Mast Cell Activation Syndrome (MCAS): When Histamine Goes Haywire…
Mast cells are present in most tissues throughout the human body, especially connective tissue, skin, intestinal lining cardiovascular system, nervous system, and reproductive organs. They are part of the allergic response designed to protect us from threat and injury. When the body is exposed to a perceived threat, the mast cells secrete chemical mediators, such as histamine, interleukins, prostaglandins, cytokines, chemokine and various other chemicals stored in the cytoplasm of the cell. These chemical messengers produce both local and systemic effects, such as increased permeability of blood vessels (inflammation and swelling), contraction of smooth muscle (stomach cramps and heart palpitations), and increase mucous production (congestion, sneezing, etc). Historically, we thought of mast cells only in relation to an allergic or anaphylactic response. We now know they play a profound role in immune activation, development of autoimmunity and many other disorders, such as POTS (postural orthostatic tachycardia syndrome). Sadly we are seeing a large increase in patients presenting with mast cell disorders and MCAS. I believe it is in part do to the onslaught of more pervasive environmental toxins, molds and chemicals.
Withouts mast cells, we would not be able to heal from a wound. They protect us from injury and help the body to heal. Unforunately, overactive mast cells can cause a variety of serious symptoms.
Symptoms of overactive mast cells may include:
- skin rashes/hives
- swelling/edema
- flushing
- itching
- abdominal pain
- nausea/vomiting
- diarrhea
- wheezing
- shortness of breath
- heart palpitations
- anxiety, difficulty concentrating
- headaches
- brain fog
- low blood pressure
- fatigue
Mast cell activation syndrome (MCAS) is a condition symptoms involving the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems. It can be classified into primary (clonal proliferation or mastocytosis), secondary (due to a specific stimulus), and idiopathic (no identifiable cause). Proposed criteria for the diagnosis of MCAS included episodic symptoms consistent with mast cell mediator release affecting two or more organ systems with hives, swelling, flushing, nausea, vomiting, diarrhea, abdominal pain, low blood pressure, fainting, heart palpitations, wheezing, red eyes, itching, and/or nasal congestion. For a diagram of all of the varied symptoms histamine can cause, click here.
Triggers may be medications, foods, supplements, hormones, opioids, stressors (physical or emotional), cold temperature, heat, pressure, noxious odors, chemicals, insect bites, trauma or environmental toxins.
We commonly see mast cell activation syndromes associated with CIRS (chronic inflammatory response syndrome) in response to biotoxins, such as mold, inflammagens, and lyme-related toxins.
Low MSH and Mast Cell Disorders?
As mentioned above, we frequently see histamine intolerance and MCAS in patients with mold-related CIRS (chronic inflammatory response syndrome). It is interesting to note that a common finding in CIRS is low MSH. According to this study in the Journal of Investigative Dermatology, alpha-MSH plays an immunomodulatory role during inflammatory and allergic reactions of the skin. In addition, there is evidence that MSH induces mast-cell apoptosis (cell death).
Definition of Mast Cell Activation Syndrome (MCAS)
- Typical clinical symptoms as listed above
- Increase in serum tryptase level or an increase in other mast cell derived mediators, such as histamine or prostaglandins (PGD2), or their urinary metabolites,
- Response of symptoms to treatment
Mast cells can be activated by both direct and indirect mechanisms as a result of exposure of the host to pathogens.
Diseases Associated with Mast Cell Activation Syndrome (MCAS)
- Allergies and Asthma
- Autism
- Autoimmune diseases (Hashimoto’s thyroiditis, systemic lupus, multiple sclerosis, bullous pemphigoid, rheumatoid arthritis and others.Eczema
- Celiac Disease
- Chronic Fatigue Syndrome
- CIRS (chronic inflammatory response syndrome)
- Eosinophilic Esophagitis
- Fibromyalgia
- Food Allergy and Intolerances
- Gastroesophageal reflux (GERD)
- Infertility (mast cells in endometrium may contribute to endometriosis)
- Interstitial Cystitis
- Irritable Bowel Syndrome (IBS)
- Migraine Headaches
- Mood disorders – anxiety, depression, and insomnia
- Multiple Chemical Sensitivities
- POTS (postural orthostatic hypotension)
Mast cells are known to be the primary responders in allergic reactions, orchestrating strong responses to minute amounts of allergens. Several recent observations indicate that they may also have a key role in coordinating the early phases of autoimmune diseases, particularly those involving auto-antibodies.
Lab Tests for Mast Cell Activation Syndrome (MCAS)
- Lab tests specific to mast cell activation for suspected MCAS may include:
- Serum tryptase (most famous mast cell mediator)
- Serum chromogranin A
- Plasma histamine
- Plasma PGD2 (chilled)
- Plasma heparin (chilled)
- Urine for PGD2 (chilled)
- PGF2a
- N-methylhistamine
- Tryptase is the most famous mast cell mediator. Serum tryptase value is usually normal in MCAS patients, but sometimes it is elevated. Tryptase values that show an increase of 20% + 2 ng/ml above the baseline level are considered diagnostic for MCAS.
- Chromogranin A is a heat-stable mast cell mediator. High levels can suggest MCAS, but other sources must first be ruled out, such as heart failure, renal insufficiency, neuroendocrine tumors and proton pump inhibitor (PPI) use.
- Heparin is a very sensitive and specific marker of mast cell activation. However, due to its quick metabolism in the body, it is very difficult to measure reliably.
- N-methylhistamine is usually measured in a 24 hour urine test to account for the variability in release over the course of the day.
- Prostaglandin D2 is produced by several other cell types, but mast cell release is responsible for the dominant amount found in the body. PGD2 is less stable than histamine and metabolized completely in 30 minutes.
- Other less specific mast cell mediators that are sometimes abnormal in MCAS patients include Factor VIII, plasma free norepinephrine, tumor necrosis factor alpha, and interleukin-6.
Treatments to reduce MCAS symptoms and lower histamine
- H1 Blockers
- hydroxyzine, doxepine, diphenhydramine, cetirizine, loratadine, fexofenadine
- H2 Blockers
- Famotidine (Pepcid, Pepcid AC)
- Cimetidine (Tagamet, Tagamet HB)
- Ranitidine (Zantac)
- Leukotriene inhibitors
- Montelukast (Singulair)
- Zafirlukast (Accolate)
- Mast cell stabilizers –
- Cromolyn
- Ketotifen
- Hyroxyurea
- Tyrosine kinase inhibitors – imatinib
- Natural anti-histamines and mast-cell stabilizers
- Ascorbic Acid
- Quercetin
- Vitamin B6 (pyridoxal-5-phosphate)
- Omega-3 fatty acids (fish oil, krill oil)
- Alpha Lipoic Acid
- N-acetylcysteine (NAC)
- Methylation donors (SAMe, B12, methyl-folate, riboflavin)
- Certain probiotics decrease histamine production
- Lactobacillus rhamnosus and bifidobacter species
- DAO Enzymes with meals – UmbrelluxDAO
- Decrease consumption of high histamine foods (more on histamine-restricted diet)
- Avoid alcoholic beverages
- Avoid raw and cured sausage products such as salami.
- Avoid processed or smoked fish products. Use freshly caught seafood instead.
- Avoid pickles
- Avoid citrus fruits.
- Avoid chocolate
- Avoid nuts
- Avoid products made with yeast and yeast extracts
- Avoid soy sauce and fermented soy products
- Avoid black tea and instant coffee
- Avoid aged cheese
- Avoid spinach in large quantities
- Avoid tomatoes, ketchup and tomato sauces
- Avoid artificial food colorings & preservatives
- Avoid certain spices: cinnamon, chili powder, cloves, anise, nutmeg, curry powder, cayenne pepper
Specific Symptom Treatment in MCAS
- Headache⇒ paracetamol; metamizole; flupirtine
- Diarrhea⇒ colestyramine; nystatin; montelukast; ondansetron
- Colicky abdominal pain ⇒ metamizole; butylscopolamine
- Nausea⇒ metoclopramide; dimenhydrinate; 5-HT3 receptor inhibitors; icatibant
- Respiratory symptoms (mainly increased production of viscous mucus and obstruction with compulsive throat clearing) ⇒ montelukast; acute: short-acting albuterol
- Gastric complaints⇒ proton pump inhibitors
- Osteoporosis, bone pain⇒ biphosphonates, Vitamin D plus calcium
- Non-cardiac chest pain⇒ H2-histamine receptor antagonist; proton pump inhibitors
- Tachycardia⇒ verapamil; AT1-receptor antagonists; ivabradin
- Neuropathies ⇒ a-lipoic acid
- Interstitial cystitis⇒ pentosan, amphetamines
- Sleep-onset insomnia/sleep-maintenance insomnia⇒ triazolam/oxazepam
- Conjunctivitis⇒ preservative-free eye drops with glucocorticoids for brief course
- Elevated prostaglandin levels, persistant flushing⇒ incremental doses of acetylsalicylic acid (50-350 mg/day; extreme caution because of the possibility to induce mast cell degranulation)
References
- Mast Cell Activation Syndrome, A Review
- Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options
- Presentation, Diagnosis and Management of Mast Cell Activation Syndrome by Dr. Afrin
- Histamine and Gut Immune Mucosal Regulation
- Dr. Theoharides presents “Mast Cell Disorders”
- Diagram of Histamine Symptoms
- Mast Cell Aware
- A Tale of Two Syndromes
- Mold Histamine Connection
Dr. Jill-
Your presentation at the CIRS Conference was amazing! You are such a dynamic Physician , educator and healer. I am on moldy house #4. I keep jumping out of the frying pan into the fire. I was treated with CSM 3 years ago when I was exposed to Chaetoneum. Initially, I would sweat profusely upon expose. Then I started having an immediate bowel movement when I was around something I didn’t like ( I have to laugh). Now, I have EMF sensitivity that is causing me to go into seizures. I just moved to a new area and am trying to find Integrative Health Care. Psychiatrists that understand the effects of mold are seemingly impossible to locate. I am a mercury poisoned Dental Hygienist with MarCons and a husband that doesn’t want to move again. I am extremely resilient but I am at the end of my rope. Do you do phone consults? I am the poster child for CIRS and MCAS….
Gratefully,
Kay Helfant
Thank you so much, Kay!
I assume she doesn’t. You’ll have to find something else for what ails you.
Hi Kay. The EMF issue is most often if not always a Mercury issue, Definitely avoid Smart Meters, Wifi as much as possible esp on Hand Held devices but even being around it at all, and cordless phones (an cells) are all especially bad. I hope you look to safe Chelation, the safest and most effective being the Andy Cutler Chelation Protocol, which unfortunately most Doctors are not using. Good healing to you, sorry you too are poisoned (I am as well as are many others I know personally).
Hello. My son had an illness 4 years ago that doctors never diagnosed however they speculated he had an undiagnosed case of encephalitis. Since then, he has experienced several ‘flare ups’ of a cognitive fog which eventually leads to insomnia , inability to find words, difficulty communicating and anxiety. He never had these issues prior to his illness four years ago. We cannot find common triggers for when the flare ups happen. His symptoms match many of those you have listed in this article. We’ve been to 18 doctors in all different disciplines given his wide range of symptoms. Wondering if there is a list of doctors who specialize in mast cell activation diagnosis that I can take him to? Thank you!
You might try the world expert, Dr. Lawernce Afrin….
Dr. Jill – thank you for your informative article! It’s great to understand the mast cell activation syndrome. My chiropractor found my histamine problem through genetic testing/MethylGenetic Nutrition Analysis, and Professional Health Products Histamine Scavenger solved my problem (I previously had the IgG test to know what foods to avoid). My CFS is gone, my FMS is almost gone and I sleep well for the first time in decades. I love PHP products so much that I became their Colorado rep:)
Hi Angie,
thanks for sharing your story!
warmly
Dr Jill
Hi Angie,
What foods did they suggest? I have it in my bladder and can’t figure it out. It’s getting worse. Thank you so much! Debbie
Thank you so very much for this article . I was diagnosed with IBS, dispute having Adhesions removed from my Colon in 2015. Unlike the normal person who has IBS occasionally; I have pain every day. I would like to look into the Mass Cell Activation. I live Las Vegas;. Do you know of any doctors out here who do this?
Hi Jennie
You might try contacting world expert, Dr. Lawrence Afrin, to get a referral in your area
warmly
Dr Jill
Dr. Carnahan, I see you have a great article on Mast Cell Activation and a bit about Histamine Intolerance, for some great help for people that suffer from one or both of these, I would highly recommend http://healinghistamine.com This site has been very helpful to me and many I meet who don’t know much about histamine intolerance. Thanks for addressing this very challenging topic!
Dr Carnahan,
I am reading through the diet recommeded for MCAS by Dr Joneja in the link you give above and there are quite a few surprises on the list so can you comment? My wife follows a different list from Dr Ahern (in addition to strict Paleo) and it seems to help but the list in your link seems strange (why does it allow dairy, gluten and cashews for instance).
I am specifically interested in why the following are restricted:
Sweet potatoes
Berries such as blueberries, blackberries
Grapes
Unpasteurized honey
Thanks for your help!
Dr. Joneja’s diet eliminates foods that contain high histamine levels. The Paleo diet is not focused on histamine levels in food.
warmly
Dr Jill
I don’t know if I just simply have a salicylate and histamine intolerance or if its mast cell activation. I just know that I react to many vegetables , fruits, preservatives,dyes, yeast, fermented things etc. I have completely eliminated gluten products because I was getting brain fog so bad it felt like I got a concussion along with numbness and pins and needles. although putting aside the gluten from food I still get flushing , burning skin, and onset of extreme anxiety. The thing that confuses me if how fast the reaction will come on it will take often less than a minute to start having my skin burn and when I react wrong to a food and get anxiety it happens in less than a minute to and sometimes will last all day so I try to be so careful what I eat. I don’t understand what would be causing me to get such fast reactions from food. Its been hard.
That sounds like a histamine IgE reaction since it occurs very quickly. It could also be sensitivity to oxalates in food or salicylate. I suggest further testing to determine the cause.
warmly
Dr Jill
Wow, this article is amazing. I suffered for many years with chemical sensitivities, asthma, allergies & digestive issues. For about 10 years I had even had seizures. Doctors said I had everything from Lymes disease to MS, but nothing was concrete. My husband & I operated a commercial cleaning business for 20yrs. Now he has a lot of the same problems as me. Doctors have been treating him for RADS, asthma & COPD. We found the only way to cope was to be guarded about our environment. We discontinued our business, which helped me to improve, but he continues to decline. Thank you for the research going into understanding this growing problem.
For a more natural approach what do you suggest in supplementations and eating to stabilize the mast cells rather then taking any medicine. Please advise and Thank you!
Hi Judy
I have listed all the natural mast cells stabilizers in article here
Warmly
Dr Jill
Thank you for this article Dr Gill. I saw 2 allergists here in quebec, canada, and have an appointment with a third one soon, since no one helped me, they only do the skin scratch tests to confirm i have pollens, dust, cats and seafoods ige mediated allergies. Now that doesnt help me at all with my mcas symptoms, i evrn had POTS symptoms last summer that fortunatly calmed down since my diet is very stable with testing every safe food separatly ( im eaTing about 30 different foods now). My question is: how do i make sure the allergist does me the good tests to diagnose possible mcas? I cannot travel far to see a specialist, i cannot eat out and im a single mother of two. I do not take any medication. Im afraid to go back to the dentist ( had a cardio respiratory reaction with anesthesiant) . My typical reaction is sensation that something is stuck in my throat. I have much itchiness and redness on the skin. Stomach pain. Thanks for helping me.
Dear Dr. Jill
Do you have ever studied or considered the relation between the MCAS and periodic fever syndrome as PFAPA?
My son has allergies and now it seems he has PFAPA.
Dear Dr. Jill
Do you have ever studied or considered the relation between the MCAS and periodic fever syndrome as PFAPA?
My son has allergies and now it seems he has PFAPA.
It could be related but I have not seen any research on this…
I was not aware that MCAS is related to inflammation my son’s allergies are always related to food and he always had vomits and diarrhea and very specific times rashes. I believe he had FPEIS to rice. We have controlled the trigger foods (no diarrhea or vomits anymore) but he’s still bloated and underweight but growing. One year ago he started with fevers that follow a pattern we are about to get a Periodic fever syndrome diagnosis.
I really wonder if MCAS and PFAPA could be connected and maybe using some of the natural tratement that you mentioned could help.
Btw PFAPA is controled with corticosteroids
ALA is a powerful Mercury chelator and crosses the blood brain barrier. It should only be dosed low, slow and frequently based on its half-life–and only if there are no Mercury fillings in the mouth. Otherwise, one risks redistribution of the Mercury throughout the brain and body.
Hi HC
Yes, ALA must be used with caution but most patients can tolerate low dose R Lipoic Acid
warmly
Dr Jill
Hi Dr. Jill,
I have been trying claritin once a day in the morning or Benadryl once in the evening (rather than the claritin) and I am noticing a MAJOR decrease in my night-time pain attacks due to my Crohn’s disease. Since starting the histamine blockers listed above I have been able to stop taking nightly narcotics for the pain. I am also on Stelara so I need to figure out which is causing the breakthrough but the reason I tried this is because I was continuing to have pain despite the stelara. This could be a MAJOR breakthrough for me. I am going to do some experiments where I go off the histamine blockers for a week and see what happens, though I am reluctant to mess with a good thing. Very exciting.
Eve
Wonderful, Eve! I hope this continues to help you…
Dr. Carnahan,
How does one get a diagnosis of MCAS? What specialist is likely to do the diagnosing or order more tests? Immunologist, allergist, dermatologist? My PCP isn’t very open or helpful in discussing other possibilities of all of my vague symptoms. I have always had extreme/severe allergies that cause respiratory symptoms. I am very sensitive in general, to medications and environmental. I have seen an allergist off and on for about 15 years so I do have confirmed allergies. Lately I have “unknown” allergens when I eat and cause nose stuffiness and some facial tingling but no answers as to what is causing it…just that I now need to carry an epi-pen with me. I have a chronic history of: joint swelling/inflammation/stiffness mainly in my hands and back, chronic headaches and 2-3 migraines a month, I bruise extremely easy, insomnia, i flush easily and get hives on my forearms, chronic vit D deficiency, osteopenia, and bone infections in the jaw (4 rounds of antibiotics for that). Starting in 2015 I noticed heart palpitations intermittently after I started antibiotics. they still come and go. Around the same time I started having low blood pressure and have had a few instances of passing out. I was told by my PCP it’s probably just dehydration and to drink plenty of fluids. It’s frustrating to try to piece it all together and get answers. I don’t want to mask symptoms any longer.
MCAS is a clinical diagnosis. Symptoms consistent with MCAS and response to treatment.
warmly
Dr Jill
Hi Dr. Jill,
I am wondering if you have come across joint hypermobility and Ehlers-Danlos syndrome in relation to mast cell disorders? Thought you might want to add it to your list of associated conditions.
This article was just recently published. http://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31555/full
Thank you for all your great articles!
Chris
I concur with this comment. I stumbled across this article and was surprised to not see EDS listed.
Love your article & it was recommended by my Rheumatologist. I’m labeled with lots of conditions, Unspecified IBD/IBS, Inflammatory Autoimmune Disorder, Chronic Migraines, CFS, Fibromyalgia & a mental case! Recently diagnoised with Autoimmune Urticaria due to positive Basophilic Activation & a Mast Cell Disorder with extremely high IgE Fc Receptor AB & symptoms. Whatever the label is, it attacks my Skin, GI, Brain, Heart (Electrical) & my joints. I have 2 questions.
1. Can this disorder cause lesions in the white matter of the brain on MRI?
2. Best approach in discussing Mast Cell Disorder with a doctor who is unfamiliar or doesn’t believe the condition exsists?
Thank you for you time & education in these matters!
Hi Lynn,
I do not think MCAS can cause white matter lesions in the brain. Best approach would be to share the resources from Dr. Theoharides and Dr. Afrin
Warmly
Dr Jill
Hi Dr. Jill,
Do you know if mast cell activation can cause fat malabsorption? I had a 24 hour stool test come back positive for fat malabsorption but my stool elestace test was normal and hydrogen breath test was also negative. So it seems like it is not due to pancreatic insufficiency or SIBO. I also had a normal abdominal CT, colonoscopy and endoscopy so they don’t think it is crohn’s or UC. No classic gallbladder symptoms either so they are not sure what is causing the malabsorption. Mainly I have weight loss, diarrhea and left lower abdominal pain. I also have ehlers danlos and possibly pots. Thank you so much for your time! Chris
Histamine affects the gut in various ways, including increased intestinal permeability and inflammation
Dr. Jill,
Father to two year old with EoE. I noticed you mentioned that EoE may be associated to MCAS. I am curious as to your connection of the syndrome and the diseases (eosinophilic types) that typically are reactionary from IL-5, IL-13 and IL-33 proteins. Is it possible that the underlying factor is the CAPN-14 gene or other genes usually associated to a specific organ tract? Or is MCAS associated with another gene and those organs? I have felt that histamines play a big part in EoE but I haven’t seen the scholarly connections between the two (H-1 and EoE).
Hi GMC – there is an association with histamine issues/mast cell disorders and EoE. Check Dr. Theoharides work for possible references..
Warmly
Dr Jill
Hi Dr. Jill,
Thank you for your article. I am wondering if MCAS can be triggered by extreme adrenal fatigue? My daughter suffered with all of the symptoms of MCAS and we were searching for a practitioner to help her with this when we ran across information on severe adrenal fatigue, which has many of the same symptoms as MCAS! Fortunately, treating her adrenal fatigue has stopped the symptoms of MCAS as well! No more daily hives! She is basically having salt daily and nano liposomal Vit C and starting glutathione. It’s amazing how much the salt helps!! So, just curious if there is a connection between these two issues? Thank you!
Hi Madeira,
Yes, fatigue is a common part of MCAS. It can result from many reasons.
warmly
Dr Jill
Hi Dr. Jill,
Is there a specific probiotic product you would recommend for those with mast cell activation?
Thank you!
Chris
Hi Chris,
There are many things listed and it can be trial and error. One of my favorites is Neuroprotek – call 303-993-7910 if you would like to try it.
warmly
Dr Jill
Hi Dr Jill,
Quick question, I have lyme and mold (mast cell) and MCS and when I treat either lyme or mold I go into anaphylaxis. How can I get better if the tx causes the immune system to flair so drastically each time?
Thanks for your time,
Lexi
Hi Lexi
You may need to work on gentle detox before your body can handle treatment
warmly
Dr Jill
What would you consider as a gentle detox? Sweating? Oil pulling?
Thank you so much for your response!