MCAS
Mast Cell Activation Syndrome and Histamine: When Your Immune System Runs Rampant
There is undoubtedly an escalating epidemic of chronically unwell people in North America. The present method of looking at illness is geared toward a single organ, a single specialty, a single drug, and voila! – let’s hope for a cure. Often patients go from pillar to post to see various medical consultants according to specialty (gastroenterologists, dermatologists, etc.), only to discover there isn’t one underlying syndrome or root cause that explains all the assorted symptoms the patient is experiencing. Patients may be given multiple diagnoses with multiple treatment options or medications, often with conflicting interactions and side effects that are worse than the underlying condition they are meant to treat.
Recently, a number of new ways of looking at chronic multisystem, multisymptom diseases has emerged as pioneering physicians connect previously disconnected dots and make sense of disparate symptoms that were never understood as components of a single syndrome. The first is the trailblazing work of Dr. Ritchie Shoemaker on chronic inflammatory response syndrome (CIRS). This syndrome is induced primarily by mold biotoxins and the inflammagens of water-damaged buildings, ciguatera or pfiesteria infestations, or Lyme disease and co-infections. The second is the pioneering work of Dr. Lawrence Afrin on mast cell activation syndrome (MCAS). Dr. Afrin is a board-certified hematologist/oncologist who recently wrote a book, “Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity.”
Two important books that address the complex syndromes that may underlie many chronic, multisymptom, multisystem disease conditions are:
What is MCAS? Mast cell activation syndrome (MCAS) refers to a group of disorders with diverse causes presenting with episodic multisystem symptoms as the result of mast cell mediator release, often without causing abnormalities in routine laboratory or radiologic testing. Most people with MCAS have chronic and recurrent inflammation, with or without allergic symptoms. This occurs when an aspect of the innate immune system becomes overactive and releases a flood of inflammatory chemicals, which may affect every organ in the body. The symptoms of MCAS will wax and wane over time. Another way to think of this is the symptoms will flare up and go into remission, affecting different organs and body parts, over and over again throughout a person’s life, without a common unifying theme or established diagnoses to account for the patient’s presentation of symptoms.
MCAS can present subtly but may become more serious as an individual ages. If you were to chart the symptoms of MCAS on a timeline, beginning at birth you can often identify symptoms that began at a very young age.
For some, MCAS becomes a highly probable diagnosis when they notice that they have had various symptoms of an inflammatory nature over the years. Mast cell activation syndrome symptoms may include:
Any of these symptoms could indicate MCAS.
Dr. Afrin believes that MCAS is an epidemic with as many as 14 to 17 percent of the US population having MCAS – one out of every six to seven individuals. It has been said that it may take up to 10 years and numerous doctor visits before someone is adequately diagnosed and treated by a knowledgeable physician-or the patient figures it out for themselves!
Mast cells are types of white blood cells that release up to 1000 signaling chemicals, or mast cell mediators, into the body as part of an immune system stabilizing defense response against foreign invaders (parasites, fungi, bacteria, or viruses), allergens and environmental toxins.
We need mast cells to protect us from infection, heal wounds, create new blood cells, and develop immune tolerance. However, in conditions in which these cells are dysfunctional or overactive, they can cause serious issues.
Mast cells are found in most tissues throughout your body. In particular, they are found in tissues that are in close contact with the environment such as your skin, airways, and gastrointestinal tract. Mast cells are also found in your cardiovascular, nervous, and reproductive systems.
Mast cell mediators are the preformed granules secreted by mast cells in response to an outside stimulus, which can occur very quickly, in milliseconds. Mast cell mediators include histamine, proteases, leukotrienes, prostaglandins, chemokines, and cytokines. Their job is to signal and guide other cells, tissues, and organs to respond to the hostile invaders. These mast cell mediators provoke potent inflammatory responses that can include urticaria (AKA hives-skin rash and swelling), angioedema (swelling beneath the skin surface), bronchoconstriction (airway constriction), diarrhea, vomiting, hypotension (low blood pressure), cardiovascular collapse, and death, all within a matter of minutes.
Patients who come into my office with MCAS usually have multisystem, multisymptom inflammatory responses. These symptoms have often caused them to trudge from doctor to doctor, undergoing rounds of testing, causing them to feel extraordinarily confused as to what’s happening to their body. Because the symptoms of MCAS have so broad a reach and differ so considerably from person to person I’d like to break them down by nonspecific, general clues, and organ system signs.
See Keith Berndtson’s (http://havenmedical.com/) slide below: Permission to use slide given by author.
Eyes – Red eyes, irritated eyes, dry eyes, burning eyes, difficulty focusing vision, and conjunctivitis (pink eye).
Nose – Nasal stuffiness, sinusitis, postnasal drip, hoarseness, laryngitis, nose bleeds (epistaxis), and intranasal sores.
Ears – Ringing in ears (tinnitus) and Eustachian tube dysfunction (blocked, popping ears).
Throat – Vocal cord dysfunction, throat swelling, sores on tongue/mouth, itchy throat, burning mouth, and difficulty swallowing
Skin – Hives, angioedema (swelling of the skin), skin flushing, itching, skin rashes, dermatographism (when scratched skin causes a red welt), chronic itching, urticarial pigmentosa (legion/hive-like spots on the skin), flushing, bruising easily, reddish or pale complexion, cherry angiomata (skin growths), patchy red rashes, red face in the morning, cuts that won’t heal, fungal skin infections, and lichen planus.
Cardiovascular – Fainting, fainting upon standing, increased pulse rate (tachycardia), palpitations, spikes and drops in blood pressure, high pulse or temperature, high triglycerides, lightheadedness, dizzy, hot flashes, and postural orthostatic hypotension syndrome (POTS).
Respiratory – Wheezing, asthma, shortness of breath, difficulty breathing deep, air hunger, dry cough, chronic obstructive pulmonary disease (COPD), and chronic interstitial fibrosis.
GI Tract – Left upper abdominal pain, splenomegaly (enlarged spleen) epigastric tenderness, nausea, vomiting, diarrhea and/or constipation, abdominal cramping, bloating, non-cardiac chest pain, malabsorption, GERD/acid reflux, cyclic vomiting syndrome, colonic polyps, and gastric polyps.
Liver – High bilirubin, elevated liver enzymes, and high cholesterol.
Neurological – Numbness and tingling (especially in the hands and feet), headaches, migraines tics, tremors, pseudo-seizures, true seizures, waxing and waning brain fog, memory loss, poor concentration, difficulty finding words, and spells of cataplexy (suddenly becoming disconnected from and unresponsive or unreactive to the world around).
Musculoskeletal – Muscle pain, fibromyalgia, increased osteopenia, osteoporosis, weakness, and migratory arthritis (joint pain).
Coagulation – History of clots, deep vein thrombosis, increased bruising, heavy menstrual bleeding, bleeding nose, and cuts that won’t stop bleeding.
Blood disorders – Anemia, increased white blood cell count, platelets, decreased white blood cell counts, decreased neutrophils, decreased lymphocytes, decreased platelets, reductions in CD4 helper lymphocytes, reductions in CD8 positive suppressor lymphocytes, reductions or excesses of IgA, IgG, IgM, IgE, a known condition called MGUS, myelodysplastic syndrome (reduced red cells, white cells, platelets), and increased MCV (mean corpuscular volume).
Psychiatry – Anxiety, panic, depression, obsessive compulsive disorder (OCD), decreased attention span, attention deficit/hyperactivity disorder (ADHD), forgetfulness, and insomnia.
Genitourinary – Interstitial cystitis, recurrent bladder infections, sterile bladder infections, and frequent urination.
Hormones – Decreased libido, painful periods, heavy periods, infertility, and decreased sperm counts.
Dental – Deteriorating teeth.
Anaphylaxis – Difficulty breathing, itchy hives, flushing or pale skin, feeling warm after exposure, weak and rapid pulse, nausea, vomiting, diarrhea, dizziness and fainting.
There are a number of illnesses and conditions that can exacerbate MCAS, including chronic inflammatory response syndrome (CIRS), poor methylation as determined by genetic MTHFR defects (leading to low SAMe, which degrades histamine intracellularly), deficiencies in histamine-N-methyltransferase enzyme (HNMT; degrades histamine in the liver) and deficiencies in the gut-based diamine oxidase (DAO) enzyme, which degrades histamine found in food. Histamine is one of the many inflammatory mediators released by individuals with MCAS. For those with healthy DAO levels, nearly all the histamine derived from food sources are broken down by their DAO enzymes.
But when there’s a lack of DAO, a DAO deficiency, histamine can assist in creating intestinal permeability and upregulated inflammation. If a person suffers from small bowel intestinal overgrowth (SIBO) or has significant small intestinal issues (called dysbiosis), the lining of the small intestine may be disrupted. This leads to even lower levels of the DAO enzyme and hence, intestinal permeability.
A woman who struggles with chronic fatigue and malaise throughout her life gets pregnant and suddenly feels energetic and wonderful throughout her pregnancy. Studies suggest this could be because DAO levels are up to 500 times higher than normal during normal pregnancies.
Alternatively, a person who was previously quite healthy develops a bacterial infection, is prescribed a 10-day course of antibiotics and suddenly develops severe reactions to certain foods. When looked at closely, these foods are found to contain high histamine levels. The current fads of consuming bone broths and fermented foods such as sauerkraut and kombucha only help to exacerbate this condition.
Histamine can have a powerful effect on a person’s wellbeing, making it important to be aware of the symptoms that indicate MCAS.
Mast cell activation syndrome (also referred to as mast cell activation disorder (MCAD)) is sometimes confused with histamine intolerance. The major difference is that with MCAS and mast cell activation disorder, a person’s mast cells secrete many mediators of inflammation, such as leukotrienes and prostaglandins, not just histamine-although histamine is an important component. Histamine intolerance is considered a subset of MCAS where too much histamine is released from mast cells, too much histamine is taken in by consuming histamine-containing foods, histamine is not broken down in the gut because of DAO gut enzyme deficiency, or not broken down in the liver because of HNMT deficiency.
However, histamine is not all bad; it serves useful functions as a neurotransmitter, helps to produce stomach acid, and is an important immune mediator when not in excess.
A proper diagnosis of mast cell disorder requires the presence of several symptoms from the above list. In addition, other disorders should be ruled out by a specialist in functional medicine.
MCAS is so difficult to diagnose because it may present in so many varied ways that traditional health care providers are not always trained to assess. There is a tremendous range of possible presentations, with local and remote effects which wax and wane over time.
If MCAS is suspected at our office, I send patients home with Chapter 6 of the book Mast Cells – Phenotypic Features, Biological Functions and Role in Immunity by David Murray. This chapter was written by Dr. Afrin, entitled Presentation, Diagnosis, and Management of Mast Cell Activation Syndrome. It describes, system by system, most of the symptoms that can be attributed to this diagnosis. Patients then return the symptom check list, which we review together slowly in order to establish the clinical diagnosis. I then order the lab tests to prove its existence.
In Dr. Afrin’s own words, “The general presenting motif of MCAS is chronic multisystem polymorbidity, generally of an inflammatory theme and with assorted elements waxing and waning over time, sometimes in synchronization with one another but more often cycling with different periods and amplitudes. The range of mast cell mediators and their effects is so great that “unusual” presentations actually become de riguer.”
Lab tests can be done to check for mast cell mediators. Tryptase is one of the most common mediators released by mast cells in those with mastocytosis (abnormal numbers of mast cells), but not for those with MCAS (abnormal release of proinflammatory mediators by mast cells, but not an increased number, as in the much rarer mastocytosis). Lab tests can also check for other mediators, such as histamine and prostaglandins; however, most doctors and many labs, particularly those in Canada, will not run the tests that are required to make the diagnosis.
Sometimes patients are able to identify triggers of their MCAS. These may be food or non-food triggers. Pay close attention to what you’ve eaten and have been exposed to when symptoms worsen.
After symptoms have been identified, other conditions have been ruled out, lab tests have been analyzed, and some treatment techniques have proven to relieve symptoms, an official diagnosis of MCAS is made.
If you’re struggling or suspect you have MCAS, it’s in your best interest to reduce your exposure to these triggers, including:
Studies have shown that eliminating foods high in histamine and other triggers can significantly improve symptoms. Ten of the highest histamine foods include:
Because MCAS is a chronic, multisystem, multisymptom condition with an inflammatory theme, it’s been associated with a number of conditions and diseases, including:
In general, inflammation accompanies MCAS and most of its coinciding or associated illnesses. If you are struggling to get one of these illnesses under control, there’s a possibility MCAS could be causing further complications.
It’s a good idea to check for MCAS if you have any of the above conditions and vice versa.
You can take our Hoffman Centre for Integrative Medicine MCAS Questionnaire HERE.
MCAS can be difficult to diagnose because lab test results may fluctuate as symptoms wax and wane. Many tests may need to be repeated during times of symptom flare-ups. Poor handling of specimens by the laboratory is also a real issue affecting results. Lab testing may thus result in false negatives despite a clinical history highly consistent with MCAS. Furthermore, MCAS doesn’t always cause abnormalities in lab work, adding to the complexity of diagnosis. Positive lab work is obtained only 20% of the time.
If you’re interested in getting lab work done to check for MCAS, I recommend the tests listed below. The top five, in bold, are the most important and necessary to establish a diagnosis:
Many of these tests require specimens that are chilled by using a special centrifuge as the mast cell mediators are fleeting and degrade very quickly if not handled properly.
Further tests that may be of help:
These tests can help you identify whether MCAS is the cause of your mysterious and seemingly unrelated symptoms.
Treatments for Lowering Histamine and Reducing MCAS Symptoms
Now, you might be thinking, “Why can’t I just take an antihistamine?”
Antihistamines don’t actually reduce histamine release. They only block histamine receptors, preventing you from feeling the symptoms. You may need a round-the-clock blockade of the H1 and H2 receptors, every 12 hours.
H1 and H2 blockers must be taken every 12 hours for maximum effect. It may take up to 12 months to achieve maximum therapeutic effect. The doses may need to be increased to up to three times the recommended over-the-counter dosing.
It can be incredibly discouraging to feel so sick for so long and not find any answers. It is my hope that we continue to learn more about multisystem conditions such as MCAS and spread useful information so it may end up in the hands of those suffering.
Share this article with friends and family to help spread the word about MCAS symptoms. They may discover it’s more than allergies that’s keeping them down.
Yasmina Ykelenstam – excellent resource: www.healinghistamine.com.
Dr. Afrin’s website – the main researcher: www.mastcellresearch.com. Many links to mast cell information are available on this website.
