What is MCAS what is the connection to hypermobility/ EDS?

What is MCAS and Mast Cells ?

Mast cells are a type of immune cell that play a crucial role in protecting the body. They are part of our innate immune system, acting as first responders to injury, infection, or allergens.

• Mast cells are found throughout the body, especially in the skin, gut, lungs, heart, connective tissue, and around nerves and blood vessels.

• They contain tiny storage sacs (granules) filled with chemical mediators such as histamine, tryptase, prostaglandins, leukotrienes, cytokines and many more.

• When triggered, mast cells degranulate, releasing these chemicals into the surrounding tissue and bloodstream.

This is a normal process that helps the body respond to threats for example, releasing histamine to make blood vessels leaky so immune cells can reach an infection site, or to create swelling that helps contain injury.

Mast cells can behave abnormally. Instead of responding only to genuine threats, they release mediators too often, too strongly, or at the wrong time. This “misfiring” leads to chronic, multi-system symptoms because mast cells influence so many parts of the body/brain.

Simply put, mast cells are found in our bodies, in the connective tissues in our skin and mucous areas. These are our ‘allergy’ cells and the first responders to perceived and real attacks on the body. They are a very important part of our immune system for dangerous diseases, injuries, or infections. For some of us, mast cells can lead to over-sensitivity and over-reaction, thus releasing too much histamine alongside other chemicals. This is called de-granulation. Histamine combined with other chemicals allow the blood flow to increase to the area of infection or injury thereby swarming to counteract the danger to the rest of the body which can build up to a storm, termed a cytokine storm. This, unfortunately, leads to less blood flow for good functioning of local organs.

MCAS is considered a rare condition as it is hard to diagnose but often occurs with EDS HSD POTS.

What does the research say?

Studies suggest a connection between MCAS, Ehlers-Danlos syndromes (EDS/HSD), and autonomic nervous system disorders (dysautonomia) such as POTS. This cluster is sometimes referred to as the “trifecta” seen in many patients. Some think more of septad as most have gastrointestinal issues 'ibs', autoimmune and neurodivergence (Autism ADHD Dyspraxia Dyslexia TS )

Research highlights that connective tissue may influence mast cell behaviour and mast cells themselves release substances that can affect connective tissue, potentially worsening hypermobility symptoms.

• Increasing evidence links mast cells to even more issues like chronic urticaria and might suggest an immunological factor in hypermobility disorders.

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  MCAS is still under-recognised, partly because symptoms vary greatly between individuals and partly because laboratory tests are rarely positive as there is such a short time between an attack and testing for a positive result (e.g., histamine, tryptase, prostaglandins) are not always reliable. However management and support can make MCAS manageable for many people but needs empathy, belief and many different approaches.

  
  

  How mast cells affect you

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  If you are sensitive to pollen, you may suffer from hay fever seasonally in spring, drippy nose syndrome called rhinitis which makes your nose runny and makes you feel like you need to blow it, and at other times the nose is stuffy and you might be constantly sneezing or even wheezing (i.e, pseudo asthma). If this gets more severe, the throat might close up and panic ensues. Itchy eyes to hot burning orbs for eyes which can also stream with tears.

  NOTE: Mast cells are found throughout the body, MCAS is a multi-system condition. Symptoms often wax and wane, making it difficult to predict or manage but they also can improve.

  

  
  

  Common symptoms :

  The environment and stress factors can also impact on our sensitive physiology and this in turn may lead to MCAS flares. Other factors are temperature, water, foods, illness, injuries, perfumes and medications.

  
  

  Our skin becomes itchy with rashes or hives and can sometimes swell up in different areas or whole limbs, and this is called angioedema and varies in severity. For others it can lead to severe pain in the stomach and belly, and even fever, vomiting, bloating, wind, constipation, or diarrhoea.

  
  

  Blood pressure can drop leading to racing heart, as if we had just run for our lives from an incensed beast, with adrenaline, other enzymes, hormones and chemicals overexerting themselves which can lead to increased palpitations and can also cause brain fog and dizziness.

  
  

  • Blood pressure drops

  • Flushing, tingling in mouth

  • Hot and itchy skin surface, hives wheals

• Streaming nasal fluids, eyes

• Swelling under skin from fluid (idiopathic angiodeoma) feels heavy

• Constipation / Diarrhoea

• Severe Bloating, stomach cramps

• Coughing pseudo asthma

• Feeling unwell

While part of the treatment for MCAS is using antihistamines and there are different types of antihistamine blockers which inhibit the histamine receptors. Be aware of your triggers.

It might not always be seasonal and can be induced by anxiety, food, exercise, temperatures, mould, alcohol (e.g., salicylates). There are also special creams to use topically on localised skin areas. H2 antihistamines are used more long-term. Stabilisers are medications cromolyn sodium and are good stabilisers for MCAS but this will be in line with a medical practitioner. During acute stages of unexpected serious attacks like anaphylaxis affecting airways and breathing for example epi pens might be advised.

Amongst the triggers are a variety of different foods, exercise, chemicals, fragrances and stress. Many sufferers struggle to identify their triggers and continue to discover new triggers for many years after diagnosis. (EDS ) Ehlers-Danlos syndromes and hypermobility Spectrum Disorders (HSD) often have MCAS/MCAD which might be part of a bigger picture like dysautonomia.

Interestingly MCAS is also associated with neurology conditions/disorders like neurodivergence, headaches / migraine and psychiatric disorders like depression, anxiety, dysautonomia and more . it also has associations to infections like viruses, bacteria, fungi and parasites. So Lyme Disease, Long Covid can also be affected with MCAS flares.

Refs:

Green J 2019, Presentation Green J 2020 webinar Assert

Filcek, M. Discovery of Pathophysiological Mechanism Underlying Symptoms of ASD and PTSD: The Role of Mast Cell Hyperactivation and Histamine Metabolic Imbalance.

https://www.peeref.com/abstracts/10015/-discovery-of-the-mechanism-of-covid-19-sirs-and-sepsis-defense-and-treatment-mast-cells-and-histamine-storm-an-overlooked-aspects-in-covid-19-and

Quigley EMM, Noble O, Ansari U. The Suggested Relationships Between Common GI Symptoms and Joint Hypermobility, POTS, and MCAS. Gastroenterol Hepatol (N Y). 2024 Aug;20(8):479-489. PMID: 39205953; PMCID: PMC11348541.

Weinstock LB, Nelson RM, Blitshteyn S. Neuropsychiatric Manifestations of Mast Cell Activation Syndrome and Response to Mast-Cell-Directed Treatment: A Case Series. J Pers Med. 2023 Oct 31;13(11):1562. doi: 10.3390/jpm13111562. PMID: 38003876; PMCID: PMC10672129.

This has been updated since 2020 and my original Ode to MCAS.

ODE TO A MAST CELL by Jane Green MBE 2021

Cytokine storms, histamine’s release,

A cascade of signals that never cease

Swelling, blisters, redness, pain

The cycle ignites then flares again.

Not only genetics, but triggers combined,

Environment, stressors, immune intertwined.

Not just in the skin, but body and brain,

Guts, bowels, heart all tied in the chain

No refuge in sight, no soothing reprieve

Sleep fractured by welts that burn and seethe.

A hidden agenda, relentless within

Mast cells whisper then riots begin.

Key words Neurodivergence Hypermobility Ehlers-Danlos syndromes, HSD EDS, Autism ADHD Dyspraxia Neurodivergent allergies MCAS histamine Mast Cells antihistamines dysautonomia

Jane Green MBE