Mast Cell Activation Disorder / Syndrome, Immune Dysregulation or Histamine Intolerance: Understanding the Difference and Appreciating the Immune System
If you read my article last week, you will have recognised that there are still certain foods that I cannot eat, and things that cause my system to suffer or struggle. I received several comments after posting that article - one of which I will cover today, the other I will touch on next week.
That first question was:
"What’s the difference between what happens to YOU and just having a food sensitivity to the vegetable proteins? You can’t possibly say that these are inflammatory for everyone if it’s just YOUR digestive system or just YOUR immune system – perhaps you’re just the odd one out?"
Within this question is highlighted the main issue when tackling immune conditions: how do you know what you’re actually dealing with, what’s the difference between all the different immune activations - and does that change the recommended treatment and/or dietary choices?
The answer to these questions is, unfortunately, not cut and dried - but if you know that your immune system is doing something and you’re trying to distinguish what - the following might help.
IS IT GUT PERMEABILITY, AUTOIMMUNITY, MCAS / MCAD OR HISTAMINE INTOLERANCE - AND HOW CAN YOU TELL THE DIFFERENCE?
Drawing hard lines when it comes to a discussion of immune conditions is tricky. The reason for this is because the immune system has two branches - and within each of those branches a whole network of ways in which it responds. The two branches of the immune system allow it to be either incredibly specific or to be overwhelmingly generalised. Understanding from our symptoms which of these branches (or potentially both) is being activated is sometimes impossible - but some guidelines to interpreting immune function are below.
Sensitivity and Mass Intolerances
The distinction between intolerance and sensitivity largely revolves around whether the immune system is involved, or whether reactions to things are founded on other issues (in the digestive system these other issues can be poor acid, enzyme or bile production and microbiome dysbiosis, for example).
Sensitivities are the latter - where the immune system isn’t involved (up front, at least - though it might be later).
Intolerances emerge from immune reactivity, mediated through IgG and IgM antibodies (potentially IgD as well, though this is poorly studied). These tend to be gut-centric intolerances in which hyperpermeability of the intestinal lining has led to the immune system surrounding the gut to come into contact with substances which it knows it ‘shouldn’t’ allow into the body. An antibody is created to defend against it.
Having a hyperpermeable gut and the sensitivities that arise from this create localised and systemic inflammation. This causes generalised discomfort which is created by the immune system’s release of both antibodies and some inflammatory compounds as it feels it needs to eliminate the threats coming through the gut wall.
Autoimmunity
Autoimmunity works on the same principle as the above - with the immune system becoming wary of an antigen that it feels is either where it shouldn’t be or looks a little threatening. Here, the immune system decides to make an antibody for tissues which are actually part of the host’s own body. This can happen almost invisibly, with no inflammation occurring as a result. This is how coeliac, Hashimoto’s, Rheumatoid Arthritis and other conditions can go undiagnosed for years, sometimes decades: the antibodies are being made but the inflammation that requires immune system release of inflammatory compounds does not overtly occur (i.e. occur enough to cause symptoms)
Mast Cell Activation Syndrome/Disorder
Mast cell conditions, in contrast to the above, can be allergenically mediated (i.e. through the creation of IgE antibodies) or not - but the response isn’t a production of antibodies, per se. Instead, it is mass release of inflammatory cytokines: histamine, prostaglandins, leukotrienes and proteoglycans. These substances are antimicrobial and/or cytotoxic - they’re designed to kill stuff… it’s a much more rapid and extreme reaction - and it isn’t finessed, as with the gentle antibody/protection mechanisms described above.
Having Mast Cell issues is very similar to having actual allergies. The responses are similar: hives, itching, angioedema, vomiting, nausea, gastric dumping, redness, heat, swelling, sneezing, coughing and even anaphylaxis. In Mast Cell conditions anaphylaxis is incredibly rare - but this is mostly due to the severity of the reaction.
In frank allergy, the reaction is ALWAYS overt, alarming and extreme. The immune system is trying to save your life. In Mast Cell Activation issues there is more of a spectrum - from mild to severe - and the reactivity can vary depending on a whole host of other factors. For this reason, the reactions tend to be more mild.
They are no less distressing, however - and they are also quick.
Histamine Intolerance
Mast Cell issues can be confused with histamine intolerance. The symptoms of this can also occur relatively swiftly but these reactions solely revolve around the excesses of (or inability to break down) just one of the above-mentioned cytotoxic substances: histamine. Instead of being a mass release of all cytokines, histamine intolerance can therefore be milder in presentation and much less of a trauma to the body.
In Mast Cell Activation the body really believes it has been through a near-death experience. In histamine intolerance, especially when the issue is with a lack of the enzyme to break histamine down, this is much more like the body is struggling to clear a backlog - it may be exhausting, but it will get there eventually.
DISTINGUISHING THE IMMUNE DIAGNOSES
Diagnosing and distinguishing between the above conditions is tricky - it’s partly done through testing (though this is challenging and often inaccurate), partly it is a process of clinical evaluation - and, to be honest, it is much to do with the experience of practitioners to help interpret a sufferer’s symptoms.
Familiarity with mast cell issues make practitioners acutely aware of the subtle differences - and these revolve around the extreme of reactivity, the upper gastric upset and also the oft-reported sense of being on fire all the time which accompanies Mast Cell issues. Speed is a lot to do with this, along with the specific responses that each patient has.
BUCKETS AND LOAD-DEPENDENT REACTIVITY
With the exception of allergy, all of the above immune reactivities are dependent upon quantities of stressors and amounts of exposures.
You may often hear an example of a ‘histamine bucket’ - a description of how your body can cope with so much stress but then things will start to overflow the bucket of total histamine and that’s when you can’t break it down. This analogy is a good one for those who are dealing with the ‘tricky backlog’ situation described above.
With the other immune reactivities, however, this is less about quantity of the inflammatory compounds and everything to do with the sensitivity and alertness of the immune system.
In all immune reaction conditions there is a degree of misunderstanding and confusion that has occurred on the behalf of the immune system:
With intolerances, the confusion arises because of the plethora of particles that have crossed a hyperpermeable gut wall
With autoimmunity the immune system has confusedly mistaken ‘self’ for ‘enemy’
With Mast Cell conditions, the immune system has either placed mast cells in locations where they can too-easily erupt and release their contents and/or the immune system is on such high alert that it doesn’t take much to degranulate (break down) the mast cells and trigger mass reactivity and inflammation
In the above situations, especially the last one, the preparedness of the immune system to fight is often nothing to do with the substance(s) that eventually gets fought. Istead, it’s about why the body was in such a heightened state of awareness in the first place.
This simple statement is at the heart of what I do - understanding triggers, stress loads, toxic burdens and all of the little (and large) things that have contributed to gastrointestinal hyperpermeability, immune confusion and heightened immune alertness.
When I look at my qualifications and certifications, and my areas of research, they seem eclectic and sometimes disparate. However, the unifying theme is an attempt to understand how a body reacts to stressors - and how to work to relieve those stressors. This is not just about foods, poisons, toxins, metals, mould, viruses or gluten (though ALL of those play a role). It’s also about trauma, distress, emotional stricture, expressions, socialisation, finding meaning and living one’s purpose.
Understanding the difference between the above conditions IS important - but once you’ve established that, we’re still left attempting to understand the ‘why’ behind the dysregulation of the immune response.
This is why, within Functional Medicine, we are not meant to stop at just identifying autoimmunity or histamine intolerance, gut permeability - or even Mast Cell issues. And no, I don’t just assume that MCAD is my diagnosis for life and talk myself into that state. I am, always, attending to the why’s of my immune hyper-reactivity. And that is a daily practice.
MCAS: THE PARANOID CANARY
You will have heard the adage of finding meaning in illness. I do subscribe to this philosophy, actually - because I genuinely believe that the body tells the truth… always. And if there is reactivity or symptoms occurring there is always a reason and a process to go through to resolve the distress.
When I look at having Mast Cell issues I do feel that what it allows me to understand - admittedly, on quite an extreme level - are the immune triggering things. Whilst some mast cell triggers are entirely individual, broadly-speaking there are substances which spark immune reactivity, and substances which don’t.
Having Mast Cell degranulation issues is like having alarmist, paranoid sentries guarding the body. They will degranulate and release the cytokines whenever it thinks appropriate - and typically that’s WAY too much. But is not entirely without rationale. Those with mast cell issues are reacting to miniscule quantities of things that the healthy immune system can struggle with. In this way, I can guide my patients (and build my recommendations) based on my first-hand experience of knowing how the body (and the immune system) receives nutrition.
This is what makes those with Mast Cell issues canaries in the coalmine. This is what makes the experience I had with vegetable proteins so fascinating - and what makes me able to extrapolate this to an understanding of the immunes system of those with chronic illness as a whole. Because MCAD makes me super-sensitive I know how other bodies will react.
It is for this reason that I know I may be the ‘odd one out’ - but that’s solely down to the severity of my reaction. In no way does this mean that legumes and grains are bad for people - they really, really aren't.
But it does confirm the point that I made last week: in those who are sensitive, digestively impaired or suffering with lowered energy and heightened reactivity (i.e. those who are going through even a small amount of immune activity in response to stressors) the likelihood is that the proteins and amino acid chains which are more biologically similar to us (i.e. animals, not plants) are going to be easier to assimilate and deal with - posing less of a risk of triggering the alarm bells of the immune system.