What specialist is best to treat a patient with Mast Cell Activation Syndrome (MCAS), Postural Orthostatic Tachycardia Syndrome (POTS), and Ehlers-Danlos syndrome?

Best Specialist to Treat MCAS, POTS, and Ehlers-Danlos Syndrome

For patients with the triad of MCAS, POTS, and Ehlers-Danlos syndrome, a multidisciplinary team coordinated by a gastroenterologist is the most practical approach, with targeted referrals to allergists/immunologists for MCAS, cardiologists or neurologists for POTS, and medical geneticists for EDS diagnosis and classification. 1

Primary Coordination and Initial Management

Gastroenterologists serve as effective coordinators for this patient population because up to 98% of hypermobile EDS patients experience gastrointestinal manifestations, and these specialists can screen for all three conditions while managing the predominant GI symptoms. 1 Gastroenterology providers should incorporate the Beighton score (≥5/9 for adults under 50) as a screening tool for joint hypermobility and can apply the 2017 diagnostic criteria for hypermobile EDS or refer appropriately. 1

For POTS screening, gastroenterologists can measure postural vital signs with an active stand test, looking for a symptomatic heart rate increase of ≥30 beats/min within 10 minutes of standing without orthostatic hypotension. 1 If POTS is confirmed through this bedside test, referral to cardiology or neurology for autonomic function testing including tilt table or sudomotor testing should be considered. 1

Specialist Referrals Based on Condition

For MCAS Management

Allergists or mast cell disease research centers are the definitive specialists for MCAS. 1 Gastroenterologists can initiate diagnostic testing with baseline serum tryptase levels and repeat measurements 1-4 hours following symptom flares, but only in patients presenting with episodic symptoms involving ≥2 physiological systems (such as flushing, urticaria, wheezing, or multisystem symptoms). 1 The diagnostic threshold requires increases of 20% above baseline plus 2 ng/mL. 1 Once MCAS is supported through clinical and laboratory findings, referral to an allergy specialist or mast cell disease research center is mandatory for additional testing and management. 1

For POTS Management

Cardiologists or neurologists with autonomic expertise should manage refractory POTS after lifestyle modifications (adequate hydration and physical exercise) have been attempted. 1, 2 These specialists can perform expanded autonomic function testing including tilt table and sudomotor testing. 1 The American College of Cardiology recommends specific interventions including fluid and salt intake expansion, compression garments for lower body venous pooling, fludrocortisone for blood volume expansion, low-dose propranolol for heart rate control, and midodrine for significant orthostatic hypotension. 2

For EDS Diagnosis and Classification

Medical geneticists are the primary specialists for definitive EDS diagnosis and classification, particularly when genetic testing is needed or when vascular EDS is suspected. 3, 4 For hypermobile EDS (the most common subtype affecting 80-90% of EDS cases), diagnosis is primarily clinical as no specific genetic markers have been identified. 4 However, genetic consultation remains valuable for applying rigorous diagnostic criteria, excluding alternative diagnoses, and coordinating surveillance protocols. 3

Critical Subspecialty Involvement

Cardiology for Vascular Surveillance

Cardiologists should evaluate all EDS patients for aortic root dilation, which occurs in 25-33% of classic and hypermobile EDS types. 3 Echocardiography should be performed every 2-3 years until adult height is reached, and every 6 months if the aortic diameter exceeds 4.5 cm or growth rate exceeds 0.5 cm/year. 3

Rheumatology for Joint Assessment

Rheumatologists often evaluate joint hypermobility using the Beighton scale and can manage musculoskeletal complications, though they are not the primary coordinators for this triad. 4

Common Pitfalls to Avoid

Do not perform universal testing for POTS and MCAS in all patients with EDS. 1 Testing should be targeted only to patients presenting with clinical manifestations of these conditions—orthostatic intolerance for POTS and episodic multisystem symptoms for MCAS. 1

Avoid routine genetic testing for hypermobile EDS, as no causative genes have been identified, and such testing is not clinically useful. 4 Reserve genetic testing for suspected vascular EDS (COL3A1 mutation testing), which is a medical emergency requiring urgent evaluation. 4

Do not overlook celiac disease screening in hEDS patients with any GI symptoms, as the risk is elevated compared to the general population. 4 Testing should be performed earlier in the diagnostic evaluation, not limited to those with diarrhea alone. 1

Recognize that opioids worsen GI symptoms in this population and should be avoided for chronic pain management. 2, 4

Practical Management Framework

The most effective care model involves a gastroenterologist-led coordination with the following referral algorithm:

• Immediate referral to allergy/immunology if MCAS is confirmed (tryptase criteria met) 1
• Referral to cardiology or neurology if POTS persists despite lifestyle modifications 1, 2
• Referral to medical genetics for formal EDS classification, family counseling, or if vascular EDS is suspected 3, 4
• Referral to psychology for brain-gut behavioral therapies when anxiety and psychological distress are present 2

This approach acknowledges that while multidisciplinary care is ideal, the reality is that integrated EDS centers are not available in most regions. 5, 6 The gastroenterologist serves as the practical hub because GI symptoms are nearly universal in this population and these specialists can perform initial screening and coordinate subspecialty involvement based on specific clinical manifestations. 1

The marked overlap among these three conditions—with 31% of patients with POTS and EDS also having MCAS (odds ratio 32.46)—underscores the importance of screening for all three conditions when any one is identified. 7 However, screening should remain clinically driven rather than reflexive. 1