Mast Cell Activation Syndrome (Part 1)

Hello Friends!

Today’s topic is about a condition called, Mast Cell Activation Syndrome (MCAS). I will start with some basic science information followed by a Q & A section later in this post with Matthew Hamilton, MD, a gastroenterologist from the Brigham and Women’s Hospital (BWH) in Boston, Massachusetts. Dr. Hamilton specializes in the diagnosis and treatment of mast cell disorders involving the gastrointestinal tract and is an integral part of the Mastocytosis Center at BWH. (Incidentally, I did my dietetic internship and spent the first 7 years of my career in the field of nutrition at BWH in Boston). 🙂

Because of the complexity of Mast Cell Activation Syndrome (MCAS), I will discuss this topic in a 3-part series. The first part of this series, I will briefly introduce the topic of mast cell disorders with a focus on MCAS. There is a broad spectrum of mast cell activation disorders from the rare disorder of systemic mastocytosis and monoclonal mast cell activation syndrome (MMAS) to a spectrum of mast cell disorders including MCAS. Mastocytosis is defined by an abnormal amount of mast cells that accumulate in many tissues in the body including bone marrow and the skin. Mast cell activation syndrome typically presents in individuals with a normal amount of mast cells.

There are some red flags that occur in patients that visit my digestive health nutrition practice that prompt me to have them follow up with their PCP or GI doctor to discuss the possibility of a mast cell disorder. In my experience, patients present with several of the below symptoms along with their GI complaints:

  • Unexplained allergic reactions, not classic IgE allergies, but eating certain foods elicits itching in the throat
  • Low blood pressure or feeling faint
  • Hives, rash, skin itching
  • Demographism (learn more here).
  • Angioedema (swelling of face, hands, lips)
  • Vertigo
  • Bloating
  • Tachycardia (elevated heart rate at rest)
  • Flushing
  • Chronic headaches
  • Severe heartburn
  • Diarrhea
  • Runny nose/ watery eyes
  • Abdominal pain

A noted uptick in the above symptoms may occur with stress– (stress releases corticotropin releasing factor which in turns can activate mast cells).

Let’s start with the basics:

What are mast cells? Mast cells are immune cells that function as “guards” for our innate and adaptive immune system. They respond to triggers of external or internal stress or danger. Mast cells reside anywhere the body interfaces with the environment such as in the skin, GI tract, urinary tract, lungs etc.  Using the most simplistic illustration imagine that mast cells are like tiny water balloons that are filled with inflammatory chemicals that release into the body when the mast cells are activated.

In the medical literature, you will read about mast cell degranulation–which, in essence, is when the mast cells are ‘activated’ and release numerous bioactive substances (histamine, enzymes, heparin) pre-formed in granules and other compounds (cytokines, chemokines, nitric oxide, prostaglandins and more). These chemical substances can be vasoactive (may increase or decrease diameter of blood vessels leading to an increase or decrease in blood pressure and heart rate) and include proinflammatory mediators.

What activates mast cells? Allergens, bacteria, drugs, fungus, toxins, viruses and stress can lead to mast cell activation. There are a number of drugs that can trigger mast cells such as vancomycin, morphine, NSAIDs (such as Advil, ibuprofen), and muscle relaxants. Bear in mind, ‘normal’ levels of mast cell activation is common and necessary.  The problem lies when mast cell activation is disordered. This can occur when there are too many mast cells or mast cells activate more readily than the necessary.

What are the symptoms one might experience with mast cell activation?

Mast cell activation can be localized or occur in multiple places in the body (systemic).  Localized mast cell activation may appear as uticaria (hives) or wheezing. A more broad range of mast cell activation can impact multiple organs and include GI distress (nausea, vomiting, diarrhea, GERD) as well as uticaria or angioedema (swelling) and/or wheezing.

What makes mast cell activation difficult to diagnosis?  It is not single symptom specific…each patient presents with their own constellation of mast cell derived symptoms. There are often coexisting conditions that may mimic mast cell disorders such as IBS, fibromyalgia, eosinophilic esophagitis, headaches, food intolerance, depression.

Reference: Theoharides, T et al. Mast Cells, Mastocytosis, and Related Disorders. N. Engl J Med 2015:372(2):163-172.

A proposed criteria for disordered mast cell activation includes all 3 criteria:

  • Episodic multi-system symptoms consistent with mast cell activation
  • Appropriate response to medications targeting mast cell activation
  • Documented increase in validated markers of mast cell activation systemically (urine and serum markers) during a symptomatic period compared to patient’s baseline values.

Reference: Akin, C Mast Cell Activation Syndrome J Allergy Clin Immunol 2017:349-355.

Here is my Q and A about mast cell activation syndrome with Dr. Matt Hamilton:

Kate: What is mast cell activation syndrome (MCAS) and how does it compare to systemic mastocytosis?

Dr. Hamilton: MCAS is a complex disorder that is poorly understood both in regards to disease mechanisms and clinical manifestations. While the mast cell has been implicated in this disorder that causes many symptoms in multiple organ systems, there may be multiple factors at play. Testing to determine objective evidence of mast cell activation is limited and the mast cells look normal in appearance and number. The syndrome is characterized by what is thought to be abnormal and inappropriate activation of mast cells which produce the characteristic allergy-type symptoms. This syndrome is different from systemic mastocytosis where there is a defined mutation in the mast cell that results in an abnormal number and likely function of mast cells in the various tissues. Patients with mastocytosis may develop organ dysfunction which is not directly observed in patients with MCAS.

Kate: How prevalent is mast cell activation syndrome? Do we know?

Dr. Hamilton: The lack of objective markers to define MCAS and the lack of awareness of this disorder among providers has hampered the ability to accurately assess the prevalence of MCAS in populations. There are about 100,000 people in the United States diagnosed with mastocytosis and specialists who take care of patients with mast cell disorders have said that there may be as many as 10 times the number of mastocytosis patients with MCAS. It is likely that many with MCAS have not sought medical attention or have not been diagnosed with this disorder by their providers.

Kate: What are some symptoms of mast cell activation?

Dr. Hamilton: Mast cells line the surfaces of the GI tract, airway passages and lungs, skin, and other parts of the body that interface with the external environment. Therefore, the predominant symptoms involve these organ systems and include flushing, itching, sweating, and hives in the skin, abdominal pain and cramping, diarrhea, nausea, bloating in the GI tract, and wheezing, shortness of breath, and throat itching in the airway passages. Other common symptoms include palpitations, headache, tingling sensations in the fingers and toes, near fainting, joint pains and bone pains.

Kate: What other disorders do you see in clinical practice that seem to overlap with mast cell activation syndrome?

Dr. Hamilton: There are several medical conditions that are known to overlap with MCAS and these include the connective tissue disorder Ehlers Danlos Syndrome (usually the hypermobility type) and dysautonomia where there are defects in parts of the nervous system that can lead to manifestations such as POTS (lightheadedness and palpitations with standing). There are several other disorders that patients with MCAS may be diagnosed with and these may be truly separate disorders or directly linked to the MCAS. These include chronic fatigue and pain syndromes, anxiety and depression, chemical sensitivities, and chronic lyme disease.

Kate: What testing is requested if MCAS is suspected?

Dr. HamiltonIf one suspects MCAS based on symptom profile, we recommend a serum tryptase, and a 24 hour urine for n-methyl histamine and ll-beta prostaglandin F2 alpha. The first two are available at most labs. In general, the patient should be seen by their PCP about this and then referred to Allergy/Immunology to work up primary allergy sources and consider other diagnoses before labeling as MCAS.

Added: April 2018! An additional resource on the emerging role of mast cells in IBS  here!

The next Mast Cell Activation Syndrome post (part 2) will include some information from a patient’s perspective along with the potential role of supplements or pharmaceutical treatments.  Part 3 will discuss the potential role and application of nutrition and stress management.