What is the best treatment approach for a patient experiencing an Ehlers-Danlos (EDS) flare?

Treatment of Ehlers-Danlos Syndrome Flares

For EDS flares, avoid opioids and parenteral nutrition, and instead prioritize a multidisciplinary rehabilitative approach centered on physical/occupational therapy with bracing, non-opioid pain management, and treatment of underlying triggers including autonomic dysfunction and gastrointestinal symptoms. 1, 2

Immediate Assessment During Flare

Identify the Flare Trigger

• Screen for POTS exacerbation by measuring postural vital signs with active stand test (heart rate increase ≥30 beats/min in adults within 10 minutes of standing without orthostatic hypotension), as autonomic dysfunction commonly precipitates symptom flares 2
• Evaluate for new joint subluxations or dislocations that may be driving acute pain worsening 3
• Assess for gastrointestinal symptom escalation (nausea, abdominal pain, constipation, bloating), which affects up to 98% of hypermobile EDS patients and frequently worsens during flares 2
• Rule out mast cell activation if patient presents with episodic multisystem symptoms (flushing, urticaria, wheezing) by obtaining serum tryptase during symptomatic period 2

Critical Pitfall to Avoid

• Never initiate or escalate opioids during EDS flares, as opioids worsen gastrointestinal dysmotility, increase infection risk, and have shown poor efficacy in this population 1, 4
• Avoid parenteral nutrition unless life-threatening malnutrition is present, as it should only serve as a temporary bridge to rehabilitative therapies and carries increased infection risk in EDS patients 1

First-Line Acute Flare Management

Most Effective Non-Pharmacologic Interventions

• Initiate or intensify occupational therapy with bracing, which showed 70% improvement rates in the largest treatment efficacy study—the highest success rate of any intervention 4
• Apply compression garments for joint stabilization and POTS symptom management 2
• Implement assistive devices (canes, walkers) to offload affected joints and prevent further subluxations 5

Pharmacologic Pain Management

• Use NSAIDs as first-line if no contraindications exist 5, 4
• Add acetaminophen for additional analgesia 4
• Consider topical analgesics for localized pain 5
• Trial neuropathic modulators (gabapentin, pregabalin, duloxetine) for neuropathic pain components, though note that 47% of patients report adverse effects requiring dose adjustment 4

POTS-Specific Treatment During Flares

• Increase fluid intake to 2-3 liters daily and salt intake to 10-12 grams daily as immediate interventions 2
• Implement compression garments (20-30 mmHg waist-high stockings) 2
• Consider pharmacologic volume expansion or heart rate control if conservative measures fail 2

Gastrointestinal Symptom Management

• Optimize oral nutrition with small, frequent meals and gastroparesis diet modifications if upper GI symptoms predominate 1, 2
• Trial mirtazapine (serotonergic neuromodulator) to increase food tolerance and body weight if significant GI-related weight loss is present 1
• Avoid elimination diets that may perpetuate or trigger avoidant/restrictive food intake disorder (ARFID), which has significant overlap with EDS 1

Multidisciplinary Team Coordination

Essential Team Members During Flare

• Pain physician for non-opioid medication optimization and consideration of interventional procedures 6
• Physical/occupational therapist for immediate joint stabilization strategies and proprioceptive training 4, 6, 3
• Pain psychologist for cognitive behavioral therapy addressing kinesiophobia, anxiety, and central sensitization 6, 7
• Gastroenterologist if GI symptoms are prominent or refractory 2
• Cardiologist or autonomic specialist if POTS symptoms are severe 2

Psychosocial Interventions

• Initiate or intensify cognitive behavioral therapy focusing on pain catastrophizing, kinesiophobia, and anxiety, which significantly burden EDS patients and worsen pain perception 6, 7
• Provide pain education about central sensitization mechanisms and the multifactorial nature of EDS pain 6, 7
• Teach coping and relaxation strategies as part of pain self-management 6

Emerging Therapies with Promising Evidence

• Low-dose naltrexone has shown promising effects for decreasing pain and increasing quality of life 7
• Transcutaneous electrical nerve stimulation (TENS) units demonstrate benefit for pain reduction 7
• Trigger point injections for localized myofascial pain 7
• Laser therapy shows emerging evidence for pain relief 7
• Medical marijuana was rated as extremely helpful by 10-24% of users in patient surveys, though this represents non-prescribed therapy use 8

When Interventional Procedures May Be Considered

• Selected patients may benefit from pain interventions to decrease pain intensity, contrary to historical concerns about local anesthetic resistance in EDS 6
• Ensure procedures are performed at centers with EDS expertise given tissue fragility concerns 5

Long-Term Flare Prevention Strategy

• Maintain regular physical therapy focusing on muscle strengthening to compensate for joint laxity and prevent subluxations 4, 3, 7
• Continue compression garments and bracing for joint protection during activities 2, 4
• Optimize cardiovascular conditioning through graded exercise programs to improve POTS symptoms 2
• Address sleep disturbances and fatigue, which contribute to pain amplification 7
• Maintain adequate vitamin D and calcium supplementation for bone health 5

What NOT to Do During EDS Flares

• Do not prescribe or escalate opioids, as they worsen GI dysmotility, increase infection risk, and show poor long-term efficacy 1, 4
• Do not initiate parenteral nutrition unless life-threatening malnutrition exists, and only as temporary bridge to rehabilitative therapy 1
• Do not perform invasive vascular procedures in vascular EDS patients due to fatal complication risk 2, 5
• Do not recommend prolonged bed rest, which worsens deconditioning and POTS symptoms 2
• Do not dismiss psychological comorbidities, as anxiety and panic disorders significantly amplify pain burden 6