Management of hEDS and Fibromyalgia Symptoms

Non-Pharmacological Interventions

• The American College of Rheumatology recommends exercise as the single strongest evidence-based intervention for hEDS and fibromyalgia patients, with graded aerobic and resistance training providing the most robust benefits for pain, sleep, and overall function 1
• The European League Against Rheumatism suggests beginning with low-resistance exercise to improve joint stability through increased muscle tone, specifically recommended for hEDS patients 2
• Combining aerobic exercise with resistance training, gradually increasing intensity over 8-12 weeks, is recommended for hEDS and fibromyalgia patients 1
• Physical therapy with myofascial release techniques should precede or accompany exercise programs to facilitate participation in hEDS and fibromyalgia patients 2
• Exercise provides benefits for pain, sleep, fatigue, and daily functioning, addressing multiple symptoms alcohol was masking in hEDS and fibromyalgia patients 1
• Cognitive Behavioral Therapy (CBT) is strongly recommended for chronic pain management in hEDS and fibromyalgia patients, promoting patient acceptance of responsibility for change and development of adaptive behaviors 2
• CBT addresses mood disorders and unhelpful coping strategies that may have contributed to alcohol use in hEDS and fibromyalgia patients 1
• Yoga is specifically recommended for chronic neck/back pain, headache, and general musculoskeletal pain in hEDS and fibromyalgia patients 2
• Meditative movement therapies and mindfulness-based stress reduction provide benefits for pain and sleep in hEDS and fibromyalgia patients 1

Pharmacological Alternatives

• Gabapentin should be initiated first, titrating to 2400 mg daily in divided doses for neuropathic pain components in hEDS and fibromyalgia patients 2
• Low-dose amitriptyline addresses both pain and sleep disturbance in hEDS and fibromyalgia patients 1, 2
• Duloxetine or milnacipran are recommended for severe pain with comorbid depression in hEDS and fibromyalgia patients 1
• Tramadol is recommended for breakthrough pain, though use cautiously given addiction potential in hEDS and fibromyalgia patients 1

Sleep Optimization

• Address non-refreshed sleep through sleep hygiene education in hEDS and fibromyalgia patients 1
• Low-dose amitriptyline or pregabalin specifically target sleep disturbance in hEDS and fibromyalgia patients 1

Autonomic Dysfunction

• Measure postural vital signs with active stand test to screen for POTS in hEDS patients 2
• If POTS confirmed, increase fluid intake to 2-3 liters daily, increase salt intake to 6-10 grams daily, use compression garments, and implement graded exercise training in hEDS patients 2

Gastrointestinal Symptom Management

• For gastritis/reflux, proton pump inhibitors, H2-blockers, or sucralfate are recommended in hEDS patients 2
• For irritable bowel symptoms, antispasmodics are recommended in hEDS patients 2

Nutritional Support

• Vitamin C supplementation may improve hypermobility as it is a cofactor for collagen cross-linking in hEDS patients 2
• Calcium and vitamin D supplementation are recommended for bone health in hEDS patients 2

Multidisciplinary Team Coordination

• A multidisciplinary team including a pain management specialist, physical therapist, psychologist/psychiatrist, gastroenterologist, and cardiologist is recommended for hEDS and fibromyalgia patients 2

Evidence‑Based Pharmacologic Recommendations for Pain and Associated Symptoms in Hypermobile Ehlers‑Danlos Syndrome

Analgesic Use

• Acetaminophen (paracetamol) is considered safe for mild‑to‑moderate pain episodes in individuals with hypermobile EDS. This recommendation is based on clinical data showing low risk of adverse effects in this population. 3

Medications to Avoid

• Nonsteroidal anti‑inflammatory drugs (NSAIDs) should be avoided in hypermobile EDS because they aggravate gastrointestinal symptoms, promote fluid retention, and may precipitate autonomic dysfunction. The contraindication applies to all patients with the syndrome regardless of pain severity. 3

Gastrointestinal Pain Management

• For abdominal pain in hypermobile EDS, neuromodulators (e.g., tricyclic antidepressants, SSRIs, SNRIs, pregabalin, gabapentin) are recommended instead of opioid therapy. Neuromodulators address both pain perception and associated dysautonomia without the dependency risks of opioids. 4

Mast Cell Activation Syndrome (MCAS) Treatment

• When MCAS is suspected (affecting up to ~10 % of hypermobile EDS patients), an H₂‑receptor antagonist such as famotidine 20 mg twice daily is advised. This helps reduce mast‑cell‑mediated gastrointestinal and systemic symptoms. 4
• A second‑generation H₁ antihistamine (e.g., cetirizine 10 mg daily) is recommended for MCAS in hypermobile EDS. It provides targeted histamine blockade with a favorable safety profile. 4
• Mast‑cell stabilizers (e.g., cromolyn sodium or ketotifen) are part of the therapeutic regimen for MCAS in hypermobile EDS. Stabilization reduces mast‑cell degranulation and related symptom flares. 4
• Leukotriene‑receptor antagonists (e.g., montelukast) are recommended for MCAS in hypermobile EDS. They address leukotriene‑mediated inflammation contributing to symptom burden. 4