Mast Cell Activation Syndrome (Syndromes)

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I devoted this article to a disease that concerns many systems, but has been evaluated as a whole over the last 10 years, and I wanted to convey it to my colleague from every branch. Until recently, as diseases associated with mast cells, only IgE-mediated allergy (type I allergy) and mastocytosis were known. In this new disease called “mast cell activation syndrome”, different symptoms occur in different systems as a result of excessive secretion of mast cell mediators. The disease is divided into primary, secondary and idiopathic and also called “mast cell activation syndromes” (1). Although there have actually been some progress in diagnosis and treatment, medical science is still at the beginning of this disease, and it seems like a very important topic that will open up new areas of study for my young friends. stops.

History of Mast Cells

Mast cells were first detected by Paul Erlich in 1878. The researcher named these cells mastzellen, considering that the granules contained in them feed other cells. It was then understood that these granules contain very important substances such as histamine, tryptase, heparin, kimaz. When mast cells are activated, they release these substances stored in their granules, which is called degranulation, while in inflammation such as cytokines, prostoglandins and leukotrienes synthesizes and secrete mediators that play a role. In fact, because special paint is needed to study mast cells, these cells have always been overlooked in routine examinations, and therefore their importance in diseases was not understood until recently.

It was understood in the 1960s that mast cells played a role in anaphylaxis, and then for many years, only type I allergy (IgE-mediated allergy) came to mind when it comes to mast cells. Another disease known from time immemorial with mast cells is mastocytosis. In the last 20 years, major changes related to mast cells have been added to medical science. For example, it was understood that these cells can secrete different mediators based on the type, intensity and duration of the stimuli even without degranulating (2,3). In addition, mast cells protect the body from pathogens such as bacteria, viruses, parasites, and directs all cells of the immune system, both natural (innate) and acquired (adaptive) immunity. has been determined to be effective (3,4). It was also revealed that mast cells regulate the physiological functions of the body (4). For example, these cells provide blood, peristalsis, acid, fluid and mucus secretion by the mediators they release when stimulated at a certain level (4).

What are mast cell diseases?

Today, skin mastocytosis, systemic mastocytosis, mast cell activation syndromes and hereditary α-triptasemi are evaluated among mast cell diseases (5).

In fact, it is suggested that in allergies mast cells are stimulated not only by IgE, but also through other antibodies, especially IgG (6,7). In this case, mast cells also play a role in allergies due to antibodies other than IgE.

Autoimmune diseases, atherosclerosis, pulmonary hypertension, male infertility, interstitial cystitis, obesity, type 2 diabetes (8), irritable bowel syndrome (IBS) (9) and neuropsychiatric diseases (10).

What is mast cell activation syndrome?

In this syndrome, which occurs as a result of excessive or inappropriate secretion of mast cell mediators, symptoms or symptoms of at least two different systems are combined. In this disease, an increase in the number of mast cells is not found or there may be very little increase. Symptoms are episodes, may belong to the skin, gastrointestinal, cardiovascular, respiratory and neurological system (1, 11, 12). The severity of the symptoms is different, sometimes they are very severe and persistent or can become increasingly aggravated. It is observed in children, adults and families. In fact, it's a disease that amazes and exhausting the patient and the doctor. The patient is surprised because the complaints he feels are miserable, but there is nothing in the examinations. His doctor does his best to initially diagnose the patient and arrange his treatment. For example, if a patient diagnosed with IBS also identifies palpitations, shortness of breath, dizziness, or excessive fatigue, he either needs the necessary examinations or cardiology and chest diseases. sends them to polyclinics. It also sends those who identify skin symptoms such as redness, itching, blistering, urticaria to allergy polyclinics. But the patient can't relax, but he can come up with some new complaints. When the results are not obtained, the destination of these patients is also antidepressants added to psychiatric clinics and drugs.

It is very natural that the disease is not recognized, because only in 2010 the first consensus meeting was held to determine its characteristics, diagnostic criteria, methods of treatment. Nowadays, it is considered a very common disease in society but rarely diagnosed (13). The frequency of this disease is reported to be around 17% in German society (14).

Mast cell stimuli and what are the symptoms of the disease?

Mast cell stimuli are numerous and varied. A group of physical factors such as hot, cold, sudden temperature changes, exercise, friction, vibration, surgical intervention (5). One group is allergens and antigens (6, 7) that bind to Fc receptors located on the surface of mast cells through IgE or other antibodies (IgG and IgA), which stimulate them. Some also stimulate mast cells by binding to estrogen receptors or their own receptors. These include foods, food additives, drinks, alcohol, drugs (opioids, antibiotics, anesthetics, contrast agents), insect-bee venom, odors, psychiatric stress, infections (5) xenoestrogens, cosmetics and cleaning products (see, website, Supplement Book, Chapter V or Book, Chapter V.).

In this syndrome; on the skin; urticaria, angioedema, redness, itching, gastrointestinal tract; nausea, vomiting, diarrhea, abdominal pain and cramps, bloating, cardiovascular system; hypotension, tachycardia, unexplained arrhythmia, chest pain, respiratory system; wheezing, shortness of breath, eye; stinging, itching, nose; congestion, weakness in addition to discharge, bone and muscle pains, headache, mind There are symptoms such as turbidity, loss of balance, anaphylaxis may develop, even anxiety and depression can be found in psychiatric diseases. In some of the female patients I followed, Ininal pain and genital discharge during attacks were added to the symptoms.

What are the diagnostic criteria?

In order to accurately diagnose this disease, the following 3 criteria must be found (11, 12).

These are:

Occupational symptoms of different systems due to mast cell activation

Good results with drugs suppressing mast cell activation

The presence of laboratory indicators of mast cell activation in the symptomatic circuit higher than the basal circuit values.

Indicators of mast cell activation:

In serum; tryptase and prostaglandin D2 (PGD2)

In 24 hours urine; histamine metabolites N-methyl histamine and 1-methyl-4-imidazole acetic acid (11), 11-β-prostaglandin F2 alpha (a, b)

The most important of these indicators is serum triptase. Because a very large portion of tryptase in the blood is caused by mast cells. The normal serum value of triptase, one of the mediators stored in the granules of mast cells, is around 5ng/mL. In fact, mast cells play a role in the regulation of normal physiological functions, so some triptase is expected to be present in the blood. Triptase, released when mast cells are overly degranulated, gets into the blood, causing a temporary increase. When serum triptase value is above 11.4 ng/mL, mast cell activation is considered (11). This value is reported in another review as 15 ng/mLans (12). Also with a formula, mast cell degranulation can be shown. Increase is considered significant if 20% of basal triptase amount is +2 ng/mL (11). Of course, for this formula to be useful, the basal triptase value must be known.

Triptase increases within 1 hour after mast cell activation and returns to its old level after 4 hours (11). In fact, a single high value may be sufficient for triptase, but for others it is desirable to have at least two higher values (11).

Histamine is also a substance secreted from granules. Its blood value is not preferable, because histamine in the blood is more often caused by basophils. It is also affected by certain factors in blood intake and storage. Therefore, the metabolites of histamine in the urine are checked, but they are also affected by urinary infection (11).

By itself, the increase of PGD2 or urine metabolite does not make sense, since it is also formed by other immune and non-immune cells. Increased values help diagnose when accompanied by another elevated indicator (11).

It is preferable to take care of urine tests 24 hours, but the examination can also be done in spot urine (11).

How is the treatment regulated?

A: Get as far away from mast cell stimuli

Patients should be trained on factors that stimulate mast cells (11)

Allergy research should be performed and immunotherapy against allergens can be considered if necessary (11)

Some recommend the prohibition of a group of foods. These are gluten, cow's milk proteins, veal, bread yeast (14). What is interesting is those who give the highest positivity in the food specific IgG test, except for veal. In this case, it is best to suggest food restriction based on this test, except for blindly restriction.

B: Drug therapy (11)

H1- and H2-histamine receptor antagonists

Mast cell stabilizers; ketotifen and chromolin sodium

Leukotriene receptor antagonists; these should be known to have psychiatric side effects

Glucocorticoids; should be tried to find the lowest dose

Omalizumab; The role of non-IgE-mediated mast cell activation is unknown

Note:For those who identify anaphylaxis, the epinephrine injector that the patient can carry around and easily apply to him. Penepin has been in our country for the last 1 year.

Unanswered questions

Can it be the role of increasing the number of patients due to mast cell stimuli that enters our lives in recent years? For example, xenoestrogens (see, website, xenoestrogens are everywhere), new additives and even genetically modified foods could have an impact on our lives?

What's the difference between mast cell activation syndromes and other diseases that have mast cell relationship? Mast cells are degranulated in diseases such as mast cell activation syndromes, IBS, interstitial cystitis, autoimmune diseases, atherosclerosis, male infertility can it be considered that the secretion of mediators of inflammation is more at the forefront? Although in the first 120 years, the importance of mast cells has not been fully understood, but the situation has changed in the last 20 years. I believe that in a very short time from now on, mast cells will be given the necessary attention and the answer to these questions will be found.

I think it would be nice to give this syndrome a short name for patients to understand. Sensitive Mast Syndrome, perhaps?

Book: Now I Can Cope With My Disease (The Myth of Mast Cells), Nobel Medical Bookstores.

E-Book

Sources

1. Valent P, Akin C, Arock M, take meat. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal.Int Arch Allergy Immunol. 2012; 157:215 -25.

2. Welsh SJ, Grimbaldeston M, Tsai M. Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat Rev Immunol. 2008, 8:478 -86.

Theoharides TC, Alysandratos KD, Angelidou A, et al. Mast cells and inflammation. Biochim Biophys Acta. 2012, 1822:21 -33.

Fourth Bischoff, SC. Physiological and pathophysiological functions of intestinal mast cells. Seminars in Immunopathology. 2009, 31:185 —205.

5.Jennings SV, Slee VM, Zack RM, take meat. Patient Perceptions in Mast Cell Disorders. Immunol Allergy Clin North Am. 2018; 38:505 -525.

6.Jönsson, F and Daëron, M. Mast cells and company. 2012, Front Immunol 3:16.

7.He SH, Zhang HY, Zeng XN, Chen D, Yang PC. Mast cells and basophils are essential for allergies: mechanisms of allergic inflammation and aproposed procedure for diagnosis. Acta Pharmacol Sin. 2013, 34:1270 -83.

8.Anand P, Singh B, Jaggi AS, Singh N. Mast cells: an expanding pathophysiological role from allergy to other disorders.Naunyn Schmiedebergs Arch Pharmacol. 2012; 385:657 -70.

Lee 9, Lee OY. The Role of Mast Cells in Irritable Bowel Syndrome. Gastroenterol Res Pract. 2016, 16:2031480.

Conti P, Shaik-Dasthagirisaheb YB. Mast Cell Serotonin Immunoregulatory Effects Impacting on Neuronal Function: Implications for Neurodegenerative and Psychiatric Disorders. Neurotox Fig. 2015 Aug 28 (2) :147-53.

11.Akin C. Mast cell activation syndromes. J Allergy Clin Immunol. 2017; 140:349 -355.

12th Frieri M. Mast Cell Activation Syndrome. Clin Rev Allergy Immunol. 2018; 54:353 -365.

13.Afrin LB, Butterfield JH, Raithel M, Molderings GJ. Often seen, rarely recognized: mast cell activation disease—a guide to diagnosis and therapeutic options. Ann Med. 2016; 48:190 -201.

Wirz S, Molderings GJ. A Practical Guide for Treatment of Pain in Patients with Systemic Mast Cell Activation Disease.

Pain Physician. 2017; 20:E849-E861.

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