Prairie Health & Wellness Newsletter — April 2025, Edition 16
Pillar of the Month: Detox
Reduce exposures to toxic chemicals & support the body's natural detoxification processes.
A Word from Dr. Grady
MCAS: Mast Cell Activation Syndrome
Introduction to MCAS
Mast cell activation syndrome (MCAS) is a dysregulation of the immune system in response to significant stress, where what we normally think of as the allergy response becomes a pervasive inflammatory condition. Instead of what we typically consider allergy symptoms such as nasal congestion, weeping eyes, or hives, MCAS can affect any body system, causing just about any symptom. A few examples of this are chronic fatigue, brain fog, pelvic pain, nerve pain, low blood pressure, rapid heart rate, and anxiety.
Our understanding of this immune system dysfunction is still in the early stages, with the first hypotheses published in 1984 and the first diagnostic criteria established in 2010. This diagnostic criteria has been revised several times since then and continues to evolve. The original criteria focused primarily on classical allergy symptoms and excluded many symptoms, such as neurological and genitourinary ones. It also required serum tryptase elevation to be demonstrated by lab analysis, when this is actually only found in a small minority of MCAS patients. Additionally, it required a clinical response to specific histamine blockers despite the fact that it can vary which histamine blockers are effective for different patients. Some patients even experience worsening symptoms due to additives or coloring in these medications and thus need them sourced from a compounding pharmacy.
MCAS is currently estimated to affect 17-19% of the population, which has increased significantly from the original estimate of only 1%. This suggests that a significant number of people are affected by this condition, yet the majority of healthcare practitioners did not even learn about it in medical school. While the three-year survival curve for MCAS patients is the same as the general population, this does not mean that their quality of life is not greatly impacted. Many of these patients will seek answers to their seemingly random array of symptoms only to find dead end after dead end in their search. As mentioned above, it is typically a great stressor or series of stressors that lead to this condition. This can be a mental/emotional stressor, such as grief or loss, infections like COVID or SIBO, surgery, or a toxic overload from exposure to heavy metals or mold. These events lead to acquired genetic mutations that cause the usual allergy response of the immune system to go haywire.
Diagnosis
Diagnosis of MCAS is often a difficult endeavor and is usually based upon clinical picture, ruling out other diagnoses, and response to treatment. The first diagnostic criteria were released in 2010, then updated in 2012 and again in 2019. This will likely continue for some time as we are still very early in our understanding of this prevalent condition. Early diagnostic approaches focused on typical allergy symptoms and did not even consider common systems affected, such as neurological or cardiovascular manifestations like fainting, headaches, and chest pain. Early approaches also assumed that lack of response to any histamine blocker ruled out MCAS, but we now understand that many patients only respond to one or two specific histamine blockers.
Further complicating the diagnosing process, mast cells degranulate, or dump, hundreds of different chemical mediators in response to a stress trigger. So, even though several mediators can be tested, the correct ones may not be selected due to the wide variation from person to person. On top of this challenge, the majority of these mediator chemicals released by the mast cells have short half-lives and are unstable at room temperature. Most labs lack the tools, such as refrigerated centrifuges, needed to collect the samples and maintain their integrity for analysis. Standard pathology staining of biopsies will not typically show an abundance of mast cells, even if they are present. Thankfully, pathologists often maintain samples for many years, so we may now be able to re-stain previous biopsy collections with CD 117, which is a biomarker that helps identify the presence of mast cells. Due to this lack of ease and clarity in diagnostic tools, we often establish the diagnosis based upon response to treatment.
Treatment
Treatment for MCAS will vary from person to person since they have varying amounts of different mediators that are being released from their mast cells in response to stress triggers. This means that some detective work is needed to identify which forms of stress or triggers cause the activation of the mast cells and which therapeutic options will benefit the condition. Some symptoms will point to certain mediator biochemical pathways, helping us to ascertain which therapeutics will more likely be helpful to a specific patient, but it is often a process of trial and error. Due to this, keeping meticulous notes and studying them to find patterns is often needed to find the best treatment plan for any individual dealing with MCAS.
The general approach for treatment is identifying triggers and avoiding or reducing exposure to them in addition to using natural and pharmaceutical inhibitors of various inflammatory pathways. These inhibitors include histamine blockers, leukotriene blockers, antioxidants, COX inhibitors, and other anti-inflammatory agents. Dietary interventions include avoiding inflammatory and histamine-containing foods, as well as increasing foods rich in antioxidants like buckwheat (containing rutin), onions (containing quercetin), and green tea (containing epigallocatechin). Histamine blockers include common medications most are familiar with like Benadryl and Pepcid, while COX inhibitors include the common pain relievers ibuprofen and aspirin.
Suspecting MCAS
When should someone suspect they might be dealing with MCAS? It may be suspected when they experience an array of seemingly unrelated symptoms that come and go, such as rapid bloating after eating, headaches triggered by changing environments, intermittent pain during urination or sex, and anxiety that appears spontaneously without an obvious cause. Symptoms often start after a major stress event or series of stressful events. Another clue might be that taking an allergy medication alleviates a symptom that doesn't seem related to allergies. Women of child-bearing age may be affected more often due to estrogen promoting mast cell degranulation and inhibiting the production of diamine oxidase (DAO), which metabolizes histamine. If you suspect that you may be dealing with MCAS, please note that this does not constitute medical advice, but don't hesitate to make an appointment with your provider to discuss your symptoms and explore potential next steps.
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