Familial Occurrence of Systemic Mast Cell Activation Disease from Admin's blog


Systemic mast cell activation disease (MCAD) comprises disorders characterized by an enhanced release of mast cell mediators accompanied by accumulation of dysfunctional mast cells. Demonstration of familial clustering would be an important step towards defining the genetic contribution to the risk of systemic MCAD. The present study aimed to quantify familial aggregation for MCAD and to investigate the variability of clinical and molecular findings (e.g. somatic mutations in KIT) among affected family members in three selected pedigrees. Our data suggest that systemic MCAD pedigrees include more systemic MCAD cases than would be expected by chance, i.e., compared with the prevalence of MCAD in the general population. The prevalence of MCAD suspected by symptom self-report in first-degree relatives of patients with MCAD amounted to approximately 46%, compared to prevalence in the general German population of about 17% (p<0.0001). In three families with a high familial loading of MCAD, the subtype of MCAD and the severity of mediator-related symptoms varied between family members. In addition, genetic alterations detected in KIT were variable, and included mutations at position 816 of the amino acid sequence. In conclusion, our data provide evidence for common familial occurrence of MCAD. Our findings observed in the three pedigrees together with recent reports in the literature suggest that, in familial cases (i.e., in the majority of MCAD), mutated disease-related operator and/or regulator genes could be responsible for the development of somatic mutations in KIT and other proteins important for the regulation of mast cell activity. Accordingly, the immunohistochemically different subtypes of MCAD (i.e. mast cell activation syndrome and systemic mastocytosis) should be more accurately regarded as varying presentations of a common generic root process of mast cell dysfunction, than as distinct diseases.


related article excerpt

More Common Than It Seems

Although it’s largely unrecognized, mast cell activation syndrome is quite common and may be the underlying cause of many conditions, Dr. Lawrence Afrin, a hematologist specializing in mast cell activation syndrome, said in an interview with Dr. Mobeen Syed.

The cause of this disease is unknown. A study estimated that 17 percent of the population of Germany (where Delapaix lives) is predisposed to developing the disease.

Studies have linked the inflammation in acute COVID-19 and many long-COVID symptoms with mast cell activation.

Mast cell activation syndrome describes a condition in which mast cells, a type of immune cell, become overly sensitive such that any foreign substance may trigger them to release compounds. Histamine is the most well-known compound released, but not all mast cell activation syndrome cases involve histamine reactions.

There are two aspects to mast cell activation:

  1. Spontaneous activation of mast cells and release of histamine and other inflammatory compounds causing inflammation in many tissues and organs
  2. Histamine intolerance, which can trigger allergic symptoms

Histamine intolerance occurs in people who can’t process histamine or whose histamine levels are so high that the body can no longer keep them under control.

Under normal circumstances, histamine is necessary. It’s released to control infections and promotes stomach acid release for digestion. Some healthy foods, such as avocados and cashews, contain histamine.

However, when the histamine level passes a certain threshold, it can cause inflammation and allergic symptoms: Blood vessels widen, airways constrict, mucus production increases, tissues swell, and the skin becomes flushed.

The threshold level of histamine is often compared to a cup: Everyone produces histamine from day to day, but as long as the baseline histamine is contained within the cup, the person won’t show symptoms. But if histamine levels exceed the parameters of the cup, the contents will start to overflow, and that’s when patients will experience a flare-up. A severe flare-up can be life-threatening.

Histamine and COVID-19

Histamine is believed to be a major contributor to severe COVID-19.

In long COVID, mast cells can be triggered by the virus. Histamine released into the brain can cause stress, neuroinflammation, and impaired brain function.

It isn’t understood how these mast cells become activated both in COVID-19 and in long COVID, but the mechanism may be driven by the spike protein, which is the inflammatory protein on SARS-CoV-2 virus surfaces, central to COVID-19.

Studies have shown that the virus infects mast cells by binding its spike protein to mast cell receptors. Animal studies have also demonstrated that isolated spike protein can activate mast cells.

Board-certified internist Dr. Keith Berkowitz told The Epoch Times that about half of his patients who developed reactions post vaccination have some form of mast cell involvement, as indicated by chronically elevated levels of circulating histamine.

Family doctor Jeffrey Nordella has likewise diagnosed patients with mast cell activation syndrome after their vaccination.

Many Triggers, Many Symptoms

Typical symptoms of mast cell activation vary from skin problems and breathing difficulties to digestive issues, according to a study published in The American Journal of the Medical Sciences.

However, mast cell activation can also trigger brain fog, neuropathy, hair loss, and bleeding abnormalities, depending on what and where various compounds are released.

Mast cell activation syndrome is often associated with systemic dysregulation, such as fibromyalgia, and dysautonomic conditions, such as postural orthostatic tachycardia syndrome (POTS). Patients may be diagnosed with either of these conditions before being diagnosed with mast cell activation. Both fibromyalgia and POTS have been reported among long-COVID patients, and POTS has been seen in vaccinated patients.

Delapaix was also diagnosed with POTS and neuropathy.

Berkowitz said many of his post-vaccine mast cell activation patients develop myriad symptoms, including brain fog, palpitations, chest pain, and even exercise intolerance.

Triggers for mast cell activation syndrome include certain foods, stress, and common allergy triggers, such as pollen and dust mites, chemicals, and medications.




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