Mast Cell Activation Disease

Mast Cell Activation Disease – The Modern Epidemics of Chronic illness – Afrin | Health Rising’s Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia Forums

Allergies are not just itching and trouble breathing or caused by hay fever, bee stings or reactions to shellfish and peanuts. While these are the most common manifestations of allergies, an entirely different allergic process can affect literally every system in your body.

In fact, it can produce among the strangest and widest variety of symptoms of any disease. 

So many that the people afflicted with these kinds of allergies usually utterly baffle their doctors. Most doctors don’t know anything about them and they are rarely diagnosed. They’re caused by a disorder called Mast Cell Activation Syndrome (MCAS) which features mast cells gone a little crazy.  

Mast Cells

So what are mast cells?

That is one of the questions that Dr Lawrence Afrin, a leading expert in the field of mast cell diseases, answers in the new book, “Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity”.

Dr. Afrin writes that mast cells “serve largely as sentinels of environmental change and bodily insults”.

When those insults occur, they “respond by releasing large and variable assortments of molecular mediators.” These mediators then directly and indirectly influence the behavior of local and distant cells and tissues in order to “maintain, or restore, homeostasis.”

In English, that means mast cells are really common and really important. So much so that they’re often called the master regulators of the immune system.

Mast cells come from the bone marrow and are filled with sacs of chemical mediators. Histamine is the most commonly known mediator but there are countless others.

Mast cells also play an important role in the body’s first line of defense. Their signals recruit other players in the immune system response and help to keep us healthy and free from disease.

Unless it all starts to go wrong.

Systemic Matocytosis (SM)

Dr Afrin began to suspect that some portion of mast cell disease might be due to the inappropriate release of chemical mediators release from a normal counts of mast cells rather than increased numbers of mast cells (SM)

Afrin’s hypothesis laid the groundwork for the identification of a spectrum of diseases that make up what is now called Mast Cell Activation Disorder (MCAD).

But Dr Afrin shows in “Never Bet Against Occam” that MCAD is a “real” illness that can effect virtually every system in the body. He does this by presenting a series of case studies that demonstrates how MCAD looks.


No body system is immune from the effects of this inflammatory disease.

Complicated Disease

To further complicate matters, mast cells don’t always activate the same cytokines in every person. In fact, they very rarely present the same in the same way twice (though there are many commonalities) and can actually cause opposite effects from one patient to the next.

It’s worth noting that mast cells can also cause immune system abnormalities.

Many with MCAD also have a long history of infections in their medical files.

Dr Afrin notes that mast cells can produce basically any and all interleukins known to man

Dr Afrin relies on and credits a database called COPE created by Dr Horst Ibelgaufts for helping him to connect the dots between seemingly disparate symptoms.


The most common tests Dr Afrin uses to diagnose MCAD are those that measure mast cell mediators. They include

  • plasma histamine n-methylhistamine (24-hr urine)
  • prostaglandins PGD2 and/or 11-b-PGF2a (24-hour urine) (avoid NSAIDs for 5+ days prior)
  • serum chromogranin A (avoid PPIs for 5+ days before testing)
  • plasma heparin (not if on heparin products) and occasionally testing for leukotrienes.


Antihistamine Drugs

Unfortunately, treatment is mostly by trial and error though many patients do ultimately see a significant amount of symptomatic relief.

Often times, antihistamines are taken in 2-3 x’s the OTC recommended dose in divided doses. There are synergistic effects from taking H1 and H2 blockers together as well that are not achieved by taking either alone. Dr Afrin provides detailed dosing guidelines in his chapters on treatment.

Mast Cell Stabilizers

Some antihistamines, like ketotifen, also have mast cell stabilizing properties. Ketotifen is currently only available in the USA through a compounding pharmacy though it is widely and cheaply available elsewhere in the world as Zaditor.

Cromolyn sodium (Gastrocrom) is the best known example of a pharmaceutical mast cell mediator. It’s available by prescription as oral vials or a nasal spray (NasalCrom)

It may take many months to see the benefit of cromolyn sodium treatment because of this.

Quercetin is a mast cell mediator that is available in a supplement form.

Studies have shown quercetin to be equivalent to sodium cromolyn for the purposes of mast cell stabilization. Typical doses seem to range from 500-2000 mg/day.

There are other examples of classes of medications that are occasionally found to be helpful

Some of these include tyrosine kinase inhibitors like imatinib or leukotriene inhibitors like montelukast (Singulair). JAK inhibitors are a new class of medications that may or may not prove useful in treating MCAD as well as TNF blockers.

NSAIDs, like aspirin, and benzodiazepines may also have a role in MCAD management. Some patients find improvement, especially with pain symptoms, with hydroxyurea.

Trigger Avoidance

Most people with MCAD instinctively learn to avoid their triggers whether they are aware of it or not. Strong smells, heat, and chemicals all can trigger reactions and most patients do better when they avoid these triggers.

Some MCAD sufferers have also employed neural retraining techniques to help keep stress from exacerbating mast cell degranulation.

Diet has also been found to play a role in treatment with some patients finding improvement in symptoms after adopting a low-histamine diet.

Some patients have their medications compounded to be free of fillers and artificial colors and find that their medications miraculously start working for them instead of against them for once.

Unfortunately, at this point treatment of MCAD is all about symptom management.

Genetic Fragility?

The mast cell gene that has been studied the most in SM is called KIT. KIT regulates the mast cell’s ability to survive, move, grow – and activate, according to Dr Afrin.

The KIT gene is not limited to mast cells though. It is also found in many other type of cells because of its corresponding protein, tyrosine kinase.

Tyrosine kinases regulate growth and differentiation of cells. This may be why drugs like imatinib, a tyrosine kinase inhibitor, have shown some clinical utility in MCAD.

Interestingly, Dr Afrin also notes that MCAD patients often find that the disease “steps up” its baseline level of activation misbehavior after exposure to some sort of stressor

Dr Afrin hypothesizes that patients may possess one or more inheritable “genetic fragility factors” which interact with different stressors like infection or other traumas to cause the occurrence of even more (non-inheritable) mutations which lead to the wide variety of confounding random mutations that occur later in illness, seemingly at random.  


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