Mast Cell Activation Syndrome

This blog is about corn allergy, but it’s no secret by now that I don’t “just” have a corn allergy. I also have a mast cell disorder, and that is likely the reason my corn reactions are so severe and sensitive. It is also the reason why I react to so many other things besides corn. More and more people with corn allergies are looking into mast cell disorders for themselves, so I figure it’s high time for me to discuss them here.

What Are Mast Cell Disorders?

Mast Cell Activation Disorders (MCAD) are abnormalities of your mast cells. Mast cells are a very important part of your immune system and are involved in your body’s defense against pathogens. They protect your body from invaders by releasing inflammatory factors including histamine, such as in an allergic reaction. When you have too many mast cells, or they are malformed or dysfunctional, you can have allergic reactivity without the same immunological pathways involved in allergies. There are two types of mast cell activation disorders: Mastocytosis, and Mast Cell Activation Syndrome (MCAS).

 

What is the difference between MCAD and an Allergy?

In allergy, IgE stimulates the mast cells to release inflammatory factors (degranulate). If an allergen hits your bloodstream, it will “dock” to the IgE on your mast cell. This particle is called an “epitope”. The epitope is usually a protein but can be a sugar or something else. 1, 2, 3 If the epitope binds to the IgE that is coating your mast cell, the mast cell will degranulate. Both the initial compounds released by mast cell degranulation, and the inflammatory mediators released later can create life-threatening clinical symptoms including multi-system events such as anaphylaxis.3

But you can have reactions from mast cell degranulation for other reasons.

If you have too many mast cells you may experience mast cell degranulation due to the increased number of cells making an increased amount of inflammation, as well as due to abnormalities in the cells causing instability. This is mastocytosis. 4

If you have mast cell activation syndrome, you have a normal number of mast cells that behave badly. In MCAS, mast cell degranulation can happen without IgE binding anything at all. It can happen from physical stimulus, from hormones, or the food particle (epitope) can stimulate the mast cell directly. 5, 6, 7, 8

Now that I’ve discussed the two types of MCAD briefly, the rest of this write-up will discuss MCAS almost exclusively.

The Practical Value of an MCAS Diagnosis

I strongly feel that in the very early stages of corn elimination, there is little practical value to an MCAD diagnosis, and pursuing it rather than focusing on corn elimination can actively harm you or your allergic loved one.

Corn is in everything. If you know you react to corn, and you feel like you are reacting to “everything,” it could still just be corn you’re reacting to. Your organic veggies are probably sprayed if you aren’t getting them direct from a farm. If you get your food from cans, the bpa-free can lining can be made from corn. Your plain dry salad at the restaurant was likely treated with citric acid to keep it from browning. Your hair products definitely contain corn derivatives such as glycerin and ethanol. The actual air contains corn if you’re in heavy traffic, because ethanol from corn is in auto fuel. It’s “supposed to” be unusual to react to these traces, but the 7,000+ members of the Facebook Corn Allergy and Intolerance group do not find it unusual at all. Rather, we find it unusual to NOT have to worry about it with corn allergy.

There could be some arguments made that there’s no way these reactions to traces follow the same immunological pathway as an allergy. That could be true. But for practical purposes, the trigger is still corn, and you need to avoid those triggers. Even if you still have triggers that aren’t corn, eliminating the ones you can avoid will only help your reactivity.

Learning how to avoid corn is a consuming and intense process. Splitting your focus from elimination of corn to also trying to pursue what is a very difficult diagnosis (more on that below) can block your progress and recovery from inflammation, while getting that diagnosis will not change the fact that you need to avoid all of these things. Also, pursuing treatment for MCAS when you are not fully aware of all the places corn can hide can actually expose you to MORE corn which will make everything worse.

The point at which it’s time to start suspecting mast cell disease is when you have truly eliminated every possible source of corn that you can–both airborne and ingested–and you are still having reactions, or you are reaction free but not eating a balanced diet or not able to live life fully, e.g. are shut into your house to avoid airborne reactions.

This is important: MCAS reactions still have triggers. These triggers may be inside your own body such as to your own stress hormones, or may be to seemingly impossible things like being jostled, or weather or temperature changes. But there are still triggers. And it is very important to identify and avoid your triggers as much as possible. Many mast cell patients and support groups focus on medicating your reactions away, and this may be your only choice. But it’s important to do as much as possible to avoid reactions in addition to taking medication.

There are medications you can take to reduce reactivity, but none of them will completely eliminate the need to avoid your triggers, and many of them have side effects. These side effects can range from merely difficult (weight gain), to serious if long term (dry mouth leading to poor dental health) to permanently life-altering (organ dysfunction leading to bypass or removal). From my personal experience, the progression from no side effects to annoying ones to “well this is becoming an actual problem” is quite fast. So please, start with avoiding as many triggers as you possibly can.

Many people with MCAS end up heavily medicalized with ports, frequent IV infusions, feeding tubes, and other permanent medical fixtures. There is nothing wrong with having these things if you need them, but each of them changes your life a little and can put you at risk for medical complications.  Some people will need these procedures and fixtures no matter what they do. However I believe that but focusing on pharmaceuticals without considering triggers is definitely a good way to end up in the fast lane for them.

The purpose of diagnosis is not necessarily treatment: The most common treatments for MCAS are the same as for allergies, and you can do these treatments without a diagnosis. The purpose of a diagnosis is really about safety in medical treatments, and preparedness for health conditions requiring specialists. If you have MCAD, you are at higher risk for medical emergencies and unplanned medical procedures. These events put you at risk of a reaction both because of corn in medical supplies and because you are likely to be sensitive to more than just corn, so you need doctors to understand and plan for the possibility of reactions. You also are at risk for comorbidities such as EDS9, Dysautonomia9, Eosinophilia 10, Immunodeficiency11, and many other conditions You will need a team of specialists to manage these, and all of them need to understand the risks and effects of your mast cell disorder.

I’ve now spent quite a lot of time telling you to not go running off looking into mast cell disease too quickly, and then a small amount of time telling you how important it is to make sure you have a care team in place to handle mast cell disease if you have it. I realize these things may seem at odds. There is some finesse to deciding where your efforts are best placed. The question to ask yourself is whether a diagnosis of MCAS would change your course of action in the immediate future. If the answer is yes, then it’s time to look at it. If, however, you are looking at MCAS because you think a diagnosis is going to lead to a “cure” or somehow stop you having to avoid corn, think again. An MCAS diagnosis will NOT allow you to eat whatever you want. Ask literally anyone with a diagnosis of MCAS and they’ll tell you.

Getting Diagnosed With MCAS

Mastocytosis has a very different and more well understood set of diagnostic criteria than MCAS. Diagnosis for mastocytosis involves a bone marrow biopsy to check for an increased number of mast cells, or mast cells with specific abnormalities. A blood test for tryptase may also be done as a preliminary check.

When many doctors “test” for mast cell disease, they are thinking of mastocytosis, and they are thinking of tryptase. They will often check for tryptase and say that a low  baseline (meaning not during a reaction) tryptase level “rules out” MCAD. This is incorrect.  Baseline tryptase is normal in most MCAS patients and 10% of Systemic Mastocytosis patients.

In fact, to be clear, there are NO tests for MCAS that truly “rule it out.”  The mediators being tested for are not produced all of the time, even if you have MCAS.  So positive tests prove a positive diagnosis, but negative tests do NOT prove that you do not have the condition.  They just prove that either your sample was messed up (in the case of the temperature sensitive mediators), or that you were not producing the mediator *at that time.*

The diagnosis of MCAS involves:

  • Ruling out IgE allergies to your reaction triggers.
  •  Ruling out mastocytosis.
  •  Showing that mast cell degranulation is what is causing your symptoms.
  •  Showing that treatments which inhibit histamine have a positive effect on your symptoms.

Basically, most of the diagnosis for MCAS is based on clinical symptoms, and lab tests are all about “proving” that your mast cells degranulating are correlated with these symptoms. The lab tests can be quite tricky though- tryptase elevated by 20% over baseline after a reaction is the preferred diagnostic mediator, but many people with MCAS find that they do not have elevated tryptase even after a reaction.

If elevated tryptase is not seen, the other mediators that can be checked are prostaglandins and histamines. The testing for these is even harder because they are very temperature sensitive and have very short half-lives in the body. The typical tests are prostaglandins and methlyhistamine as a 24-hour urine collection.

This collection is comical and maddening because the samples must be kept cold at all times. The mediators being looked for, especially prostaglandins, denature in mere minutes at room temperature. Proper specimen handling involves not only chilling your collection jug, but actually chilling each round of collected urine before pouring it into the main container. Then keeping it on ice all the way to the lab, and hoping that no lab tech leaves the sample on the counter for a few minutes while they do something else, because that will undo all your hard work. There are pages and pages of advice in the mast cell support groups on how best to perform your 24 hour urine collections. Doing at least one (usually more like three or more) of these collections is a rite of passage for the suspected mastie.

There are other mediators that can be used to indicate mast cell activity, but they aren’t as widely accepted by clinicians, so it would be best to get your diagnosis based on tryptase, prostaglandines, or histamine/methylhistamine.

More info on diagnostic criteria and testing:

The Mastocytosis Society: Overview, Diagnosis, Definitions and Classification.
Initial diagnosis and treatment of mast cell activation disease: General notes for guidance
Mast Cell Disease Fact Sheet
The Provider Primer Series: Mast cell activation syndrome (MCAS)

Treatment

As I’ve said at length in this post already, the absolute BEST treatment for MCAS is to identify and avoid triggers. Identifying triggers is a matter of observation, but if your trigger is stress or cold weather, it’s not like you can really avoid those things entirely. You can likely arrange your life to some degree to limit exposure though. Triggers like scents, chemicals and detergents are a very important one to look into  though. Many people with MCAS and MCS have issues with even the “green” cleaners many people use in their homes, and if you can replace these with safer-for-you products, you can make your home a safe haven and reduce your overall reactivity that way.

I am going to write a couple paragraphs about healing protocols, but mostly to tell you that I’m not going to talk about them yet. Ideally, it would be great if we could identify a cause for destabilized mast cells and treat the cause rather than the symptoms. However this is easier said than done.  People with MCAS have had success with looking into and addressing:  gut dysbiosis, mold toxicity, heavy metal toxicity, bacterial, fungal or parasitic infection, autoimmunity, and many other things. Many people use healing protocols to address these issues and see improvement in their reactivity. These healing protocols are not one size fits all, and are often based in a lot of guesswork without any clear scientific evidence that they work. Which is okay for the most part: you don’t need studies if something is helping you. But while you look for the the right healing protocol for yourself, there is a strong chance to fall into a very weird part of the internet, and try a bunch of things and probably waste a bunch of time and money.

I actually firmly believe that no treatment for MCAS should be enacted without some level of complementary therapy,  at the very least to support your body and maintain the best health you possibly can. I just think that that entire topic is complicated, has many pitfalls, and requires its own post after a lot more research.  Please do your own research and pursue any healing protocols you want to that you know won’t harm you and think may help you.  I’m just not going to discuss or recommend anything just now.

Pharmaceutical treatment for MCAS is pretty much the same as for allergies, just in higher doses. A daily h1 antihistamine (usually non-drowsy antihistamines like zyrtec, allegra, claritin) and h2 antihistamine (zantac, pepcid, tagamet) are typically the first thing that is prescribed. Often both will be in much higher doses than would be normal for “just” allergies, however. Many people take 4 or more times the normal dose of daily h1 antihistamines, and will take more than one daily antihistamine in that high of a dose. Asthma meds such as xolair and singulair are often prescribed for MCAS. Mast cell stabilizers such as cromolyn, quercetin, and multifunction drugs like ketotifen can also be very helpful.

Cromolyn Sodium is a mast cell stabilizer that can help many people when taken orally (Gastrocrom), ihhaled (Intal), or nasally (Nasalcrom). This medication can take a bit of time to work and can even cause more reactions when you are first using it. It also needs to be taken with precise timing for maximum effectiveness.

Quercetin is an over-the-counter plant flavinoid that is actually a powerful mast cell stabilizer. This supplement is almost always derived from legumes. Even when it is derived from a plant that *sounds* like a tree, typically if you check the botanical family the plant is  a member of, it’s a legume still. So if you have to avoid legumes (I do because of g6pd deficiency), you will probably not be able to find safe quercetin.

A daily antihistamine, mast cell stabilizer, and leukotriene inhibitor called ketotifen is a relatively safe med that helps a lot of people with MCAS significantly. It isn’t well known and isn’t available in a premade format in the USA and must be compounded. The most common use of ketotifen is for asthma, however there have been many findings of it being helpful for many kinds of mast cell response including urticaria13,  and food allergy14. Typical dose for MCAS starts at 1mg twice daily, and then the dose is increased weekly by 1mg twice daily to maximum effectiveness, which should not be more than 6mg per dose. You can also increase to up to 4x per day at the max of 6mg per dose.12 The main side effects of ketotifen are sedation, which frequently starts out strong and decreases over time, and weight gain. Ketotifen may take up to a month to reach full effectiveness although many people see results sooner than that.

Ketotifen is definitely my “magic drug.” It’s helped me exist in the world and be able to leave my house again.

There are many more medications that can be used to treat MCAS- those are just a few of the most common ones with the fewest side effects. For anything else I’ll defer to MastAttack.

Here is a post I wrote about precisely what meds I take to treat my reactions.

References
1) Structural biology of allergens, Aalberse, Rob C., Journal of Allergy and Clinical Immunology , Volume 106 , Issue 2 , 228 – 238 Link. Summary: IgE antibodies can bind to non-peptidic (non-protein) allergens.

2) Aalberse, R. C. and Crameri, R. (2011), IgE-binding epitopes: a reappraisal. Allergy, 66: 1261–1274. doi:10.1111/j.1398-9995.2011.02656.x Link. Summary: General discussion on IgE binding.

3) Vaughan K, Peters B, Larche M, Pomes A, Broide D, Sette A. Strategies to Query and Display Allergy-Derived Epitope Data from the Immune Epitope Database. International archives of allergy and immunology. 2013;160(4):334-345. doi:10.1159/000343880. Link. Describes methods for searching non-peptidic (non-protein) epitopes in a database.

4) Akin C, Scott LM, Kocabas CN, et al. Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with “idiopathic” anaphylaxis. Blood. 2007;110(7):2331-2333. doi:10.1182/blood-2006-06-028100. Link. Summary: Description of effects of mastocytois.

5) Akin C, Metcalfe DD. Mastocytosis and mast cell activation syndromes presenting as anaphylaxis. In: Castells MC, editor. Anaphylaxis and hypersensitivity reactions. New York: Humana Press; 2011. p. 245-56. https://link.springer.com/chapter/10.1007%2F978-1-60327-951-2_15 Summary: Description of mast cell reactions.

6) Silva I, Carvalho S, Pinto PL, Machado S, Rosado Pinto J. Mastocytosis: a rare case of anaphylaxis in paediatric age and literature review. Allergol Immunopathol (Madr). 2008 May-Jun;36(3):154-63. http://www.ncbi.nlm.nih.gov/pubmed/18680704 Summary: Decriptions of mast cell reactions.

7) Jennings S, Russell N, Jennings B, Slee V, Sterling L, Castells M, et al. The Mastocytosis Society survey on mast cell disorders: patient experiences and perceptions. J Allergy Clin Immunol Pract. 2014 Jan-Feb;2(1):70-6. http://www.ncbi.nlm.nih.gov/pubmed/24565772 Summary: Descriptions of mast cell reactions.

8) Boyden SE, Desai A, Cruse G, Young ML, Bolan HC, Scott LM, et al. Vibratory Urticaria Associated with a Missense Variant in ADGRE2. N Engl J Med. 2016 Feb 18;374(7):656-63. http://www.ncbi.nlm.nih.gov/pubmed/26841242 Summary: Descriptions of mast cell reactions.

9)Ingrid Cheung, Peter Vadas, A New Disease Cluster: Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome, and Ehlers-Danlos Syndrome, In Journal of Allergy and Clinical Immunology, Volume 135, Issue 2, Supplement, 2015, Page AB65, ISSN 0091-6749, https://doi.org/10.1016/j.jaci.2014.12.1146. (http://www.sciencedirect.com/science/article/pii/S0091674914029273) Summary: Connection between EDS, MCAS, POTS.

10)Kovalszki A, Weller PF. Eosinophilia in Mast Cell Disease. Immunology and allergy clinics of North America. 2014;34(2):357-364. doi:10.1016/j.iac.2014.01.013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083463/ Summary: Connection between MCAS and eosinophilia.

11) Szczawinska-Poplonyk A. “An Overlapping Syndrome of Allergy and Immune Deficiency in Children”. Journal of Allergy. 2012: 1–9. doi:10.1155/2012/658279.https://www.hindawi.com/journals/ja/2012/658279/ Summary: Connection between MCAS and Immunodeficiency.

12) Afrin, L. B. (2013). Presentation, diagnosis, and management of mast cell activation syndrome. In Mast Cells: Phenotypic Features, Biological Functions and Role in Immunity (pp. 155-232). Nova Science Publishers, Inc. https://www.novapublishers.com/catalog/product_info.php?products_id=42603 Summary: MCAS treatment including ketotifen dosage.

“Ketotifen in the management of chronic urticaria: resurrection of an old drug“
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309375/ Summary: Ketotifen to treat urticaria.

Effect of ketotifen premedication on adverse reactions during peanut oral immunotherapy
https://aacijournal.biomedcentral.com/articles/10.1186/1710-1492-10-36 Summary: Ketotifen for food allergy.

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