Mast Cell Activation Syndrome: Beyond Histamine and Tryptase

Histamine and tryptase have traditionally been the primary mediators associated with the complex disorder known as mast cell activation syndrome. However recent research is unveiling that there may be a whole lot more to the story than these two compounds.?

So, in this blog post, we’re going to explore exactly what mast cells are, what really happens when these sophisticated cells degranulate, and what this newfound understanding means for the diagnosis and treatment of mast cell-related disorders moving forward. Let’s dive in.

What Are Mast Cells?

Mast cells are highly specialized and complex immune cells that serve as sort of first responders within your body. They work via a process that goes something like this:1,2

• Mast cells patrol your tissues, vigilantly watching for anything that might be a threat.?
• When a threat is detected, mast cells jump into action – undergoing a process known as degranulation.
• During degranulation, mast cells spew out a cascade of different chemical messengers – sort of like a pinata busting open and releasing its contents.
• This degranulation and release of chemical mediators sound the alarm to alert the rest of your immune system of the threat while kickstarting the inflammatory response.
• Once inflammation is initiated and the rest of the immune system is deployed, mast cells continue to release compounds that amplify the immune response until the threat is neutralized.
• Once the threat has been appropriately dealt with, mast cells are designed to enter the resolution phase where they release substances that promote tissue repair and regeneration while gradually ramping down the immune response.

Mast cells are pivotal players in your immune response and serve an invaluable role when it comes to protecting you from invading pathogens, irritating allergens, and injuries. But they are designed to maintain a delicate balance. And when this balance gets disrupted it can have serious consequences.

Case in point – the condition known as mast cell activation syndrome.

What Is Mast Cell Activation Syndrome?

In mast cell activation syndrome or MCAS, you have a normal, healthy amount of mast cells patrolling your body. But these mast cells become hypervigilant – reacting rapidly and aggressively to anything that even resembles a potential threat. These overzealous mast cells spew out their inflammation-stoking contents much too often and much too aggressively – sending your immune system into high alert unnecessarily.

These misbehaving mast cells can translate into a whole host of unpleasant symptoms and conditions ranging from skin and digestive issues to respiratory problems and mood disorders. You see, because mast cells are dispersed throughout your entire body and release well over a dozen different mediators – with each mediator having a range of different potential actions within your body – overactive mast cells can create all kinds of problems that are notoriously difficult to trace back to mast cell activation.3,4

So how on earth are you supposed to know if your mystery symptoms are indeed related to mast cell activation syndrome??

How Is Mast Cell Activation Syndrome Diagnosed?

Mast cell activation syndrome diagnosis typically requires a little bit of detective work. Most conventional medicine doctors have little to no understanding of this complex disorder. So diagnosis usually requires partnering with a doctor who specializes in a Functional Medicine approach and has an understanding of the real impact of overactive mast cells.

The exact diagnostic criteria are too extensive to delve into in this blog post, but you can read more about how MCAS is diagnosed in my article Mast Cell Activation Syndrome: How It's Diagnosed and 2 Exciting New Treatments. But one of the primary criteria currently used to identify MCAS is the presence of two distinct mediators that mast cells are known to release during degranulation – which are:5,6

• Histamine: A compound contained within mast cells that facilitates the immune response by widening blood vessels and increasing tissue permeability to allow immune cells to more easily travel to the site of the threat
• Tryptase: An enzyme found primarily in mast cells that contributes to inflammation by promoting the activation of other immune cells and enhancing the permeability of blood vessels

While the presence of these mediators can certainly serve as valuable and accurate diagnostic markers for MCAS, recent research is finding that identifying mast cell-related disorders may actually be even trickier than we originally thought. You see, when mast cells become activated and degranulate, they release a whole lot more than just histamine and tryptase. And this slurry of additional immune mediators can stir up all kinds of trouble when it comes to your health.

Mast Cell Activation Syndrome: What Do Mast Cells Release When Activated?

While histamine and tryptase are undoubtedly key players when it comes to mast cell activation syndrome, they are by no means the only signaling molecules these sentinel cells can release. Mast cells actually secrete and release a whole host of pro-inflammatory mediators beyond just histamine and tryptase. Mast cells have receptors allowing them to sense and respond to allergic, autoimmune, environmental, neurohormonal, pathogenic, and stress triggers. And different triggers can elicit countless different responses from mast cells.

Just some of the additional mediators that can be released by mast cells include:7,8

• Chymase
• Interleukins
• Prostaglandins
• Cytokines
• Chemokines
• Proteases
• And more

And to make matters more complicated, some of these molecules can be released without mast cell degranulation. Understanding this variety of pro-inflammatory molecules that go far beyond just histamine and tryptase is critical when it comes to detecting and addressing mast-cell-mediated conditions.

What Does This Mean For The Diagnosis and Treatment Of Mast Cell Disorders?

This newfound understanding helps give us the following insight:

• Increased complexity: Mast cell activation syndrome is indeed even more complex than we originally thought. Understanding the numerous mediators released by these cells sheds light on the fact that activated mast cells are undeniably involved in many other conditions – making diagnosis challenging and treatment difficult.
• Broader diagnostic guidelines: Knowing that mast cell activation goes far beyond just histamine and tryptase means diagnosis should not be limited primarily to these two diagnostic markers – subsequently meaning many more patients may qualify for a diagnosis of mast cell activation disorders.
• More effective treatment approaches: Because overactive mast cells can release dozens of different mediators, treatment should focus on inhibition of mast cell activation, in addition to inhibiting the effects of selective mast cell mediators.

More time and research are needed to truly understand the implications of these findings, but this insight is promising. The more we understand about how these complex cells function, the closer we get to finding answers for those struggling with the difficult-to-pinpoint, and often life-altering symptoms that come with mast cell-related conditions.

Are You Concerned You May Be Struggling With Mast Cell-Related Symptoms?

While we may not have all the answers yet, one thing I know for sure is that Functional Medicine is at the forefront when it comes to charting the murky and strange waters of malfunctioning mast cells. If you or a loved one is struggling with an ongoing condition that doesn’t seem to improve no matter what you try or you’re grappling with vague symptoms that you can’t quite seem to get to the root of, it may be time to dig a little deeper and see if overactive mast cells could be part of the problem.?

If you’re at all concerned about a mast cell-related condition, I encourage you to download my Ultimate Guide To MCAS. This guide will walk you through everything you need to know to get started on understanding, identifying, managing, and even healing your overactive mast cells. And the best part is, it’s totally free – all you have to do is enter your name and email and you’ll have instant access.

Arming yourself with knowledge and partnering with health professionals who understand this perplexing condition is crucial if you want to address mast cell imbalances at the source. And there’s no better place to start than with my Ultimate Guide – so grab yours today!

Resources:

1. The Role of Mast Cells in the Defence against Pathogens – PMC (nih.gov)
2. Mast Cell: A Multi-Functional Master Cell – PMC (nih.gov)
3. Mast Cell Activation Syndrome: Proposed Diagnostic Criteria – PMC (nih.gov)
4. The impact of psychological stress on mast cells (annallergy.org)
5. Diagnosis, Classification and Management of Mast Cell Activation Syndromes (MCAS) in the Era of Personalized Medicine – PMC (nih.gov)
6. Mast Cell Activation Syndrome: Proposed Diagnostic Criteria – PMC (nih.gov)
7. Mast cell activation: beyond histamine and tryptase: Expert Review of Clinical Immunology: Vol 19, No 6 (tandfonline.com)
8. Recent advances in our understanding of mast cell activation – or should it be mast cell mediator disorders?: Expert Review of Clinical Immunology: Vol 15 , No 6 – Get Access (tandfonline.com)

* These statements have not been evaluated by the Food and Drug Administration. The product mentioned in this article are not intended to diagnose, treat, cure, or prevent any disease. ? The information in this article is not intended to replace any recommendations or relationship with your physician. ?Please review references sited at end of article for scientific support of any claims made.