Surviving and Thriving with Chronic Illness

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Is it MCAS or a condition that mimics MCAS?

 Is mast cell activation syndrome (MCAS) the reason for your illness – OR – do you have a condition that mimics MCAS? This is a critical distinction because the underlying causes are likely different and treating it as a mast cell activation disorder in error can result in continual illness.

Many of us know these signs and symptoms all too well – flushing, sensitivities to foods, chemicals, and some scents, itching, poor temperature control, tachycardia, POTS, rashes, fatigue, headaches, even abnormal moods. Many of us can get some symptom improvement with antihistamines so we assume (and often our doctors assume) that it MUST be MCAS. Especially with the fairly new understanding that EDS (Ehlers-Danlos syndrome) with POTS (postural orthostatic tachycardia syndrome) is sometimes related to MCAS, I see many more patients and physicians are jumping to this conclusion.

See my post about the new tryptase gene here.

If it looks like a duck and quacks like a duck, it must be a duck, right? Unfortunately, no, and this assumption can lead to ongoing suffering by patients.

One key point to remember is that when mast cells are activated, tryptase will be released. If tryptase is negative, it should be checked again (preferably after a bout of symptoms including flushing). If it remains negative, this is not a mast cell problem at its heart.

Other mediators can be checked in the urine and blood when evaluating the patient for MCAS, and I’ve seen many patients with negative tryptase who were diagnosed with MCAS (incorrectly) because other mediators were measured as high in the face of negative tryptase. Doctors assumed it *must* be MCAS, despite the negative tryptase. The patients had all signs of symptoms of MCAS, they had POTS, and many of them had EDS – so they assumed it had to be MCAS. Let’s take a closer look at the other mediators that are often evaluated for MCAS to figure out what may be happening.

In addition to tryptase, other mediators usually measured include histamine, leukotrienes, prostaglandins, chromogranin A. We must understand that these mediators are NOT specific to mast cells. They can increase in many forms of inflammation. They are non-specific markers of inflammation.

For example, Prostaglandin D2 can be released by mast cells, but it can also be released by basophils, eosinophils, monocytes, macrophages, and neutrophils. High prostaglandin D2 does not support a diagnosis of MCAS, it only suggests inflammation in the broad term, and could involve most any inflammatory cell. Here is a chart of inflammatory cells and some of these popular mediators too often used to suggest MCAS:

Most inflammatory conditions are not specific to one cell. Inflammation is instead a cascade – one cell or chemical calls in other cells or chemicals and it becomes a party of inflammatory cells, inflammatory cytokines, and inflammatory chemokines. We must stay in the science, and analyze these test results very carefully to understand and treat this presentation as closely to the source as possible.


Katie, a recent patient at POTS Care is a great example of disability from misdiagnosis. She came to POTS Care with a diagnosis of MCAS from a mast cell expert, despite negative blood work (tryptase and other typical mediators were negative). She wore a facial mask, constantly fearing anaphylaxis upon exposure to chemicals. Katie’s life changed dramatically when she was set free from this diagnosis, and inflammation was treated differently. You can read her story here.  I don’t believe she is alone in her presentation nor misdiagnosis (even my kids and I also went down the same road for a while).

We must remember that EDS/POTS/MCAS are indeed seen together, but that other forms of inflammation can mimic MCAS, and joint hypermobility can occur for other reasons besides genetic disorders of collagen. Until genetics has fine-tuned our ability to locate the specific genetic attributes, we must carefully analyze each case individually. Only then can answers be found, and the appropriate treatment begun.

This is a challenging journey, my friends, but we CAN get answers.

Gentle hugs,

Dr. Diana

If you have high levels of inflammation, don’t forget the role of your vagus nerve (the anti-inflammatory pathway of the body)! This is a key part of recovery for many and has been recently awarded a patent:


The Driscoll Theory covers MCAS, and how mast cells may not be the true underlying problem for many. The Driscoll Theory is here.


Dr. Diana Driscoll is now working full time at POTS Care. A recovered POTS/EDS patient, and mom of children who have now also recovered, she has been instrumental in finding the underlying medical conditions responsible for this and other potentially disabling “invisible” illnesses. 


Stone K, Prussin C, Metcalfe D. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl2):S73-S80.

Kovalszki A, Weller P. Eosinophilia in mast cell disease. Immunol Allergy Clin North Am. 2014 May;34(2):357-364.

Frieri M. Mast cell activation syndrome. Clinical Reviews in Allergy and Immunology (2015). Doi:10.1007/s12016-015-8487-6.

Siracusa M, Kim B, Spergel J, Artis D. Basophils and allergic inflammation. J Allergy Clin Immunol. 2013 Oct;132(4):789-788.

Baptista-dos-Reis R, Muniz V, Neves J. Multifaceted roles of cysteinyl leukotrienes in eliciting eosinophil granule protein secretion. Biomed Res Int. 2015;2015:848762.

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