Management of Ehlers-Danlos Syndrome with Elevated Tryptase and Cardiac Disease
The management approach must be stratified by EDS subtype, with vascular EDS (vEDS) requiring aggressive vascular surveillance and celiprolol therapy, while hypermobile EDS (hEDS) with elevated tryptase suggests concurrent mast cell activation syndrome requiring antihistamine therapy alongside standard cardiac monitoring.
Critical First Step: Determine EDS Subtype
Genetic testing for COL3A1 variants is mandatory to definitively diagnose vascular EDS, as this determines whether the patient faces life-threatening vascular complications or a more benign cardiac course. 1, 2 Clinical diagnosis alone is insufficient—26.4% of clinically diagnosed EDS cases have alternative genetic conditions requiring different management. 3
Vascular EDS (Type IV) - High-Risk Cardiac Management
If COL3A1 pathogenic variant is confirmed:
Baseline vascular imaging from head to pelvis using non-invasive modalities (Doppler ultrasound, CT, or MRI) must be performed immediately to evaluate the entire aorta and branch vessels. 2 This is critical because:
- Medium-sized artery dissections, aneurysms, and ruptures occur unpredictably starting in adolescence 1
- Aortic dissection (both type A and B) occurs in up to 10% of patients 1
- Life expectancy is reduced to an average of 51 years 1
Annual surveillance imaging is mandatory for all vEDS patients to monitor dilated or dissected segments. 1, 2
Medical Therapy for Vascular EDS
Celiprolol (a beta-blocker with vasodilatory properties) is recommended to reduce vascular morbidity, with treatment initiation reasonable after 10 years of age. 1, 2 This recommendation is based on two retrospective studies and one randomized open-label trial showing reduced vascular events. 1
Aggressive blood pressure control to maintain normal range is essential, using RAAS blockers as first-line agents. 1
Critical Pitfalls in Vascular EDS
Never perform invasive vascular procedures, diagnostic catheter angiography, or invasive hemodynamic monitoring in vEDS patients—these carry risk of fatal complications. 2, 3 Non-invasive imaging must be used exclusively. 2
Hypermobile EDS - Moderate-Risk Cardiac Management
For patients with hEDS (or hypermobility spectrum disorder):
Baseline echocardiography should be performed to screen for mitral valve prolapse (present in 7.5%) and thoracic aortic dilatation (present in 20.7% of hEDS patients). 4 The cardiovascular manifestations are typically mild, especially in females (>90% have only mild dilatation). 4
If aortic dilatation is detected at baseline, ongoing surveillance echocardiography is required to monitor for progressive dilatation, though the optimal interval has not been defined. 4
Notably, contrary to older literature, recent studies using current diagnostic criteria show MVP prevalence in hEDS (6.1%) is not significantly different from controls (7%). 5 However, extra-aortic arterial involvement can occur, including cervical artery dissection and spontaneous coronary artery dissection in 1.9% of cases. 4
Elevated Tryptase: Mast Cell Activation Syndrome Connection
Elevated tryptase in hEDS patients strongly suggests concurrent mast cell activation syndrome (MCAS), which is commonly associated with hypermobile EDS and requires specific management. 6
MCAS Management in hEDS Patients
Pre-treatment with histamine receptor antagonists (H1 and H2 blockers) and/or mast cell stabilizers should be considered for patients with suspected MCAS, particularly before any procedures or interventions. 6
Screen for MCAS symptoms including reactions to mechanical stimuli, temperature changes, flushing, gastrointestinal symptoms, and cardiovascular symptoms (palpitations, presyncope). 6 These patients may have POTS (postural orthostatic tachycardia syndrome) requiring:
- Increased fluid and salt intake 2
- Exercise training and compression garments 2
- Pharmacological treatments for volume expansion, heart rate control, and vasoconstriction if conservative measures fail 2
Cardiac Symptom Management
Cardiac symptoms are more frequent in EDS patients than controls:
Ambulatory electrocardiographic monitoring should be performed to evaluate for arrhythmias, particularly in patients with palpitations or documented structural abnormalities. 1
Multidisciplinary Approach
A multidisciplinary team involving cardiology, genetics, gastroenterology (for MCAS/POTS), and physical medicine is essential for comprehensive EDS management. 2 Regular follow-up with this team is recommended for all EDS subtypes. 2
Surgical Considerations
If cardiac surgery becomes necessary:
Meticulous surgical technique with careful tissue handling is mandatory to prevent wound dehiscence, using pledgeted sutures for all anastomoses. 2, 3 Tissue fragility increases bleeding complications and delays wound healing. 2
For vEDS patients, surgical repair carries extreme risk and should only be performed for vital indications, with decisions made by a Multidisciplinary Aortic Team. 2 Endovascular approaches may be preferred when feasible to minimize tissue trauma. 2