What is the best approach for managing chronic pain in a patient with Ehlers Danlos syndrome (EDS)?

Pain Management in Ehlers-Danlos Syndrome

Chronic pain in Ehlers-Danlos syndrome requires a mandatory multidisciplinary approach combining physical therapy, cognitive behavioral therapy, and non-opioid pharmacotherapy, with opioids strictly avoided due to worsening outcomes and increased complications. 1, 2

Initial Assessment and Diagnostic Considerations

• Screen for comorbid conditions that amplify pain burden, including postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), anxiety disorders, and avoidant/restrictive food intake disorder (ARFID), as these are highly prevalent in hEDS and require specific management 1, 2

• Document specific pain patterns: musculoskeletal pain from joint subluxations/dislocations, neuropathic pain from nerve compression, gastrointestinal pain (present in 98% of hEDS patients meeting DGBI criteria), headaches, temporomandibular joint pain, and dysmenorrhea 1, 3

• Evaluate for gastroparesis and gastric dysmotility in patients with chronic upper GI symptoms, as abnormal gastric emptying is more common than in the general population 1

• Test for celiac disease with serological testing followed by endoscopic biopsies, as the risk is elevated in hEDS/POTS compared to the general population 1

Core Treatment Framework

Non-Pharmacological Interventions (First-Line)

• Physical therapy with low-resistance exercise and myofascial release techniques to increase muscle tone and improve joint stability, addressing the underlying proprioceptive disorders and muscle weakness 4, 2, 5

• Cognitive Behavioral Therapy (CBT) is strongly recommended for chronic pain management, particularly addressing kinesiophobia (fear of movement) and anxiety disorders that increase pain burden 4, 5, 6

• Pain self-management education including coping strategies, relaxation techniques, and graded exercise programs delivered through multidisciplinary pain clinics 5, 6

• Occupational therapy to optimize daily function and provide adaptive strategies for activities of daily living 4, 6

Pharmacological Management Algorithm

Step 1: Non-opioid analgesics

• Acetaminophen up to 3g daily as the safest first-line option 4
• Avoid NSAIDs if gastrointestinal manifestations are present, as they worsen outcomes 2

Step 2: Neuropathic pain agents

• Gabapentin or pregabalin with appropriate renal dose adjustments for neuropathic pain components 4, 7
• SNRIs (duloxetine) or tricyclic antidepressants for neuropathic pain 4

Step 3: Topical agents

• Topical lidocaine or capsaicin for localized neuropathic pain 4

Critical contraindication: Opioids must be avoided entirely in hEDS patients, especially when gastrointestinal manifestations are present, as they worsen outcomes, increase complications including opioid use disorder, and exacerbate gastrointestinal dysmotility 1, 2, 7

Management of Comorbid Conditions

For POTS:

• Increase fluid intake to 2-3 liters daily and salt intake to 10-12 grams daily for volume expansion 1, 2
• Lower body compression garments during upright activities to reduce venous pooling 1, 2
• Exercise training as a core component 1
• Pharmacological treatments (fludrocortisone, midodrine, beta-blockers) in consultation with cardiology or neurology for refractory cases 1

For MCAS (when confirmed):

• H1 receptor antagonist (cetirizine 10mg daily) combined with H2 receptor antagonist (famotidine 20mg twice daily) 1, 2
• Mast cell stabilizers (cromolyn sodium) as adjunctive therapy 1
• Identify and avoid triggers including specific foods, alcohol, temperature changes, mechanical stimuli, emotional distress, and certain medications (opioids, NSAIDs, iodinated contrast) 1

For gastroparesis/GI symptoms:

• Metoclopramide 5-10mg three times daily before meals for nausea and early satiety 2
• Gastroparesis diet with small, frequent meals, low fat and fiber 1, 2
• Low-FODMAP diet for irritable bowel syndrome symptoms 1, 2
• All dietary interventions must include nutritional counseling to prevent restrictive eating patterns and ARFID development 1, 2

Interventional Pain Procedures (Selected Cases Only)

• Trigger point injections for localized myofascial pain 8, 6
• Peripheral nerve blocks for specific nerve-mediated pain 8
• Radiofrequency ablation for facet-mediated pain after conservative measures fail 8
• Peripheral nerve stimulation for refractory shoulder or knee pain in carefully selected patients 8

Note: The concern that hEDS patients are resistant to local anesthetics is unwarranted and should not prevent appropriate interventional procedures 5

Mandatory Multidisciplinary Team Composition

Core team members required:

• Pain physician or primary care provider experienced in chronic pain 1, 4
• Physical therapist 4, 5
• Pain psychologist for CBT and behavioral interventions 4, 5
• Occupational therapist 4
• Gastroenterology (for GI manifestations) 1, 2
• Cardiology or neurology (for POTS management) 1, 2
• Nutrition specialist (for dietary interventions and ARFID prevention) 1, 2

Monitoring and Follow-Up

• Establish functional goals focusing on pain severity reduction, quality of life improvement, and restoration of daily activities rather than complete pain elimination 1, 4

• Regular reassessments at each contact to evaluate comfort, function, and treatment-related adverse events 1, 4

• New pain requires thorough reevaluation and should not be treated simply by increasing current medications; assess for new pathology, treatment failure, or intercurrent life events 1, 4

Critical Pitfalls to Avoid

• Never prescribe opioids for chronic pain in hEDS, as they worsen gastrointestinal dysmotility, increase infection risk, and lead to opioid use disorder without improving outcomes 1, 2, 7

• Avoid parenteral nutrition except in life-threatening malnutrition as a temporary bridge, as it reinforces maladaptive behaviors and increases catheter-related bloodstream infections 1

• Do not implement restrictive diets without nutritional counseling, as hEDS patients are at high risk for developing ARFID 1, 2

• Do not perform MCAS testing (serum tryptase, mast cell staining on biopsies) for isolated GI symptoms without evidence of multisystem involvement 1

• Build therapeutic partnership through empathy, reflective listening, and believing the patient's pain expression, as pain is subjective and validation is therapeutic 1, 4

• Set realistic expectations that the goal is functional restoration and improved quality of life, not complete pain elimination 1, 4