Mast Cell Activation Syndrome (MCAS) 3/3

Admin Good Health Uncategorized

A Spectrum of Symptoms – Again

Let’s start this post where we started the first post in this series, visiting a support group, a support group which you now know to be one for people with mast cell activation syndrome (MCAS). Here is how four members describe their problems:

The first member shares that they have a lot of skin problems – redness itching, hives. They also have a lot of sneezing plus bouts of diarrhea. The second member struggles with mild low blood pressure, mild headaches, cough, mild shortness of breath, mild diarrhea, nausea, mild abdominal cramping. The third member has long-standing and prolonged problems with: feeling inflamed all over, skin problems like the first member, almost constant diarrhea combined with frequent nausea, a chronic cough, fatigue, and depression. The fourth member has truly been disabled by their problems:  daily sweating, frequent fevers, severe skin problems, shortness of breath with wheezing, severe gut pain plus cramping and frequent vomiting, almost constant diarrhea, and worst of all, unpredictable episodes of anaphylactic shock for which they must carry an epi-pen.

Like hypermobility and hypermobile Ehelrs-Danlos Syndrome and like dysautonomia, MCAS occurs on a spectrum among those who have it from mild to severe and localized (sometimes only in the skin) to whole body. Given this diversity, what can the treatment be?

Treatment {1,2,3,5,11, 15}

One of the best summaries of treatment for MCAS that we have seen is in a relatively short pithy journal article by Gerhard Molderings and others. In 2011, he wrote:

“The cornerstone of therapy is avoidance of identifiable triggers for mast cell degranulation such as animal venoms, extremes of temperature, mechanical irritation, alcohol, or medications (e.g., aspirin, radiocontrast agents, certain anesthetic agents). Individual patients may have variable tolerance patterns and avoidance lists, but it is also not uncommon to have no identifiable triggers… Drug treatment of MCAD patients is highly individualized. Curative therapies are not available, and each MCAD patient should be treated in accordance with his [sic] complications. Irrespective of the specific clinical presentation of MCAD, evidence-based therapy consists of trigger avoidance, antihistamines and mast cell membrane-stabilising compounds … supplemented as needed by medications targeting individual mast cell mediator-induced symptoms or complications. {5, pg. 5}”

Said more simply, the first line, or first steps, of treatments for MCAS are 1. finding and avoiding triggers, 2. Antihistamine medications and medications to help prevent the mast cells from releasing inflammatory chemicals, and 3. Treatment of specific symptoms such as headaches, diarrhea, and pain (to list just a few). After this first steps of therapy, there are more advanced levels of therapy.

Non-pharmacological Treatment

Finding individual triggers is sometimes quite hard and sometimes quite easy and as was stated above, sometimes there are no identifiable triggers. Still, for the patient with MCAS, self-monitoring to find the things that make them feel bad is a crucial first step.

Below is a table of common MCAS triggers compiled from a number of sources (some referenced, some not). We divide the list into four main categories. Take a minute to look it over and remember that just because a trigger is common does not mean it is a trigger for any given individual with MCAS, and there can be others not listed here.

Environmental Strong odors. examples: gasoline, perfume Cleaning agents Laundry detergent Mold Dust Venom especially bees Poison ivy, poison oak Pesticides Amalgam dental fillings Rapid temperature changes Changes in barometric pressure Sun exposurePhysical/ Emotional Psychological or emotional stress Strong emotions Self-negativity Extreme mental exertion High sexual arousal Caffeine Physical overexertion Physical stimuli such as vibration, friction, shock or impact Menstrual cycle changes Infection
Dietary Fruits and vegetables with higher levels of pesticides Alcohol Gluten Cow’s milk proteins Baker’s yeast Tomatoes Chocolate Spinach Fermented foods Citrus Preservatives  Medications Antibiotics: Cefuroxime, Vancomycin Anticonvulsants: Carbamazepine, Topiramate Cardiovascular drugs: ACE inhibitors, beta adrenoceptor antagonists Intravenous narcotics: Methohexital, Phenobarbital, Thiopental Local anesthetic: Lidocaine, Articaine, Tetracaine, Procaine Opioids: Meperidine, Morphine, codeine Acidic NSAIDS such as Ibuprofen Nerve medicines: Icatibant, Cetrorelix, Sermorelin, Octreotide, Leuprolide, Bupropion Plasma substitutes: Hydroxyethyl starch, gelatin Muscle relaxants: Atracurium, Miva curium, Rocuronium X-ray contrast materials

We encourage patients with MCAS to start a daily diary in which they note things like:  emotional stress level (which can be noted from 0 = none to 10 = horrible), temperature, barometric pressure, all foods eaten, and especially anything that caused an immediate response. Here in the Pacific Northwest, indoor mold is such a common problem that it is the single most common trigger that patients report to us.

Some of the most difficult triggers to identify can be food triggers. While it can be easy to identify simple single items, identifying groups or families of foods or foods processed in the same way can be difficult. Here is where trial of an elimination diet can be very useful and instructive even though this is not always easy to do. There are a number of good books on this subject and websites. A little research will give more guidance than we can here.

Obviously, once triggers have been identified, effort must  be made to avoid them – changing laundry detergent, changing diet, wearing a mask, etc. – a little effort may produce big rewards.

A final thought about triggers. Looking for triggers when one feels ill and stressed can be hard. Take this slowly. It can be easy to let the search for triggers make a person feel frightened of their world. This is not helpful. Get support as needed. We will talk more about this at the end.

First Line Drugs and Supplements

In any conversation about medications and MCAS, the first recommendation is that the patient look at the medications they are taking. As you can see above, there are a number of medications which can trigger MCAS flare-ups. So, when in doubt, the patient is advise to review their medication list with their physician or pharmacist.

When starting new medications for MCAS, one author gives some clear suggestions:

… Medications should usually be added one at a time, with an adequate interval of time between the addition of successive drugs. Some patients need to begin medications at a lower dose and then gradually escalate to a standard dose. Patients need to be told that the time for noticing an initial symptomatic response may be a few weeks. {3, pg. 234}

The treatments for MCAS are not instantaneous. Patience is needed.

The first line medications used in MCAS are targeted at limiting or blocking the effect of mast cell mediators.

  • Medications used to block histamines: hydroxyzine, doxepin, diphenhydramine, loratadine, fexofenadine, cetirizine, ranitidine, cimetidine, famotidine.
  • Medications used to block leukotrienes: monteleukast, zileuton, ketotifen.
  • Medications used to block cytokines: low-dose naltrexone.

Another first line of defense is medications which stabilize the mast cells so that they do not release their mediators so easily. These medications may include: cromolyn sodium and ketotifen.

There are also a number of supplements which may inhibit mediators and/ or stabilize the mast cell. Some of these are: quercetin, Vitamin C, bromelain, flavonoids, reservatrol, melatonin, cannabinoids, curcumin.

Some of the medications and supplements listed above are available over the counter. It is always important to work with your physician rather than attempting to self-medicate.  Some medications and supplements can have interactions and can cause problems when taken in combinations.

Advanced Treatments {6,15}

For difficult cases of MCAS resistant to the first line of treatment, there can be more advanced treatments. In a deeply referenced review article, Gerard Molderings and colleagues review not only the first line, basic treatments but also go on to describe second, third fourth and fifth lines of therapy. {15}. While we will not go into depth about these higher levels of treatment here, this open access article might be instructive to the inquisitive patient and/ or their provider in a case not making the desired progress.

Pain in MCAS {6}

Three quarters or more of patients with MCAS have MCAS-driven pain. Part of this may be due to the fact that mast cells frequently live close to nerve/ blood vessel bundles, and several of the mediators released by mast cells are also nerve transmitter molecules which can cause pain nerves to fire. {6. Pg E851}. Mast cell mediators can also cause direct inflammation of the nerves, called neurogenic inflammation. This inflammation may be limited to a small area, more widespread or even body wide. In many cases the first line medications and supplements described above will help with this pain.

Getting Help

One of the biggest challenges facing patients with MCAS can be finding a knowledgeable health care provider to work with. While many allergists and rheumatologists are experts at diagnosis and management of MCAS. More and more geneticists are playing a role in healthcare too and can be an excellent source of guidance. Knowledge of MCAS treatment is not limited to specialists though.

We have seen many primary care physicians who have a high level of knowledge and skill with MCAS cases. Lists of primary care physicians usually start with medical and osteopathic doctors specializing in family or internal medicine.  In Oregon and Washington plus a number of other states, naturopathic physicians may also be included in the list of primary care doctors. While a skilled naturopath can be helpful with the medications discussed here, they may also be particularly helpful with supplements and with guidance regarding elimination diets. We have known many excellent and highly skilled chiropractic physicians, and in some regions of the country, they may function as primary care physicians. However, it is our understanding  that in most states, while chiropractic physicians can give guidance on supplements, they cannot prescribe drugs, and so would be limited with more advanced cases of MCAS.

If you suspect that you have MCAS, we strongly encourage you not to try to self-diagnose. Do have a conversation with your primary care provider first. See what they think. If you do not have a primary care physician, seek out a social media support group where there is a ‘hive-mind’ of knowledge regarding local practitioners such as who knows how to manage MCAS, who is accepting patients, and who might accept your insurance. We have found several national MCAS support groups on Facebook. If you have MCAS and cannot find a local group, perhaps you might start one. If you have Ehlers-Danlos Syndrome, there are also a number of online support groups. In Oregon, the Oregon Area Ehlers-Danlos support group on Facebook is an excellent resource including for MCAS.  

Our next blog post series will look at digestive problems and gut pain in hypermobility spectrum disorder and hypermobile Ehlers-Danlos Syndrome.

Until then, cheers!

Zebbie & Mark

Zeborah Dazzle, PT, WWF & Mark Melecki, PT, DPT, OCS

Good Health Physical Therapy and Wellness.

References (Note: all the references below are open access on the internet.)

  1. Valent, P., et. al., Diagnosis, Classification and Management of Mast Cell Activation Syndromes (MCAS) in the Era of Personalized Medicine. International Journal of Molecular Sciences, 2020, 21, 9030; doi:10.3390/ijms21239030
  2. Valent, P., et. al., Mast Cell Activation Syndromes: Collegium Internationale Allergologicum Update 2022. Int Arch Allergy Immunol 2022; 183: 693-705; doi:10.1159/000524532
  3. Senevirante, S.L., et. al., Mast Cell disorders in Ehlers-Danlos Syndrome. American Journal of Medical Genetics Part C (Seminars in Medical Genetics) 175C:226-236, 2017, doi: 10.1002/ajmg.c.31555
  4. Afrin, L., et. al., Diagnosis of Mast Cell Activation Syndrome: A Global “Consensus – 2”. Diagnosis 2021, 8(2): 137-152, https://doi.org/10.1515/dx-2020-0005
  5. Molderings, G.J., et. al., Mast Cell Activation Disease: A Concise Practical Guide for Diagnostic Workup and Therapeutic Options. Journal of Hematology and Oncology 2011, 4:10, http//WWW.jhoonline.org/content/4/1/10
  6. Wirtz, S. & Molderings, G.J., A Practical Guide for the Treatment of Pain in Patients with Systemic Mast Cell Activation Disease. Pain Physician 2017, 20:E849-E861.
  7. Shibao, C., et. al., Hyperadrenergic Postural Tachycardia Syndrome in Mast Cell Activation Disorders, Hypertension 45(3), 1 March 2005, 385-390, https://doi.org/10.1161/01.HYP.0000158259.68614.40
  8. Amin, K., The Role of Mast Cells in Allergic Inflammation, Respiratory Medicine (2012) 106, 9-14.
  9. Valent, P., et. al., Definition, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal. In Arch Allergy Immunol 2012; 157: 215-225. DOI:10.1159/000328760.
  10. Alvarez-Twose, I., et. al., Current State of biology and Diagnosis of Clonal Mast Cell Disease in Adults. International Journal of Laboratory Hematology 2012; 34: 445-460, doi:10.1111/j.1751-553x.2012.01427.x
  11. Valent, P., et. al., Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook Toward the Future. Cancer Res. 2017 March 15; 77(6): 1261-1270. Doi:10.1158/0008-5472.CAN-16-2234
  12. Amin, K., The Role of Mast Cells in allergic Inflammation. Respiratory Medicine (2012) 106, 9-14; doi:10.1016/j.rmed.2011.09.007
  13. Kohn, a., Chang, C., The Relationship Between Hypermobile Ehlers-Danlos Syndrome (hEDS), Postural Orthostatic Tachycardia Syndrome (POTS), and Mast Cell Activation Syndrome (MCAS). Clinical Reviews in Allergy & Immunology (2020) 58: 273-297; https://doi.org/10.1007/s12016-019-08755-8.
  14. Leru, P.M., et. al., Mast Cell Activation Syndromes – Evaluation and current Diagnostic Criteria and Laboratory Tools in Clinical Practice (Review). Experimental and Therapeutic Medicine 20:2348-2351, 2020. Doi:10.3892/etm.2020.8947.
  15. Molderings, G., et. al., Pharmacological Treatment Options for Mast Cell Activation Disease. Arch Pharmacol (2016) 389:671-694; doi:10.1007/s00210-016-1247-1