Mast Cell Activation Syndrome

[nanna1]

A recent POIS paper (2019) tested the MCAS and systemic mastocytosis models for POIS.

"The particularity of the case is that the patient had no obvious local or generalized allergic reaction, which can delay and even obscure the diagnosis...
2. Systemic Mastocytosis;... The second differential diagnosis was invalidated, because of the absence of major and/or minor criteria for mastocytosis. There were no obvious rashes or hematological changes in the number or morphology of mast cells."
POST COITAL ALLERGY - A CASE REPORT OF POST ORGASMIC ILLNESS SYNDROME. Med. Surg. J. - Rev. Med. Chir. Soc. Med. Nat., Iaşi - 2019 - vol. 123, no. 2

  They looked at the mast cells of this patient under the microscope and found them to be normal in quantity and appearance. The researchers could not observe any signs of mast cell activation.

[Muon]

A recent POIS paper (2019) tested the MCAS and systemic mastocytosis models for POIS.

I haven't read anything about the testing of a MCAS model.

The researchers could not observe any signs of mast cell activation.

Where did you read that? I can't find it.

[nanna1]

A recent POIS paper (2019) tested the MCAS and systemic mastocytosis models for POIS.

I haven't read anything about the testing of a MCAS model.

The researchers could not observe any signs of mast cell activation.

Where did you read that? I can't find it.

  To make a long story short, the paper "POST COITAL ALLERGY - a case report of post orgasmic illness syndrome" looked for signs of anaphylaxis in the POIS patient they studied. They did not find that anaphylaxis was apart of this patient's POIS. With the exception of abdominal pain-nausea, the POIS patient's symptoms (see Section: CASE REPORT) do not match the characteristic features of mast cell activation syndrome (MCAS) and anaphylaxis. Anaphylaxis is the first diagnostic criteria for MCAS given by the American Academy of Allergy Asthma and Immunology.

  I used a standard definition of mast cell activation syndrome (MCAS). There are many non-standard descriptions of MCAS on the internet. But without a clear definition (diagnostic criteria), the concept of MCAS can be stretched to include any disease. The definition of MCAS that I used, comes from the American Academy of Allergy Asthma and Immunology (AAAAI). They state the following:
"Section: IDIOPATHIC MAST CELL ACTIVATION SYNDROME
MCAS is a condition in which the patient experiences repeated episodes of the symptoms of anaphylaxis - allergic symptoms such as hives, swelling, low blood pressure, difficulty breathing and severe diarrhea....Evaluation for MCAS starts with determining whether the symptoms occur in separate attacks and are typical symptoms of an anaphylactic reaction without a clear cause." -American Academy of Allergy Asthma and Immunology: MAST CELL ACTIVATION SYNDROME (MCAS)

The AAAAI states that there are three stages to diagnosing MCAS. In summary,

• Measure the presence of anaphylaxis (hives, low blood pressure, vomitting, etc... see Section: SYMPTOMS)
• Measure mast cell mediators (tryptase, N-methyl-histamine, etc...) during acute phase and baseline (see Section: MEDIATORS)
• Block mast cell mediators and observe symptom reduction

  The POIS patient in this paper failed the first diagnostic criteria for MCAS (anaphylaxis), which also overlaps with mastocytosis. So under the AAAAI definition of MCAS, the patient would not be diagnosed with MCAS. Below, I have added additional quotes from the paper to make this clearer:

"The particularity of the case is that the patient had no obvious local or generalized allergic reaction, which can delay and even obscure the diagnosis...
Past medical history: no history of allergy...
Family history: one of his children was diagnosed with atopic dermatitis. No family history of allergies or diabetes...
Physical exam: absence of physical signs or symptoms, no local or generalized eruption or swelling, normal blood pressure and pulse...
2. Systemic Mastocytosis;... The second differential diagnosis was invalidated, because of the absence of major and/or minor criteria for mastocytosis. There were no obvious rashes or hematological changes in the number or morphology of mast cells."
POST COITAL ALLERGY - A CASE REPORT OF POST ORGASMIC ILLNESS SYNDROME. Med. Surg. J. - Rev. Med. Chir. Soc. Med. Nat., Iaşi - 2019 - vol. 123, no. 2

  Furthermore, it is unclear how an IgE allergen could past from the prostate to the blood stream and diffuse throughout the entire body without causing anaphylaxis-allergy. Mast cell are in every part of the body. The paper also claims that injecting the POIS patient's autologous semen caused different symptoms than the patient's typical POIS symptoms. Is there something about the allergy-hypothesis that I do not understand?

[Quantum]

Video about 'Brain Allergy':

'Brain Allergy' and ASD - T. Theoharides, MD, PhD

Interesting, lots of info in the video.  He seems to show a preference for luteolin as a good mast cells stabilizer.   It is a great natural mast cells stabilizer, indeed.  It was part of the list I made in 2016:   https://poiscenter.com/forums/index.php?topic=2372.msg19856#msg19856 .  It would be great if this autism research would lead to the availability of luteolin supplements.  For now, I have been using artichoke, rosemary oil, chamomile and the like, as sources of luteolin.  By comparison, it is much easier to have good quercetin or L-theanine supplements.   

The article I give the link to in my above mentioned post is still a very good reference for natural mast cells stabilizers:  https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.12138

[Muon]

Episode #106: Bartonella and MCAS with Dr. Tania Dempsey, MD

She also mentions getting results with carnivore and ketogenic diet.

Key Takeaways:

- What are the vectors for Bartonella transmission?
- What are the hallmark symptoms of Bartonella infection?
- Is Bartonella more common and more devastating than Lyme itself?
- How does Bartonella impact the neurological system and result in symptoms that may appear to be mental and emotional?
- What testing approach has been most helpful for identifying Bartonella?
- What is the role of Bartonella in autoimmunity and in conditions such as PANS, Rheumatoid Arthritis, POTS, dysautonomia, insulin resistance, and Type 1 diabetes?
- What is the connection between Bartonella and MCAS?
- What is MCAS, and how does it impact the body?
- How common is MCAS in the general population and in the chronically ill population?
- What are the best tools to test for the presence of MCAS?
- What is the QEESI, and how do MCAS and MCS overlap?
- What is the role of the vagus nerve in MCAS?
- How does one detoxify the body if toxins themselves lead to mast cell activation?
- Is CIRS a mast cell activation syndrome induced by mold?
- How is MCAS treated? 
- What is the role of genetic and epigenetics in MCAS?
- What is the role of neuroplasticity or limbic system retraining in MCAS?

[romies]

Great work guys. I have also been in the camp too that a lot of POIS cases are under the umbrella of MCAS.

[aswinpras06]

Luckily for Animus he doesn't have POIS caused by hot/cold showers, extremes of temperature and other allergies.  Because for all these, surgery will never work.

[Muon]

Check the tables for an overview:

Recent advances in our understanding of mast cell activation - or should it be mast cell mediator disorders?

[Muon]

Interstitial cystitis/BPS:

Mast cell activation syndrome

Her second suggestion applied to other locations within the genitourinary system would be of interest to POIS research, replace the words bladder biopsies and IC/BPS patients by urethra/prostate biopsies and POIS patients:

''If there appears to be no difference between the two groups, next steps should include use of an electron microscopy using time lapse photography on bladder biopsies from IC/BPS patients and controls to see if the mast cells in the biopsies of IC/BPS patients are degranulating at a more frequent rate, or releasing inflammatory mediators without degranulating compared to the control group.''

Rheumatoid Arthritis:

Mast Cells Mediate Rheumatoid Arthritis - Inhibitory Role of IL-37

[Muon]

MCAD genetics:

See figure 3 for an overview:
The genetic basis of mast cell activation disease - looking through a glass darkly

Systemic mast cell activation disease: the role of molecular genetic alterations in pathogenesis, heritability and diagnostics

Familial Occurrence of Systemic Mast Cell Activation Disease

MCAS family symptom frequency:

Characterization of Mast Cell Activation Syndrome

Extensive list in Supplementary Material.

[Muon]

Table 1: Symptoms and findings in mast cell (MC) activation disease, Potential manifestations of mast cell disease:

Often seen, rarely recognized: mast cell activation disease - a guide to diagnosis and therapeutic options

The supplemental data including therapeutic options is not included in the paper itself but can be downloaded for free in docx format:

https://www.tandfonline.com/doi/suppl/10.3109/07853890.2016.1161231?scroll=top

[Muon]

Luckily for Animus he doesn't have POIS caused by hot/cold showers, extremes of temperature and other allergies.  Because for all these, surgery will never work.

He actually has allergies. I wonder if the allergies have contributed to the increased responsiveness of his genitourinary mast cells.

Because I have Allergies, and POIS never ever felt like an Allergy to me.

That's because POIS probably isn't an allergic activation of the mast cell.

[Muon]

A recent POIS paper (2019) tested the MCAS and systemic mastocytosis models for POIS.

I haven't read anything about the testing of a MCAS model.

The researchers could not observe any signs of mast cell activation.

Where did you read that? I can't find it.

  To make a long story short, the paper "POST COITAL ALLERGY - a case report of post orgasmic illness syndrome" looked for signs of anaphylaxis in the POIS patient they studied. They did not find that anaphylaxis was apart of this patient's POIS. With the exception of abdominal pain-nausea, the POIS patient's symptoms (see Section: CASE REPORT) do not match the characteristic features of mast cell activation syndrome (MCAS) and anaphylaxis. Anaphylaxis is the first diagnostic criteria for MCAS given by the American Academy of Allergy Asthma and Immunology.

  I used a standard definition of mast cell activation syndrome (MCAS). There are many non-standard descriptions of MCAS on the internet. But without a clear definition (diagnostic criteria), the concept of MCAS can be stretched to include any disease. The definition of MCAS that I used, comes from the American Academy of Allergy Asthma and Immunology (AAAAI). They state the following:
"Section: IDIOPATHIC MAST CELL ACTIVATION SYNDROME
MCAS is a condition in which the patient experiences repeated episodes of the symptoms of anaphylaxis - allergic symptoms such as hives, swelling, low blood pressure, difficulty breathing and severe diarrhea....Evaluation for MCAS starts with determining whether the symptoms occur in separate attacks and are typical symptoms of an anaphylactic reaction without a clear cause." -American Academy of Allergy Asthma and Immunology: MAST CELL ACTIVATION SYNDROME (MCAS)

The AAAAI states that there are three stages to diagnosing MCAS. In summary,

• Measure the presence of anaphylaxis (hives, low blood pressure, vomitting, etc... see Section: SYMPTOMS)
• Measure mast cell mediators (tryptase, N-methyl-histamine, etc...) during acute phase and baseline (see Section: MEDIATORS)
• Block mast cell mediators and observe symptom reduction

  The POIS patient in this paper failed the first diagnostic criteria for MCAS (anaphylaxis), which also overlaps with mastocytosis. So under the AAAAI definition of MCAS, the patient would not be diagnosed with MCAS. Below, I have added additional quotes from the paper to make this clearer:

"The particularity of the case is that the patient had no obvious local or generalized allergic reaction, which can delay and even obscure the diagnosis...
Past medical history: no history of allergy...
Family history: one of his children was diagnosed with atopic dermatitis. No family history of allergies or diabetes...
Physical exam: absence of physical signs or symptoms, no local or generalized eruption or swelling, normal blood pressure and pulse...
2. Systemic Mastocytosis;... The second differential diagnosis was invalidated, because of the absence of major and/or minor criteria for mastocytosis. There were no obvious rashes or hematological changes in the number or morphology of mast cells."
POST COITAL ALLERGY - A CASE REPORT OF POST ORGASMIC ILLNESS SYNDROME. Med. Surg. J. - Rev. Med. Chir. Soc. Med. Nat., Iaşi - 2019 - vol. 123, no. 2

  Furthermore, it is unclear how an IgE allergen could past from the prostate to the blood stream and diffuse throughout the entire body without causing anaphylaxis-allergy. Mast cell are in every part of the body. The paper also claims that injecting the POIS patient's autologous semen caused different symptoms than the patient's typical POIS symptoms. Is there something about the allergy-hypothesis that I do not understand?

If you use to first criteria of AAAAI's definition then yes you are right, you can discard MCAS. This is also the only criteria which differs between other MCAS diagnostic algorithms btw.

Mast cells can release selectively. Mast cells being triggered by stress for example would not release tryptase nor histamine but release cytokines only.  Her investigation is not sufficient to exclude mast cell activation. Measuring tryptase alone while there are over 200 mediators, looking for spindle shaped mast cells and proliferation which doesn't play a role in most MCAS cases and saying she tested a model for MCAS is like shooting yourself in the foot. She cleary stated that she investigated Mastocytosis rather than a more generalized form of mast cell disorder like MCAS or hyperresponsive mast cells without degranulation.

''the concept of MCAS can be stretched to include any disease''
The diagnostic criteria of MCAS is more like a placeholder at the moment.

[Nas]

I agree with many of your points Muon but my experience with MCAS group and talking to many people had sent me to the conclusion that MCAS is strongly identified by anaphylaxis and histamine. Anti-histamines should work even if slightly but in our case it's a not at all situation. If Mast Cells turned out to be truly involved then it would be an oddity within the MCAS spectrum.

[Nas]

However I do have a mucusal issue with my urethra after orgasm. I tried so many mast cells stabilizers but not even a slight improvement.

[aswinpras06]

An excellent recent article on influence of mast cells in gut and brain on neural diseases.

Major depression, emotional, and chronic stress lead to the activation and alteration in limbic regulation of the hypothalamic–pituitary–adrenal (HPA) axis, whose altered regulation is usually associated with centralized pain syndromes (Menke, 2019). Under normal conditions, an acute stress induces the hypothalamus to release the corticotrophin-releasing factor (CRF) that induces the anterior pituitary gland to release adrenocorticotropic hormone (ACTH), which causes the adrenal cortex to release glucocorticoids that play metabolic roles (Herman et al., 2003). A negative feedback loop turn off the HPA axis activation (Kageyama and Suda, 2009). Subjects with pain syndromes present altered signaling from HPA axis but also mood disorders, including depression and anxiety (Bao and Swaab, 2019). The crucial link connecting these disorders is the inflammation mediated and modulated by cells, whose leaders are the mast cells (MCs).


It also explains nicely why mast cell stabilizers don't work for many because still more research is needed in effective mast cell stabilizers.

https://www.frontiersin.org/articles/10.3389/fncel.2019.00345/full

[Muon]

IBS:

Mast Cells in Irritable Bowel Syndrome: A Systematic Review.

Symptoms of mast cell activation syndrome in functional gastrointestinal disorders

The Emerging Role of Mast Cells in Irritable Bowel Syndrome

Mast cells are increased in the small intestinal mucosa of patients with irritable bowel syndrome: A systematic review and meta‐analysis

Colitis:

Increased Mast Cell Counts and Degranulation in Microscopic Colitis

Chronic spontaneous urticaria:

Evidence for bradykinin release in chronic spontaneous urticaria

Innate and adaptive Immunity

''however, as shown in Fig. 1, there is evidence that, depending on the circumstances, mast cells can either enhance innate responses that help to clear bacterial infections or exacerbate pathology associated with infections.''

See Figure 1:
Mast cells in allergy and infection: Versatile effector and regulatory cells in innate and adaptive immunity

See Table 2, Salient features of mast cells and traditional phagocytes:
Mast Cells in Infection and Immunity

See Figure 1 for mast cell receptors which are involved in pathogen recognition:
The Role of Mast Cells in the Defence against Pathogens

POTS

Evidence of Mast Cell Activation Disorder in Postural Tachycardia Syndrome

Hyperadrenergic Postural Tachycardia Syndrome in Mast Cell Activation Disorders

Restless Legs Syndrome

Restless legs syndrome is associated with mast cell activation syndrome

I wonder how long it will take before we'll see a paper like: Symptoms of mast cell activation syndrome in Post Orgasmic Illness Syndrome or The Emerging Role of Mast Cells in Post Orgasmic Illness Syndrome.

[Muon]

''that POIS is caused by Type‐1 and Type‐IV allergy to the males' own semen, as soon it is triggered by ejaculation.'' Ref

Mast cells are part of the innate and adaptive immune system. They can behave both as a type 1 and type IV hypersensitivity. Doesn't the above conclusion insinuates two type of cells are involved, mast cells and T-cells? I think the mast celll is the culprit here behaving as it is a type I and type IV allergy but not antibody mediated. There is something going on with the mast cell itself. They can also undergo phenotypic changes by the way.

If there is something wrong with mast cell behaviour other true parallel allergies perhaps might change the phenotype of mast cells.  IgE can activate mast cells in MCAD without the need for allergen-IgE binding, coupling to high affinity IgE receptors is sufficient, same for IgG receptors.

[Nas]

So Muon what would you say the cause for mast cell activity in the CNS? Ejaculation or orgasm?

[Muon]

So Muon what would you say the cause for mast cell activity in the CNS? Ejaculation or orgasm?

In my mind...mutations in genes of epigenetic regulators could be the cause. POIS symptoms could be ignited by any potential change in the body induced by sexual activity that is able to interact with mast cells. Mast cells are close to nerves and can tap into the CNS. God knows what it's doing from there on. The symptoms may not even come from the mast cells itself directly but from other cells by CNS signaling. These are my two cents, ask someone else and you will get a different answer. If gene mutations are involved people can be sorted into groups of mutations and those groups might respond to the same 'treatment'.