Eosinophilic GI Disease

 Eosinophilic GI Disease (EGID) is a group of conditions that occur when there are elevated levels of eosinophils in segments of the GI tract, either the esophagus, stomach, small intestines or colon.  These conditions are called Eosinophilic Esophagitis (EoE), Eosinophilic Gastritis or Gastroenteritis (EoG), Eosinophilic Enteritis (EoN), and Eosinophilic Colitis (EC or EoC).  I have heard reference to Eosinophilic Duodenitis Eosinophilic Rectitis but I don't think either are official conditions.  The esophagus is the one part of the GI tract that doesn't normally have eosinophils, whereas the rest of the GI tract does.  This has led some to speculate that EoE is a different entity than the other EGIDs.  

EGIDs are diagnosed by biopsy.  Tissue samples are collected during endoscopy or colonoscopy, and then sent to a pathologist who looks at the samples under a microscope to identify the presence of eosinophils.  If the numbers are too high, a diagnosis is made.  Symptoms vary depending on the form of EGID a person has, and can be mild to severe.  In EoE, a common symptom, the one that often leads to diagnosis, are food impactions in the esophagus that require medical care to remove.  Symptoms of lower EGIDs tend to be vague such as cramping and pain, vomiting, nausea, diarrhea, food intolerances and a severely restricted diet, malnutrition, and bone pain (usually in the legs).  

Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis

Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study

Molecular analysis of duodenal eosinophilia

Elimination diets are often used by doctors to identify problem foods, as there are no tests to identify eosinophilic triggers.  Treatment often begins by having the patient avoid identified (or suspected) triggers.  If this doesn't adequately control symptoms, various medications can be used, including topical steroids such as Budesonide or Fluticasone (steroids that is swallowed), a PPI (Protono Pump Inhibitor), Singulair, or oral steroids to control flares.  A type of medication called biologics are starting to be used for some EGIDs, in particular Dupilumab (brand name Dupixent).  Eosinophils are the same cells that tend to be responsible for asthma so many of the same medications are used.  Some people describe EGIDs as "like asthma but in your GI tract".  If those treatments fail, it is not uncommon for people with EGIDs to require artificial nutrition such as elemental formula, a feeding tube, or even TPN (IV nutrition).  People with EoE can develop strictures in the esophagus, areas where the tissue has scarring which narrows the width of the esophagus.  This can be treated with dilations, a procedure in which the area is mechanically stretched.

Crafting a Therapeutic Pyramid for Eosinophilic Esophagitis in the Age of Biologics

The leading center for diagnosis and treatment of EGIDs, especially EoE, is Cincinnati Children's Hospital (they also work with adults with EGIDs) 

Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE

Food-specific IgG4 is associated with eosinophilic esophagitis

Common and disparate clinical presentations and mechanisms in different eosinophilic gastrointestinal diseases

Histopathology of Eosinophilic Gastrointestinal Diseases Beyond Eosinophilic Esophagitis
"EoG and eosinophilic duodenitis (EoD) are strongly associated with food allergen triggers and TH2 inflammation, whereas EoC shows minimal transcriptomic overlap with other EGIDs. The level of expression of certain genes associated with TH2 immune response is associated with certain histopathologic findings of EoG, EoD, and EoC. Current immune therapy for EoG depletes tissue eosinophilia with persistence of other histopathologic features of disease."

The Dual Lens of Endoscopy and Histology in the Diagnosis and Management of Eosinophilic Gastrointestinal Disorders—A Comprehensive Review
"Eosinophils, a specific type of leukocyte derived from CD34+ CD125+ stem cells in the bone marrow, are crucial in defending against pathogens, such as bacteria and parasites. Additionally, they play a pivotal role in modulating humoral immune IgA and cellular T-cell responses, and in maintaining tissue homeostasis.

In the context of EGIDs, the abnormal accumulation of eosinophils is primarily driven by interleukin-5 (IL-5), interleukin-4 (IL-4), and interleukin-13 (IL-13). These cytokines are primarily produced by type 2 helper lymphocytes (Th2) in response to exposure to aeroallergens and food allergens. The overproduction of interleukins is further amplified by dysregulated cells in the innate immune system, including Group 2 innate lymphoid cells (ILC2s) that mature directly in tissues like the GI tract or lungs, plasma cells, and mast cells.  Pathogenesis of Th2 inflammatory drive in Eosinophilic Gastrointestinal Disorders (EGIDs), especially EoE. Exposure to initial food antigens triggers lymphocyte-Th2 activation, resulting in the accumulation of eosinophils in the esophagus. Following stimulation with Eotaxin 3, eosinophil degranulation promotes acute damage to the esophageal epithelium, followed by subsequent chronic fibrotic remodeling of the esophagus, which is dependent on TGF-beta.

Th2 cytokines, particularly IL-13, along with other inflammatory mediators such as Tumor Necrosis Factor Alpha (TNF-α) and other chemokines, play a direct role in the activation and degranulation of eosinophils. Eotaxin-3 serves as the primary chemokine involved in these processes and contributes significantly to eosinophilic chemotaxis and accumulation in GI tissues. The release of proteins from eosinophilic granules, including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), and major basic protein (MBP), leads to acute cytotoxic and oxidative damage to the tissue. This acute damage results in compromised barrier function through the downregulation of Desmoglein 1 (DSG1), Filaggrin (FGN), and the Epidermal Differentiation Complex (EDC).
The course of acute eosinophilic Th2 inflammation is typically self-sustained and progressive, often leading to chronic damage. This chronic state is often driven by T regulatory lymphocytes’ activation, accompanied by the recruitment of other cell types, including mast cells and basophils [26]. The persistent inflammatory insult can result in sub-mucosal fibrotic tissue deposition and muscular hypertrophy, primarily induced by Transforming Growth Factor beta (TGF-beta). 

A recent study on colonic biopsies conducted by Shoda et al. revealed that EoC is distinct from other EGIDs, with pathophysiological mechanisms that are not completely dependent on allergic inflammatory reactions [186]. The study identified 987 differentially expressed genes that were overexpressed in EoC tissues, thereby defining the “EoC transcriptome”.  Interestingly, the pathogenesis of EoC seems to have only a weak correlation with Th2-related allergic pathogenesis.  (A)dults typically experience chronic abdominal pain and watery diarrhea [25,179,180]. Additional symptoms can include nausea, vomiting, and weight loss. The presence of atopy history in EoC patients often complicates the clinical picture with conditions like asthma, food allergies, rhinitis, or eczema.

The depth of eosinophilic infiltration in the colonic wall allows for the identification of three disease patterns [147].

The mucosal involvement (type 1), defined as eosinophil infiltration of the mucosa, is the most common. This type often follows a continuous disease course (>6 months) without remission, with patients exhibiting symptoms such as bloody diarrhea, microcytic iron-deficiency anemia, and protein-losing enteropathy [5].

Transmural involvement (type 2) occurs when eosinophils infiltrate the muscular layer. It is associated with symptoms like abdominal spasms, pain, and a possible impact on intestinal motility. Complications such as intestinal obstructions, strictures, volvulus, and perforations may occur. The course of the disease in this form is typically recurrent [5].

The serosal subtype (type 3) is the rarest and occurs when eosinophilic infiltration reaches the serosa. This form can be associated with more severe symptoms, including eosinophilic ascites and intense abdominal pain [5].

Radiological signs include intestinal wall and mucosal fold thickening and submucosal edema [150,153]. Mucosal thickening, stenosis, and sub-mucosal edema form the basis of the “halo sign,” characteristic of EoC. The “arachnoid limb-like sign” may also be observed via radiological imaging [150]. In cases of transmural involvement, stenosis, particularly at the cecum, may be observed.

 

In approximately 70% of EoC cases, no alterations in the colonic mucosa are observed during endoscopic evaluation [183,187,188]. However, when abnormalities are present, they typically involve the colon segmentally, with only about 10% of patients presenting with pancolitis [14,25,183]. The endoscopic findings of EoC are often non-specific and do not correlate with the severity of symptoms [7].

 

Drug-induced colitis, triggered by antiplatelet drugs (clopidogrel, aspirin, and ticlopidine), Non-Steroidal Anti-Inflammatory Drug (NSAIDs) (especially ibuprofen), and estrogenic-progestogen agents is another cause of colonic hypereosinophilia [194,195].  Among connective tissue diseases, rheumatoid arthritis uniquely exhibits patterns of colonic eosinophilia [200]. 

 

In addition to hypereosinophilia, other microscopic characteristics that typify EoC histology include extensive degranulation, eosinophilic micro-abscesses, architectural distortion, fibrosis with mucosal atrophy, loss of mucin, and follicular lymphoid hyperplasia, often accompanied by lymphocytes and plasma cells [187,188].

 

According to the strongest evidence, a PEC with more than 50 eosinophils per HPF in the right colon, more than 35 eos/HPF in the transverse colon, or more than 25 eos/HPF in the left colon, along with a consistent clinical and symptomatic profile, indicates a diagnosis of EoC [14] 

 

adults typically receive steroid anti-inflammatory therapy, such as prednisone or budesonide, as the initial treatment [170,180]. If adults experience a relapse after discontinuing prednisone, indicating steroid-dependent disease, Budesonide Controlled Ileal Release (CIR) can be an effective maintenance therapy. Budesonide CIR has the advantage of primarily topical activity, minimizing the long-term adverse effects associated with steroids [202].

Immunomodulators like azathioprine and methotrexate also represent alternatives to maintenance therapy for EoC. Additionally, Montelukast, a leukotriene receptor antagonist, is beneficial in maintenance therapy due to its ability to block eosinophil homeostasis and prevent their infiltration into the intestinal wall [131]. Fecal microbiota transplantation has been suggested as a rescue strategy in EoC, though this evidence is limited to case reports [203]. Emerging therapies for EoC have mainly been tested in animal models. Studies evaluating the efficacy of anti-Siglec-F antibodies (targeting a sialic acid-binding immunoglobulin superfamily receptor) and anti-CCR3 (cysteine–cysteine chemokine receptor 3) antibodies have shown promising results [204,205]. Future therapeutic options are anticipated with the validation of biological drugs like dupilumab, reslizumab, and mepolizumab, which are currently undergoing testing.

 

 

 

 

Dietary Fats and Oils

Sources of oils and fats

Microbes in intestines convert fiber into short-chain fatty acids.  This should be vegetable fiber, NOT grain fiber or capsules/drink.  

Salmon Roe - richest source of omega-3 fatty acids (EPA and DHA), contains 1800 of EFAs in one ounce of salmon roe.  Excellent support for the neurological system.  Also high in other nutrients as well.

Salmon Roe – Unsurpassed for Nourishing the Brain

Speak - This is a supplement that is a combination of oils that supports brain function, especially in regards to speech.

Specific Oils and Fats

Black Seed Oil is a mast cell stabilizer.

Chia Seed - contains omega-3 fatty acids and other essential fatty acids including alpha-linolenic and linoleic acid, oleic acid, and palmitic acid.

CLA (Conjugated Linoleic Acid) found in red meat and grassfed dairy, has anti-tumor properties.  

Coconut Oil contains Lauric Acid, an antiviral, and Caprylic Acid, which is antifungal.  

Cod Liver Oil (CLO) Source of omega-3 fatty acids oils as well as vitamin A and vitamin D.  Omega-3 fatty acids increase brain-derived neurotrophic factor (BDNF) which supports growth of new neurons.  They are also anti-inflammatory, especially in the brain. 

Lard is a natural source of vitamin D and choline and contains some vitamin E.  Avoid lard that has been hydrogenated.  

Olive Oil is an excellent source of omega-9 fatty acids, including oleic acid.  It has the highest proportion of monounsaturated fatty acids of all of the liquid vegetable oils.  It contains 13% of RDA of vitamin E and about 10% of RDA of vitamin K.  The extra-virgin variety has a higher mount of polyphenols, which are natural antioxidants.  

What Does Research Actually Say About Healthy Fats? 

Is Saturated Fat Bad For You?
Ketogenic diet therapy doesn't have to include any saturated fat; many people eat a vegan keto diet or one that is vegetarian without dairy, or some other specialized form of keto.  It's possible to make a keto diet that is compliant with almost any other restriction, such as vegan, vegetarian, Mediterranean, carnivore, and others.

Saturated fat, the estimated absolute risk and certainty of risk for mortality and major cancer and cardiometabolic outcomes: an overview of systematic reviews
Absolute risk is much more informative than relative risk- relative risk sounds more catchy but doesn't actually tell you as much.  When thinking about what a study means for you, whether its conclusion means you need to make changes, depends on the quality of evidence and not just the presence or absence of evidence.  This paper found that the evidence supporting a risk from consuming saturated fat was low or critically low quality.  When looking at the results of reducing or replacing saturated fat in terms of cancer mortality, the authors found that the evidence showed a range of 8 fewer deaths to 3 additional deaths per 1,000 people, and the certainty of evidence (quality) was low to very low.  So no clear-cut link between saturated fat consumption and risk of death from cancer.  When considering the impact of saturated fat in the diet and cardiac deaths, they found a rate of two deaths per 1,000 people with low to moderate certainty.  This does not support the strength of the message we get through doctors and public health to avoid saturated fat.

There are other factors to consider when seeing if the results of a study means anything for you individually.  To illustrate this point, consider one study that was included in this meta-analysis (with moderate quality evidence) that found 24 fewer deaths per 1,000 people from all-cause mortality in a treatment group that reduced saturated fat intake.  We need to look at the details to see what the implications are.  Most people being studied are eating the standard American diet, high in ultra-processed foods, and get their saturated fat from sandwiches, desserts and sweet snacks like cookies, cakes, ice cream, pastries; and rice and grain-based dishes like pasta and pizza, and milk and yogurt which is usually sweetened and flavored.  These foods are all high in sugars and simple starches.  Natural foods, including plain meats, cheeses, butter, etc are lower on the list.  The question then is how do you eat- if you eat lots of junk food, fast food, and processed food, then this study might apply to you.  If you already eat a diet primarily of whole foods and low processed foods then these results probably have no relevance for you.

"Nutrition science is full of low quality evidence that applies to a general population eating a low quality diet".  As a patient, we all deserve to have care providers who treat us as individuals.

A short history of saturated fat: the making and unmaking of a scientific consensus 

Dietary Saturated Fats and Health: Are the U.S. Guidelines Evidence-Based?

Medical Gaslighting and "Somatization Disorders" (Rebranded Hysteria)

The Curse of a ‘None of the Above’ Disease
This article talks about people suffering from health conditions that are under-diagnosed or mis-diagnosed, including Chronic Fatigue Syndrome, Fibromyalgia, and IBS, but more so people whose symptoms get dissmissed or written off as fake or psychosomatic.  Many doctors are quick to jump to this conclusion about patients without doing any testing, based just on their appearance and the symptoms they present with.  It is also common for doctors to have an inflated sense of how much they know and lack of recognition of the limits of their education and the field of medicine itself.  One example cited is that of stomach ulcers, "(o)nly a few decades ago, chronic ulcers were chalked up to stress and diet rather than an infection by Helicobacter pylori, because scientists thought it unimaginable that such microorganisms could endure stomach acid."  

 When Anxiety or Depression Masks a Medical Problem

 

What Do Doctors Have to Say About It?
From Dr Courtney Snyder (In a blog post about Mold Illness)
"Symptoms of mold toxicity impact many parts of the body. Often there are many symptoms that seem unrelated, which is why many who are unknowingly dealing with this, end up seeing multiple specialists and are left feeling their doctors think it’s “all their head.” The diagnosis of anxiety or panic, depression, obsessive compulsive disorder, ADHD/ADD, pseudoseizures and conversion disorder are fairly common. I empathize with doctors who have been trained to relieve symptoms as opposed to seek deeper root causes. Still, I do think all physicians (myself included) can benefit from realizing and saying repeatedly, “There’s so much we don’t know,” or even “I don’t know why you are having your symptoms.” The lack of humility or inability to admit one doesn’t have the answer, sadly can lead to some doctors to discount symptoms as “psychiatric” or even blame their patients for feigning their symptoms."

Misdiagnoses Happen. Medical Gaslighting Should Not
Written by Dr Anne Maitland, one of the leading allergy/immunology doctors in the country, about how common it is for immunological disorders (even ones as well known as asthma, food allergies, and anaphylaxis) to be misunderstood, misdiagnosed, or missed altogether, causing an immeasurable but very large amount of unnecessary suffering.

"Missteps and misunderstandings, even by well-seasoned medical professionals, are human, but medical gaslighting is not. Medical professionals must take a step back and recognize that the interpretation of test results is only as good as the practitioner glancing at the numbers. Moreover, normal test results in patients with chronic pain, unexplained sensitivities to the world, or fatigue should provoke more investigation, rather than a weak handoff to a mental health provider. One potential remedy to avoid these misdiagnoses and medical misdemeanors may be to rebuild the patient-practitioner partnership: the medical home. We should be empowering the patient to take charge of their health care, and we should be reminding the practitioner to be a mindful partner in health, rather than a patriarchal purveyor of prescriptions and procedures."

The Martha Mitchell Effect

Martha Mitchell was married to the attorney general in the Nixon administration, John Mitchell.  She spoke up about the illegal activities that she was witnessing, but her claims were written off as delusional until the actual events of the Watergate scandal became public, when she was vindicated.  Sometimes a patient reports events to a doctor or other health care provider that the provider finds difficult to believe and considers to be delusions even when what the patient is reporting is actually true.  This is called the "Martha Mitchell effect" in reference to her experience of being wrongfully considered delusional.  This is particularly likely to happen when a patient's symptoms are the result of the malicious actions of another person, such as harm resulting from harassment or abuse.  This might include poisoning, stalking, gangstalking (group harassment), or gaslighting.  Abusers sometimes deliberately do things to their victims that make the victim sound crazy if they report it.  This is also more likely to occur if the patient reports harm from a medical procedure, treatment, or another medical provider, or from someone who is powerful or well known.

This effect was seen recently when some people presented to the hospital during the COVID 19 pandemic suffering adverse events from the COVID vaccines and were diagnosed as delusional when they were suffering actual side effects that were later acknowledged by the medical establishment and public health authorities.

Examples of medical gaslighting include:

The Incidence of Misdiagnosis in Patients with Ehlers–Danlos Syndrome
"A retrospective chart review was conducted. Among the 429 patients, 405 patients (94.4%) said yes to at least one of the questions, with only 24 patients (5.6%) not having been misdiagnosed with psychiatric illnesses. A total of 378 patients (88%) were told that they were “making it up”, 326 patients (76%) were told that they were attention-seeking, 286 patients (67%) were diagnosed with conversion disorder, 255 patients (60%) were told that “it was in their head”, and 16 patients (4%) were diagnosed with Munchausen syndrome by proxy or a factitious disorder.A retrospective chart review was conducted. Among the 429 patients, 405 patients (94.4%) said yes to at least one of the questions, with only 24 patients (5.6%) not having been misdiagnosed with psychiatric illnesses. A total of 378 patients (88%) were told that they were “making it up”, 326 patients (76%) were told that they were attention-seeking, 286 patients (67%) were diagnosed with conversion disorder, 255 patients (60%) were told that “it was in their head”, and 16 patients (4%) were diagnosed with Munchausen syndrome by proxy or a factitious disorder."

Inappropriate Sinus Tachycardia
“Like Postural Tachycardia Syndrome IST is underappreciated by many in the medical profession and many doctors mistakenly consider it to be a psychological condition. People with IST can find themselves increasingly disabled and may experience high levels of anxiety.”

The Case of CIRS (Chronic Inflammatory Response Syndrome) and Mold Illness
There are many examples of medical conditions that were first described by patients and doctors, for which no physical cause was found for many years.  They were given "placeholder" names as syndromes until such time as their biological mechanism could be figured out, which they eventually were.  There is a list of conditions including Sick Building Syndrome, Chemical Sensitivities, Environmental Illness, Chronic Inflammatory Response Syndrome (CIRS), Toxicant Induced Loss of Tolerance (TILT), Mold Illness, Biotoxin Illness, that had been identified accurately based on patient reports, and in some cases treatments were even discovered based on patient reports of benefits.  These conditions are now understood to be manifestations of Mast Cell Disease, Mitochondrial Dysfunction, and genetic variants that limit detoxification of various compounds capable of inducing excessive inflammation, among other things.  The biological understanding came in time and validated the experiences that patients reported.  

Nagging Pain
This is a Slate article about a program of "boot camps" for people, mostly children, diagnosed with chronic pain (including Fibromyalgia and Central Sensitization) that attempts to "rewire" the symptoms out of the person through brutal and painful exercise and experiences.  Many of the children sent to these "camps" with a diagnosis of AMPS (for "amplified musculoskeletal pain syndrome"), a made-up diagnosis based on an untested theory.  The treatment, which was also made-up based on a this theory, doesn't have any real scientific evidence to support it, just the theory.  The "evidence" that these boot-camp programs work are self-reported questionnaires given to participants at the end of the program.  Part of the program is aggressively drilling into the participants NOT to talk about or report pain or any pain symptoms, so then asking them to self-report is dubious at best.  Everything about this diagnosis, treatment, and these programs is exactly what a cult is and how cults function.  The "patients" are aggressively indoctrinated and brainwashed, their will is broken down, using the exact techniques that cults use- coercive control.  There are no "good" applications of coercive control.  

This is a list of some of the medical diagnoses that survivors of these "boot camp" style programs were later diagnosed with:
Ehlers-Danlos Syndrome or other Connective Tissue Disorders
MCAS
POTS
SCN9A channeloppathy (causing paroxysmal extreme pain disorder with severe dysautonomia including life threatening autonomic storming)
Yao Syndrome
Gastropareses
Adrenal Insufficiency

The following is a comment I submitted as written testimony for a legislative hearing in Oregon regarding reclassifying various pain disorders with Somatoform Disorders in the state's medical code system:

I wish to address the proposal to group Fibromyalgia and chronic pain disorders with Somatoform Disorders.  When a patient presents to the doctor with physical symptoms, including pain, there is nothing scientific about assuming that the patient has a mental health condition rather than a physical one, and that mental health treatment is appropriate.  Cursory testing does not rule out the presence of a physical condition.  Many legitimate physical conditions aren't correctly diagnosed for many years, and may be misdiagnosed many times in the process.  For example, on average a person with celiac disease is properly diagnosed 8 years after first presenting to a doctor with symptoms.  During those 8 years, it can be said that no physical cause has been found for the patient's distress, but it makes no sense to say that they have a psychiatric condition that they are miraculously cured of when they are finally correctly diagnosed with celiac. 

The fact that there are simply so many physical conditions with a significant lag time between the time when a patient presents with complaints and accurate diagnosis should cast doubt on the usefulness and even the existence of actual somatoform disorders.  I lost count a long time ago of the number of cases I know of in which a person presented to the doctor with pain and other non-specific symptoms, was patronizingly dismissed and told to get counseling, eventually given pain meds, and then finally given testing only to be told that they have late stage cancer.  In a number of cases they were actually told "if only you'd come in sooner, we could have treated it".  Many of those people died.  It is also worth noting that new disorders are still being discovered, that medical testing is never 100% accurate, and there are over 7,000 rare diseases listed by the National Organization for Rare Diseases.

Somatoform Disorders are basically the updated name for "hysteria", an archaic concept based more on the misogynist ideas of it's time than any physical reality.  At that time, medicine was considered "scientific", but not exactly in the way we see it now- as a practice based on the sciences of biology and chemistry.  At that time, eugenics was considered science, and was deeply enmeshed in the theory and practice of medicine.  This historical reality has been swept under the rug, but the pseudoscience of eugenics still lingers in the medical practices of today- and I believe that the concept of "Somatoform Disorders" is one example.

The practice of medicine requires that patients be listened to and treated as the experts about life in their own bodies.  Treating them as misbehaving children, putting on a show for attention, has no place in a scientific practice.  I myself was subjected to this gaslighting and abuse for years while struggling to survive an illness which is life-threatening on a daily basis.  I was shamed and shunned until I myself arranged to have a tissue sample from a previous biopsy prepared by the lab that was storing it according to the instructions I got over the phone from the leading pathologist in the country for the disease that I knew I had, and then shipped to her hospital by Fed Ex.  Once she gave me the diagnosis, I was taken seriously and received more than 10 additional diagnoses. 

The delay in treating my medical condition, which I had been both laughed at and yelled at for daring to suggest I had, caused my condition to degenerate such that I have lived on life support since then.  At my lowest point, I was on oxygen, unable to eat and dependent on IV nutrition to survive, requiring continuous infusions of 2 medications, needed a central line which has resulted in 2 DVTs and 15 blood infections, was mostly bed bound, my back broken in 5 places, unable to take any pain meds and needed to undergo my surgeries without anesthesia, had skin cancer removed, had all of my teeth removed due to breakage, have had multiple heart attacks, and more.  There are many, many other people like me.  Most haven't survived.  You could say that "Somatoform Disorders" have a very high fatality rate- but not for the same reason that other deadly disorders do.  Please, it's the year 2024- isn't it time that our medical system reflected that?

This recent study shows examples of people with legitimate physical disease who were misdiagnosed with psychosomatic and psychiatric conditions, and the long-term harm it did them:
“I still can’t forget those words”: mixed methods study of the persisting impact on patients reporting psychosomatic and psychiatric misdiagnoses
"Patient-reported psychosomatic and psychiatric (mis)diagnoses are associated with persisting adverse impacts in multiple domains including mental health, medical relationships, self-worth, and some healthcare behaviours. Health services and clinicians should consider these potential adverse impacts on patients and offer support to reduce any persisting negative impacts."

Mold-Induced Illness

(work in progress)

Significant exposure to mold and related organisms, usually prolonged, can cause a wide range of symptoms and conditions.  This is a common cause or exacerbating factor for MCAS.  Common symptoms of mold illness include fatigue, headaches, digestive problems, respiratory problems (including asthma and shortness-of-breath), cough, sore throat, allergies and reactions that look like allergies (such as sneezing, hives, rashes), excessive thirst, muscle cramps, joint pain, stiffness in the morning, sleep problems, night sweats, brain fog and related cognitive issues (such as problems with memory and executive function), light sensitivity, blurred vision,  numbness, tingling, and tremors.

Mold illness can be diagnosed as many things, including- ME/CFS, Fibromyalgia, MS, Somatization disorders, anxiety, depression, PTSD, ADHD, dementia, Irritable Bowel Syndrome, and more.  That is to say that you may meet criteria for one or more of these diagnoses, but mold exposure is the reason that you have the symptoms in the first place.  For some people, treating and healing from the mold illness allows them to heal and lose the diagnosis.  Whether or not they "actually had" the illness then becomes a semantic issue rather than a scientific one.

The Basics of Mold Illness and Toxicity
Mold Toxicity - Depression, Anxiety, Fatigue, Brain Fog & Inattention 
Mold "can contribute to Pyrrole Disorder due the stress it puts on the body.  It can lead to elevated copper by overwhelming one of the antioxidants in the body that regulates copper.  Because it interferes with the immune system, it can lead to a susceptibility to candida/yeast, Lyme and its co-infections.  It also frequently worsens mast cell activation."

Mold can thrive in water damaged buildings or anywhere indoors where there is retained moisture, including AC units and ductwork.  The mold thrives because it has the ideal conditions for growth and because it doesn't have the competition that keeps it in check outdoors.  Additionally, mold spores and toxins build up inside without the natural ventilation that exists outside.  Mold can poison us with toxins and it can also colonize our bodies, such as our sinuses and GI tract.  Some people also have mold allergy.

"Seemingly 25% of people are unable to make antibodies to mold toxins. Add to that the 50% of buildings that have water damage, and you have a lot of people who are unknowingly becoming toxic while spending time in affected homes, schools, workplaces, cars, dorms, and nurseries."

"Mold toxins basically go from the body, to the liver and gallbladder where they are bound to bile and sent out into the gastrointestinal tract. The bile, however, is recycled (as a means of conservation), and thus take toxins back into the body."  

Some of the symptoms that she lists that I don't see listed often include: electric shock sensations, ice-pick pains, Atypical Parkinson's Disease, Atypical ALS, Psychogenic seizures or pseudo-seizures​​, Tics, spasms and seizure like events; Sensitivity to light touch, Suspected or Diagnosed PANS/Pediatric Acute-Onset Neuropsychiatric Syndrome, Rapid weight gain, Body temperature dysregulation, and diagnosis of fibromyalgia, or chronic fatigue.  
Detection of Mycotoxins in Patients with Chronic Fatigue Syndrome
"Urine specimens from 104 of 112 patients (93%) were positive for at least one mycotoxin (one in the equivocal range). Almost 30% of the cases had more than one mycotoxin present. OTA was the most prevalent mycotoxin detected (83%) with MT as the next most common (44%). Exposure histories indicated current and/or past exposure to WDB in over 90% of cases. Environmental testing was performed in the WDB from a subset of these patients. This testing revealed the presence of potentially mycotoxin producing mold species and mycotoxins in the environment of the WDB. Prior testing in a healthy control population with no history of exposure to a WDB or moldy environment (n = 55) by the same laboratory, utilizing the same methods, revealed no positive cases at the limits of detection."

Most doctors who specialize in mold illness use urinary mycotoxin testing to figure out which mycotoxins a patient is dealing with, as treatment consists largely of the use of binders and different ones bind different toxins  

Comprehensive Guide to Mycotoxin Binders

MCAS & Mold: Fungal Colonization of the Sinuses (video)

Mold often co-occurs with other organisms, such as bacteria, in water-damaged buildings.
Aerobic Actinomycetes of Clinical Significance

CIRS (Chronic Inflammatory Response Syndrome)
There is another condition called CIRS (Chronic Inflammatory Response Syndrome) which seems to me to be essentially another name for MCAS, but was recognized and described without as thorough an understanding of the underlying immunological mechanisms.  CIRS-WDB refers specifically to the condition when developed after prolonged exposure to the inside of water-damaged buildings.  According to this 2024 study, CIRS is "an acquired medical condition characterized by innate immune dysregulation following respiratory exposure to water-damaged buildings (WDB).", and states that ME/CFS is "a common misdiagnosis of CIRS".  MedicineNet gives a more detailed description of CIRS "a multisystem and multi-symptom illness that occurs when a person gets exposed to toxins such as mold spores or biotoxins found in tick or spider bites. These toxins get attached to the immune system to trigger an inflammatory response and induce hormonal changes. The immune system produces an excess of cytokines that can lead to the immune system attacking its tissues, causing inflammation and other associated symptoms."  This source further defines biotoxins as "fat-soluble molecules that travel from cell to cell without entering the bloodstream" and further states that "measuring biotoxins in the blood is difficult, but doctors usually identify them by the damage inflicted on various organs."

According to Dr Shoemaker, there are some HLA-DR/DQ haplotypes (combinations of genes that are inherited together) that make a person less able to clear biotoxins, such as mold toxins, from their bodies, making them more likely to develop CIRS when exposed to mold, which then cause the innate immune system to overreact and lead to chronic inflammation.  These include:
HLA-DR4-3-53
HLA-DR7-2/3-53
HLA-DR11-3-52B
HLA-DR13-6-52A/B/C
HLA-DR17-2-52B
HLA-DR18-4-52A

Diagnostic Process for Chronic Inflammatory Response Syndrome (CIRS): A Consensus Statement
Report of the Consensus Committee of Surviving Mold
"Clinical management of patients with a complex, multisystem, multi-symptom illness identified as a chronic inflammatory response syndrome (CIRS) has expanded. Often associated with illness due to exposure to low molecular weight biotoxins and inflammagens found (i) inside water-damaged buildings (WDB); (ii) following exposure to blooms of cyanobacteria; (iii) following consumption of ciguatoxic fish; and (iv) following confirmed acute Lyme disease, persistent despite reasonable use of antibiotics, CIRS is increasingly recognized. A need for a formal case definition and case management protocol has arisen. Patients with CIRS will have abnormalities in innate responses, reduced levels of
regulatory neuropeptides MSH and VIP, elevated inflammatory markers of C4a, MMP9 and TGF beta-1.  Systemic illness, based on abnormal gene activation and suppression, as shown by RNA Seq and transcriptomics, requires a multi-factorial, rigorous diagnostic assessment to assist in both differential diagnosis and monitoring response to therapy. A consensus statement is herein provided to assist practitioners in case identification and management."

Chronic inflammatory response syndrome: a review of the evidence of clinical efficacy of treatment

Dr. Scott McMahon, a board-certified pediatrician and CIRS specialist (Podcast)

Treatment for Mold Illness
The Shoemaker Protocol is widely recognized as the best treatment for mold-induced illness, whether or not you call it CIRS.  

Doctors who specialize in treating people with mold-induced illness tend to use urinary mycotoxin testing to identify which mycotoxins a person is dealing with, and prescribe substances that bind and remove those specific toxins as part of the treatment protocol.  Examples of binders include bentonite clay, activated charcoal, chlorella, cholestyramine, and colesevelam HCI. 

Finding and Remediating Mold in Your Environment
Consensus Statement for Microbial Remediation 2020
(Indoor Environmental Professional Panel of Surviving Mold)

Dr Jill Carnahan is considered by many to be an authority on cleaning mold and mold remediation.  This page from her website has the basics:
How to Get Rid of Mold – Definitive Mold Removal Guide

"Michael Rubino provides valuable resources and professional guidance on safely addressing mold issues in your home. His website offers detailed information on proper mold cleaning techniques, prevention, and the importance of air quality in maintaining a healthy living environment."

This is information given to me by someone with specialized knowledge of building materials:
"MDF is Medium-Density Fiberboard. There is also OSB, or Oriented Strand Board, and there are number of other building products like particle board made with the tailings or trash from milling lumber, held together by resins. The wood millings are damp from cutting, lay around in damp piles, and develop mold. The mold in this wood is fed by the resins used to make it into building materials. The paper backing on drywall has the same issue. I understand that there is now third-party certified mold-free OSB and MDF made differently."

ImmunoLytics swab tests

Resources Regarding Mold and Mold Illness:
Dr Ritchie Shoemaker's "Surviving Mold" website

International Society For Environmentally Acquired Illnesses / ISEAI website

American Academy for Environmental Medicine 
(database of practitioners who treat environmentally acquired illnesses including mold)

Dr Neil Nathan, MD is an expert in mold illness.  This book from him is highly regarded:
Toxic: Heal Your Body from Mold Toxicity, Lyme Disease, Multiple Chemical Sensitivities, and Chronic Environmental Illness

Dr Jill Crista, ND is a highly respected mold doctor.  "Dr. Jill focuses on conditions that cause injury to the brain and nervous system, including mold, PANS/PANDAS, Lyme disease, and concussion."
Dr Jill Crista online courses about mold 

Dr. Efrat Lamandre focuses on integrative and functional medicine, offering solutions for mold toxicity, chronic illnesses, and environmental health issues. Her practice emphasizes a holistic approach to diagnosing and treating mold-related conditions. Her website provides information and support for those navigating mold toxicity and other environmental health concerns.
Toxic Overload and Chronic Illness: How Mold, Plastics and Pesticides Make You Sick

#moldfinders: RADIO (Podcast)
Mold expert Brian Karr shares his secrets on how to find and remove mold and mycotoxins from your home,

The Virginia Center for Health and Wellness (has video series from Dr Andrew Heyman 

National Institute of Environmental Health Sciences Mold Information

CDC Information About Mold 

EPA Information About Mold

RealTime Laboratories, Inc. (RTL)
"RealTime Laboratories, Inc. (RTL) is a CAP and CLIA accredited clinical and environmental diagnostic laboratory that specializes in testing for and identifying hazardous mold, toxins, and infectious diseases."  They have a free e-book called:
Mycotoxins 101: An Introduction to Crucial Facts

MyMycoLab provides mycotoxin testing

Mold prevention strategies and possible health effects in the aftermath of hurricanes and major floods

The Hidden Connection: COVID, Mold Exposure, and Viral Reactivation 

A comprehensive review of mold research literature from 2011 - 2018

Legal Resources
Well.Law is a legal practice that understands the complexities of mold-related and environmental illness cases. They support clients navigating housing issues, disability rights, and toxic exposure with compassion and legal expertise. She started the personal injury firm she couldn't find.

How to get the most insurance money for mold remediation
"Learn the secrets insurance companies don’t want you to know that will maximize your insurance coverage amount."

Mold Insurance Playbook with Corey Levy (Podcast)
"It can be really expensive... But what if you didn’t have to pay full price for remediation? That’d be awesome! Today we share our entire playbook on how to maximize your coverage! Here is the quick overview... and we go in depth on each one of these in the episode: 1) DON’T CALL YOUR INSURANCE COMPANY! 2) STOP the water 3) Mold Inspection 4) Get Remediation Bids 5) Hire a public adjuster 6) Now you can contact your insurance company... If you go out of order you can literally cost yourselves tens of 1,000s of dollars!"

The Interconnection Between Mast Cell Disease and Eosinophilic Disease

I have EC and am in contact with many other people who do also. We tend to be very sick and stay quite sick for a long period of time, I have never heard of anyone "getting better". Oral Allergy Syndrome is a common underlying cause or trigger, which is when environmental allergies (usually to tree pollen such as birch or alder) cause cells in the GI tract to react leading to GI tract symptoms. This is very hard to figure out on your own. OAS usually causes intense itching and scratchy feeling in your mouth and throat and can feel like anaphylaxis. If you develop an Eosinophilic GI Disease such as EC, exposure to the allergen in the environment can cause you to have GI symptoms such as pain, burning sensation, cramping, and diarrhea. However, many people never figure out if they have allergen triggers or what they are. People with EC commonly also have excess numbers of eosinophils in other parts of the GI tract too. Treatment doesn't tent to help much and we often end up only able to consume 10 or fewer different foods. It's not uncommon for us to not tolerate any foods at all, or only one or two which can't provide enough nutrition or calories, so we end up consuming a medical food replacement called "elemental formula". In severe cases like mine, people end up TPN-dependent. This is when all of a person's nutrition and calories are given intravenously through a central line, which is a semi-permanent IV line placed in your arm or chest, in order to completely bypass the GI tract. Feeding tubes don't generally help people with EC because they don't bypass the colon. Most people on TPN due to EC do not eat at all. It is invasive and considered high risk, but people can do well and live for decades this way. You get used to it. Honestly the relief from the symptoms means it's actually a big improvement in quality of life, even with the complications. 

Mast Cell and Eosinophil Counts in Gastric and Duodenal Biopsy Specimens From Patients With and Without Eosinophilic Gastroenteritis
"Mast cells are believed to contribute to the development of eosinophilic gastrointestinal disorders (EGIDs)...  Gastric and duodenal biopsy specimens from patients with EGIDs had significant increases in mean mast cell counts compared with biopsy specimens from patients without EGIDs."

Strong association of mast cells with eosinophilic esophagitis-specific signatures
“Several studies have consistently found increased intraepithelial MCs in EoE biopsies, and positive correlations with some disease markers have also been reported. Our analyses reveal a broad and striking relationship between MCs and most EoE transcriptional signatures, including inflammation, eosinophil recruitment, epithelial remodeling, and fibrosis. Although these findings are strictly correlative, they significantly add to the body of evidence for MC involvement in EoE pathogenesis and suggest these cells may be a key disease driver. Given the limited clinical effect of eosinophil-directed therapies in EoE to date, our data support exploring the clinical benefit of anti-MC agents in EoE.”

Expression of CD25, mast cell markers and T-cell markers in eosinophilic esophagitis
“mast cells were highlighted by CKIT and tryptase in EOE, and not seen in other clinically mimicking cases. There were also significantly higher densities of CD25 and pan-T-cell marker staining in EOE cases. These findings suggest an inflammatory cellular milieu in EOE, beyond just eosinophils, that can be demonstrated by immunohistochemistry” 

“Abonia et al. described the presence of a mast-cell-associated transcriptome in EOE, corroborated by a subsequent study that found strong correlation between mast cell-specific protease carboxypeptidase A3 (CPA3) and transcripts of genes involved in fibrosis and epithelial remodeling.”

Cardiac Manifestations of MCAS, with an Emphasis on POTS/Dysautonomia, Long COVID, and COVID Vaccine Injury

Cardiac Manifestations of MCAS with Dr. Andrew Maxwell
(interviewed by Tanya Dempsey, transcript here.  Dr. Maxwell is a board-certified pediatric cardiologist and pediatrician. He received his medical degree from Johns Hopkins Medical School and a residency in pediatrics at the University of California at San Francisco, followed by clinical and research fellowships in pediatric cardiology at Lucille Salter Packard in Stanford Hospitals and Children's Hospital of Philadelphia)

"Dr. Maxwell walks us through his thinking and how MCAS is linked to POTS and Long COVID. This episode is a must-listen for patients and practitioners alike."  He says this connection is more important than ever because " in the age of COVID where we're seeing more POTS, Kounis syndrome, myocarditis and even inappropriate sinus tachycardia, which I see a lot of, which is probably a localized version of myocarditis."

Mast cells can cause dysautonomia and POTS, and this is often connected with Ehlers-Danlos Syndrome (EDS).  He says the major issue underlying MCAS is an environmental exposure which can be a pathogen (like a virus) or a toxic substance.  In the case of Long COVID and COVID vaccine injury, he says it's probably the spike protein that is the toxic element activating mast cells because that's what the virus and the vaccine have in common.  He says that "mast cells are doing a lot of the things that we are seeing in these patients causing post COVID long haul syndrome leading to POTS with or without the post COVID long haul. I mean, it could be very specifically POTS, it could be very specifically Kounis syndrome. It could be very specifically myocarditis, could be very specifically inappropriate sinus tachycardia. But I believe mast cells are very frequently the underlying mediator of that inflammation. Now, it could be where it’s partly a mediator and something more direct or some other thing as being a mediator as well. But I see time and time again a pretty good response to full mast cell suppression. So that, that again informs us that very commonly it’s mast cells doing the mediation."

"Kounis syndrome is basically an allergic spasm of the coronary arteries. And so when you have a spasm of the coronary arteries, you have essentially all the signs and symptoms of the angina that might lead one to believe they’re having problems with coronary perfusion. And you are. But it is reversible with, with mast cell medications."  He says he doesn't think his colleagues are making the connection that this chest pain is related to mast cell activation and therefore can be treated with mast cell meds effectively.  He also believes that Kounis Syndrome is much more common than previously thought, so it's important to get the word out and inform more doctors about it.

He says he identifies MCAS patients by taking a close look at their clinical picture, really looking at their symptoms across body systems, and taking a thorough medical history.  This shows if a viral infection seems to have been the trigger.  He points out that some patients have never had a positive test for COVID but were known to have been exposed and developed "long haul" symptoms following the exposure at the right time, so they were just asymptomatic.  "What I kind of look, try to look for is the food sensitivities, the GI distresses that are a little bit different with mast cell activation. And then the one particular feature, what I call rushes of flushes, which is sure there’s tachycardia and palpitations, burst of racing heart palpitations, but you can find that in both the straightforward dysautonomia and mast cell activation. So how do you tell the difference between the two? You get the flushing and the rashiness with rushes of flushes. And that’s kind of how I say, okay, this is definitely a mast cell phenomenon going on."

In diagnosing and treating mast cell disease, he doesn't rely much on lab testing.  He feels it doesn't add much to his understanding of the patient or how he will treat them, which is driven by their symptom presentation "we might start with that type of therapy including fludrocortisone, midodrine, corlanor, beta blockers, pyridostigmine, that type of medication directed toward dysautonomia slash POTS."  After that, he will employ what he calls his "bicycle tire management strategy" which means:

"What I mean by the bicycle tire management strategy is you gotta consider mast cell activation like a bicycle tire with about seven holes in it. And those holes are you know, excessive histamine consumption in the diet. The GI tract as being a source of additional mast cell activation, so having the GI tract in order, and then mast cell action itself, both systemically and within the GI tract. And then those particular receptors of histamine, H1 and H2. So therapy would be an H1 blocker, an H2 blocker, mast cell suppression systemically with usually a lukast. Zafirlukast is what I prefer. I usually avoid montelukast and with a cromolyn substance in the gut. So Gastrocrom here in the US. Finally, quercetin is a natural version of the systemic mast cell stabilizer. So I usually have patients on quercetin. I consider it kind of a freebie that not really being exposed to a med is very safe, so why not? And then making sure the GI motility is working well, making sure that there’s no evidence of what we call SIBO, small intestinal bacterial overgrowth, doesn’t necessarily mean I work them up for that in any way. I just mean I put ’em on probiotics. Make sure if they have any evidence of slow GI motility, put ’em on a burra, gass or ginger root extract (not sure what "burra" or "gass" refer to). Rarely have to go something more extensive medication-wise with that. And then of course, put them on a low histamine diet, make sure they’re not adding histamine to their system. That’s usually the, the, in my view, patching all seven holes of that bicycle tire. And when you have all seven holes patched, You can expect a change."

When asked why he prefers Zafirlukast over Monteleukast, he says it is primarily because he sees Monteleukast cause a lot of depression in his patients.  He attributes this to mast cells releasing elastases, that breakdown the blood-brain-barrier (and also the gut barrier and the endothelial layer in capillaries) by breaking down small proteins called cadherins that hold these things together, making them "leaky".  He says he sees similar results with a lot of the dopamine agonist antagonists like Reglan.  He speculates that this scenario may be more common in children.  Dr Dempsey points out that she sees better responses to Monteleukast (and other meds) when they are compounded, so the excipients used in the standard formulations may be the problem.  

(This is his complete quote from above, included because it may be of particular interest to some readers "Mast cells not only secrete histamine, but they secrete elastases and elastases breakdown the little proteins that hold things together, what are called cadherins and maybe other proteins too. But I really focus on the cadherins. Cadherins hold together, the GI epithelium, that’s the E-cadherin. So that’s where your leaky gut comes from and it holds together what are called VE-cadherins hold together, the capillaries, the endothelium within capillaries. And so if they break down, you get increased leaky capillary in general, but blood-brain barrier. And we see that with not only montelukast, we see it with a lot of the dopamine agonist antagonists like Reglan where patients will much more commonly have extra pyraminal effects being put on Reglan and other types of dopamine modifying agents.")

They go on to discuss the idea of grouping together conditions like MCAS, POTS, and other commonly comorbid conditions because it's clear that these conditions frequently occur together.  At first, doctors referred to "the triad" which included MCAS, EDS, and dysautonomia.  It then expanded to "the pentad" when GI dysmotility (GI involvement in general) and autoimmunity were added.  The direction of causality is unclear- which condition came first?  Did the leaky gut become an "auto-antibody generator over time"?  Did the autoimmunity start this whole progression?  The idea of identifying the 5 main pieces is that a patient would then need to set up a team of 5 doctors to manage these conditions, although in reality that is often not possible to do.  Then the next two conditions were added, bringing it to "the septad"- many patients had underlying infections, such as Lyme Disease, and they also had what is often called "ME/CFS" which is now generally recognized to be mitochondrial dysfunction.  Dr Dempsey than added 3 more things to bring it up to a "decad" including small fiber neuropathy, cervical instability and tethered cord, and autoimmune encephalopathy (such as PANDAS/PANS).  This last component acknowledges the brain fog and cognitive issues, the neuropsychiatric issues, and endocrine issues especially thyroid, adrenal, and sex hormone issues.  Dr Maxwell adds that he sees many of these additional pathologies that are being added to the list as sub-forms of things already on the list, so it may not make much difference how much you expand the list or keep it short in terms of making sure that you recognize and treat the patient's whole picture.  

It's worth noting that in the above discussion, Dr Maxwell puts forth the idea that there can be localized expressions of some of these conditions that may not meet full criteria, that were caused by a localized environmental exposure.  For example, a person who was exposed to "something that’s aerosolized and breathed in, and what happens is you have a localized nasal pharyngeal mast cell activation that then causes havoc in the nasal pharyngeal region, specifically CCI, TMJ issues, and then loss of airway. So the airway becomes floppy for different reasons. And so you see these particular patients and they’re kind of a setup for this phenomenon I see and call "spiky leaky syndrome." (CCI is cranial cervical instability, meaning the vertebrae in the neck are unstable).

Dr Maxwell is then asked if how he sees the patient picture changes how he treats the mast cells and he says generally, no, that he pretty much starts everyone on his usual mast cell protocol.  If a patient seems to need more than that, he says "another strategy I have are IV infusions of mast cell meds... getting saline along with Benadryl, Toradol, Ativan, and famotidine and IV form, and oftentimes on ondansetron as well. And so that often works much more effectively than the oral forms."  He may also increase the dose of LDN (Low Dose Naltrexone).  He also adds that if a patient is really "POTSie" and has "angina type symptoms and you’re thinking the mast cell meds aren’t gonna work fast enough for that, you might try some antianginal type strategy, something like a nitric oxide releaser to open up their coronaries as quick as possible."  

They then go on to discuss how mast cells are related to and can cause Dysautonomia and POTS, and specifically how the COVID virus and the COVID vaccines have both been shown in research to contribute to the onset of both Dysautonomia and POTS specifically.  This discussion begins at [00:26:26] in the interview- if this is very interesting to you, I suggest going to the interview and reading the entire very long quote.  This is my summary of what Dr Maxwell is saying:

POTS is basically what happens when the person's venous system becomes "saggy" and "stretchy" rather than as rigid as it needs to be to appropriately control blood flow throughout the body as the body moves around and changes position.  When the person stands up, the venous system is too "saggy" to bring the full amount of blood up to the heart to fill it when ti pumps so it pumps partially empty, resulting in low cardiac output.  This causes the heart to beat faster, as tachycardia, in an attempt to increase cardiac output.  One of the reasons that MCAS more broadly and COVID or COVID vaccine injury more specifically can cause this situation is that the spike protein activates mast cells, which then release mediators that break down the connective tissue of the venous system itself, causing it to become too "saggy" to function properly. 

He says there are also several ways that mast cell activity can affect the functioning of the autonomic nervous system directly, which is the branch of the nervous system that regulates things like circulation, heart rate, and blood pressure.  "(M)ast cells activated in the gut can then cause inflammation of the sensory portion of the Vagus nerve. It’s the information heading back to the brain. And so if it’s irritating and inflaming the sensory portion of the Vagus nerve, it’s as I consider it like almost like a CPU u you know, computer system with information going into the CPU, if it’s garbage in, it’s gonna be garbage back out. And so, it affects how the motor portion of the Vagus nerve works. And so you have a dysautonomia of the motor portion of the Vagus nerve that results from a inflammation of the sensory portion of the Vagus."

He outlines another way that mast cell activation can lead directly to dysfunction of the Vagus nerve as well as several other cranial nerves, which could also be leading to POTS and Dysautonomia in patients following a COVID infection or vaccine injury.  Mast cells in the neck becoming activated could be releasing the mediators mentioned above that can "tenderize" connective tissues, in this case ligaments in the neck that hold the cervical vertebrae in place.  This could in theory result in a situation very similar to what is called CCI (Cranial Cervical Instability) and is often seen in EDS patients (Ehlers-Danlos Syndrome, which is often comorbid with MCAS). He sees this as essentially "carpal tunnel syndrome" of the neck but says that because it acquired by mast cell activation, it is more of a clinical diagnosis and may not show up on the radiology and other types of testing used to identify CCI in EDS patients, that is more structural.  In this scenario, the C1 vertebra (aka the atlas) becomes loose and unstable, and gets pushed forward, which compresses the cranial nerves 9, 10 (the Vagus nerve), and 11 that are exiting the spine at that spot.  Those nerves are then compressed against the jugular vein, which is then compressed against the stylo hyoid ligament.  If this situation becomes chronic, these nerves can become damaged, which can then lead to dysfunction of the parasympathetic nervous system by way of a little bit of CCI.  

More evidence that this happening is that you’re also seeing cranial nerve 9 and cranial nerve 11 dysfunction, which can present as tinnitus, phonophobia (sensitivity to and/or fear of certain sounds) and hyperacusis (an abnormally strong reaction to sound, occurring within the auditory pathways), vertigo, and what’s called globus feeling of a mass in the back of the throat.  Dr Maxwell says he also sometimes sees "what’s called eagle syndrome type symptoms with turning the head and having pain upon turning your head. From side to side, sharp stabbing pains in the neck or pain at the base of the tongue. Those are all glossopharyngeal nerve findings. And then the cranial nerve 11 is a motor nerve to the trapezius and it innervates the trapezius. So when it’s injured, oftentimes will cause a knottiness something beyond coat hanger pain in the trapezius, but rather a knottiness in the trapezius. So when you hear these patients complaining of all these symptoms, that it sounds almost crazy that they’re related. No, there’s one place in the body where these three nerves are together and they happen to run right in front of the lateral process of c1. So when that slips forward and chronically does so, I think it causes this, this list of symptoms together."

When Dr Maxwell is asked how he manages and treats this situation with the slipped C1 vertebra if he suspects it, he responds "I will get the physical therapist involved. And I’ll often assess their airway as well, because if they have that going on, they may have a floppy airway as well, and they may be losing it at night and showing what we call upper airway resistance syndrome, which is a subtle form of sleep apnea. So we oftentimes, I get sleep studies to look at that. Oftentimes I’ll get ENT and the oral airway doctors including oral surgeons involved to make sure that they’re not losing their airway, myofunctional therapists to help strengthen the musculature of the airway. And then there’s a class of physical therapists that are geared entirely toward CCI. So I will get them and get them involved. One of the things that I’ve found useful as a test of concept in these patients is what happens if they were to get some what’s called NUCCA therapy, NUCCA. And that’s a particular form of chiropractic therapy that focuses on the Atlas. And so these NUCCA chiropractors have been very, very helpful in putting C1 back in place. And these patients can respond right away to their POTS like symptoms. Their dysautonomia improves right away."  He says this is a test of concept because while the NUCCA therapy is very effective, the improvements don't last long. He discusses prolotherapy as an option and says that he encourages the therapist to inject platelet-rich plasma (from the patient in order to avoid MCAS being triggered by something foreign).  

He sees this therapy, like he does the POTS therapies, as "band-aid" therapies to help as the longer-term stabilization of the mast cells and treatment of any residual COVID is taking effect.  This may include the body clearing residual spike protein, treating a lingering COVID infection, or treating another infection that was latent and reactivated from the immune suppression of the COVID or vaccine (such as HHV6, EBV, or Lyme).  He says he will treat with anti-virals if "the PCRs are positive or if the IGMs for those viruses are positive".  

They discuss this paper Apparent risks of postural orthostatic tachycardia syndrome diagnoses after COVID-19 vaccination and SARS-Cov-2 Infection, which found a significantly higher risk of developing certain conditions associated with POTS after both COVID infection and COVID vaccines, including Dysautonomia, POTS, and MCAS, as well as some other conditions including UTIs, lower back pain, and symptoms like dizziness, fatigue, and anxiety.  They go on to talk about how complicated it is to weigh the costs and benefits of vaccination for the population of people who already have any of these conditions or who are at higher risk for developing them, especially given that the nature of COVID infection has changed. 

Dr Maxwell's last message for patients "for the patients seeking help, you know, find the right provider that works with you. Don’t let someone dismiss you. I hear again and again being told, you know, there’s no point in managing anything. You’re gonna get better with your long COVID. And you know, we’ve seen long COVID patients two years out who were just struggling, not everybody. And it’s great to see some patients getting better even on their own. But you never know who thoses are gonna be, and so you’re gonna want to try to modify what could be a very long road. And so you know, make sure you’re finding someone who’s addressing your issues that has a a pretty good handle on the underlying causes that can do it in a systematic way. And I think you’ll have some success."

Further information on the topics discussed in this interview:

Mast cells in the autonomic nervous system and potential role in disorders with dysautonomia and neuroinflammation
"Mast cells... having potential involvement in the pathophysiology of dysautonomias and neuroinflammatory disorders. MC are located perivascularly close to nerve endings and sites such as the carotid bodies, heart, hypothalamus, the pineal gland, and the adrenal gland that would allow them not only to regulate but also to be affected by the autonomic nervous system (ANS). MC are stimulated not only by allergens but also many other triggers including some from the ANS that can affect MC release of neurosensitizing, proinflammatory, and vasoactive mediators. Hence, MC may be able to regulate homeostatic functions that seem to be dysfunctional in many conditions, such as postural orthostatic tachycardia syndrome, autism spectrum disorder, myalgic encephalomyelitis/chronic fatigue syndrome, and Long-COVID syndrome."

Phonophobia and Hyperacusis: Practical Points from a Case Report

NUCCA

Prolotherapy

POTS association with COVID-19 vaccination and COVID-19 infection
"Although any comparison of post-exposure rates should be interpreted cautiously, given the baseline differences in POTS incidence in the two mutually exclusive populations, these results indicate that POTS might be occurring at a higher-than-expected frequency following COVID-19 vaccination, although at an overall rate lower than the frequency of POTS occurring following SARS-CoV-2 infection."

Apparent risks of postural orthostatic tachycardia syndrome diagnoses after COVID-19 vaccination and SARS-Cov-2 Infection
 "POTS-related diagnoses appear to be acquired with increased frequency after, compared to before, COVID-19 vaccination, particularly when compared to more commonly diagnosed conditions"

"For new diagnoses made after vaccination, we found that the five conditions with the highest post-vaccination odds of new diagnoses were myocarditis, dysautonomia, POTS, mast cell activation syndrome and urinary tract infection (UTI). Two POTS-associated conditions had lower odds, with fatigue demonstrating a moderate ratio and Ehlers–Danlos syndrome (EDS) having the second from the lowest ratio."

"There is biological plausibility for the association between POTS and COVID-19 vaccination in particular. Before the pandemic, mRNA vaccination had been administered in small trials predominantly involving cancer therapy, demonstrating rare off-target neurological effects such as Bell’s palsy, which has also been seen with COVID-19 vaccination^25,26. In SARS-CoV-2 infection, multiple reports of post-infection POTS invoke the possibility of an immune-mediated mechanism triggered by an antigenic component of the spike protein shared with vaccination^13,24,27. Given the broad expression of ACE2 preceptors, inflammasome activation by synthetic spike protein could result in multi-systemic effects, including neurocardiogenic targets and potential induction of variable types of autoimmunity^28,29,30. Additionally, the lipid nanoparticle coating in mRNA vaccine formulations is known to be highly inflammatory, although effects related to the lipid coating appear less likely contributors than spike-protein-mediated effects³¹. Further research is needed to clarify potential mechanisms related to either vaccine formulation or vaccine target."

Postural orthostatic tachycardia syndrome after COVID-19 vaccination
"Ten patients (3.9%) at a quaternary-care POTS clinic reported new or worse POTS symptoms after the mRNA COVID-19 vaccine. All patients had pre-existing comorbidities, suggesting a potential group of patients to monitor for post-vaccine POTS. Symptoms responded to guideline-directed POTS therapy."  (Pre-existing conditions included previous COVID-19 infection, Hypermobile EDS, MCAS, and auto-immune cardiac, neurological, and gastrointestinal symptoms)