What tests should my Doctor order to test for Mast Cell Activation Syndrome?
Nothing kicks up despair more than being told that “nothing is wrong with you”; when you know something is concerningly off kilter.
If one is anxious, restless, wheezy, sneezy, swollen, itchy, has malaise, has brain-fog, bloated, crampy, has rashes, and chemically sensitive or any combination of these issue then I begin to suspect mast cell disease.
But you will see arriving at a diagnosis is much more.
Mast cells are immune cells that populate throughout the body. They are part of the innate immune system. Our body keeps a reserve of them to respond to environmental and infectious threat. In the rested state they are loaded with tiny vesicles that look like purplish water balloons on a pathology slide. If a receptor on the surface of the mast cell binds to a protein; then these vesicles burst (a.k.a.) degranulate. And release what are called mast cell mediators that generate all kinds of responses in the body.
These receptors may be activated by the acquired immune system. Such as in the case where someone has an IgE allergy to corn. At the moment the corn allergy developed their immune system developed a whole army of IgE antibiotics to a protein sequence that comes from corn.
Once that corn protein comes on the scene (or something that mimics that protein aka molecular mimicry) then the protein binds bind to the IgE antibody which plugs into the mast cells for its immune response. More on that later. Other similar scenarios may exist with IgG antibodies, and T-cells (i.e. in autoimmune disorder or chronic infection). Also realize IgE antibodies can develop against mold and mycotoxin and many other environmental agents.
By both direct activation and cell-mediated activation of receptors on the surface of the mast cells, degranulation of vesicles within mast cells leads release of mast cell chemical mediators (I’ve heard estimates of 390).
More detailed discussion about mediators here.
These mediators include serotonin, leukotrienes, prostaglandins, heparin, and proteases.
For most these reactions go on behind the scenes all day long and not much is noticed.
Yet for the chemically sensitive, chronically infected, environmentally toxin-burdened, autoimmune patient; these mast cells may be degranulating to the point of developing a condition called Mast Cell Activation Syndrome (MCAS).
There are variants of MCAS called primary MCAS, Secondary MCAS, or idiopathic mcas.
MCAS falls under an umbrella of Mast Cell Related Diseases that include includes systemic mastocytosis (SM), cutaneous macrocytosis (CM), smoldering mastocytosis (SSM), advanced disease variants, and hereditary alpha tryptasemia (HaT). (Gülen et al., 2021; Molderings et al., 2011)
Histamine Intolerance (HT) or Histamine Sensitivity is not considered tightly in this group. HIT is more a condition of reacting to histamine rich foods and may a result of Diamine Oxidase (DAO) deficiency.
For most these reactions go on behind the scenes all day long and not much is noticed.
Yet for the chemically sensitive, chronically infected, environmentally toxin-burdened, autoimmune patient; these mast cells may be degranulating to the point of developing a condition called Mast Cell Activation Syndrome (MCAS).
There are variants of MCAS called primary MCAS, Secondary MCAS, or idiopathic mcas.
MCAS falls under an umbrella of Mast Cell Related Diseases that include includes systemic mastocytosis (SM), cutaneous macrocytosis (CM), smoldering mastocytosis (SSM), advanced disease variants, and hereditary alpha tryptasemia (HaT). (Gülen et al., 2021; Molderings et al., 2011)
Histamine Intolerance (HT) or Histamine Sensitivity is not considered tightly in this group. HIT is more a condition of reacting to histamine rich foods and may a result of Diamine Oxidase (DAO) deficiency.
This article really focuses more on MCAS.
When mast cells are active the symptoms are vast starting from itchy, rash, wheezy, sneezing, brain-fog malaise, swelling, mood changes, focus changes, anxiety, insomnia, and so much more.
This post doesn’t do justice to the wide variety of MCAS symptoms.
Yet I will try.
Mast cell activation in the brain can lead to:
· Brain Fog
· Confusion
· Difficulty multitasking
· Dizziness
· Dysautonomia
· Brain fatigue
· Headache
· Insomnia
· Irritability
· Lightheadedness
· Inability to find the right words
· Memory loss
This is a scenario called brain inflammation (neuroinflammation)
And mast cell activation outside of the brain can cause:
· Body fatigue
· Sinus congestion
· Cough/wheezing
· Skin rashes and itching
· Edema
· Palpitations
· Paresthesia
· Temperature dysregulation
· Flushing
· Low blood pressure
· Bloating
· Reflux
· Diarrhea
· Abdominal pain and discomfort
Getting an MCAS diagnosis
Everybody loves a test that is accurate, reliable, and affordable to prove something right?
Well unfortunately when it comes to mast cell issues, we can’t check all those boxes.
How do you explore whether or not your mast cells are a culprit?
There are blood tests and urine tests to establish a Mast Cell Activation Disorder diagnosis.
Yet the criteria for a Mast Cell Activation Syndrome diagnosis is debatable. There is are two widely accepted criteria called the Valent criteria and Molderings Criteria. Proper diagnosis usually includes symptom presentation, testing, and response to treatment.(Gülen et al., 2021; Molderings et al., 2011)
Symptomatic criteria
Take the Moldering Criteria for example. Symptoms of MCAS must effect a minimum of 2–4 organ systems. see image below.
Laboratory criteria
Then there is lab testing.
The most widely accepting biomarker of MCAS is serum tryptase . In fact “20% +2 “ criteria of tryptase is the gold standard of diagnosis.
Serum tryptase, chilled is taken at baseline (when asymptomatic) and again when symptomatic. The symptomatic test must be done within 2–4 hours of symptom activation. It is available at labcorp and quest .
It is important to note that persistent elevated serum tryptase that is > 20 ng/mL in two or more specimens should be referred for a discussion related to potential biopsy to screen for systemic mastocytosis ; a quite serious mast cell disorder.
The 20%+2 criteria means that elevation of the serum tryptase level by at least 20% over the individual baseline plus 2 ng/mL absolute (e.g., from 15 ng/mL to at least + 3 + 2 ≥20 ng/mL) within a 2–4 h window after the reaction. (Valent et al., 2019)
Other tests that may be used to strengthen diagnosis:
1. 24-N-methylhistamine Urine , frozen. Available at Quest
2. Histamine, Plasma, frozen. Available at Labcorp and Quest
3. Prostaglandin D2, plasma chilled Available at Labcorp and Quest
4. Chromogranin A , Serum, must avoid PPIs for 5 days prior to testing. Available at Labcorp.
5. Prostaglandin D-2, urine, frozen, Random, Available at Labcorp.
6. Prostaglandin D2, Urine, frozen, 24-hour. Available at Quest
There are others: such as plasma heparin and urine leukotrienes B4, C4, D4, and E4.
Perhaps the most overlooked test to order a helpful test to order is a biopsy stain of CD117 cells that may be ordered as part of a endoscopy. In fact, even if an endoscopy was done years ago the pathology lab can often add this tissue. This can be done by a physician contacting the pathology lab that holds the tissue and placing an order for the stain. Or it can be ordered by the gastroenterologists who ordered the endoscopy. The CD117 stain indicates density of mast cells in the intestinal lining. High amounts are indicative of a mast cell disorder. Note mast cell related biopsies are often done in the bone marrow and possibly also skin when systemic mastocytosis is suspected.
However, unless in an active flare these tests often come back negative. So, it often makes diagnosis murky.
Treatment Criteria
A third criteria that is used is therapeutic response to mast cell targeted drugs. These drugs include antihistamines, leukotriene modifiers, cyclooxygenase inhibitors, and Mast cell stabilizing-stabilizing agents.
other criteria
Seasoned providers that deal with MCAS then may pursue further details and testing to identify primary (genetic) or secondary drivers of mcas. Mast cells can become activated by environmental triggers (i.e. mycotoxins, chemicals, hormones, stress, infections (yes Covid), and more). It is important to note there is often a co-occurring MCAS disorder with hypermobile Ehlers-Danlos syndrome (hEDS) or postural orthostatic tachycardia syndrome (POTS).
Getting a diagnosis of MCAS is quite laborious and sometime resources are simply not available to make a proper diagnosis and a “soft” diagnosis is made based on response to treatment. While not preferred, this is sometimes the only practical option for some.
I am seeing MCAS patients and while I am not an allergist or immunologist or neuroendocrinologist; I consider myself an extension of their team. I refer to these specialists and develop a team approach to managing this condition. I also help sleuth out secondary causes of MCAS activation through careful history taking and functional medicine testing. Find out more at www.soundintegrative.com also at http://ada I would be amiss to not mention Dr. Jessica Pizano who taught me a lot about MCAS and certain patients (you know who you are) who started me on this journey of understanding this condition.
References:
Gülen, T., Akin, C., Bonadonna, P., Siebenhaar, F., Broesby-Olsen, S., Brockow, K., Niedoszytko, M., Nedoszytko, B., Oude Elberink, H. N. G., Butterfield, J. H., Sperr, W. R., Alvarez-Twose, I., Horny, H. P., Sotlar, K., Schwaab, J., Jawhar, M., Zanotti, R., Nilsson, G., Lyons, J. J., … Valent, P. (2021). Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review. Journal of Allergy and Clinical Immunology: In Practice, 9(11), 3918–3928. https://doi.org/10.1016/j.jaip.2021.06.011
Molderings, G. J., Brettner, S., Homann, J., & Afrin, L. B. (2011). Mast cell activation disease: A concise practical guide for diagnostic workup and therapeutic options. In Journal of Hematology and Oncology (Vol. 4). https://doi.org/10.1186/1756-8722-4-10
Valent, P., Bonadonna, P., Hartmann, K., Broesby-Olsen, S., Brockow, K., Butterfield, J. H., Triggiani, M., Lyons, J. J., Oude Elberink, J. N. G., Arock, M., Metcalfe, D. D., & Akin, C. (2019). Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome. In International Archives of Allergy and Immunology (Vol. 180, Issue 1, pp. 44–51). S. Karger AG. https://doi.org/10.1159/000501079