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EDS, MCAS, And POTS: Unveiling The Hidden Connections

In medical education, emphasis is placed on the ability to think about the most likely causes of illnesses, referred to as “horses,” rather than rare cases, or “zebras.” This helps to diagnose common problems more quickly, but often leads to the overlooking of rare conditions. Therefore, the symbol of rare diseases, such as Ehlers-Danlos syndrome, is a zebra — to remind doctors of the importance of considering unusual cases. Now, let’s talk about this and other “zebras.”

MCAS, EDS, and PODS are three conditions that are often found together and can significantly impact a person’s quality of life. Although each of these conditions has its unique characteristics, they also share common features that can complicate diagnosis and treatment. Patients often spend years searching for the right diagnosis, visiting up to 20 doctors before finding a specialist capable of accurately diagnosing their condition. This is the “zebra effect.”

EDS (Ehlers-Danlos syndrome) is a group of genetic disorders affecting connective tissue. This can lead to joint hypermobility, stretchy skin, easy bruising, and other problems. It is important to note that there is hypermobility (HSD) not associated with genetics. More details on this topic can be found here: Discover the phenomenon of joint hypermobility and its associated risks.

It is fundamentally incorrect to consider EDS/HSD as diseases; it is more of a bodily characteristic that can lead to various illnesses.

MCAS (mast cell activation syndrome) is a condition in which mast cells, a type of immune cell, become hyperactive and release histamine and other chemicals excessively. This can lead to a wide range of symptoms, including allergic reactions, skin reactions, gastrointestinal problems, neurological issues, and more. More details on this topic can be found here: Living With MCAS: Symptoms, Diagnosis, And Modern Therapies.

PODS (postural orthostatic tachycardia syndrome) is a condition in which heart rate sharply increases upon transitioning from a lying position to a standing position. This can cause dizziness, pre-fainting state, and even loss of consciousness. More details on this topic can be found here: What is postural orthostatic tachycardia syndrome (POTS)?

Additionally, some symptoms of these conditions may overlap, while others are specific to certain conditions. A list of symptoms may help to suggest the presence of other conditions if one has already been diagnosed.

Common symptoms for all three conditions

  • Fatigue
  • Weakness
  • Dizziness
  • Abdominal pain
  • Diarrhea/excessive gas/constipation
  • Low blood pressure
  • Intolerance to physical exertion
  • Concentration problems
  • Headaches
  • Tachycardia

Unique symptoms for each condition:

Hypermobility (EDS/HSD):

  • Excessive joint mobility
  • Excessive skin elasticity
  • Ease of skin injury
  • Hernias
  • Chronic pain
  • Ease of bruising


  • Skin reactions (itching, redness, hives)
  • Gastrointestinal symptoms (abdominal pain, diarrhea, nausea)
  • Respiratory problems (wheezing, shortness of breath)
  • Redness around the eyes, eye irritation
  • Throat irritation
  • Dermatographia
  • Angioedema


  • Vertigo
  • Mild dizziness
  • Blurred vision

Common symptoms for combinations of two conditions


  • Chest pain

Hypermobility and POTS

  • Fainting
  • Poor sleep
  • Dizziness

Hypermobility and MCAS

  • GERD (gastroesophageal reflux disease)

Current prevalence estimates

  • Ehlers-Danlos syndrome (EDS): Prevalence estimates range from 1 in 500 to 1 in 20,000 people. This condition may be more common than previously thought, especially considering the wide variability of symptoms.
  • Hypermobility Spectrum Disorders (HSD): Estimates suggest the prevalence of hypermobility spectrum disorders may range from 10% to 20% in the general population. This means that every tenth person may exhibit signs of joint hypermobility.
  • Postural Orthostatic Tachycardia Syndrome (POTS): The prevalence ranges from 1 in 100 to 1 in 1,000 people. POTS is more common in women, especially in young women aged 15 to 50 years.
  • Mast Cell Activation Syndrome (MCAS): The exact prevalence is not established. Some studies suggest that up to 17% of the population may experience symptoms consistent with mast cell activation to some degree, but specific data on MCAS are less defined.

Issues that can lead to EDS/HSD, MCAS, POTS

Let’s examine common issues that may precede or trigger the development/manifestation of hypermobility (EDS/HSD), mast cell activation (MCAS), and postural orthostatic tachycardia syndrome (POTS):

  • Genetic factors: Heredity plays an important role in the development of these conditions. Genetic mutations affecting the structure of connective tissues, mast cell function, or cardiovascular system regulation can increase the risk of their development.
  • Congenital defects: People with congenital anomalies in the structure of connective tissue or immune system function are more susceptible to developing these conditions.
  • Environmental factors: Exposure to external factors such as infection, stress, lack of physical activity, improper diet, or prolonged exposure to mold- or heavy metal-contaminated environments can contribute to the onset and exacerbation of symptoms.
  • Chronic stress: Persistent stress, both emotional and physical, can negatively impact the immune system and overall health, increasing the risk of developing or exacerbating these conditions.
  • Hormonal imbalances: Hormonal imbalances, such as low estrogen or norepinephrine levels, can play a role in the onset of symptoms and exacerbate conditions, as hormones influence connective tissue functions and cardiovascular system regulation.
  • Organ and system damage and stress: Prolonged injuries, trauma, or even simple physical exertion can worsen symptoms or trigger exacerbations due to connective tissue instability, mast cell reactions, or blood pressure regulation disorders.

Interaction of conditions

Now let’s see how these conditions can affect each other, that is, why they occur together. Connective tissue plays an important role in many body functions, including the immune system, blood vessels, and joints. When connective tissue functions differently, it can lead to a range of problems, including EDS/HSD, PODS, and MCAS. Although each of these conditions has its unique characteristics, they also share common features that can make it difficult to determine which one is primary and which is secondary.

EDS/HSD as the primary condition

When EDS/HSD is the primary condition, it can lead to dysfunction in various body systems, which can then lead to the development of MCAS and PODS.

  • MCAS: Connective tissue damage in EDS may lead to mast cell activation, which can have a widespread negative impact on the mucosal barriers of the intestines and lungs and histamine release, exacerbating MCAS symptoms.
  • PODS: Joint instability, especially in the cervical spine, can cause irritation of the vagus nerve (cervicovagopathy), leading to dysfunction of the autonomic nervous system and exacerbation of POTS symptoms.

PODS as the primary condition

When PODS is the primary condition, it can lead to reduced blood flow, which can then lead to the development of MCAS and EDS.

  • MCAS: Changes in circulation and dysfunction of the vagus nerve can weaken mucosal barriers, promoting the release of inflammatory mediators and allergic reactions, exacerbating MCAS symptoms.
  • HSD: Dizziness with PODS can lead to more frequent dislocations and subluxations.

MCAS as the primary condition

When MCAS is the primary condition, it causes symptoms that can then lead to the development of HSD and PODS.

  • HSD: Mast cell hyperactivation in MCAS can lead to connective tissue damage, which is a hallmark of HSD.
  • PODS: Release of inflammatory mediators (including histamine) in MCAS can affect the cardiovascular system, causing tachycardia and other POTS symptoms.


MCAS, EDS, and POTS are complex and interconnected conditions that often occur together and significantly impact patients’ quality of life. Diagnosing and treating these conditions can be challenging and time-consuming, as they have many overlapping symptoms. Awareness of potential symptom intersections can help patients and physicians recognize and diagnose coexisting conditions, improving the approach to treatment and symptom management. Accelerating diagnosis and improving the quality of treatment require increasing knowledge and understanding of these conditions among healthcare professionals and society as a whole.