The path to health leads many Lyme/MSIDS patients down numerous rabbit holes.  A pathogen invasion of various bacteria, funguses, viruses, and nematodes depletes the body of many important things.  We are literally being feasted upon, and patients find that they need to supplement their deprived bodies of many things after becoming infected.

Pathogen invasion also causes autoimmunity, where the body attacks itself. Cytokine cascades are continually being set off and the body is in a state of immunoconfusion with a pro-inflammatory response.  The immune system can no longer identify bad guys from good guys.  For many, getting the immune system straightened out is at least half the battle.

Mast Cell Activation Syndrome (MCAS) can cause these things as well.

Dr. Lawrence Afrin, M.D. wrote about MCAS in his book, Never Bet Against Occam.  In reading the book, it becomes clear there are as many nuances with MCAS as there are with Lyme/MSIDS.  Every patient is truly, uniquely different. In treatment, there is much trial and error, with each patient responding to differing things.

Our personal experience with MCAS stems from my daughter who developed allergy-type symptoms over years which came to a head with she developed severe Epstein Bar Virus (EBV).  Prior to that she would frequently have to stop running or walking due to severe itching (exercise induced urticardia).  http://www.mayoclinicproceedings.org/article/S0025-6196(11)63475-7/fulltext  Our LLMD uses LDA/LDI for those with immunoconfusion with success.  Although, she thankfully doesn’t present with Lyme/MSIDS, she definitely struggles with a confused immune system and EBV.  Read here for more on LDA/LDI:  https://madisonarealymesupportgroup.com/2016/05/30/new-kids-on-the-block-ldaldi/  In her case, she reacted strongly to the LDA.  The injections are  somewhat separated so you can visibly see what your issues are.  She developed a facial rash which was deep and painful.  Within a day of her shot it resolved completely, showing how skin symptoms can definitely be caused by allergens and immunoconfusion.

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Mast Cell Activation Syndrome (MCAS): When Histamine Goes Haywire…

Published on October 31, 2016
Jill C. Carnahan, MD – Used with permission
Founder, Medical Director, Flatiron Functional Medicine

Mast cells are present in most tissues throughout the human body, especially connective tissue, skin, intestinal lining cardiovascular system, nervous system, and reproductive organs. They are part of the allergic response designed to protect us from threat and injury. When the body is exposed to a perceived threat, the mast cells secrete chemical mediators, such as histamine, interleukins, prostaglandins, cytokines, chemokine and various other chemicals stored in the cytoplasm of the cell. These chemical messengers produce both local and systemic effects, such as increased permeability of blood vessels (inflammation and swelling), contraction of smooth muscle (stomach cramps and heart palpitations), and increase mucous production (congestion, sneezing, etc). Historically, we thought of mast cells only in relation to an allergic or anaphylactic response. We now know they play a profound role in immune activation, development of autoimmunity and many other disorders, such as POTS (postural orthostatic hypotension). Sadly we are seeing a large increase in patients presenting with mast cell disorders and MCAS. I believe it is in part do to the onslaught of more pervasive environmental toxins, molds and chemicals.

Without mast cells, we would not be able to heal from a wound. They protect us from injury and help the body to heal. Unfortunately, overactive mast cells can cause a variety of serious symptoms.

Symptoms of overactive mast cells may include:

skin rashes/hives
swelling/edema
flushing
itching
abdominal pain
nausea/vomiting
diarrhea
wheezing
shortness of breath
heart palpitations
anxiety, difficulty concentrating
headaches
brain fog
low blood pressure
fatigue

Mast cell activation syndrome (MCAS) is a condition symptoms involving the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems. It can be classified into primary (clonal proliferation or mastocytosis), secondary (due to a specific stimulus), and idiopathic (no identifiable cause). Proposed criteria for the diagnosis of MCAS included episodic symptoms consistent with mast cell mediator release affecting two or more organ systems with hives, swelling, flushing, nausea, vomiting, diarrhea, abdominal pain, low blood pressure, fainting, heart palpitations, wheezing, red eyes, itching, and/or nasal congestion.

Triggers may be medications, foods, supplements, hormones, opioids, stressors (physical or emotional), cold temperature, heat, pressure, noxious odors, chemicals, insect bites, trauma or environmental toxins.

We commonly see mast cell activation syndromes associated with CIRS (chronic inflammatory response syndrome) in response to biotoxins, such as mold, inflammagens, and lyme-related toxins.

Low MSH and Mast Cell Disorders?

As mentioned above, we frequently see histamine intolerance and MCAS in patients with mold-related CIRS (chronic inflammatory response syndrome). It is interesting to note that a common finding in CIRS is low MSH. According to this study in the Journal of Investigative Dermatology, alpha-MSH plays an immunomodulatory role during inflammatory and allergic reactions of the skin. In addition, there is evidence that MSH induces mast-cell apoptosis (cell death).

Definition of Mast Cell Activation Syndrome (MCAS)

Typical clinical symptoms as listed above
Increase in serum tryptase level or an increase in other mast cell derived mediators, such as histamine or prostaglandins (PGD2), or their urinary metabolites,
Response of symptoms to treatment

Diseases Associated with Mast Cell Activation Syndrome (MCAS)

Allergies and Asthma
Autism
Autoimmune diseases (Hashimoto’s thyroiditis, systemic lupus, multiple sclerosis, bullous pemphigoid, rheumatoid arthritis and others.                                            Eczema
Celiac Disease
Chronic Fatigue Syndrome
CIRS (chronic inflammatory response syndrome)
Eosinophilic Esophagitis
Fibromyalgia
Food Allergy and Intolerances
Gastroesophageal reflux (GERD)
Infertility (mast cells in endometrium may contribute to endometriosis)
Interstitial Cystitis
Irritable Bowel Syndrome (IBS)
Migraine Headaches
Mood disorders – anxiety, depression, and insomnia
Multiple Chemical Sensitivities
POTS (postural orthostatic hypotension)

Mast cells are known to be the primary responders in allergic reactions, orchestrating strong responses to minute amounts of allergens. Several recent observations indicate that they may also have a key role in coordinating the early phases of autoimmune diseases, particularly those involving auto-antibodies.

Lab tests specific to mast cell activation for suspected MCAS may include:

Serum tryptase (most famous mast cell mediator)
Serum chromogranin A
Plasma histamine
Plasma PGD2 (chilled)
Plasma heparin (chilled)
Urine for PGD2 (chilled)
PGF2a
N-methylhistamine

Tryptase is the most famous mast cell mediator. Serum tryptase value is usually normal in MCAS patients, but sometimes it is elevated. Tryptase values that show an increase of 20% + 2 ng/ml above the baseline level are considered diagnostic for MCAS.
Chromogranin A is a heat-stable mast cell mediator. High levels can suggest MCAS, but other sources must first be ruled out, such as heart failure, renal insufficiency, neuroendocrine tumors and proton pump inhibitor (PPI) use.
Heparin is a very sensitive and specific marker of mast cell activation. However, due to its quick metabolism in the body, it is very difficult to measure reliably.
N-methylhistamine is usually measured in a 24 hour urine test to account for the variability in release over the course of the day.
Prostaglandin D2 is produced by several other cell types, but mast cell release is responsible for the dominant amount found in the body. PGD2 is less stable than histamine and metabolized completely in 30 minutes.
Other less specific mast cell mediators that are sometimes abnormal in MCAS patients include Factor VIII, plasma free norepinephrine, tumor necrosis factor alpha, and interleukin-6.

Treatments to reduce MCAS symptoms and lower histamine

H1 Blockers – hydroxyzine, doxepine, diphenhydramine, cetirizine, loratadine, fexofenadine
H2 Blockers Famotidine (Pepcid, Pepcid AC), Cimetidine (Tagamet, Tagamet HB) Ranitidine (Zantac)
Leukotriene inhibitors: Montelukast (Singulair), Zafirlukast (Accolate)
Mast cell stabilizers -Cromolyn, Ketotifen
Tyrosine kinase inhibitors – imatinib
Natural anti-histamines and mast-cell stabilizers
Ascorbic Acid
Quercetin
Vitamin B6 (pyridoxal-5-phosphate)
Omega-3 fatty acids (fish oil, krill oil)
Alpha Lipoic Acid
N-acetylcysteine (NAC)
Methylation donors (SAMe, B12, methyl-folate, riboflavin)
Certain probiotics decrease histamine productionLactobacillus rhamnosus and bifidobacter species
DAO Enzymes with meals – Xymogen HistDAO or Histamine
Decrease consumption of high histamine foods (more on histamine-restricted diet)
Avoid alcoholic beverages
Avoid raw and cured sausage products such as salami.
Avoid processed or smoked fish products. Use freshly caught seafood instead.
Avoid pickles
Avoid citrus fruits.
Avoid chocolate
Avoid nuts
Avoid products made with yeast and yeast extracts
Avoid soy sauce and fermented soy products
Avoid black tea and instant coffee
Avoid aged cheese
Avoid spinach in large quantities
Avoid tomatoes, ketchup and tomato sauces
Avoid artificial food colorings & preservatives
Avoid certain spices: cinnamon, chili powder, cloves, anise, nutmeg, curry powder, cayenne pepper

Specific Symptom Treatment in MCAS

(Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options)

Headache⇒ paracetamol; metamizole; flupirtine
Diarrhea⇒ colestyramine; nystatin; montelukast; ondansetron
Colicky abdominal pain ⇒ metamizole; butylscopolamine
Nausea⇒ metoclopramide; dimenhydrinate; 5-HT3 receptor inhibitors; icatibant
Respiratory symptoms (mainly increased production of viscous mucus and obstruction with compulsive throat clearing) ⇒ montelukast; acute: short-acting albuterol
Gastric complaints⇒ proton pump inhibitors
Osteoporosis, bone pain⇒ biphosphonates, Vitamin D plus calcium
Non-cardiac chest pain⇒ H2-histamine receptor antagonist; proton pump inhibitors
Tachycardia⇒ verapamil; AT1-receptor antagonists; ivabradin
Neuropathies ⇒ a-lipoic acid
Interstitial cystitis⇒ pentosan, amphetamines
Sleep-onset insomnia/sleep-maintenance insomnia⇒ triazolam/oxazepam
Conjunctivitis⇒ preservative-free eye drops with glucocorticoids for brief course
Elevated prostaglandin levels, persistant flushing⇒ incremental doses of acetylsalicylic acid (50-350 mg/day; extreme caution because of the possibility to induce mast cell degranulation)

For more on MCAS, Lyme/MSIDS, and parasites:  https://madisonarealymesupportgroup.com/2017/03/23/rebecca-keith-on-mcas-parasites-lymemsids/

References

Mast Cell Activation Syndrome, A Review http://www.jillcarnahan.com/downloads/MCASReview.pdf
Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options  http://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-4-10
Presentation, Diagnosis and Management of Mast Cell Activation Syndrome by Dr. Afrin  http://www.jillcarnahan.com/downloads/MCAS-Afrin.pdf
Histamine and Gut Immune Mucosal Regulation  http://www.jillcarnahan.com/downloads/Histamine-gut.pdf
Dr. Theoharides presents “Mast Cell Disorders”  https://www.youtube.com/watch?v=92nrFwcNSwc&feature=youtu.be
Diagram of Histamine Symptoms  https://mastcellblog.files.wordpress.com/2013/11/mast-cell-symptoms.jpg
Mast Cell Aware  http://www.mastcellaware.com
A Tale of Two Syndromes  http://www.dysautonomiainternational.org/blog/wordpress/a-tale-of-two-syndromes-pots-and-mcas/
Mold Histamine Connection  https://healinghistamine.com/the-mold-histamine-link/