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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 exposure

Physical/ 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

So Many Weird Symptoms

Welcome back. We have been talking about a confusing and challenging problem which clinicians know to very often be associated with hypermobility and hypermobile Ehlers-Danlos Syndrome, although we do not know why.

Take a moment to look at the following table. Can you see what all of these symptoms  might have in common?  

Constitutional – fatigue, temperature sensitivity, sweats, chills, decreased appetite, weight gain or loss, chemical sensitivities	GI System – diarrhea, constipation, nausea, vomiting, bloating, difficulty swallowing, abdominal pain, bad absorption. Diabetes
Teeth – deterioration of teeth and gums despite good hygiene	Immunological – increased vulnerability to infections, autoimmunity, poor healing
Eyes/ Ears – blurred vision, dry eyes, twitching lids, ringing, hearing loss	Liver/ Gall Bladder – abnormal liver tests; gallbladder inflammation
Nose/ Mouth – Nose bleeds, congestion, post-nasal drip, chronic sinus irritation or infections. Burning mouth, sores, white patches, abnormal color or texture	Reproductive/ Urinary – painful urination, frequent urination, incontinence, bladder pain, chronic kidney disease, cystitis, vaginal inflammation, endometriosis, painful intercourse, painful periods, decreased libido
Thyroid — Hypothyroidism, hyperthyroidism	Musculoskeletal – joint pain, bone pain, thinning of the bones, muscle pain, tendinitis
Lungs/ Breathing – Sore throat, hoarseness, chronic cough, laryngitis, wheezing, shortness of breath, obstructive sleep apnea, sensitivity to smells and odors.	Lymph System – enlarged lymph nodes, inflamed spleen
Heart/ Circulation – chest pain, palpitations, high blood pressure, high cholesterol, POTS, Raynaud’s disease	Nervous System/ Brain – numbness, tingling, muscle weakness, seizures, low muscle tone or too much muscle tone, headaches, memory deficits, brain fog; changes in taste, hearing, smell, vision; sleep disorders/ insomnia, restless leg syndrome
Blood – changes in blood tests with too many or too few of different cell types	Skin  — rashes, sores, small red spots, hives, hair loss, brittle fingernails, warts, skin tags

We have been talking about diseases involving mast cells. Mast cells are born in the bone marrow and migrate in an immature form to the tissues of the body where they mature. They are all over the body but especially in places where the internal environment comes into contact with the external world – skin, respiratory system and gut. They are part of the immune system and closely linked to some kinds of allergic reactions. Mast cells give off chemicals called mediators, the first job of which is to create inflammation which is a defensive reaction of the body. Health mast cells are essential. Unhealthy mast cells can create all kinds of problems.

There are two main types of mast cell diseases. In one type of disease, too many mast cells grow in the body. In the second type, mast cells are too sensitive and release their mediators too quickly and easily leading to inflammation. This inflammation can either be either local, often in the skin, or whole body (“systemic”). The too many and too sensitive diseases are not mutually exclusive. Both problems may occur at the same time. Since the great majority of cases of mast cell disease in hypermobility are thought to be of the ‘too sensitive’ type, this will be our focus in this article.

MCAS

Back to our list (above). This is a list of symptoms which can result from mast cells being too sensitive. This is called Mast Cell Activation Syndrome (MCAS or MCAD, mast cell activation disease). In MCAS, the patient is sensitive to one or many, often ordinary, things which can trigger a flare up of limited or systemic inflammation affecting one or several organ systems. These “triggers” can range from dietary to inhaled things like molds to strong emotions or sometimes just heat or cold. While there are common triggers, each individual with MCAS is unique in their triggers.

If you take a moment to look at this list with the eyes of a physician trying to diagnose, you may begin to see how almost every symptom on this list can be caused by anywhere from one-to-many different diseases. This is part of what makes MCAS sometimes so challenging to diagnose. And to make things even more complex, patients with MCAS can present with symptoms that are anywhere on a spectrum from mild to severe, and one individual with MCAS may go through periods of mild symptoms and periods of severe symptoms.

Diagnosing MCAS {1, 2, 3, 4, 9, 10, 11, 14}

So how IS MCAS diagnosed? The current medical consensus is to follow a three-step process.

Criteria One: The first step is to begin to connect the dots of seemingly unrelated symptoms.

In some syndromes like this, there are screening questionnaires which ask specific questions to see if the clinician should dig deeper in the direction of a particular diagnosis. While there are questionnaires available for MCAS, we have not yet found any which have been scientifically validated. So, at this point, the first step toward diagnosing MCAS is simply to look at the list above, or one like it, and check off every symptom that echoes a concern or problem that the patient has. If there are more than a few, MCAS should be considered.

Criteria Two: The second step is to look for elevated levels of mast cell mediators within a short period of time after a flare up of symptoms.

Mast cells have long been a subject for serious study because of how complex they are and how many different functions they perform in the body with much still to be learned. In fact, while reading for this post, we found that authors did not even agree on how many mast cell mediators there are. Estimates ranged from 60-100. Of these mediators, many cannot be isolated by regular medical testing laboratories, and some that can be isolated are so expensive that testing is cost-prohibitive. However, the consensus of scientists is that one test is the first and most important.

The most common test for MCAS is a blood serum test for tryptase. Normal levels of tryptase in the blood range from 0-11.4 ng/mL (nanograms per milliliter of blood). The object of testing for serum tryptase is to see if there has been a surge of tryptase levels in association with a flare up of symptoms. A positive test is a serum tryptase level of 14ng/mL or higher. However, it can be very easy to get this test wrong.

The serum tryptase blood sample is stable and can be kept at room temp, refrigerated or even frozen and the test is reliable, but the sample must be taken at the right time. When a patient with MCAS encounters something that triggers a flareup, tryptase levels in the blood surge but then begin to fall off after two hours. This means that a blood sample for a tryptase test must be collected within that window of time which can be hard or impossible for some patients to do.

In the last post we talked about a type of MCAS called hereditary alphatryptasemia (which is much easier to call HaT). This is a hereditary condition which can be identified by genetic testing. The literature recommends that patients with a blood level of tryptase of 8ng/mL or higher have the genetic test for HaT. {1}

A secondary mediator test is for the chemicals left by the breakdown of histamine in the urine. Urine is collected over a 24-hour period. One practical problem with this test is that the urine sample must be kept chilled, or the test will give a false negative – a test saying there is not a problem when there is. {3}

 Criteria Three: The third step for a textbook positive diagnosis of MCAS is that the patient’s symptoms improve or resolve in response to certain medications. As we will explore in the next part of this series, the most common medications for MCAS are often old well-established anti-allergy medications, antihistamines. There are also medications which help to stabilize mast cells, so they are less likely to release their mediators.

Given some of the complexities we have described here, it might not surprise you that in clinical practice physicians can have a hard time getting a textbook level diagnosis. Because the potential side effects of the medications are generally quite low, some physicians will opt to go straight to a trial of medications if they recognize a pattern in symptoms. The complexity of this process has been recognized in scientific literature.

“…MCAS is a very complex disease from the clinical molecular level (including mediators, genes, and epigenes)… As such, a clinical diagnosis of MCAS – i.e., a case of MCAS worthy of treatment – virtually certainly will never rest on meeting merely a single diagnostic criterion (e.g., a single laboratory test meeting a specific threshold). As is the case with most syndromes, the diagnosis of MCAS will continue for many years to rest on the demonstration of a specific constellation of findings in the context of other findings also congruent with the diagnosis.” {4, pg. 145}

How Common is MCAS? {4, 5, 13}

As we pointed out in the last post, there is still much research needed to clarify the scope of MCAS as a problem. As Kohn and Chang point out:

There have been no epidemiologic studies on mast cell activation syndromes either, and the epidemiology of these syndromes has been more difficult to estimate, as they have only recently been defined. {13, pg. 283}

Estimates in the general population range from “rare” to 17% {4, pg. 139}. One of the leading scientists in this area of study, scientist Gerhard Molderings, writing with other leaders in the field stated in 2011:

MCAD comprises disorders affecting functions in potentially every organ system by release of mediators from and/ or accumulation of genetically altered mast cells. There is evidence that MCAD is a disorder with considerable prevalence and thus should be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity of unknown cause. In most cases of MCAD, diagnosis is possible by relatively non-invasive investigation. Effective therapy often consists simply of antihistamines and mast cell membrane-stabilising compounds supplemented with medications targeted at specific symptoms and complications. {5 pg. 6}

In the third and final post of this series, we will look at how MCAS is treated.

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

2023.07.12 Mast Cell Activation Syndrome Blog. 1

Different But the Same

Four people with chronic health problems met in a support group. They all have the same problem, see if you can tell what problem the four group members share. {2}

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.

Baffled? Well, you are not alone. At first glance, these four people seem to have only a few symptoms in common and the ones they do have do not immediately seem to point to any one disorder or problem. So, it may not come as a surprise that their doctors struggled to identify their problem as well.

These four people all have Mast Cell Activation disorders. Member one has localized reactions. Member two has mild whole-body reactions. Member three has chronic reactions and member four has severe whole-body reactions.

Why is this topic important to our patients? Because these disorders are recognized by many clinicians as common in patients with hypermobility spectrum disorders and hypermobile Ehlers-Danlos Syndrome. Additionally, they are becoming recognized as common in the population.

Mast Cells {8, 9, 10}

So, what are these mast cells and why are they giving these four people so many problems? Mast cells are actually a very good thing. We really want to have them in our bodies. In fact, they are so good that virtually all mammals have them showing that they are a very old feature of our physiology from an evolutionary perspective.

They are considered to be a part of the immune system. Mast cells are sentinels. They perform many functions but first and foremost they guard the body against foreign substances and invaders such as bacteria, viruses, dirt, thorns, splinters and such.

Mast cells sense and release their mediators in response to a number of different kinds of substances including foreign chemicals and toxins and venoms. They also release in response to some internal proteins of the body. And they release their mediators in response to foreign invaders to the body such as bacteria, viruses, thorns, splinters and generally dirt. Sometimes they link up with the proteins used by the immune system, especially immunoglobulin E (IgE, a protein used by the immune system), to create an allergic reaction, sometimes they do not.

There are more than 60 identified mediators released by the mast cells. One of the strongest functions of the mediators is to create inflammation. Inflammation is not infection. It is one of the first lines of defense of the body. The word inflammation comes from the same root as the word flame. So, when you think of inflammation, think red, hot, swollen, painful.

There are mast cells all over the body. They are born in the bone marrow as immature cells and then travel through the blood to mature and reside in the connective tissue. They are especially found wherever our body comes in to contact with the external environment such as the skin, digestive tract and the respiratory tract including the nose and throat. They are commonly grouped around nerves, blood vessels and lymphatic vessels. (The lymphatics are the backup waste removal system of the body.)

Hopefully, you can see even from this brief description how good it is to have mast cells. But like the person in the nursery rhyme, when they are good, they are very good and when they are bad, they can be very bad.

Mast Cell Diseases {1,2,3,9,10,11}

There are a number of diseases which are caused by mast cells. And this topic can become very complex very quickly involving genetics, epigenetics, immunology, oncology, and a great deal of biochemistry. We will try to keep it simple both for you and because we too are limited in how far we can go down this deep rabbit hole.

A mast cell full of mediator granules. Image courtesy of WikiMedia Commons

In very general terms, mast cell disorders fall into two categories: those involving too many mast cells and those involving mast cells which are too sensitive and release their mediators too easily. But these two categories can overlap where there are both too many mast cells, usually imperfectly formed or defective, plus where cells are hypersensitive and too quick to release their inflammatory mediators.

Mastocytosis

The most common term used for too many mast cells is mastocytosis. In this condition, mast cells grow wildly and are called clonal or monoclonal cells. The process of this wild growth is called neoplasia which is the word used to describe tumor formation. (This does not necessarily mean cancer.)  Mastocytosis can be localized and just in the skin, or throughout the body — systemic.

Included in the types of mastocytosis are localized tumors which may be benign (i.e., not cancerous) or malignant (cancerous). There is a category of mast cell disorders in which too many mast cells grow but are not neoplastic – called mast cell hyperplasia. And a category where they are cancerous and circulate in the blood, a form of leukemia. While patients with hypermobility and hypermobile Ehlers-Danlos Syndrome can be afflicted by a disorder involving too many mast cells, these conditions are rare, and the too-sensitive disorders are the rule.

Mast Cell Activation Syndrome (MCAS)

When mast cells become overly sensitive and release their mediators too quickly causing unneeded inflammation, this is called Mast Cell Activation Syndrome (or disease or Disorder), abbreviated MCAS. There are five categories of MCAS.

1. Primary MCAS. This is a case where mastocytosis is present AND the mast cells are too sensitive. (Mastocytosis may occur without MCAS too.) This may be limited to the skin or systemic. In recent years, a genetic defect in a factor which helps the mast cells mature has been found, a KIT D861V mutation.
2. Secondary MCAS. As we have said, mast cells work intimately with the immune system and IgE. In secondary MCAS an allergic reaction hypersensitizes the cells. Tests for genetic defects are negative in contrast to primary MCAS.
3. HaT+ MCAS. In the last few years, scientists have found a genetic defect which affects an enzyme: alpha tryptase. This can lead to elevated blood levels of alpha tryptase, which is an important mast cell mediator. Since this defect is genetically transmitted and so runs in families; the defect is identified with a genetic blood test.
4. Mixed forms of MCAS. This is a category in which there is some combination of mastocytosis, allergy, and/ or HaT+. Patients with Mixed MCAS may be at a very elevated risk of anaphylaxis which is a severe life-threatening allergic reaction. These patients tend to be particularly sensitive to bee stings and need to carry an epi-pen.
5. Idiopathic MCAS. In these cases, the criteria for diagnosing MCAS are met (see below) but there is no mast cell neoplasia, no allergic reaction and no HaT genetic defect. This is thought to be the main type of MCAS among patients with hypermobility.

MCAS and POTS {7}

If you have been following these blog posts, you may have read our description of dysautonomia and POTS (postural orthostatic tachycardia syndrome). Dysautonomia is an imbalance of the automatic (aka autonomic) nervous system and can occur as a result of a number of different kinds of disease processes but is very common in patients with hypermobility and hypermobile Ehlers-Danlos Syndrome. POTS is the more severe end of the dysautonomia spectrum and results in racing heart and feeling dizzy or ill with sustained standing. There are several mechanisms in the body which can cause this, in one of these mechanisms, the least common, the “fight or flight” half of the autonomic nervous system gets stuck in a fast forward or “on” mode. This is called hyperadrenergic POTS.

We found one study which evaluated a solid number of patients (177) for MCAS and analyzed the results in-depth. As a result, the authors concluded that there are some patients with MCAS in whom the excessive release of histamine in their system, which causes opening of blood vessels, was a factor in their POTS. They concluded that patients with POTS who report flushing, reddening of their face or chest, as part of their symptoms, should be evaluated also for MCAS.

MCAS and Hypermobility Spectrum Disorder (HSD)/ Ehlers-Danlos Syndrome (hEDS) {3, 13}

In preparing this blog post, we searched the literature for information that might clarify what the relationship is between HSD/hEDS and MCAS. The strongest article we found in the search concludes:

There is currently no scientific evidence of any association between MCAS, POTS, or hEDS. We are not refuting that a possible association between these clinical entities may exist; we are simply arguing the need for reevaluation of these associations in light of new considerations, such as updated diagnostic criteria and updated guidelines for each. Furthermore, a scientific approach is warranted in linking these clinical entities. An evidence-based, common pathophysiologic mechanism between any of these two conditions, much less all three conditions, has yet to be described. {13, pg. 293}

Wow. Ok. So, before you ask the question “if there’s no proof, why am I bothering to read this blog?,” please let us give you some context. In a few words, what these authors are doing, and doing very well with an exceptionally well written article is saying to the research community “get on it people!.”

These authors are correct, there has been too little research in the connections between MCAS and HSD.hEDS (and too little research between the connection between POTS and HSD.hEDS.)

Why is this so? The first reason is the natural evolution of medical knowledge. The association between MCAS, POTS and hEDS has been noticed by clinicians for some time. Clinicians are empirical (trial and error) scientists who need to know right now what researchers have decades to figure out. And it often does take researchers decades to  really define all the aspects of a problem — IF they are ‘on it’. In this case, that problem is: how many hypermobile patients have MCAS and why?

The second factor here is a matter of definitions. Before you can research a problem well, you must define it. And the precise diagnostic definitions for both hEDS and MCAS have both been published relatively recently. The diagnostic criteria for hEDS were published in 2017 and the leading paper on the diagnosis of MCAS appeared in 2012. It can take time for the connection between problems to be quantified (often by studies that look back across a number of years at patient cases) and then hypotheses about the reason for the connection to be formed and tested. There simply has not yet been enough time for clear evidence to emerge. Yet, clinicians need to know right now.

In part 2 of this blog series on MCAS, we will start with talking about diagnosis. Here is a little spoiler though. It is tricky to diagnose. All of the many different kinds of symptoms can occur in many other diseases, and there are some challenges to getting accurate testing. Even before that though, given how recently the diagnostic criteria have been defined, there are more than just a few physicians out there who may not know or even consider MCAS as a diagnosis. The first hurdle to getting it diagnosed can be having the possibility come into the physician’s mind for consideration.

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

Zeborah Dazzle, PT here spokes-zebra for Good Health Physical Therapy and Wellness.

June is Pride month in the US. Happy Pride month!

One of the puzzles of working with a special focus on hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos (hEDS) syndrome is the number of patients who come for care who are gay, lesbian, transgender, bi, queer and/or non-binary – a higher percentage of our patient population than most experienced clinicians have seen in other clinical settings. While we feel lucky and privileged to be serving so many amazing, strong, gentle people, as clinical scientists, we do puzzle about whether there is a physiologic relationship between HSD/hEDS and identifying as LGBTQ.

We will tell you up front that there is as yet no answer to this and almost no literature overall looking at it. No literature was found on EDS and diversity of sexuality. What literature we have found looks at the prevalence of EDS among patients who have what is called in the medical world “gender dysphoria.” Gender dysphoria is the medical term used for individuals who experience incongruence, or mismatch, between the sex they were assigned at birth and their gender identity. During this month, we thought it might be a service to look at what is out there, and specifically three recent journal articles.

The first article {1} comes out of Oregon Health Sciences University from the plastic and general surgery department. The study looks at 1363 patients who came for gender reassignment surgery between 2016 and 2020. They looked at two things: how common EDS was in that group of patients and how those patients healed after their surgery. (Since EDS is a connective tissue disorder, the study authors wanted to know if there were healing problems.)

Out of the 1363 patients, 36 had a diagnosis of Ehlers-Danlos syndrome (EDS). Looking at this number and comparing it to the different estimates of how often EDS occurs in the general population, the study authors concluded:

Our investigation revealed the prevalence of Ehlers-Danlos syndrome in patients seeking gender-affirming surgery at our institution to be 132 times the highest reported prevalence in the general population. (pg. 5)

This is pretty astounding. And the study left us with a question. Reading this paper closely, they only looked for EDS as a diagnosis. They did not look at HSD. This makes us wonder how much higher the number of patients and the prevalence would have been if they had looked at all patients on the hypermobility spectrum.

Oh, by the way, they did not find any difference in surgical complications when matched against a control group of their patients who did not have EDS. So, it does not appear that individuals with hypermobility who seek gender affirming surgery are at higher risk of complications than non-hypermobile patients.

The second article {2} comes from Kansas City, Missouri. The authors looked at 166 adolescent patients seen in a multi-disciplinary EDS clinic between January 2020 and May of 2022. Specifically, they looked at how many of these patients were experiencing gender dysphoria based on their self-reports. This study did include both hEDS and HSD in their definition of an EDS patient.  They identified 28 patients out of the 166 which is 17%. Since the high-end estimate of adolescents with gender dysphoria in the general population is 1.3% {2, pg. 2} this means the prevalence of gender dysphoria in this EDS population was 13 times higher than the general population.

This study also looked at a number of interesting characteristics of this group of 28 patients:

89% were assigned female at birth, 12% male, with gender identity as follows: > Cisgender 4% T > Transgender 61% > Nonbinary 14% > Gender Fluid 11% > Agender 7% > Unsure 3% Reported pronouns: > He/Him 47% > She/Her 14% > They/ Them 39% The most common health problems for the 28 patients were: > Joint pain 79% / Muscle pain 36% > Mast Cell Activation Disorder 21% > Anxiety 75% > Attention deficit hyperactivity disorder (ADHD) 21% > PTSD 18% > Dysautonomia 61% / Postural Orthostatic Tachycardia Syndrome (POTS) 29% > GI/ Digestive Issues 68% > Headaches 75%

The third study {3} we looked at for this blog post came out of Children’s Hospital of Philadelphia which some who read this will recognize as one of the leading places in the country for the treatment of dysautonomia and POTS. This was a case series, meaning a journal article looking at three different cases they treated. All three of the cases were transgender men. All three patients had POTS. (If you are not familiar with POTS, please see the blog series on dysautonomia and POTS posted earlier this year). All three patients transitioned with the assistance of testosterone hormone therapy and all three had some relief of their POTS symptoms with introduction of the hormone therapy.

So, as the study authors point out, while the patients did have some decreased symptoms with the introduction of testosterone, this does not mean that testosterone should be tried for POTS. It does however lead to a recommendation that for transgender patients with POTS undergoing gender affirming therapy with hormonal treatments, further study is merited to see if and how their symptoms are affected. Why might this be important? In the Kansas study {2}, the majority of gender dysphoric hypermobile patients were transgender and almost a third had POTS.

So, if you are still reading after all these nerdy facts and figures, what are we to conclude?

We think this confirms a suspicion that we have had. While certainly not all gender diverse patients have HSD/hEDS the incidence is much higher than in the general population, and we can say too that the available literature suggests that the incidence of gender dysphoria among patients with HSD/hEDS is higher than the general population as well. Is there any hint in the literature as to why this might be? None at all that we have found so far. It is a puzzle.

We do believe though that there is an important takeaway from this information.  Increased awareness within the LGTBQ+ community of hypermobility spectrum disorders and the related health problems could help many make sense of seemingly mysterious, often chronic, health concerns and pains. When in doubt, screening for hypermobility by a physician or physical therapist might be of great benefit.

Thanks for reading! In future posts we hope to look more deeply at Mast Cell Activation Disorder as well as other topics.

Cheers,

Zebbie

Zeborah Dazzle, PT, WWF

Thanks to Dr. Mark Melecki, PT, DPT for his assistance in preparing this post. You know, it’s hard to type when you have hooves and not fingers. You rock Mark!

References:

1. Najafian, A., et. al., Ehlers-Danlos syndrome: prevalence and outcomes in gender affirming surgery – a single institution experience. Plast Aesthet Res 2022; 9:35; DOI: 10.20517/2347-9264.2021.89
2. Jones, J.T., et.al, Gender Dysphoria in Adolescents with Ehlers-Danlos Syndrome. SAGE Open Medicine 10:1-6; DOI: 10.1177/20503121221146074
3. Boris, J.R., et. al., Clinical Course of Transgender Adolescents with Complicated Postural Orthostatic Tachycardia Syndrome Undergoing Hormonal Therapy in Gender Transition: A Case Series. Transgender Health 4: (2019) DOI: 10.1089/trgh.2019.0041

Since it is May, Ehlers-Danlos Awareness month, I thought it might be good to explore just how common HSD and EDS are. Now, there is a reason I went into physical therapy and not mathematics – it is so easy to get lost in the numbers rather than have them tell a story. But let’s see what we can do. First a review.

 Hypermobility spectrum disorder as well as all of the thirteen types of Ehlers-Danlos Syndromes are connective tissue disorders resulting in a constellation of problems first and foremost being hypermobile and painful joints. The earliest references to loose joints may have been by Hippocrates in 400 BC {2}. Diagnostic classifications for the connective tissue disorders have evolved over a long period of time.

Ehlers and Danlos were two physicians in the early 1900s. Edvard Lauritz Ehlers was a Danish Dermatologist who published a comprehensive report on patients with hypermobile joints and fragile elastic skin in 1901. And Henri-Alexandre Danlos was a French dermatologist who consulted on a patient diagnosed by Ehlers and gave a contrasting opinion. {2}

The effort to classify the disorders as they are now diagnosed began in 2012 with the formation of an international consortium of experts which published the current diagnostic criteria in the American Journal of Medical Genetics in 2017 {2}. That was only six years ago.

When trying to determine how common any diagnosis is in the population, the specifics of how that diagnosis is made are very important. In other words, how you define something very much affects how it is counted. Before 2017, rather than classifying Hypermobility Spectrum disorder and Hypermobile Ehlers Danlos Syndrome separately, they were lumped together into one category: joint hypermobility syndrome {1}. So, as you might expect, the conversation about how common HSD, hEDS and each of the twelve other types of EDS are, is an ongoing one.

So, are HSD and EDS common? I have translated the diagram provided by the EDS Society {1}, which gives the best recent estimates of case numbers, into the table below and added a column. Since we are talking about cases per million, and since the population of the US in 2021 was 332,278,200 (according to Siri), the column at the right estimates how many cases there may be in the US.

Condition	Estimated Cases per 1 Million People	Estimated Cases in the US
All EDS and HSD	2000	664,556
hEDS and HSD Only	1900	631,329
hEDS	320	106,329
Classical EDS	50	16,614
Vascular EDS	10	3,323
Other Types of EDS: Arthrocalasia Brittle Cornea Syndrome Classical-Like EDS Dermatospraxis Kyphoscoliotic EDS Musculocontractural EDS Myopathic EDS Periodontal EDS Spondylodysplastic EDS	Less than 1	332

A condition is thought to be rare if it affects less than 1 person in 2,000 which is the same as 500 in a million. As you can see above then, all of EDS types combined and also HSD combined with hEDS are not rare, but each of the other categories of EDS would be considered rare. This assumes that the studies are getting an accurate estimate of numbers. And that is a big assumption. As more doctors learn how to diagnose these conditions, these numbers may change.

We are still thinking about what to write about next in this blog series. Future topics may include mindfulness, digestive issues in HSD and hEDS and others.

Until then, cheers!

Zebbie

Zeborah Dazzle, PT, WWF

Spokes-Zebra and Patient Educator for Good Health Physical Therapy and Wellness.

Thanks to Dr. Mark Melecki, PT for his assistance in preparing this blog. (It is very challenging to type with hooves rather than fingers. Thanks Mark.)

References:

1. Ehlers-Danlos Society, Are the Ehlers-Danlos and Hypermobility Spectrum Disorders Rare or common?   https://www.ehlers-danlos.com/is-eds-rare-or-common/ 2023
2. Stott, P., Purdin, H., Introduction to HSD/EDS: Course Notes. Medbridge Online continuing Education. https://www.medbridgeeducation.com/sign-in 2022
3. Demmler, JC, et. al., Diagnosed Prevalence of Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorder in Wales, UK: A National electronic Cohort Study and Case Control Comparison. BMJ Open 2019; 9:e031365. Doi: 10.1136/bmjopen-2019-031365.

4.24.2023

POTS 3: Exercise

For the past two blog posts, we have been talking about Postural Orthostatic Tachycardia Syndrome (POTS). This is an imbalance of the involuntary nervous system which may occur in a number of different health situations, such as post COVID, but is common especially for patients with hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos Syndrome (hEDS).

POTS is the more severe end of a spectrum of symptoms all due to imbalances of the involuntary nervous system (the autonomic nervous system) called dysautonomia. The main symptoms of POTS are a racing heart that happens when the person stands up and feeling lightheaded, dizzy or just ill.

There are conservative and medication treatments for all of these types of POTS, and these are summarized in the last blog post (POTS 2). But one conservative treatment that research is showing to be beneficial for all of the types of POTS is exercise. {6}

Studies of patients with POTS have shown that cardiac atrophy, or weak heart, is a key component of the pathology. {4} Exercise improves but does not necessarily normalize heart function. {4} Exercise study participants lowered their resting heart rate and improved pain, sleep, overall energy, work capacity and several other indicators of quality of life. {3} More than one study has shown that exercise can help patients move fully into remission from POTS with 47-70% of participants going into remission in two studies.{3} One study found that exercise was better than the drug propranolol in helping the heart improve function. {1}

What Kind of Exercise?

Now we know from experience of working with patients that exercise is not always an easy sell for someone who already feels bad day to day. But we also know the incredible strength and courage of our patients. So, take a deep breath, and let’s ease in to talking about this.

Overall, we are talking about both aerobic conditioning exercises such as swimming, rowing, cycling, elliptical trainer, treadmill walking, or running. Additionally, in many cases resistance training, such as therapy bands, weight lifting or Pilates, is a very important part of the program. As we have talked about previously, POTS is a syndrome which represents the more severe end of dysautonomia, but even in this more sever end there is a spectrum of severity and so the exercise program itself must be tailored to fit.

Aerobic Exercise {2,3, 4, 5}

     What Does it Mean: Exercise Tailored to Fit?

There are a number of variables that are considered in designing a plan: intensity, frequency, and duration are the most common.

     Intensity

Before deciding the intensity of the exercise, how hard it is, the severity of the POTS case must be considered and the type of exercises chosen. For patients who are having severe symptoms, all exercises are started lying down. The more severe the case, the closer to lying flat the program is started. There are types of exercise bikes that can be done by someone lying supine. Swimming can also be done with the body in the horizontal position. After a number of months, these exercisers can progress to more upright exercises such as a recumbent bike or a rowing machine. And after additional time, upright exercises can be added such as an upright bike, elliptical trainer, walking, and running.

 For each individual exercise the cardiac intensity, how hard the heart is working, can be judged one of three ways: heart rate, rating of perceived exertion and, sometimes simply, a “talk test”.

     Judging Cardiac Intensity

For each person there is a maximum number of heart beats per minute which their heart is capable off, called heart rate max (HR Max). The number that is normally used as a reference in textbooks is 220 beats per minute. But this number gets lower with age. So, heart HR Max is estimated with the a formula: (220-persons age) +/- 5 beats per minute.

For example, a 30-year-old would have a theoretical HR Max of (220-30) = 190 +/- 5 beats. For exercise, a percentage of this is taken to determine how hard the person is working, usually between 60-85% of HR Max.

Another good indicator of intensity is to ask the exerciser to rate how hard they are working. This is called “rating of perceived exertion” (RPE) and while there are some different scales for this, a common one is the “Borg Scale” based on a number rating from 6-20.

RPE	How hard are you working?
6	No exertion; sitting, resting
7	Extremely light
8
9	Very light
10
11	Light
12
13	Somewhat Hard
14
15	Hard
16
17	Very Hard
18
19	Extremely hard
20	Maximal exertion

In Germany, for many years, there have been hiking clubs where they keep exercise at a moderate level by singing, or at least talking as they hike. If a person is having trouble singing while they exercise, they are working too hard. This is one kind of a “talk test”.

     Workout Intensity Levels

In the exercise programs for POTS there are three levels of intensity for workouts whether the exerciser is supine, sitting or upright: Base Pace, Maximal Steady State and Recovery.

Base Pace. This is the basic level of exercise and is normally preceded and followed with a 5 minute warm-up and a 5 minute cool down. Base pace intensity exercise just starts to make it challenging to talk, perceived exertion is rated between 13-15 (between somewhat hard and hard), and results in a heart rate around around 75% of HR Max.

Maximal Steady State. This is intense exercise usually undertaken later in the workout program when fitness levels are improving. During this level of intensity, the patient will not easily be able to talk or sing, rates their exertion between 16-18 (very hard) and results in heart rate around 85% of HR Max.

Recovery. Recovery workouts are done on days after a Maximal Steady State workout. At this level of intensity, the talk test is easily passed, rating of perceived exertion is between 6-12 (fairly easy) and results in heart rate around 60-65% HR Max.

     Frequency and Duration

How often (frequency) the person exercises and how long (duration) — meaning both the total program length and the daily workout length — will all vary depending on where the person is on the spectrum of POTS symptoms. Again, patients at the severe end of the spectrum will start all exercises with their body horizontal, such as lying down or swimming.

The Children’s Hospital of Philadelphia plan {5} describes a 5-month program. Exercisers will progress to more upright forms of workout at the end of the first or second month depending on their body. The researchers at Texas Health {2} describe a 3-month program. Exercisers with a mild or intermediate level of POTS may start all exercises sitting or sometimes even standing.

Initially, exercisers will participate in 3-4, 25-30 minute workouts per week at a Base Pace. Progression to the next level of workout may be started at the end of the first to third months of the program or even longer depending on how the person’s body responds. In the next harder level, exercisers will progress to one and then two Maximal Steady State workouts per week. This level of workout is always followed by a Recovery workout. By the end of program, exercisers will be performing 5-6 workouts per week of 45-60 minutes each.

As with all exercise, to attain the desired response from the body, persistence and consistency are needed. So, if more than two workouts are missed in a week, that week is repeated. If two weeks or more are missed, the entire program is restarted.

Resistance Training {2, 3, 4, 5}

Especially in cases where hypermobility is involved, resistance training is another part of the exercise program. Resistance training can and often does mean weight lifting, but may also include resistance bands and the resistance of the exercisers own body weight. Pilates exercise is a good example of this.

Exercisers are well advised to be mentally ready to be sore. This means sore muscles but should not include flaring up sensitive areas. To avoid this starting at the right level, which may be very light for some, and progressing gradually are important.

Especially for those with more severe POTS will begin lying down or sitting. Those with mild or intermediate symptoms may begin standing but should sit immediately after exercise. Workouts begin once per week for 15-20 minutes and gradually increase to twice per week building to 30-40 minute sessions. In selecting exercises, special emphasis is placed on lower extremity and core strengthening. It is important to take at least two days off between resistance workouts – this is the time when the body adapts and grows stronger.

As you can tell from reading all of this, the direction of a skilled therapist will be very important for this kind of treatment. Even though it can be challenging to find a therapist who is knowledgeable about hypermobility, dysautonomia and POTS, seeking one out can be very worthwhile.

We are still thinking about what to write about next in this blog series. Future topics may include mindfulness, digestive issues in HSD and hEDS and others.

Until then, cheers!

Zebbie

Zeborah Dazzle, PT, WWF

Spokes-Zebra and Patient Educator for Good Health Physical Therapy and Wellness.

Thanks to Dr. Mark Melecki, PT for his assistance in preparing this blog. (It is very challenging to type with hooves rather than fingers. Thanks Mark.)

References:

1. Fu, Q and Levine, BD, Exercise and Non-Pharmacological Treatment of POTS, Auton Neurosci. 2018, December; 215:20-27.
2. Fu, Q, et. al., Exercise Training Versus Propranolol in the Treatment of the Postural Orthostatic Tachycardia Syndrome, Hypertension Volume 58(2), August 2011; pages 167-175
3. Adger, K and Lynch, H., Exercise in the Management of Orthostatic Tachycardia Syndrome, Journal of Kinesiology and Wellness, 9(2), July 2020, pages 28-37
4. Shibata, S., et. al., Short-term Exercise Training Improves Cardiovascular Response to Exercise in the Postural Orthostatic Tachycardia Syndrome, J. Physiol 590.15 (2012) pages 3495-3505
5. Children’s Hospital of Philadelphia, Instructions for POTS Exercise Program, unpublished paper.
6. Zadourian, A., et. al., Postural Orthopedic Tachycardia Syndrome: Prevalence, Pathophysiology, and Management. Drugs (2018) 78:983-994
7. https://www.texashealth.org/ieem/Patient-Care/Syncope-and-Autonomic-Dysfunction-Clinic

4.17.23

In the previous post in this series, we started talking about POTS (postural orthostatic tachycardia syndrome). POTS is the more severe end of dysautonomia which means an imbalance of the involuntary nervous system.

As we talked about in the last post, dysautonomia and POTS are common in people with hypermobility spectrum disorder (HSD) and with hypermobile Ehlers-Danlos Syndrome (hEDS). There are physical mechanisms: 1. Neuropathic which is caused by damage to the small nerves in the legs that control the size of the small arteries; 2. Hypovolemic which means low blood volume caused by the kidneys getting rid of too many electrolytes and too much fluid; 3. Hyperadrenergic which means that the fight or flight side of the involuntary nervous system is too active for any one of a number of reasons.

Like many medical problems, dysautonomia exists on a spectrum. When we think about a spectrum, we can imagine a graph that charts severity of symptoms across all sufferers. A good illustration with this is the graph shown here. For all the patients with dysautonomia, some (on the left side of the graph) will have very few symptoms, many will have a moderate number of symptoms (center) and some will be on the severe end (right side of the curve).

All of these kinds of POTS have both conservative, non-drug, and medication treatments. In this post we would like to review some of the treatment approaches.

Conservative Treatment

For our purposes, conservative treatment of POTS is any kind of treatment that does not involve medications. And there are a number of tips and techniques to keep the problem at bay.

     Things to Avoid

There is no one uniform way of treating POTS. There are a number of medications that can make POTS worse. It is not the purpose of this article to direct medications. A list of some medications which can worsen symptoms is in Table 1. These should be discussed with the prescribing physician.

Table 1: Medication Types Which Can Worsen POTS {2} Alpha receptor blockers Angiotensin converting enzyme inhibitors Beta blockers Calcium channel blockers Diuretics Ganglionic blocking agents Hydralazine MAO inhibitors Nitrates Opiates Phenothiazines Sildenafil citrate Tricyclic antidepressants Oral contraceptives containing drosperinone Norepinephrine transporter inhibitors Serotonin reuptake inhibitors

People with POTS are also advised to avoid alcohol and extreme heat.

     Hydration and Electrolytes

Patients with POTS and other levels of dysautonomia frequently have an imbalance in the hormonal system the kidneys use to determine how much water and how much of the body’s electrolytes to release in the urine. So, these people are chronically dehydrated and low on minerals. The answer is to drink and supplement electrolytes.

Recommended levels of fluid intake per day are between 2-3 liters {1,2,3}. This translates into 68-101 ounces, or 8.5-13 cups, or 0.5-0.8 gallons.

Recommendations in the literature for salt intake vary from 8-10 grams {1} to 10-12 grams {2, 3}. We have found that these numbers are individual and can vary. One way to manage salt intake when seeking to improve symptoms of POTS is to start with about 3gm of added salt per day and increase by 1 gram per day up to a maximum of 12 gm per day depending on symptoms. In other words, if the person feels best at 9 gm/ day, that should be their intake unless symptoms change. Doctors can also test for sodium levels by blood test which can give a measure of how well supplementation is working.

All of the references we have found so far describe electrolyte supplementation in terms of salt intake. If taking an electrolyte supplement such as Nuun, Pedialyte or Gatorade, the number of milligrams of sodium can be used as a reference or follow the gradual increase approach described above. (Remember, 1000mg = 1 gm)

     Elevation of Head

There is some evidence that sleeping with the head of the bed raised by 4-6 inches may help with POTS symptoms. {3}

     Muscle Squeezes

Since for many with POTS the pooling of blood in the lower part of the body can lead to increased pounding, feeling ill and/ or dizziness when the person changes positions, movements or muscle contractions that help move the blood up out of the legs are a part of avoiding symptoms with position changes. These can include exercises done lying down before sitting up, exercises done sitting before standing, and exercises to be done while standing. A physical therapist can prescribe specific exercises.

     Compression Garments

Persons with the Neuropathic and/ or Hypovolemic types of POTS generally benefit from wearing compression garments. Here again, depending on the severity of symptoms, different levels and lengths of garments may be useful. For those with more severe cases of POTS, a compression garment worn over the entire lower extremity and including the abdomen is recommended. {3} Here again, for stronger POTS symptoms, garments that give compression in the 30-40 mmHg (millimeters of mercury) range are suggested {3}. We have had many patients that get very good benefit from calf high or thigh high compression. And too, we have had many patients who get good relief from wearing compression garments giving 20-30 mmHg. Experimentation with different garments is key.

   Exercise

Regardless of the type of POTS, exercise is a recommended non-medication form of treatment {1,2,3}. Current research strongly suggests that patients with POTS have some degree of heart muscle atrophy, weakening of the heart. This can be improved with a carefully structured exercise program. We will explore this in much more depth in the third and final blog post, but meanwhile here is an interesting tidbit. The original exercise approaches for people with POTS were modeled after exercise programs developed for astronauts weakened by prolonged weightlessness in space, such as the crew of the space station. These approaches have also been modified for use with people who have been confined to bed for a sustained period. More later.

Medical Treatments with Medications

While non-drug approaches to treatment form a very important foundation for treatment, many patients whose symptoms are not well controlled using conservative approaches alone may require supplements and/ or medications.      

     Neuropathic POTS

In this kind of POTS, dilated blood vessels in the lower extremities lead to pooling of blood there with less blood available for the brain. Medications used to counteract this can include the following. See Table 2.

Table 2. Medications Targeting Vasoconstriction { 1, 2} Midodrine Droxidopa Octreotide Dextroamphetamine Methylphenidate

     Hypovolemic POTS

If increased fluid intake and electrolyte intake are not adequate, there are several medications which can help to increase fluid volume in the body. See Table 3

Table 3 Medications to Improve Fluid Retention {1,2} Fludrocortisone Desmopressin Erythropoietin

   Hyperadrenergic POTS

Regulating the sympathetic nervous system can be much more complicated than the other two types of POTS above. The medications are often not as well tolerated and may have more unwanted side effects. For people with high resting heart rates, Propranalol is the single most common medication prescribed. People taking any of these should work closely with their physician to achieve the desired results. See Table 4.

Table 4 Medications for Sympathetic Support {1,2} Propranolol Ivbradine Clonidine A-Methyldopa Pyridostigmine

      MCAS and POTS

Some patients with POTS may have symptoms largely caused by mast cell activation disorder {5}. Simply said, mast cells are naturally occurring cells in the body which cause inflammation as part of the body’s defense system. These can get overly sensitive and release too many inflammatory chemicals. Some of these chemicals, like histamine, may cause opening of blood vessels in the legs in some patients with hyperadrenergic POTS. We hope to do a series of blog posts on mast cell activation later this year.

In the third and final post of this series, we will look at exercise as a form of treatment for POTS. As you might imagine, we PTs have some thoughts about this and there is a good deal of information.

Until then, cheers!

Zebbie

Zeborah Dazzle, PT, WWF

Spokes-Zebra and Patient Educator for Good Health Physical Therapy and Wellness.

Thanks to Dr. Mark Melecki, PT for his assistance in preparing this blog. (It is very challenging to type with hooves rather than fingers. Thanks Mark.)

References:

1. Raj, S., Postural Tachycardia Syndrome (POTS), Circulation 2013; 127: 2336-2342.
2. Zadourian, A., et al, Postural Orthostatic Tachycardia Syndrome: Prevalence, Pathophysiology, and Management, Drugs (2018) 78: 983-994
3. Fu, Q. and Levine, B., Exercise and Non-pharmacological Treatment of POTS, Auton Neurosci. 2018 December; 215:20-27
4. Olshanksy, B., et al, Postural Orthostatic Tachycardia Syndrome (POTS): A critical assessment. Prog Cardiovasc Dis. 2020; 63(3): 263-270
5. Shibao, C., et al, Hyperadrenergic Postural Tachycardia Syndrome in Mast Cell Activation Disorders, Hypertension Volume 45, Issue 3, 1 March 2005; 385-390

2023.03.20

Dysautonomia and POTS, 1: Physiology

Dizzy when you change positions, slow digestion or even cramps and gut pain, nausea, trembling, heart palpitations, lightheadedness, chronic anxiety, fatigue, brain fog, always too warm or too cold, blurred or tunnel vision, poor sleep, intolerance to exercise, feet turn red or even purple for no apparent reason — these are all possible symptoms of dysautonomia, an imbalance of the involuntary nervous system.

In the body, there are two major divisions of the nervous system: voluntary which makes conscious movement possible, and involuntary (also called autonomic) which controls the non-conscious functions of the body like breathing, heart rate, blood pressure, temperature regulation and some parts of digestion. Two halves of this involuntary/ autonomic nervous system constantly work to keep the body in balance: the sympathetic or “fight or flight” nervous system, and the parasympathetic or “rest and relax” nervous system.  

While there can be many causes for each of the symptoms above (thus making it hard for doctors to come to a diagnosis), dysautonomia symptoms are VERY common in patients with hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos Syndrome (hEDS). And these symptoms can range in severity from mild to disabling.

Sometimes, these symptoms become severe enough that they meet the definition of a syndrome called POTS: postural orthostatic tachycardia syndrome – a very long name which mostly means that the patient’s heart races (100 beats per minute or higher) and they feel worse and worse the longer they stand up including often feeling dizzy or light-headed. POTS can be quite disabling.

POTS is a syndrome, not a specific disease and many disorders with similar symptoms exist.  The diagnostic criteria for POTS however are:

1. An increase in heart rate of 30 beats per minute or more (40 in children) within 10 minutes of changing from lying down to standing.

2. Symptoms worsen when standing and improve with lying down.

3. Symptoms last 6 months or longer.

4. Absence of other causes such as active bleeding, medication reaction or acute dehydration.

Why are dysautonomia and POTS problems for patients with HSD and hEDS? This has to do with the way these inherited connective tissue disorders affect the way the body works. There are three most common types of POTS, that is, three most common physical mechanisms by which the syndrome arises. At times there may be more than one mechanism causing a person’s symptoms.

Neuropathic POTS.

The word neuropathic means a non-specific injury to a nerve. In the case of patients with HSD or hEDS, there can be accumulated damage to the involuntary nerves especially in the lower extremities. This results in less stimulation to the tiny muscles that wrap around the arteries. If those tiny muscles are too relaxed, the blood vessels open up and blood will pool in the legs. There is only so much blood in the body, so when too much blood pools in the legs, there is less for the upper body. When the person tries to stand up, there is too little blood to the brain and sensors in the neck tell the brain that the blood pressure is too low. All of this results in heart racing, dizziness and/or just feeling ill.

Hyperadrenergic POTS.

There are three most common mechanisms for this kind of POTS, but first some background.

The sympathetic nervous system, as we said above, is the “fight or flight” nervous system. The main chemical that serves as a nerve transmitter for the sympathetic nervous system is norepinephrine which is also called adrenaline. When too much of this hormone is in the blood, this is said to be “hyperadrenergic”. Too much norepinephrine throws the body systems out of balance. Specifically, with this kind of POTS, blood pressure levels tend to go too high as well as increased heart rate.

In Central Hyperadrenergic POTS, the sympathetic nervous system is simply too active. The reasons for this can vary. This kind of POTS is thought to be 10% or less of all cases. There may be a genetic link to developing this. In some few cases, there may be an autoimmune condition called Morvan’s syndrome. There are some rare tumor types that produce norepinephrine and which can mimic this kind of POTS. There may be an association with hyperadrenergic POTS and sleep apnea in many patients.

A second type of hyperadrenergic POTS, Norepinephrine Transporter Deficiency, is due to a genetic mutation that causes loss of function of a protein molecule that helps the body to clear away norepinephrine. Body chemicals are produced by cells but also all require some mechanism for elimination. As you might expect, if a transporter molecule needed for elimination of norepinephrine is lacking, too much will build up in the body system. This will cause high blood pressure and high heart rate. While this mutation is relatively rare, Norepinephrine Transporter Deficiency can also be caused by some medications that block the molecule. This can include certain medications used for depression, and also, for attention deficit disorder.

The third type of hyperadrenergic POTS is not directly related to norepinephrine. Mast Cell Activation Syndrome (MCAS) is another common set of problems which may arise with patients with hypermobility or hypermobile Ehlers-Danlos Syndrome. MCAS will be the topic of future blog posts, but for now, a quick summary is to say that mast cells are important sentinels in the body which will release inflammatory chemicals in the body as part of its defense system. These can become over sensitive and too quick to release their chemicals. Some of the inflammatory chemicals, histamine for example, when excessive, can create POTS symptoms especially high heart rate and high blood pressure in some patients.

Hypovolemia.

Hypovolemia means low blood volume – too little of the fluid part of the blood, plasma. Some patients with hypovolemic POTS may be low by as much as 13%. While the mechanism that causes this is known, how that the mechanism gets out of balance is not well understood.

The kidneys are the chief organ of the body responsible to regulate how much fluid the body holds on to and how much the body eliminates. There is an important system of hormones given off by the kidneys called the “renin-angiotensin-aldosterone system”. In many people with HSD or hEDS, this system is thrown out of balance causing the kidneys to eliminate too many minerals (electrolytes) and with them too much fluid leaving the person chronically dehydrated.

Which type do you have? Reviewing, in general terms, all of the types of POTS described here result in high heart rates and feelings of dizziness or illness when the person stands for a period of time. In Neuropathic and Hypovolemic POTS, the blood pressure tends to fall. In the different types of hyperadrenergic POTS, not only does heart rate go up with standing, or activity, so does the blood pressure.

The basic diagnostic test for POTS is called a tilt table test. The patient is asked to lie down on a flat tiltable table and their heart rate, blood pressure and symptoms are recorded. Then the table is tilted up by degrees until the patient is standing and changes in heart rate, blood pressure and any symptoms are closely monitored. A similar type of test, the “Standing Test”, can be done in the office for diagnosis by a physician or screening by a therapist. These tests will identify POTS but may not give enough guidance about which type of POTS to guide prescription of medications if needed.

While there are a number of primary care physicians who have educated themselves about POTS and it’s management, treatment is often done by specialists, especially autonomic neurologists (a very hard to find sub-specialty) or more commonly by a cardiologist.

In the next blog post, we will look at how the different kinds of POTS are managed including both conservative (non-drug) treatments and some general principles of how physicians manage with drugs too.

Until then, cheers!

Zebbie

Zeborah Dazzle, PT, WWF

Spokes-Zebra and Patient Educator for Good Health Physical Therapy and Wellness.

Thanks to Dr. Mark Melecki, PT for his assistance in preparing this blog. (It is very challenging to type with hooves rather than fingers. Thanks Mark.)

References:

1. Raj, S., Postural Tachycardia Syndrome (POTS), Circulation. 2013; 127: 2336-2342
2. Olshansky, B., et. al., Postural Orthostatic Tachycardia Syndrome (POTS): A Critical Assessment. Prog Cardiovasc Dis., 2020; 63(3): 263-270.
3. Walker, A., The Trifecta Passport, US: Kindle Direct Publishing, c. 2021, ISBN 978-1-7337117-2-2

Website: tamingthezebra.org

Mailing List: https://www.tamingthezebra.org/join-the-email-list

Excerpt from: Taming the Zebra – It’s Much More than Hypermobility: The Definitive Physical Therapy Guide to Managing HSD/EDS, Volume 1 Systemic Issues and General Approach 

(Due out Winter of 2023)

Dysautonomia, HSD/EDS and the GI System

The GI system has just as many nerves as the spinal cord. The patient and practitioner cannot overlook the Autonomic Nervous System (ANS) when dealing with gut issues. They are one in the same. The GI system’s nerve supply is primarily the ANS. The Vagal Nerve (or Vagus nerve) part of the ANS, innervates the digestive tract from the esophagus to the splenic flexure of the colon. The sacral parasympathetic nucleus (another part of the ANS) innervates the colon and rectum. When someone has low Vagal tone, or a dysfunctioning ANS, this will impair GI motility. Dysfunction of the Vagus nerve can cause poor mobility in the esophagus as well, causing difficulty swallowing (see figure 6.7). A well functioning Vagus nerve also may help reduce inflammation in the gut as low tone in this nerve is associated with higher levels of inflammation within the body. The GI system and the ANS can be a chicken-or-egg scenario when symptoms occur. Knowing the answer to which came first may not be as important for some as addressing both systems to reduce symptoms. Exploring that complex question can be very helpful in regards to long term care and control of health.

Conditions to Investigate with Difficulty Swallowing

DysautonomiaEsophageal dysfunction (structural or functional)Local nerve irritation to the throat musculatureUpper cervical instabilityEagle SyndromeUpper thoracic or cervical spine involvement

Figure 6.7 Difficulty swallowing can be due to a number of conditions. These should be explored with the patient to avoid missing a condition that will require a referral to a specialist.

Episodes of Dysautonomia may also be triggered by events that happen in the gut. We see this with gastric dumping. For someone with impaired motility/movement of the food through the GI system, one will lose the rhythmical small contractions, and the stomach may dump its contents rapidly into the small intestine. With this, the food is not fully broken down, and one is left with larger particles than the small intestine is used to taking care of, along with a larger portion of food at one time that can cause some stretching of the small intestine. When the small intestine registers this stretch occurring in the organ, the nerves try to increase its response to help move the food through the area and this can cause local pain to the small intestine. Along with a physical pain response, the body releases additional hormones along with shifting the blood flow back to the GI system to assist with this “emergency” of a dumping response. When the blood flow is adjusted to the system, this begins to trigger a shift in the Sympathetic Nervous System and may cause an overall systemic autonomic response as the body struggles to find balance again (see Figure 6.8).

Figure 6.8 Dumping Syndrome is a reaction of the ANS seen in those with Dysautonomia and/or motility issues in the gut.

Early or late dumping responses may occur within the same patient. Early dumping is an ANS response from the reaction that occurs within 30 minutes of eating because the small intestine is being stretched, there is an increase in hormone release, and the ANS overcompensates to assist in the event. This can be seen in the GI system as malnutrition in protein energy and manifest in the rest of the body as the following:

• Heart palpitations
• Tachycardia (increased heart rate)
• Feeling the need to lie down after meals
• Flushing or paleness
• Sweating
• Lightheadedness
• Drop in blood pressure
• Headaches
• Possible fainting
• Feeling full soon into eating
• Stomach pain
• Nausea
• Abdominal area cramping
• Bloating
• Rumbling/gurgling in the GI system after eating

Late dumping can be seen one to three hours after eating a meal. This can be from an increase in the hormones secreted into the GI system, chronic GI inflammation, Dysautonomia, or a history of Diabetes. Symptoms include:

• Sweating
• Faintness
• Decreased concentration, brain fog
• Varying levels of consciousness

Late dumping is less common than early dumping. An individual can have both early and late dumping occur with meals. Specific meal strategies can be found later in this GI management section. Treatments for the ANS can be found later in this book (Chapter 16). Both are recommended in combination as treatment strategies when dumping is suspected.

Hello, Zeborah Dazzle, PT, WWF here. I am the spokes-zebra and patient educator for Good Health Physical Therapy and Wellness. As some of you know, while I am a physical therapist who treats all kinds of problems, including all kinds of bone and muscle problems, my special interest is hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorder (HSD). Sometimes it is wise to pause and go back to basics. That is what I will focus on with this post.

How are the laxities caused by HSD and hEDS Treated?

As we discussed in our last post, many of the effects of HSD and hEDS are on skin and joint laxity. While lax skin may not cause a lot of pain, lax joints often do. Medical doctors that we work with frequently rely on two approaches to help patients with these diagnoses: medications or supplements to help manage pain and physical therapy.

In physical therapy, while there are many variations on how we do this, our approach overall is to seek to restore balance within the body. More specifically what that means is to help get the joints back in a normal alignment, assure that the tissues are in balance around the joints allowing normal movement and strengthening to help keep the joints strong and stable.

We rely on both exercise and manual therapy to achieve strong, stable balanced joints and movement. Oh, and since our job as physical therapists is to help people to move and function better, we also bring in a lot of teaching: how to protect joints; tips and tricks for conservative management of pain; and how to recenter a joint which has gone out.

As we have also already discussed, the symptoms for both HSD and hEDS are on a spectrum, with some people having very few and some being challenged by a great deal of debility. So too then, restoring strength and balance around the joints for some patients is a quick, easy process, and for some a slow and gradual journey toward health.

This said though, we strongly believe in the potential of all of our patients to achieve a higher level of function.

How are the associated problems of dysautonomia/ POTS and mast cell activation treated?

Accompanying HSD and hEDS, for most patients, are isolated symptoms or full syndromes involving the involuntary nervous system, and/ or mast cells. As we have discussed, an imbalance of the involuntary nervous system is called a dysautonomia; this imbalance can reach the level of a syndrome known as POTS (postural orthostatic tachycardia syndrome). Most patients with HSD or hEDS have at least a symptom or two of dysautonomia. Mast cells are front line sentinels in the tissues of the body monitoring for wounds, foreign bodies, and infections. When they are triggered by a trauma or a foreign invader, they release chemicals called mediators which cause inflammation. Connective tissue disorders can set both the involuntary nervous system and the mast cells on edge, so they are more easily triggered.

Both dysautonomia/ POTS syndrome and mast cell imbalance (called mast cell activation syndrome) have treatment approaches which involve conservative interventions as well as drug-based treatments.

Overall, the conservative approaches for dysautonomia/ POTS involve methods to: help keep the blood from pooling in the legs which causes dizziness, blood pressure drop and rapid heartbeat; emphasis on hydration with extra electrolytes since patients with dysautonomia frequently do not absorb and retain electrolytes well; and finally, gradual progression of exercise. If conservative measures alone do not restore balance, cardiac medications may be prescribed usually to help support blood pressure and/ or to moderate heart rate. There are several medical specialties skilled in managing POTS. Many of our patients have worked successfully with cardiologists, heart doctors.

The conservative approach for Mast Cell Activation Syndrome (MCAS), is first to identify factors which lead to flare ups. Sensitized mast cells may be easily triggered to release their inflammatory chemicals by both emotional and environmental causes. While the list of common triggers is long, each patient’s particular triggers are unique to them. These can include, strong emotions, stress, excessive heat or cold, molds, pollution, specific chemicals, and very often specific foods. Patients very often already know what kind of weather, or chemicals or foods make them feel bad. For some patients, additional testing for sensitivities or elimination diets may be helpful. When additional help is needed to identify triggers, working with a functional medicine physician and/ or a naturopathic physician can be very helpful.

There are a number of supplements which can be helpful with MCAS and medications too. The focus of treatment are supplements or medications which make the mast cells less likely to release inflammatory chemicals or which reduce the amount released. Many of the medications used for this purpose have been in use for many years and are over the counter. Regardless, it is important to work with a physician to find the right supplements, medications, and dosages. Most of our patients work quite successfully with their primary care physician for this.

In coming blog posts, we will look more in depth at POTS and MCAS and we will discuss a topic requested by our office staff – insurance benefits and helping the helpers help you.

Until then, Cheers! Zebbie

P.S. More information is available at the Ehlers-Danlos Society website. I particularly like this downloadable PDF overview: https://ehlers-danlos.com/wp-content/uploads/EDS_Awareness_2017_v3_img_2021.pdf

Thanks to Dr. Mark Melecki, PT for his assistance in writing this blog. (It is very challenging to type with hooves rather than fingers. Thanks Mark.)