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April 25, 2025Frontiers in Neurology16 citationsOpen Access

Association of postural orthostatic tachycardia syndrome, hypermobility spectrum disorders, and mast cell activation syndrome in young patients; prevalence, overlap and response to therapy depends on the definition

LYLilian YaoKRKatherine RajaTPTripti Pandey

Key Result

The prevalence of mast cell activation syndrome in young patients with POTS varied widely from 2% using strict criteria to 87% using clinical criteria, with 82% of treated patients responding positively to MCAS-targeted therapy.

Study Design

Type

Observational (n=100)

Multicenter

Yes

Structured PICO

Does the diagnostic definition of MCAS affect its prevalence and the observed response to therapy in young patients with POTS?

P
Population
100 young patients (mean age 17.2 years, 80% female) with postural orthostatic tachycardia syndrome evaluated retrospectively to determine the prevalence of hypermobility and mast cell activation syndrome across different diagnostic criteria.
E
Exposure
Mast Cell Activation Syndrome (MCAS) therapies
O
Outcome
Frequency of Joint Hypermobility Disorders (JHD) and MCAS using different diagnostic criteria, and effectiveness of MCAS therapies

Using overly strict diagnostic criteria for MCAS in POTS patients may underdiagnose the condition and withhold potentially effective therapies, as clinical diagnosis yields similar therapeutic responses.

Limitations

  • Study was limited specifically to patients with orthostatic intolerance syndromes that meet POTS criteria, excluding other forms of orthostatic intolerance.
  • Categories for joint hypermobility disorders were somewhat arbitrary due to a lack of established biomarkers and evolving consensus criteria.
  • Potential for circular reasoning and bias by including therapeutic response as part of the loose diagnostic criteria for MCAS.
  • The corresponding author is an author of the Consensus-2 publication, which could introduce bias despite blinding efforts.

Abstract

Background: The close association of syndromes of orthostatic intolerance with and without postural orthostatic tachycardia syndrome (POTS) with Joint Hypermobility Disorders (JHD) including Hypermobility Spectrum Disorder (HSD) and hypermobile Ehlers Danlos Syndrome (hEDS) and with Mast Cell Activation Syndrome (MCAS) is now firmly established. However, the prevalence of each entity relative to the other is not well established and is affected greatly by the various definitions used for each syndrome. Use of restricting definitions for each syndrome can be problematic in the clinical setting as it under-estimates the presence of disease, thereby preventing clinicians from considering potentially helpful therapeutic options. Methods: A retrospective review of the clinical records of 100 young patients meeting POTS criteria was undertaken to determine the frequency of HSD, near-hEDS, and hEDS as well as the frequency of MCAS using consensus-1, conservative consensus-2, and clinical criteria regardless of lab support. Effectiveness of MCAS therapies was assessed in relation to the method of MCAS diagnosis. Results: From records of 392 patients with orthostatic intolerance syndromes, 100 patients met POTS criteria. The frequency of JHD ranged from 13% using strict criteria of hEDS to 34% using HSD Criteria. The frequency of MCAS ranged from 2% using consensus-1 criteria, to 37% using conservative consensus-2 criteria, to 87% using clinical criteria. Patients diagnosed by clinical criteria with or without the aid of labs responded to therapy similarly to those diagnosed with stricter criteria. Conclusion: Using overly strict criteria to diagnose conditions which have a high prevalence of co-occurrence misses opportunities for potential therapeutic strategies.

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Cite This Study

Yao et al. (2025) conducted an observational in Postural orthostatic tachycardia syndrome (POTS) (n=100). Different diagnostic criteria definitions (strict, conservative, loose) was evaluated on Prevalence of Mast Cell Activation Syndrome (MCAS) and Joint Hypermobility Disorders (JHD). The prevalence of mast cell activation syndrome in young patients with POTS varied widely from 2% using strict criteria to 87% using clinical criteria, with 82% of treated patients responding positively to MCAS-targeted therapy.

synapsesocial.com/papers/6aa5f8155175d8ad9439739chttps://doi.org/10.3389/fneur.2025.1513199
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