The MCAS, POTS and hEDS Overlap: What Patients Need to Know

Last reviewed: October 2026 · 28 sources

The short answer

  • They often show up together. In one study of people with POTS, 31% met the criteria for hEDS and another 24% had generalized joint hypermobility [1]. In another, 42% of POTS patients had symptoms plus a lab marker suggesting mast cell activation [2].
  • The numbers depend on the definitions. In a 2025 study of young people with POTS, MCAS was found in 2%, 37% or 87% depending on which criteria were used [3].
  • Why they cluster isn’t known. A 2020 review found little original research and no shared mechanism yet described [4]. Other researchers see a strong clinical overlap worth taking seriously [1, 3].
  • What helps most in practice is coordination: one clinician who sees the whole picture, care that accounts for all your conditions, and caution with medicines that can affect more than one of them [5, 6].

Many people find this site after collecting diagnoses one at a time. First it’s the joints that slip out of place. Then it’s the racing heart and lightheadedness when standing. Then the flushing, hives and food reactions. Each specialist looks at their piece, and nobody seems to look at the whole person.

If that sounds familiar, you’re not imagining the pattern. This post explains what’s known about how mast cell activation syndrome (MCAS), postural orthostatic tachycardia syndrome (POTS) and hypermobile Ehlers-Danlos syndrome (hEDS) overlap, what isn’t known yet, and how to get care that fits together. Each condition has its own page: MCAS, POTS and hEDS.

The three conditions in a sentence each

  • hEDS is a heritable connective tissue disorder that causes generalized joint hypermobility, joint instability and chronic pain. It’s diagnosed clinically with the 2017 criteria, since there’s no genetic test yet [5, 7].
  • POTS is a disorder of the autonomic nervous system in which heart rate rises too much on standing, with symptoms like lightheadedness [8, 9].
  • MCAS is a condition in which mast cells release their chemical messengers too easily, causing episodes that affect more than one body system [10, 11].

How often do they overlap?

hEDS and POTS

This is the best-studied pairing. In a study of 91 people with POTS who were examined using the 2017 criteria, 31% met the criteria for hEDS and another 24% had generalized joint hypermobility [1]. Specialist clinics report that autonomic problems are frequently seen in hEDS, though exact rates haven’t been measured [12]. Dysautonomia International lists Ehlers-Danlos syndromes and joint hypermobility among conditions linked with POTS [8].

POTS and MCAS

In one clinic study of 69 people with POTS, 42% had additional symptoms plus at least one lab marker suggesting mast cell activation [2]. Dysautonomia International also lists mast cell activation disorders among conditions linked with POTS [8].

hEDS and MCAS

The Ehlers-Danlos Society lists mast cell activation diseases among conditions people with hEDS may have [5], and some researchers have proposed a role for mast cells in EDS [13].

Why the numbers vary so much

Definitions matter. In a 2025 study of 100 young people with POTS, the rate of MCAS ranged from 2% to 37% to 87% depending on the criteria used, and the rate of joint hypermobility disorders ranged from 13% to 34% [3]. The authors found that patients diagnosed with broader criteria responded to treatment similarly to those diagnosed with stricter ones [3]. The Miller study also found that more people reported having hEDS than met the 2017 criteria when examined [1].

Why might they cluster?

Honestly, no one knows yet.

  • A connective tissue idea. One long-standing theory is that looser connective tissue in hEDS makes blood vessels stretch more, so blood pools when standing. The Miller study notes this theory has become widely accepted despite there being no evidence to support it, and that small-fiber nerve problems, which are more common in EDS, may also play a part [1].
  • A mast cell idea. Some researchers propose that mast cells contribute to symptoms in EDS [13], and a 2005 study found that people with POTS and mast cell activation had an exaggerated adrenaline-type response to standing [6].
  • The skeptical view. A 2020 review by Kucharik and Chang concluded that current evidence doesn’t establish a relationship among the three, partly because they share vague, overlapping symptoms [4]. A 2025 Canadian MCAS review says these links have never been shown in people who clearly meet the strict MCAS criteria [11].

Both views are worth knowing. You can take the overlap seriously as a pattern in your own life without assuming a single cause.

Living with more than one: practical tips

Find a “home base” clinician

The Ehlers-Danlos Society notes that care often involves several providers [5]. It helps to have one clinician, often a primary care doctor, who keeps the whole picture in view and helps coordinate referrals to, for example, an allergist/immunologist, a dysautonomia specialist and a physical therapist who understands hypermobility.

Keep a one-page summary

List your diagnoses, who made them and with what criteria, your medicines and reactions, and your main symptoms. Bring it to every appointment. Our printable Trifecta reference can help you organize it.

Watch for medicines that cross over

  • Beta-blockers are sometimes used in POTS, but the 2005 study concluded they “should be used with great caution, if at all” in people with POTS and mast cell activation [6]. Make sure the prescriber knows about both.
  • Other medicines can trigger mast cell reactions, including some painkillers, antibiotics and contrast dyes [14]. Tell every clinician and dentist about a mast cell disorder before procedures or new prescriptions [15].
  • Procedures and surgery: let your surgical team know you have hEDS, since certain precautions may be needed [16].

Build movement carefully

Exercise matters for both POTS and hEDS, but the details differ. POTS guidelines suggest starting with exercise that doesn’t require being upright, such as rowing, recumbent bikes or swimming, and building up gradually [9]. For hEDS, physical therapy aims to build strength, stability and joint position sense without causing injury [17]. A 2022 review suggests a physical therapist with specific expertise for people with POTS who also have hypermobility [18]. Exercise and heat can be mast cell triggers for some people too [14], so a slow, steady plan is usually easier on all three.

Track symptoms across systems

A symptom shared by all three, such as dizziness, gut trouble or fatigue, can have different causes on different days. Note what happened just before: standing for a long time, heat, a meal, a new food, stress or a joint injury. The 2017 hEDS criteria point out that symptoms like fatigue, gut problems and dysautonomia “may be more debilitating than the joint symptoms” and should always be asked about [7].

Take care of your mental health

Living with several chronic conditions is hard. Anxiety and depression are commonly reported in hEDS [7], and the Canadian MCAS review notes that anxiety is a normal response to unpredictable episodes [11]. POTS itself is not caused by anxiety [8]. Support helps, and if you’re in crisis, call or text 988 in the U.S. [19].

What about mold?

Many people in our community also wonder about mold. Many patients and some clinicians report mold as a trigger for mast cell symptoms, but research so far is mostly lab-based [20, 21]. A few small studies have reported more autonomic symptoms in people from damp buildings, but cause and effect hasn’t been shown [22, 23], and we didn’t find research showing that mold causes or worsens hEDS. See our post on mold and MCAS.

What’s known and what’s debated

Generally accepted: each condition is real and has published diagnostic criteria; hEDS and hypermobility are common among people with POTS [1, 7, 9, 24].

Debated: how strongly MCAS is linked to POTS and hEDS; which MCAS criteria to use; and whether a shared mechanism exists [3, 4, 11].

Questions to ask your doctor

  • Do I meet the 2017 hEDS criteria, or is hypermobility spectrum disorder a better fit [25]?
  • Should I be checked for POTS with a stand test or tilt test?
  • Which criteria are you using to evaluate me for MCAS?
  • Will any of my medicines for one condition make another one worse?
  • Can you refer me to a physical therapist experienced with hypermobility?
  • Who should coordinate my care across specialists?

When to get urgent help

Call 911 or your local emergency number for signs of anaphylaxis, such as trouble breathing, swelling of the face, eyes or tongue, or passing out, and use epinephrine as your specialist has instructed [26]. Also call if someone faints and doesn’t become alert within a couple of minutes, or has chest pain or a pounding or irregular heartbeat [27], or for a suspected dislocation with a limb that’s pale, cold or blue below the joint [28].

The bottom line

If you live with two or three of these conditions, the overlap is real in your life, even though science hasn’t explained it yet. You don’t need a unifying theory to get better care. You need a team that talks to each other, medicines chosen with all your conditions in mind, and a pace of change your body can handle. Our POTS daily management and MCAS flares posts have practical next steps.

Sources

Numbers in brackets in the text link to these sources. Links were checked in October 2026. Some sources are written by people who support a particular approach; we've tried to say so in the text.

  1. Miller AJ, Stiles LE, Sheehan T, et al. Prevalence of hypermobile Ehlers-Danlos syndrome in postural orthostatic tachycardia syndrome. Auton Neurosci. 2020;224:102637. PMID: 31954224. https://pmc.ncbi.nlm.nih.gov/articles/PMC7282488/
  2. Kohno R, Cannom DS, Olshansky B, et al. Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association. J Am Heart Assoc. 2021;10(17):e021002. PMID: 34398691. https://pmc.ncbi.nlm.nih.gov/articles/PMC8649306/
  3. Yao L, Subramaniam K, Raja KM, et al. 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. Front Neurol. 2025;16:1513199. PMID: 40352770. https://pmc.ncbi.nlm.nih.gov/articles/PMC12063504/
  4. Kucharik AH, Chang C. The Relationship Between Hypermobile Ehlers-Danlos Syndrome (hEDS), Postural Orthostatic Tachycardia Syndrome (POTS), and Mast Cell Activation Syndrome (MCAS). Clin Rev Allergy Immunol. 2020;58(3):273-297. PMID: 31267471. https://doi.org/10.1007/s12016-019-08755-8
  5. The Ehlers-Danlos Society. Hypermobile Ehlers-Danlos Syndrome (hEDS). Web page, accessed October 10, 2026. https://www.ehlers-danlos.com/heds/
  6. Shibao C, Arzubiaga C, Roberts LJ, et al. Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders. Hypertension. 2005;45(3):385-390. PMID: 15710782. https://doi.org/10.1161/01.HYP.0000158259.68614.40
  7. Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8-26. PMID: 28306229. https://doi.org/10.1002/ajmg.c.31552
  8. Dysautonomia International. Postural Orthostatic Tachycardia Syndrome. Web page, accessed October 10, 2026. https://www.dysautonomiainternational.org/page.php?ID=30
  9. Sheldon RS, Grubb BP, Olshansky B, et al. 2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm. 2015;12:e41-e63. PMID: 25980576. https://pmc.ncbi.nlm.nih.gov/articles/PMC5267948/
  10. Valent P, Akin C, Arock M, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215-225. PMID: 22041891. https://pmc.ncbi.nlm.nih.gov/articles/PMC3224511/
  11. Lee E, Picard M. Diagnosis and management of mast cell activation syndrome (MCAS) in Canada: a practical approach. Allergy Asthma Clin Immunol. 2025;21:49. PMID: 41272881. https://pmc.ncbi.nlm.nih.gov/articles/PMC12639879/
  12. Hakim A, O'Callaghan C, De Wandele I, et al. Cardiovascular autonomic dysfunction in Ehlers-Danlos syndrome-Hypermobile type. Am J Med Genet C Semin Med Genet. 2017;175(1):168-174. PMID: 28160388. https://doi.org/10.1002/ajmg.c.31543
  13. Seneviratne SL, Maitland A, Afrin L. Mast cell disorders in Ehlers-Danlos syndrome. Am J Med Genet C Semin Med Genet. 2017;175(1):226-236. PMID: 28261938. https://doi.org/10.1002/ajmg.c.31555
  14. The Mast Cell Disease Society (TMS). Symptoms and Triggers of Mast Cell Activation. Web page, accessed October 10, 2026. https://tmsforacure.org/signs-symptoms-triggers/symptoms-and-triggers-of-mast-cell-activation/
  15. The Mast Cell Disease Society (TMS). Medications to Treat Mast Cell Diseases. Web page, accessed October 10, 2026. https://tmsforacure.org/treatments/medications-treat-mast-cell-diseases/
  16. Fikree A, Chelimsky G, Collins H, Kovacic K, Aziz Q. Gastrointestinal involvement in the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):181-187. PMID: 28186368. https://doi.org/10.1002/ajmg.c.31546
  17. Engelbert RH, Juul-Kristensen B, Pacey V, et al. The evidence-based rationale for physical therapy treatment of children, adolescents, and adults diagnosed with joint hypermobility syndrome/hypermobile Ehlers Danlos syndrome. Am J Med Genet C Semin Med Genet. 2017;175(1):158-167. PMID: 28306230. https://doi.org/10.1002/ajmg.c.31545
  18. Harris CI. COVID-19 Increases the Prevalence of Postural Orthostatic Tachycardia Syndrome: What Nutrition and Dietetics Practitioners Need to Know. J Acad Nutr Diet. 2022;122:1600-1605. PMID: 35697326. https://pmc.ncbi.nlm.nih.gov/articles/PMC9186518/
  19. National Institute of Mental Health (NIMH). Help for Mental Illnesses. Web page, accessed October 10, 2026. https://www.nimh.nih.gov/health/find-help
  20. Kritas SK, Gallenga CE, D'Ovidio C, et al. Impact of mold on mast cell-cytokine immune response. J Biol Regul Homeost Agents. 2018;32(4):763-768. PMID: 30043558. https://europepmc.org/article/MED/30043558
  21. Niide O, Suzuki Y, Yoshimaru T, et al. Fungal metabolite gliotoxin blocks mast cell activation by a calcium- and superoxide-dependent mechanism. Clin Immunol. 2006;118:108-116. PMID: 16213796. https://doi.org/10.1016/j.clim.2005.08.012
  22. Hyvönen S, Lohi J, Tuuminen T. Moist and mold exposure is associated with high prevalence of neurological symptoms and MCS in a Finnish hospital workers cohort. Saf Health Work. 2020;11(2):173-177. PMID: 32596012. https://pmc.ncbi.nlm.nih.gov/articles/PMC7303478/
  23. Heinzow HS, Heinzow BGJ. Commentary: Severe sequelae to mold-related illness as demonstrated in two Finnish cohorts. Front Immunol. 2017;8:1694. PMID: 29270170. https://pmc.ncbi.nlm.nih.gov/articles/PMC5725433/
  24. Valent P, Akin C, Bonadonna P, et al. Proposed Diagnostic Algorithm for Patients with Suspected Mast Cell Activation Syndrome. J Allergy Clin Immunol Pract. 2019;7(4):1125-1133.e1. PMID: 30737190. https://pmc.ncbi.nlm.nih.gov/articles/PMC6643056/
  25. Castori M, Tinkle B, Levy H, Grahame R, Malfait F, Hakim A. A framework for the classification of joint hypermobility and related conditions. Am J Med Genet C Semin Med Genet. 2017;175(1):148-157. PMID: 28145606. https://doi.org/10.1002/ajmg.c.31539
  26. MedlinePlus (U.S. National Library of Medicine). Anaphylaxis. Web page, accessed October 10, 2026. https://medlineplus.gov/ency/article/000844.htm
  27. MedlinePlus. Fainting. Web page, accessed October 10, 2026. https://medlineplus.gov/ency/article/003092.htm
  28. MedlinePlus. Dislocation. Web page, accessed October 10, 2026. https://medlineplus.gov/ency/article/000014.htm

This is educational information only. Always consult licensed healthcare providers for personal medical advice.

Related free guide

The Overlap Trifecta →

Learn about the conditions

MCAS → POTS → hEDS →