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. 2025 Apr 25:16:1513199.
doi: 10.3389/fneur.2025.1513199. eCollection 2025.

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

Lilian Yao  1 , Kavya Subramaniam  1 , Katherine M Raja  1 , Abi Arunachalam  1 , Aubrey Tran  1 , Tripti Pandey  1 , Sahana Ravishankar  1 , Sahan Suggala  1 , Caitlyn Hendrickson  1 , Andrew J Maxwell  1
Affiliations

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

Lilian Yao et al. Front Neurol. .

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.

Keywords: Ehlers-Danlos syndrome; POTS; autonomic neuro-immune axis dysfunction; dysautonomia; hypermobility spectrum disorder; mast cell activation syndrome.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Venn diagram of patients with POTS with or without MCAS based on “strict criteria” of consensus 1 criteria and with or without hEDS based on 2017 hEDS criteria.
Figure 2
Figure 2
Venn diagram of patients with POTS with or without MCAS based on “conservative criteria” of laboratory-supported consensus 2 criteria and with or without near-hEDS as defined in this study.
Figure 3
Figure 3
Venn diagram of patients with POTS with or without MCAS based on “loose criteria” of clinically-supported consensus 2 criteria and with or without modified-HSD as defined in this study.
See this image and copyright information in PMC

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