Postural orthostatic tachycardia syndrome and the potential role of mast cell activation
Open accessAbstract
Though a sizeable amount of data connects mast cell activity to the neurologic system, less is known about the true clinical implications of this relationship. Even less is understood about treatment strategies in those with both allergic and neurologic complaints. This is particularly true in postural orthostatic tachycardia syndrome (POTS), a common type of dysautonomia, where patients are burdened by symptoms of orthostatic cerebral hypoperfusion and several other comorbidities that are likely influenced by autonomic tone. Some patients describe characteristic allergic symptoms, in the absence of typical IgE mediated triggers, and also improvement with traditional mast cell directed medications. Further work is necessary to determine whether these anecdotal observations are valid. The answer to this question will likely be addressed as the mechanisms of POTS are better characterized, which may include a phenotype with distinct mast cell involvement.
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Mast cell degranulation causes release of vasoactive substances (histamine, prostaglandins, platelet-activating factor) into the circulation, potentially causing excessive vasodilation and blood pooling in the lower extremities.
“Mast cell degranulation causes a variety of vasoactive substances (histamine, prostaglandins, platelet-activating factor) to be released into the circulation, potentially causing excessive vasodilation and blood pooling in the lower extremities (31).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [31]
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“This will be discussed in more detail later, in its potential relationship to POTS and MCAS.”
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“Mast cell degranulation causes a variety of vasoactive substances (histamine, prostaglandins, platelet-activating factor) to be released into the circulation, potentially causing excessive vasodilation and blood pooling in the lower extremities (31).”
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“A hopeful beneficial treatment would be to block these mediators in pediatric POTS patients with MCA, which merits further research (85).”
BackgroundMechanisms and management of gastrointestinal symptoms in postural orthostatic tachycardia syndrome
Tu, Y., Abell, T. L., Raj, S. R., & Mar, P. L. (2020) · Neurogastroenterology & Motility · doi:10.1111/nmo.14031 · Cited by 26 · see citing works
Observational case series of postural tachycardia syndrome (PoTS) in post-COVID-19 patients
Gall, N. P., James, S., & Kavi, L. (2022) · British Journal of Cardiology · doi:10.5837/bjc.2022.003 · Cited by 24 · see citing works
Postural orthostatic tachycardia syndrome and migraine: A narrative review
Mueller, B. R., & Robinson‐Papp, J. (2022) · Headache The Journal of Head and Face Pain · doi:10.1111/head.14365 · Cited by 24 · see citing works
Verdi, M., Candido, D., Madan, J. C., Bernstein, J. A., Bukstein, D. A., Anagnostou, A., Greenhawt, M., Mustafa, S. S., Wang, J., Nowak-Wegrzyn, A. H., et al. (2025) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2025.05.020 · Cited by 21 · see citing works
Self-citationRestless legs syndrome is associated with mast cell activation syndrome
Weinstock, L. B., Walters, A. S., Brook, J. B., Kaleem, Z., Afrin, L. B., & Molderings, G. J. (2020) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.8216 · Cited by 19 · see citing works
“42,43 46 There is upregulation of hypoxia-inducible factor 1-alpha, vascular endothelial growth factor, and nitric oxide synthase in brains of patients with RLS compared to brains in control patients.”
Joint Hypermobility Syndrome in Patients With Functional Dyspepsia
Carbone, F., Fikree, A., Aziz, Q., & Tack, J. (2020) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000220 · Cited by 16 · see citing works
Postural orthostatic tachycardia syndrome and post-acute COVID-19
Amekran, Y., Damoun, N., & Hangouche, A. J. E. (2022) · Global Cardiology Science and Practice · doi:10.21542/gcsp.2022.13 · Cited by 15 · see citing works
“These may include sympathetic dysregulation, hypovolemia, hyperadrenergic stimulation, deconditioning [12, 58], autoantibody mediated response [58], and mast cell activation [59, 60].”
BackgroundAfrin, L. B., Dempsey, T. T., & Weinstock, L. B. (2022) · Vaccines · doi:10.3390/vaccines10010127 · Cited by 14 · see citing works
“Furthermore, with cohorts of POTS patients recently being found to have adrenergic or muscarinic autoantibodies [36,77,78], and given known MC surface expression of adrenergic and muscarinic receptors which are active in the regulation of MC function [36], it even becomes possible, at least in theory, to drive MC acti…”
BackgroundNon-invasive Vagus Nerve Simulation in Postural Orthostatic Tachycardia Syndrome
Chakraborty, P., Farhat, K., Morris, L. M., Whyte, S., Yu, X., & Stavrakis, S. (2023) · Arrhythmia & Electrophysiology Review · doi:10.15420/aer.2023.20 · Cited by 11 · see citing works
Loughnan, A., Gall, N. P., & James, S. (2020) · Autonomic Neuroscience · doi:10.1016/j.autneu.2020.102762 · Cited by 11 · see citing works
Risk Factors for Orthostatic Hypertension in Children
Hu, Y., He, B., Han, Z., Wang, Y., Tao, C., Wang, Y., Jin, H., & Du, J. (2020) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2020.07.030 · Cited by 11 · see citing works
Postural Orthostatic Tachycardia Syndrome (POTS): A Frequently Missed Diagnosis
George, A., & Winters, B. A. (2022) · The Journal for Nurse Practitioners · doi:10.1016/j.nurpra.2022.08.022 · Cited by 7 · see citing works
Postural Orthostatic Tachycardia Syndrome as a Manifestation of Post-COVID-19 Syndrome
Trisvetova, E. L. (2022) · Rational Pharmacotherapy in Cardiology · doi:10.20996/1819-6446-2022-04-11 · Cited by 8 · see citing works
Pathophysiology and Classification of PoTS
Lloyd, M., & Raj, S. (2020) · Postural Tachycardia Syndrome · doi:10.1007/978-3-030-54165-1_5 · Cited by 4 · see citing works
Bayrak, Y. E. (2024) · Northern Clinics of Istanbul · doi:10.14744/nci.2023.64920 · Cited by 3 · see citing works
“It was observed that the symptoms of patients decreased when a mast cell stabilizer or leukotriene antagonist was used in the treatment [5, 6].”
MethodIntroduction to Neuroimmunology
Coyle, P. K. (2019) · Current clinical neurology · doi:10.1007/978-3-030-24436-1_1 · Cited by 3 · see citing works
Gynaecological Considerations in PoTS
Tailor, V. K., & Khullar, V. (2020) · Springer eBooks · doi:10.1007/978-3-030-54165-1_18 · Cited by 2 · see citing works
Urological Considerations in PoTS
Tailor, V. K., & Khullar, V. (2020) · Springer eBooks · doi:10.1007/978-3-030-54165-1_17 · Cited by 2 · see citing works
Dizziness, Syncope, and Autonomic Dysfunction in Children
Kakavand, B. (2022) · Progress in Pediatric Cardiology · doi:10.1016/j.ppedcard.2022.101512 · Cited by 2 · see citing works
Complex breathlessness in postural tachycardia syndrome and autonomic dysfunction
Gall, N. P., & Reilly, C. C. (2022) · European Respiratory Society eBooks · doi:10.1183/2312508x.10013621 · Cited by 2 · see citing works
Non-pharmacological Management (Hydration, Diet and Compression)
Eftekhari, H., & Bruce, D. (2020) · Springer eBooks · doi:10.1007/978-3-030-54165-1_25 · Cited by 2 · see citing works
Comorbid Conditions of Ehlers–Danlos Syndromes and Vulvodynia: A Latent Class Analysis
Glayzer, J. E., Bray, B. C., Kobak, W. H., Trujillo, C., Patil, C. L., Li, H., Francomano, C. A., & Schlaeger, J. M. (2026) · Pain Management Nursing · doi:10.1016/j.pmn.2026.03.005 · Cited by 1 · see citing works
“…sharing the symptoms of weakness, fatigue, functional gastrointestinal disorders, hypotension, exercise intolerance, impaired cognition, headaches, and palpitations (Brock et al., 2021; Doherty & White, 2018; Kucharik & Chang, 2020; Mathias et al., 2021; Theoharides et al., 2024; Wu & Ho, 2024).”
Approach to Postural Orthostatic Tachycardia Syndrome
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Garonzi, M. P. (2022) · L'Espace Politique · doi:10.4000/espacepolitique.10568
Itchy rash and general malaise
Maitland, A. L. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95082-4.00022-0
Parasympathetic and Sympathetic Nervous System Dysfunction and Monitoring
DePace, N. L., Soloway, S., Yayac, M. F., & Colombo, J. (2025) · Springer eBooks · doi:10.1007/978-3-031-88769-7_13
Mauriello, D., Mitchell, B., & Klaas, K. M. (2026) · Pediatric Annals · doi:10.3928/19382359-20260112-04
Azola, A. M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-23516-0.00124-0
- Authors
- Doherty, T. A., & White, A. A.
- Affiliations
- University of California San Diego (US)
- Scripps Health (US)
- Corresponding author
- White, Andrew A.
- Venue
- Autonomic Neuroscience
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 215
- Pages
- 83-88
- ISSN
- 1566-0702 (ISSN-L)
- OpenAlex
- W2799349326
- Cited by
- 37
- References
- 79
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 9 · 2021: 1 · 2020: 12 · 2019: 4 · 2018: 1
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autonomic Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Keywords
- postural orthostatic tachycardia syndrome, mast cell activation, mast cell stabilizers, autonomic dysfunction, allergic symptoms, autonomic tone, mast cell phenotype
- MeSH terms
- Humans, Mastocytosis, Comorbidity, Postural Orthostatic Tachycardia Syndrome
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