EDITOR’S SUMMARY: Aches ‘n pains from inflammation, headaches, upper respiratory discomfort, and melancholy. These are merely a handful of markers that may represent MCAS running rampant through your system. The tricky thing is that these symptoms, along with others, may instead coincide with other illnesses, having little to do with mast cell activation syndrome. There then begins a process of exploration and elimination, in an attempt to get to the source of imbalance, and improve the way you feel—physically, mentally, and emotionally.
By Jennifer Wolff-Gillispie HWP, LC
Mast cells are one type of white blood cells that originate from stem cells in your bone marrow, andare primarily found in connective tissues, particularly near blood vessels and nerves. Their presence is particularly noted in tissues that interface with the external environment, such as your skin, lungs, and gastrointestinal tract.The use of the term “mast” cell was adopted by Paul Erlich, a Nobel Prize winning German physicist and pharmacologist in 1878. He dubbed the cells “Mastzellen,” which means “fattening” in his native German, as he initially believed that the cells had a “nutritional function because of their granules.” His original observation that mast cells fed other cells was later found to be incorrect. Nonetheless, Erlich’s discovery allowed for more research that would eventually identify these cells as being part of the immune system.
Mast cells (a.k.a. mastocytes) are in fact a unique and integral part of your immune system, playing critical roles in both defending your body against pathogens, and contributing to various allergic and inflammatory conditions. These immune cells are often overlooked, yet are pivotal in maintaining homeostasis (balance within the body systems). Sometimes, however, this necessary component of your immune system can malfunction, causing a cascade of symptoms that are often indistinguishable from other conditions. This is called mast cell activation syndrome (MCAS), which can be very complicated to diagnose. In order to decipher the cause of this mysterious immune dysfunction, you must first understand the function of mast cells.
Mastocytes serve as sentinel cells in the immune system. They detect pathogens and environmental threats through pattern recognition receptors (PRRs) that identify danger signals. They promote tissue repair/remodeling, secrete factors that promote healing, and are involved in regulating blood flow. However, they are best known for their role in allergic reactions, where their activation leads to symptoms such as itching, swelling, and respiratory distress. In the lungs, the release of mediators can lead to bronchoconstriction, which is a key feature of asthma.While mast cells are there to serve the purpose of overseeing the immune system, the delicate balance they maintain can sometimes lead to pathological conditions. MCAS is characterized by inappropriate and excessive activation of mast cells, leading to a range of symptoms that can significantly impact your quality of life. Understanding MCAS requires a look into its potential triggers, mechanisms, and the challenges it presents in terms of diagnosis.
Mast cells are characterized by their large granules filled with various mediators. These mediators include histamine, cytokines, heparin, and proteases. When the mast cells detect a foreign pathogen, allergen, or stimuli, they release the appropriate mediator in defense. This is known as degranulation. Once degranulation has begun, these inflammatory mediators are responsible for your symptoms. According to Science Direct, “Mediator”:
“Mediators can be defined as compounds that are either locally released or carried in blood or tissue fluids and that may participate in initiating, perpetuating, or aggravating a pathological process.”
There are over 100 known mediators, each having a specific purpose in immune response. The most common ones attributed to MCAS are listed below:
Histamine– Dilates the blood vessels allowing more blood to flow; constricts “smooth” muscles of the body including the cardiovascular, digestive, and reproductive systems; allows small molecules and cells to permeate the walls of blood vessels; promotes respiratory mucosal secretions and gastric acid production. Symptoms: Itching, hives, swelling, runny/stuffy nose, GI upset, headaches/migraines, shortness of breath, irregular/fast heartbeat, menstrual dysfunction, fatigue, anxiety, and brain fog.
Cytokines (including interleukins, chemokines, interferons, and tumor necrosis factors) – Activate fighting infection; direct immature cells to develop into specific types of cells that are needed; order specific cells to replicate, and promote pro- or anti-inflammatory processes depending on what is required. Symptoms: Fever, chills, fatigue, nausea/vomiting, diarrhea, and low blood pressure.
Heparin – A natural anticoagulant produced in the body that prevents blood from clotting. Symptoms: Blood clotting, bleeding, bruising, hemorrhaging.
Proteases (enzymes such as pepsin, trypsin, and chymotrypsin that break down protein) – Produced in either the intestinal lining or the pancreas depending on the type. Proteases allow the protein you eat to be digested, and the nutrients absorbed. Proteases are also responsible for regulating inflammation, wound healing, blood clotting communication between cells, and programmed cell death (apoptosis). Symptoms: Asthma, blood vessel damage, abdominal aortic aneurysm, arthritis, and hypertension.
MCAS can occur when mast cells release their mediators inappropriately or excessively. This dysregulation may result from genetic predispositions, environmental factors, or underlying conditions. Some individuals may have mutations in genes related to mast cell regulation, leading to heightened sensitivity and activation. For instance, mutations in the KIT gene can cause mast cell proliferation and abnormal activation. Exposure to allergens, infections, certain medications, or toxins can also provoke mast cell activation syndrome. Common triggers include food and environmental allergens, insect stings, infections, environmental stressors (heat, physical exertion, life events), specific pharmaceuticals (such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids), and vaccines. In 2024, a research paper out of the NIH’s National Library of Medicine, “Safety and Tolerability of COVID-19 Vaccine in Mast Cell Disorders Real-Life Data from a Single Centre in Italy,” states:
“Vaccine-associated anaphylaxis is, in fact, rarely described in the general population, with an estimated incidence of one reaction per one million injections for most vaccines. However, in the first few months, some cases of vaccines-related hypersensitivity reactions were observed and worries about the safety of COVID-19 vaccines emerged. This led to a slowdown of the vaccination process due to the suspected increased risk of anaphylactic reactions, especially in high-risk patients. Hypersensitivity reactions are defined as an exaggerated or inappropriate response of the immunity against an antigen, and conventionally classified by Coombs and Gell into four forms, according to the underlying molecular mechanism. Most reactions are mild and self-limiting; however, they could rarely be life-threatening or result in major complications, especially in high-risk patients (e.g., patients with mastocytosis [mast cell activation of the skin, bone marrow and internal organs]).”
Covid-19 vaccinations are not the only vaccines that MCAS is linked to. Flu, shingles, and HPV (human papillomavirus) have all been linked to and studied for their role in mast cell activation. In a case report on post-HPV vaccination and mast cell activation, it is noted:
“For nearly a decade, case reports and series have emerged regarding dysautonomias—particularly postural orthostatic tachycardia syndrome (POTS)—presenting soon after vaccination against human papilloma virus (HPV). We too have observed a number of such cases (all following vaccination with the Gardasil product), and have found several to have detectable mast cell activation syndrome (MCAS) as well as histories suggesting that MCAS was likely present long before vaccination.”
In many of these studies, it is suggested that MCAS may have been present, whether diagnosed or not, previous to the mast cell activation event. It is unknown, however, whether earlier adult or childhood vaccines may have played a role in the initial activation. According to the Centers for Disease Control and Prevention (CDC), babies born in 2016 had anywhere between 69.7%–92.5% compliance to the vaccine schedule by 24 months old. This suggests that the opportunity for exposure to potential triggers for MCAS is high with the vaccination schedule alone. For some, various disorders, such as autoimmune diseases, may predispose individuals to MCAS by altering immune responses and mast cell function. One such disease, Ehlers-Danlos Syndrome (EDS) (a genetic connective tissue disorder), can also be complicated by mast cell activation. The Ehlers-Danlos Society explains this connection:
“Cells of the body are surrounded and supported by a network called the Extracellular Matrix (ECM), which can be made from structural materials like collagen. Structural materials like collagen play an important role in the connective tissue of the body generally, and are associated with the Ehlers-Danlos syndromes (EDS). MCs [mast cells] can stick to the ECM, which in turn alters their behavior. EDS, as a connective tissue disorder, could change the ECM enough to cause a change in MC behavior.
Mast cell activation disorder (MCAD) is a condition where someone has an increased activity of MCs. A proportion of people with the hypermobile type of EDS (hEDS) also have MCAD, leading to the possibility of a link between the conditions; research appears to support this link. In one study, 66% of patients with both a high heart rate when standing (Postural Tachycardia Syndrome or POTS) and EDS also had symptoms consistent with a form of MC activation.”
Capturing the Diagnosis
One of the significant challenges in diagnosing MCAS is that its symptoms overlap with a multitude of other conditions. This similarity often leads to misdiagnosis or delayed diagnosis. The acute symptoms of MCAS, such as itching, hives, or respiratory distress, can mimic traditional allergic reactions, complicating differentiation. Severe mast cell activation can lead to anaphylactic reactions, which may not be immediately recognized as stemming from MCAS. Symptoms like fatigue, joint pain, and gastrointestinal issues (IBS or food intolerances) can also be present in autoimmune diseases, making MCAS difficult to identify. Headaches, anxiety, or mood disturbances of unknown origin can overlap with both mast cell activation and various hormonal, psychological, and neurological conditions.
The diagnosis of mast cell activation syndrome is often a lengthy and complex process. The diverse range of symptoms associated with MCAS often leads patients to multiple specialists without a clear diagnosis. Many healthcare providers may not be familiar with MCAS, leading to underdiagnosis or misdiagnosis. Symptoms can vary greatly between individuals and can change over time, making it difficult to establish a consistent clinical picture, yet having symptoms from within several body systems (ex: allergies, plus symptoms in at least two other body organs) is a strong clue. While testing (serum tryptase), a medication response test (medicine targets mast cell mediators blocking symptoms and confirming diagnosis), gastrointestinal scans, bone scans, allergy tests, and bone marrow biopsies (to rule out other conditions) can support a diagnosis of MCAS, they are often not definitive. A comprehensive evaluation, including patient history and response to treatment is usually necessary but takes time. Dr. Dean Mitchell, M.D., board-certified immunologist and allergist, confirms the inconsistencies in conventional diagnostic testing, and offers a clear way to help confirm a MCAS diagnosis:
“Many patients at my practice that I see come because they are concerned that they have mast cell activation syndrome. And it can be diagnosed easier than you think! Mast cell activation syndrome has only been discovered in the last several years but probably has been around forever. A lot of patients who have allergic reactions whether it’s to foods, environmental exposures to even vaccines may have mast cell activation syndrome. Now there are some sophisticated tests that we can do in the blood to check for mast cell activation but they’re not always that accurate.
Believe it or not, one of the easiest ways to have an idea if you should be further evaluated for mast cell activation actually involves a simple stroking of the skin… I’m gonna stroke his skin like this, two lines, and as you can see almost immediately it wheals [local reaction where skin raises and turns red] up. I can write this patient’s name on his back. This is called dermatographism… now dermatographism is in 5% of the population but 90% of the patients that have mast cell activation have dermatographism.”
Initiating Therapeutic Practices
Mast cell activation syndrome represents a prime example of how mast cells—multifunctional components of your immune system—can turn from unsung heroes into troubling villains. While complicating the clinical landscape with their unpredictable symptoms, they are capable of contributing to serious pathological conditions when dysregulated. While it is noted that there is no cure for MCAS, there are steps you can take to manage, reduce, and eliminate symptoms. If you suspect you may have MCAS, adopting an anti-inflammatory and antihistamine (a.k.a. “low-histamine) diet can eliminate potential dietary triggers. Foods such as tuna, pork, cured meats, aged cheeses, fermented foods, and alcohol are high in histamines. Incorporating anti-inflammatory foods like salmon, walnuts, berries, ginger, and turmeric can support and nourish your body, while avoiding provocation of mast cells. Lactose- and gluten-free diets should also be considered. Embarking on an elimination diet to better identify potential dietary triggers can be effective. This involves removing all potentially offending foods, and after a certain amount of time has passed (typically two to six weeks), reintroducing them gradually, one by one to see if any mast cell activation symptoms occur.
Along with prospective dietary disrupters, you can also examine environmental factors that may play a role. Although dearly loved, pets with their dander and saliva could be perpetuating the problem. One idea is to take a trip away from home for several days to a pet-free environment, and notice if your symptoms die down. Be aware of “exercise intolerance” that increases histamine, and slow your roll as needed. Short, leisurely walks can be effective as physical activity, without exacerbating your condition. Take a look at all medications (prescribed or over the counter) and vaccines you have received, to see if they align with the onset of symptoms. If so, discuss with your doctor if there are alternatives. Unfortunately, many general practitioners (and specialists) often do not understand MCAS or how to support their patients with natural alternatives. If you run into this road block, functional medicine doctors and naturopathic doctors can better help you navigate through this.
As awareness of MCAS grows, it is essential for patients and healthcare providers to recognize the signs, understand the potential triggers, and traverse the complexities of diagnosis. While understanding mast cells and their role in health and disease is still unfolding, ongoing research holds promise for better management strategies, and improved quality of life for those affected by MCAS. Listening to your body, and paying close attention to the signs it is giving you, will allow better management of any condition you are experiencing. The journey from symptom to diagnosis may be a long one, but with patience, education, and action, you can be your own best advocate.
~
Published on January 09, 2025.
If you’ve found value in this article, please share it!
To support the research and health education of AVFC editorial, please consider making a donation today. Thank you.