Friday, October 16, 2015

Mast Cell Disease Explanation + Update

Mast Cell Diseases are diseases that impact mast cells. 

What is a mast cell?

A mast cell is a type of cell found in the connective tissues in the body. They are located in the skin, lining of the gastrointestinal tract, bone marrow, airway, and other organs. Mast cells contain granules that store chemicals. These chemicals are released as part of the body's normal response to injury or exposure to something the body deems as a threat, like an allergen. The chemicals released can cause a host of allergic and non-allergic presenting signs and symptoms. [x]

There are numerous types of Mast Cell Disease. 

The most common is called Mastocytosis
  • mast - in reference to a mast cell
  • cytosis - a condition in which there are more than the normal number of cells
Therefore, Mastocytosis is a condition in which there is an abnormal number of mast cells in the body. 


There are two types of Mastocytosis: [x]
  1. Cutaneous Mastocytosis: where mast cells numbers are increased in the skin, but not elsewhere in the body. It causes abnormal lesions, spots, and bumps on the skin. 
  2. Systemic Mastocytosis: Primarily effecting adults, mast cells proliferate in the tissues, like the skin, organs, and bones. 
There are various forms of Systemic Mastocytosis. The disease is classified as either indolent, which means it is slow-growing, or aggressive, which means it is fast-growing. As the number of mast cells builds up in an organ, the symptoms of the disease may get worse. Systemic Mastocytosis can become cancerous, resulting in Mast Cell Leukemia or Mast Cell Sarcoma. [x]

Also under the umbrella of Mast Cell Diseases is:

  1. Mast Cell Activation Syndromes (MCAS, MMAS): presenting much like Systemic Mastocytosis symptom wise, it is defined as having normal number of mast cells (or very mild proliferation) that have an activation problem. The mast cells constantly "misbehave" and release their chemicals over anything and everything.  It is a condition with signs and symptoms involving the skin, GI tract, cardiovascular, respiratory, and neurologic systems. It can be classified into primary, secondary, and idiopathic.[x] 
What do mast cells do? 

As an immune cell, mast cells release a variety of enzymes and chemicals when the body is injured or exposed to a trigger (like an allergen). Mast cells release histamine, which is why antihistamines are vital drugs for sufferers. In addition, mast cells also release an enzyme called tryptase. In people with Mast Cell Disease, the high levels of histamine, tryptase, and other chemicals in the body lead to painful symptoms. Tryptase levels can be measured in the blood, but this test can be unreliable, as low tryptase levels do not necessarily rule out mastocytosis. 

An increase in mast cells and/or improper activation causes excessive mediator release when mast cells are triggered. Common triggers are foods, medications, stress, heat or cold, airborne and applied chemicals from perfumes, lotions, detergents, hair products, soaps, etc. Once mast cells are triggered, they can continue to degranulate, or release chemicals, over literally anything...even water. It is similar to an allergy where the triggers constantly change; although, mast cell patients do not have to test positive for true IgE allergies.

Symptoms include:
  • Life threatening anaphylaxis 
  • Organ swelling
  • Low or high blood pressure
  • Fainting
  • Flushing
  • GI Distress (nausea, vomiting, diarrhea, etc.)
  • Hives and Itching
  • Bone pain 
  • And more
What causes Mast Cell Disease? 

Mastocytosis is an orphan genetic disease. An orphan disease is one that is very rare. Genetic means that it involves hereditary transmission and/or some form of mutation. In most cases of Mast Cell Disease, especially in Mastocytosis, usually this mutation affects the KIT gene, which normally encodes for a protein in the receptor tyrosine kinase family of proteins. KIT protein signaling is important for the development of certain cell types, including mast cells (which are a type of immune cell). [x

Since mast cells live in connective tissues, Mast Cell Diseases (often related to Mast Cell Activation), are commonly diagnosed along with connective tissues disorders, like Ehlers Danlos Syndrome. Mediator release from mast cells compromise the connective tissues, which is the glue that holds the body together resulting in joint laxity often seen in Ehlers Danlos Syndrome type 3 and Joint Hypermobility Syndrome. The complete understanding of the genetic and environmental link is still unknown. [x]

That explanation leads me to my update regarding the new treatment I am starting next week, as well as the new findings from genetic testing completed over a year ago. 

Despite not knowing exactly which type of Mast Cell Disease that I have due to the biopsies not being done properly, my medical team and I have gathered enough information to give to the specialist so that he feels comfortable suggesting the next step in my treatment. It has been decided that I will be beginning a type of chemotherapy drug in the drug class called Tyrosine Kinase Inhibitor (TKI). The particular drug I will be starting is called Gleevec. It is more of a last resort type of treatment and it is kind of trial and error. They do not have the ability to test for all of the mutations that cause Mast Cell Diseases, but because they usually involve the KIT gene that encodes for a protein in the receptor of tyrosine kinase, TKI drugs have proven helpful in many cases. However, we do not know if Gleevec is the proper fit for my particular mutation, or even one of my mutations if there are multiple. If it is not, I could get no relief and must trial another TKI drug. It could also provide great symptom relief if it is the correct fit. The side effects are scary. It is a huge risk to even introduce the medication because it cannot be compounded without fillers and preservatives, which I usually have anaphylaxis to. We are hoping that being on the continuous Benadryl drip will keep any major reactions to it at bay before it begins to work. There is also a huge hurdle to figure out because I must be able to eat in order to take the medication or else it can make me very ill. They have had me trialling foods in order to find something that causes the least severe reactions and I have not been successful. Everyone is still trying to figure out what to do regarding that issue, but I should be beginning the drug early next week! Along with the TKI, they are compounding various antihistamines and other medications that target the harmful mediators released from mast cells. I stopped tolerating the ones I was previously on back in May; however, we are hoping it is because of the fillers/preservatives that were in them and that once I am more stable I will start tolerating them again if they are compounded properly. 

Over a year ago I underwent a muscle biopsy, skin biopsy, special stress test, and spinal tap as part of a genetic workup. The doctor who did all of this is located in Atlanta, GA. A couple months following the tests, the doctor emailed my family stating that my muscle biopsy was clear, other results are still pending, and that they found something through my spinal tap called Cerebral Folate Deficiency. The email explained that I apparently have this condition, but that he does not know why because I do not seem to have many of the symptoms or present like usual. I was given a prescription for a medication called Leucovorin and was told to have my other doctors figure it out. For nearly two years the results on that paper have been passed around to doctor after doctor and nobody knew. I did not consistently take the medication for it because it could not be explained why I needed it. Once I became anaphylactic to everything, it had to be stopped anyways. 

Earlier in the week, a new doctor was put on my case. Praise God he was consulted because he knew what Cerebral Folate Deficiency is and its relation to my case. With Cerebral Folate Deficiency, when I ingest folate it cannot pass the brain barrier properly - leaving the folate and neurotransmitter levels in my spinal fluid super low. I also have antibodies against the folate receptor in my brain. In combination with that, I tested positive for a MTHFR mutation, which plays a major role in the CFD. He explained that I do not present like most with CFD because I am only heterozygous for the MTHFR gene. This is all related to the Mast Cell Disease somehow, as well as all of my other health conditions. They are all one and nobody knows which one causes which. It is like the saying: "I don't know what came first - the chicken or the egg?" I started treatment for the Cerebral Folate Deficiency a couple days ago. I am reacting to it, but it has not been severe enough to cause me to have to stop thanks to the continuous Benadryl drip. Once I am at a proper dose, it could take up to a year to notice any improvements from it. My Mast Cell Disease can improve some if we treat this condition. Also because of all of this, the doctor explained that it leaves me prone to developing other conditions, more specifically, autoimmune diseases. He said that they start inviting all of their "cousins" - which could be Lupus, Rheumatoid Arthritis, Thyroid Diseases, etc. In my case I have now developed autoimmune thyroid disease. I also have striated muscle antibodies and some antibodies against other things that I won't bother going into. At this point we are not treating the thyroid problem. It is just something we will keep an eye on and we are hoping it will resolve itself once my Mast Cell Disease gets under control. 

Being that the doctor in Atlanta stopped seeing patients, we never got word on the pending results following being emailed regarding the Cerebral Folate Deficiency. We assumed all else was normal. Anyways, because we were so desperate for some answers, my mom got the records faxed to this hospital. My stress test that was done there showed that I have Ischemic Myocardial Dysfunction. That basically means not enough oxygen is going to my heart due to reduced blood flow from some sort of blockage and can lead to a heart attack and arrhythmias.  Usually that is caused by clogged arteries. We know that is not the case with me. What is frustrating is that that test was completed in November 2013 and we were never contacted about this. Since we got word from that, my doctor is concerned and said "Great...in the midst of this crisis we now have this to figure out." Cardiology was consulted. Cardiology thinks it is related to everything else going wrong in my body. We are, however, unsure if it is just exercise induced or if it is a problem occurring at other times. I need an echocardiogram to rule other causes out and once we get passed this hurdle with beginning chemo, the stress test will be repeated and we will go from there. 

So that is pretty much everything new! Symptom wise I am still the same - anaphylaxis any time I eat more than a bite or two orally; still not getting enough nutrition in because I am reacting to tube feeds with bad neurological and GI symptoms; my Dysautonomia (caused from the Mast Cell Disease) has been really severe, causing my autonomic nervous system not to be able to regulate my heart during postural changes - every time I try to stand my pulse is getting as high as 180 and my blood pressure either shoots up or drops causing pre syncope (blackouts). The stress on my body from that is causing full blown mast cell attacks. Introducing these new treatments is going to be a lengthy process, but I am praying it is the answer to get me stable enough to get off of the 24/7 Benadryl drip and back on to IV benadryl every 6-8 hours (or as needed), tolerating tube feeds and some food without anaphylaxis or dangerous symptoms, and to get my Dysautonomia to improve enough to where I can stand and walk without major issues. 

-Cheyanne