What is the best approach to manage back pain and suspected mast cell activation in a patient with Ehlers-Danlos syndrome?

Managing Back Pain and Suspected Mast Cell Activation in Ehlers-Danlos Syndrome

For back pain in hEDS patients, prioritize physical therapy and occupational therapy with bracing while avoiding opioids entirely, and only pursue MCAS testing if the patient presents with episodic multisystem symptoms (flushing, urticaria, wheezing) involving ≥2 physiological systems—not for isolated musculoskeletal pain. 1, 2, 3

Initial Assessment of Back Pain in hEDS

Confirm hEDS Diagnosis First

• Apply the 2017 diagnostic criteria for hypermobile EDS, available at https://www.ehlers-danlos.com/wp-content/uploads/2017/05/hEDS-Dx-Criteria-checklist-1.pdf 2
• Calculate the Beighton score: ≥5/9 for adults under 50 years, ≥4/9 for those over 50, and ≥6/9 for prepubertal children 2
• Assess for soft, velvety, or hyperextensible skin by gently pulling skin on the volar forearm 2
• Document easy bruising patterns and abnormal scarring or tissue fragility 2

Evaluate for Pelvic Floor Dysfunction

• Consider anorectal manometry, balloon expulsion test, or defecography given the high prevalence of pelvic floor dysfunction in hEDS, which can refer pain to the lower back 1, 2

When to Test for MCAS (Critical Decision Point)

Do NOT routinely test for MCAS in all hEDS patients with isolated back pain. 1, 2

Only Test If Patient Has:

• Episodic multisystem symptoms involving ≥2 physiological systems: flushing, urticaria, wheezing, abdominal pain, diarrhea, or anaphylaxis 1, 2, 4
• If criteria met, obtain baseline serum tryptase and repeat 1-4 hours following symptomatic flare 1, 2, 4
• Diagnostic threshold: 20% increase above baseline plus 2 ng/mL 1, 2, 4

Common Pitfall to Avoid:

The 2025 AGA guideline explicitly warns against performing MCAS testing in all hEDS patients with isolated GI or musculoskeletal symptoms, as validated clinical tests for mast cell-mediated mechanisms of isolated pain are lacking. 1

First-Line Treatment for Back Pain in hEDS

Physical and Occupational Therapy (Most Effective)

• Occupational therapy with bracing showed 70% improvement rate in the largest retrospective cohort of 98 hEDS patients 3
• Physical therapy focuses on joint stabilization, proprioceptive training, and preventing subluxations 3, 5
• These modalities prevent joint injury while managing chronic pain symptoms 5

Medications to Consider:

• Neuropathic modulators (gabapentin, pregabalin, duloxetine) for chronic pain, though 47% of patients reported adverse effects in one cohort 3
• NSAIDs for acute flares, though long-term use should be limited 3
• Muscle relaxants for muscle spasm component 3
• Acetaminophen as adjunctive therapy 3

Medications to AVOID:

• Opioids must be avoided entirely in hEDS patients with chronic pain 1, 2
• For patients already on opioids, facilitate cessation through a careful multidisciplinary approach 1

If MCAS is Confirmed: Add Mast Cell Stabilization

First-Line Anti-Mediator Therapy:

• H1 antihistamines (cetirizine, fexofenadine) at 2-4 times FDA-approved doses 4, 6
• H2 antihistamines (famotidine) added to H1 therapy for enhanced symptom control 4, 6
• Combined H1 and H2 therapy is more effective than monotherapy 4

Second-Line Options:

• Cromolyn sodium 200 mg QID showed clinical improvement in diarrhea, flushing, headaches, abdominal pain, and itching in mastocytosis patients within 2-6 weeks 7, 8
• Montelukast if urinary leukotriene E4 levels are elevated or inadequate response to antihistamines 4, 8

Refractory Cases:

• Omalizumab for patients with refractory symptoms despite maximal anti-mediator therapy 4
• Refer to allergy specialist or mast cell disease research center 1, 4, 6

Screen for Common Comorbidities That Worsen Pain

Postural Orthostatic Tachycardia Syndrome (POTS):

• Measure postural vital signs with active stand test: heart rate increase ≥30 beats/min in adults (≥40 beats/min in adolescents) within 10 minutes of standing without orthostatic hypotension 1, 2, 6
• POTS affects up to 37.5% of hEDS patients and can exacerbate pain through autonomic dysfunction 2, 6
• Refer for tilt table testing if postural vital signs confirm POTS 1, 2

Gastrointestinal Dysfunction:

• Up to 98% of hEDS patients experience GI manifestations 2
• Screen for celiac disease with serological testing earlier in hEDS patients with any GI symptoms 1, 2
• Consider gastric emptying studies for chronic upper GI symptoms after excluding structural disease 2

Multidisciplinary Referral Strategy

When to Refer:

• Gastroenterology: for refractory GI symptoms despite appropriate management 2
• Allergy/Immunology: when MCAS diagnosis is supported through clinical and/or laboratory features 1, 4, 6
• Autonomic specialist: for confirmed POTS with failed lifestyle modifications 2
• Medical genetics: for definitive EDS classification and genetic counseling 2
• Pain management: for comprehensive pain control strategies avoiding opioids 3

Specialized Centers:

The NCCN emphasizes that comprehensive care of patients with mast cell disorders requires a multidisciplinary team approach, preferably in specialized centers with expertise in mast cell disorders. 1

Complementary Approaches

• Complementary/alternative treatments were the most commonly used modalities (n=88 in one cohort), though specific efficacy data were limited 3
• Psychological support and self-management strategies may benefit patients with hEDS/hypermobility spectrum disorders 5
• Educate patients about their condition and the importance of preventing joint injury 5, 9