What is Mast Cell Disease (Mastocytosis)?
In the early to mid-20th century, all forms of Mast Cell Disease were undifferentiated and were grouped under the name “Mastocytosis.” Mastocytosis specifically means “an abnormal increase in the number of mast cells,” but we now know that definition, taken from the root words, relates to some very specific mast cell disorders, and may not apply to others. Some of the research done in the latter part of the 20th century laid the groundwork for much of the work done today. Over the last 30 years, there has been an explosion of interest in, and research into, the various Mast Cell Diseases, resulting in many different categories being defined, and the definitions are still evolving.
So, for the purposes of this section, we will refer to the general term Mast Cell Diseases which encompasses the following very general subcategories:
- Systemic Mastocytosis (with or without cutaneous manifestations such as Urticaria Pigmentosa)
- Aggressive Mastocytosis
- Indolent Mastocytosis
- Mastocytosis with associated Hematologic Disorder
- Mast Cell Leukemia
- Cutaneous Mastocytosis
- Urticaria Pigmentosa (UP)
- Telengiecstasia Macularis Eruptive Perstans (TMEP)
- Mast Cell Activation Syndrome/ Disorder
- More common Pediatric Mast Cell Disorders
- Solitary Mastocytoma
- Urticaria Pigmentosa
- Diffuse Cutaneous Mastocytosis
What are Mast Cell Diseases?
In 2000, at a meeting in Vienna, Austria, a consensus was reached about what criteria must be fulfilled for a diagnosis of Mastocytosis (see our Research article entitled A Consensus Document for more information). Many people met the new criteria. However, many patients who had been formerly diagnosed with “Systemic Mastocytosis” did not seem to fit into the agreed-upon criteria, possibly because their diagnostic work-up was done incorrectly, or was not conclusive, or because they were not tested for all the criteria. Over the last few decades, some researchers began differentiating between the different forms of Mast Cell Diseases. A few began individually defining new categories, one of which is called Mast Cell Activation Syndrome or Disorder (MCAS/MCAD). Although the various forms of Mast Cell Disease may present with some of the same symptoms, and may be treated with the same medications and avoidance of known triggers, the cause of the symptoms is what makes them separate, but related, entities. Indeed, Mastocytosis and other Mast Cell Disorders are heterogeneous, meaning they can present in many different ways. Ultimately, the cause of each different form of Mast Cell Disease may dictate how they are treated.
What are the Symptoms of Mast Cell Diseases?
What we know about Systemic Mastocytosis is that in many cases, it is a neoplastic disease, meaning that it involves new or abnormal cell growth. (Please note – this may not apply to most cases of pediatric and/or familial Mastocytosis.) In this case the cells involved are mast cells, which are normally contained in body tissues. Mast cells release certain mediators, or chemicals, of which one is histamine, into the body in response to certain events. People with Systemic Mastocytosis develop an increase in the number of mast cells, or they develop abnormally shaped mast cells, which may not function properly. In addition, the mast cells fail to die off when they are supposed to, further increasing the total mast cell burden. This die off is called apoptosis. Apoptosis is programmed into normal cells, but in people with mast cell disorders, the mast cells may fail to die off, resulting in an increased number of mast cells in the body. When these mast cells are triggered, they can degranulate, and release their contents all at once, or they can slowly leak their contents in response to a trigger. This can cause many acute and potentially serious symptoms, which include the following:
|· Abdominal pain||· Hives & other rashes|
|· Anaphylaxis||· Inflammation of the esophagus|
|· Blood pressure changes & shock||· Intestinal cramping and bloating|
|· Bone pain (mild to severe/debilitating)||· Itching, with and without rashes|
|· Chest pain||· Liver, spleen and other organ involvement|
|· Cognitive difficulties/brain fog||· Malabsorption|
|· Degenerative disc disease||· Migraine headaches|
|· Diarrhea||· Muscle pain|
|· Dizziness/vertigo/lightheadedness||· Nausea|
|· Faintness||· Osteoporosis/ Osteopenia|
|· Fatigue||· Peripheral neuropathy and paresthesias|
|· Flushing||· Rapid heart rate|
|· Gastroesophageal reflux||· Vomiting|
|· Hematological abnormalities|
People who have been told they have Mast Cell Activation Syndrome or Disorder (MCAS/MCAD) may have a normal, or nearly normal, number of mast cells. However, their mast cells “behave badly” – that is, they are easily triggered to release their contents, which results in many of the same symptoms that people with Mastocytosis experience. The danger of anaphylaxis and shock is present with MCAD/MCAS, but unlike Mastocytosis, this syndrome may not have the potential to progress to a more aggressive or malignant stage. Nevertheless, people with either Mastocytosis and MCAS/MCAD can be either very stable or extraordinarily ill on a day-to-day basis, and managing the unpredictability of the Mast Cell Diseases and their symptoms can be quite challenging.
What are Triggers?
Triggers are stimuli that can set off a mast cell response, potentially leading to a mast cell attack. Avoidance of various triggers (things that can set off a mast cell attack) can do much to improve quality of life and reduce the need for medication, but that is often easier said than done, as the triggers can be almost anything, including:
|· Alcohol||· Friction|
|· Anesthetic agents||· Heat|
|· Antibiotics||· Infection with viruses, bacteria or fungi|
|· Bacteria or fungi||· Mold|
|· Certain foods||· MSG|
|· Cold||· Narcotics|
|· Colors & flavorings in foods||· Perfumes|
|· Colors & flavorings in medicines||· Pesticides|
|· Emotional upset||· Plasma expanders (i.e. dextran)|
|· Environmental toxins||· Preservatives|
|· Exercise||· Room freshener sprays|
|· Fatigue||· Stress|
|· Fever||· Sunlight|
There is great variation from person to person in what is a trigger, and even within the same person. The triggers may change day-to-day – that is, heat may set off an attack on one day, but not on other days. The above list is not complete, but is meant to show the wide range of triggers that affect mast cells.
Some people with the indolent form of Mastocytosis, and/or people with Mast Cell Activation Disorder or Syndrome, have been told by some physicians that they can expect a nearly normal life expectancy, as long as they keep themselves as stable as possible by avoiding triggers and taking medications as prescribed. However, since it is not clear what is causing mast cell activation in patients with MCAD, this may not apply. Mast Cell Diseases are extremely unpredictable, and some people can very quickly develop acute symptoms that may require immediate medical attention. That is why it is advisable to stay within range of a medical facility, and to carry a written protocol from your Mast Cell Disease specialist for emergency care.
How Are Mast Cell Diseases Diagnosed?
Mast cell diseases can be diagnosed by:
- Blood tests
- Bone marrow biopsies with aspirate flow cytometry
- Bone scans
- Careful evaluation of response to treatment
- Radiologic scans
- Skin biopsies
How Are Mast Cell Diseases Treated?
While a few people manage to remain stable and healthy by avoiding dietary and environmental triggers, many people with mast cell disease take a medication protocol that involves some or all of the following:
- H1 blockers – antihistamines like hydroxyzine (Atarax®), diphenhydramine (Benadryl®), or Doxepin®
- H2 blockers – antihistamines like ranitidine (Zantac®) or famotidine (Pepcid®)
- Leukotriene inhibitors like Singulair®, Accolate®, or Zyflo®
- Mast cell stabilizers like oral cromolyn sodium (Gastrocrom®) or Ketotifen (Apo®-Ketotifen, Zaditen®)
In addition, many people require:
- A proton pump inhibitor like omeprazole (Prilosec®), esomeprozole magnesium (Nexium®), or lansoprozole (Prevacid®)
- Inhaled bronchodilators such as Albuterol (Ventolin®)
More aggressive forms of the disease may require the use of chemotherapeutic agents and/or cytoreductive therapies. Further information about the use of these agents in treating mast cell diseases can be found at cancer treatment centers.