Imagine it: you are a 35 year old female. You used to love to go to the gym, but have been diagnosed with Ehlers-Danlos Syndrome, and now you’re lucky if you can walk down the stairs without pain and open the car door without your shoulder, ankle, knee, hip, shoulder, or wrist cracking and possibly even dislocating. Usually, you’re so fatigued you can barely get through lunch, but on a good day, when you’re less tired than usual and you try to go to the gym, you get so dizzy when you’re trying to do your body weight squats, you usually can’t even finish the workout you had planned. What is the world is wrong with you and why can’t anyone help you figure it out?! The good news is recent studies are showing a connection between this disease trifecta, Mast Cell Activation Syndrome (MCAS), Postural Orthostatic Tachycardia Syndrome (POTS), and Ehlers-Danlos Syndrome (EDS). While there is no cure, it can be very manageable if you know how to figure out your underlying triggers. This is where I hope I come in! As someone with this syndrome combo, I not only can offer you a research/medical perspective, but I can also offer you my own personal journey and how to successfully navigate yours.

Mast Cell Activation Syndrome: What Is It and What Are The Symptoms?

Mast Cell Activation Syndrome (MCAS), otherwise known as Mast Cell Activation Disorder (MCAD), is an immunological condition in which mast cells release excessive amounts of chemical mediators, which can result in a myriad of physical symptoms. Remember that mast cells are a necessary part of the immune system – they are the “heros” that activate the immune system when the body perceives a foreign invader.  They are present throughout your entire body, especially in areas where your body is likely to come into contact with material from the outside, like your skin, digestive, and respiratory systems. The problem is when these same mast cell cells perceive many different things as a threat. Normal everyday things can be triggers, like medications, foods, supplements, physical and/or emotional stress, very cold or very warm temperatures, pressure, noxious odors, exercise/exertion, chemicals, bug bites, trauma, or other environmental toxins/biotoxins, like mold. I had an unfortunate run-in with some black mold last year that had me laid up for nearly 6 months. Now that I know how bad of a trigger it is for me, I need to avoid it at all costs!

Mast Cell Symptoms

How Do You Manage MCAS?

Managing your MCAS really depends on how severe your initial symptoms are. Sometimes trying a low histamine diet, like the one found in the 4-Phase Histamine Reset Plan, can be helpful in getting your symptoms under control, and as you feel better, you may be able to start adding foods back in.  Sometimes people like to supplement their diets with a mast cell stabilizer. Natural options include foods with ascorbic acid, quercetin, B vitamins, and omega-3 fatty acids. For this, I recommend HistoRelief, which will provide you with a synergistic blend of nutrients that provides natural support to help balance the immune response by allowing you to naturally stabilize your mast cells and also eat foods that you enjoy without a significant reaction. If you’re finding that you can only tolerate a handful of foods without a reaction, you may need to try some medication first in order to get your symptoms under control before you can really start figuring out what to avoid. Remember that histamine, one of the more common chemical mediators released by mast cells, binds to different receptors throughout the body. The medications that may be necessary are H1 (zyrtec, claritin etc.) and H2 (ie. pepcid AC, zantac)  blockers, which mostly act on vessels in the brain to dampen your reaction to histamine. Although these medications can be a necessary first start for extreme cases, they reduce the enzyme (DAO enzyme) responsible for breaking down histamine in the body. I would not recommend using these without guidance from a mast cell specialist. 

Postural Orthostatic Tachycardia Syndrome (POTS)

POTS is a condition caused by too little blood returning to the heart when moving from a lying down to a standing up position (orthostatic intolerance) with a rapid increase in heart rate (tachycardia). People with POTS usually have low blood volume and high levels of norepinephrine (a neurotransmitter released during stressful situations), indicating increased sympathetic nervous system activation. Other reported symptoms in people with POTS include:

  •     Blurred vision
  •     Lightheadedness, dizziness, and/or fainting
  •     Heart palpitations
  •     Headaches
  •     Difficulty concentrating
  •     Fatigue
  •     GI symptoms, such as nausea, cramps, bloating, constipation, diarrhea
  •     Shortness of breath
  •     Head, neck, or chest discomfort
  •     Feelings of weakness
  •     Sleep disorders
  •     Exercise intolerance
  •     Anxiety
  •     Cold or painful extremities

Unfortunately, the cause of POTS is not well understood. Episodes typically begin after major surgery, trauma, or a viral infection; in women, symptoms may be noticed after pregnancy or may worsen right before menstruation. The good news is most cases of POTS are very manageable and typically have a good prognosis with appropriate management. Given the variety of reasons someone may be diagnosed with POTS, there is no single treatment that is going to work for everyone. The purpose of pharmacological treatment is to improve low blood pressure and issues with the heart and vessels that may be contributing to symptoms. Lifestyle changes, like drinking more fluids, exercising, and avoiding triggers, may be all that is necessary for management.  I had difficulty exercising with my POTS: I would try to go down into a squat or a lunge and immediately, I would get dizzy even though I’ve worked out for years. If this is the case for you as well, trust me, you are not alone. Please stay tuned for my next blog post for more details on Exercise Intolerance!

POTS

MCAS and Its Relationship to POTS

New research is suggesting significant overlap between Mast Cell Activation Syndrome and disorders of the autonomic nervous system (the nervous system that you have no control over and includes things like your heart rate and breathing). MCAS should be taken into consideration in patients with POTS when the rapid increase in heart rate upon standing is also associated with intermittent flushing. Prolonged standing in patients with both MCAS and POTS may also cause the associated flushing, as well as shortness of breath, headache, lightheadedness, diarrhea, nausea, vomiting, and excessive urination. MCAS is also likely if a urine sample produced within 4 hours of a flushing episode reveals abnormally high levels of methylhistamine.

Ehlers-Danlos Syndrome (EDS)

Ehlers-Danlos Syndromes are a group of disorders that affect the connective tissues of the body, including the skin, bones, blood vessels, and other organs and tissues, caused by various genetic defects in the structure, production, and/or processing of collagen and the extracellular matrix, which is a network of carbohydrates and proteins that support the structural integrity of the cell. Collagen is the major component of most of the body’s connective tissue and provides both the strength and flexibility for us to move, bend, and stretch without anything breaking or tearing. Mutations in these genes, as seen with EDS, will result in poor collagen strength or a collagen deficiency in our tissues. There are 13 different subtypes of EDS, which are named based on the area affected. While it is outside of the scope of this article to go into each individual type, there is some overlap in the common signs and symptoms. If you think you have this disorder, the best way to determine which genetic variant you have is to undergo genetic testing to confirm an EDS diagnosis. The most common types of EDS are the hypermobility (EDS-HT), otherwise known as EDS-III, and classical subsets.  The hypermobile type affects as many as 1 in 5,000 to 20,000 people, while the classical type occurs in about 1 in 20,000 to 40,000 people. All other forms of Ehlers-Danlos syndrome are very rare.

EDS is a complex and multisystem disease process that will look different depending on what type of collagen is altered. The more common types of EDS affect the skin and joints and are relatively benign, but can range up to life-threatening issues with some of the rarer types. Remember not everyone with EDS will have all of these symptoms!

The most common EDS symptoms include:

  •     Joints: hypermobility (unusually large ranges of motion); increased incidence of joint dislocation; chronic joint pain
  •     Skin: very stretchy, fragile, increased bruising, “spider veins,” abnormal scarring and wound healing
  •     Bone: presence of osteoporosis, scoliosis from a young age
  •     Gastrointestinal: presence of hiatal hernias, downward displacement of internal organs in abdominal region       (visceroptosis), changes in gut movement
  •     Eyes: small corneas, fragility
  •     Heart: arteries with tendencies to rupture, valve issues

EDS

MCAS and Its Relationship to EDS

So it makes sense that MCAS and EDS would be related simply because mast cells are found in connective tissues throughout the body: you can’t have one without the other. When mast cells are activated, they release a variety of chemical mediators, like histamine, proteases, cytokines, and growth factors, to name a few. These compounds will cause swelling and inflammation in the surrounding tissues, which is appropriate when there is an actual threat or foreign invader. However, when mast cells are overactive, they release an overabundance of these mediators, resulting in MCAS. Mast cells tend to adhere to proteins in the extracellular matrix called fibronectin and vitronectin; this pairing can result in an increased production and release of cytokines, one of the types of proinflammatory chemical mediators released by mast cells. It is possible that the gene defects that result in collagen mutations may also contribute to abnormal mast cell functioning.

AND FINALLY: How are Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome and Ehlers-Danlos Syndrome Connected?

Researchers have discovered a subpopulation of patients with EDS-HT (hypermobility subset) and POTS that also have been diagnosed with MCAS. Patients with EDS-HT and POTS also seemed to exhibit symptoms consistent with those you would typically find in someone with MCAS. However, the relationship between the three does remain somewhat murky. Some experts think EDS causes POTS. And others will tell you that MCAS causes both POTS and EDS.  A recent study, led by Joshua Milner at the National Institute of Allergy and Infectious Diseases, took 96 people with EDS-HT and mast cell issues. POTS symptoms were also prevalent. All study participants had higher than expected tryptase in their blood. Tryptase is a protein and well-known mast cell mediator that is an integral part of an immune system reaction and may be related to many of the symptoms seen in patients with EDS-HT and POTS. Usually, people with mast cell problems have normal levels of tryptase. With further tests, Milner discovered a subset of patients that had an extra copy of the gene that codes for tryptase, TPSAB1. Two genes equals double the amount of tryptase protein.  Going back through the DNA records, it appeared that people who had high tryptase levels also had the TPSAB1 gene mutation and were all living with symptoms that were very similar to those described when talking about EDS-HT, POTS, and MCAS. The interesting thing is about 30% of people don’t make tryptase at all, so maybe it’s not necessary? Maybe a potential treatment method for this disease trifecta is figuring out how to shut down the production of tryptase?

So I Think I May Have The Trifecta: Now What?

If you’ve taken anything from this article, I hope it is something along the lines of how complex and multifactorial these diseases are, and no one treatment is going to be effective for everyone. The good news is most of the time, this trifecta is very manageable. The bad news is it’s very individualized, and it may be a process of trial and error in figuring out what works best for you and your needs.  Some people require medication and some don’t. Some have to be a low histamine diet for longer than others. The key is getting your body healthier, so you can tolerate more of the foods you love with natural mast cell stabilizers and no medications. I hope that I can help you learn from the mistakes I made during my journey with MCAS, POTS, and EDS, and I can’t wait to be a part of your story!

 

Histamine intolerance guide

 

References

1) http://www.potstreatmentcenter.com/mast-cell-activation-syndrome-postural-orthostatic-tachycardia-syndrome/

2) http://mentalfloss.com/article/87506/one-gene-mutation-links-three-mysterious-debilitating-diseases

3) https://www.jillcarnahan.com/2016/10/31/mast-cell-activation-syndrome-mcas-when-histamine-goes-haywire/

4) https://rarediseases.info.nih.gov/diseases/9597/postural-orthostatic-tachycardia-syndrome

5) http://www.potsuk.org/mcas?fbclid=IwAR08BH1TXdapeABbqlHCTLPFC4BFEvwbtIc6DzzNP4-Z-KAv4IkW1b4uQKg

6) https://www.jillcarnahan.com/2019/04/16/the-surprising-link-between-ehlers-danlos-syndromes-mast-cell-activation-syndrome/

7) https://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome#statistics