain-gut behavioral therapies, as patients with hypermobility have increased rates of anxiety and psychological distress, which may be mediated by autonomic dysfunction 4, 2
• Consider Cognitive Behavioral Therapy (CBT) for chronic pain management 1

Supplementation and Bone Health

• Start vitamin C supplementation, as it is a cofactor for cross-linking of collagen fibrils and may improve hypermobility 1
• Encourage calcium and vitamin D supplementation 1
• Recommend low-impact weight-bearing exercise 1
• Consider DXA scan if height loss greater than one inch occurs 1

Multidisciplinary Care Coordination

Coordinate care among the following specialists 2:

• Medical geneticist for diagnosis confirmation and classification 1, 3
• Gastroenterology for GI manifestations (affecting up to 98% of hEDS patients) 3, 5
• Cardiology or neurology for POTS evaluation 1, 3
• Pain management specialist 1
• Physical medicine and rehabilitation 2
• Nutrition for dietary interventions 2
• Psychology/psychiatry for behavioral therapies 4, 2

Critical Pitfalls to Avoid

• Never prescribe opioids, especially with GI manifestations present 2, 1
• Never use NSAIDs due to GI contraindications 1
• Avoid parenteral nutrition except in life-threatening malnutrition as a temporary bridge 2
• Do not rush to orthopedic surgery; exhaust physical therapy and bracing options first 1
• Ensure nutritional counseling accompanies all dietary interventions to prevent restrictive eating 2
• Do not perform MCAS testing for isolated GI symptoms without multisystem involvement 2, 3