Analogies for Mast Cell Activation Disease

by | Nov 14, 2017 | All About MCAS |

There seems to be some confusion out there about the lingo surrounding Mast Cell Activation Disease (MCAD). Mast Cell Activation Syndrome (MCAS) and MCAD are often inappropriately used interchangeably, but it’s easy to see how all of the acronyms can get mixed up. When you add in Mastocytosis and Monoclonal MCAS, things get even more cloudy! Let’s see if we can use some analogies to help clear things up…

First of all, “Mast Cell Activation Disease” (MCAD) is an umbrella term that refers to a group of disorders characterized by

  1. The accumulation of pathological mast cells in potentially any or all organs and tissues AND/OR
  2. The aberrant (abnormal) release of variable subsets of mast cell mediators

(Molderings et al, 2011)

In other words, MCAD involves either too many “abnormal” mast cells around the body, and/or the “abnormal” release of too many chemicals into the blood by mast cells.

MCAD has a number of sub-categories. As a broad generalization, there are three main categories:

  • Mast Cell Sarcoma (very rare cancer)
  • Mastocytosis (somewhat rare condition involving abnormal proliferation or increased number of mast cells; split up into several different types: ASM, SM-AHNMD, ISM, CM)
  • Mast Cell Activation Syndrome (the most common type of MCAD; involves over-active mast cells that do not tend to proliferate or increase in number)

Pyramid diagram showing the different types of MCAD


Thus, when mast cells are dysfunctional we tend to see problems with either

Quantity (ie- Mastocytosis and Mast Cell Leukemia) or

Quality (Mast Cell Activation Syndrome)

When you have mast cell quantity problems, the sheer volume of mast cells accumulates to result in dysfunctional levels of chemical mediators in the blood. When you have quality problems, mast cells are releasing chemical mediators in the blood when they shouldn’t be. Thus, the two types of problems often look alike because they both involve the same excess chemical mediators released by the same cell type, which ultimately may lead to the same types of symptoms.

The College Party

Let’s take the analogy of a college party, for instance. Things can get out of control when your low-key shindig suddenly has


  • too many people show up and the house is flooded with rowdy and loud and inebriated fraternity brothers –> quantity problems! –> Mastocytosis or Mast Cell Leukemia, OR


  • there’s a normal number of people who show up, but the ones that show up are all serious light-weights with sensitive systems that cause them to vomit after one drink –> quality problems! –> MCAS


(Let’s face it, either scenario is not ideal).

MCAS is an immunological condition in which the bodies’ sensitive mast cells cause an acute (quick) release (called “degranulation”) of chemical mediators into the blood, which can signal the body to respond with symptoms like a sudden drop in blood pressure, swelling of the airways or skin, or other acute allergic reaction signs. With MCAD, the body interprets normally “benign” threats as harmful danger signals, and the mast cells start a cascade effect that leads to a spectrum of mild symptoms all the way to anaphylaxis in some cases.

This can be especially harmful in other ways when it occurs on a regular basis. When an inappropriate over-activity of mast cells occurs over time, symptoms can also manifest into chronic gastrointestinal, neurological, cardiovascular, respiratory, and dermatological problems. Symptoms tend to wax and wane and affect multiple systems of the body in an inflammatory manner. Essential systems that govern the immune response, fight or flight sympathetic reactions, hormonal balances, and many other processes in the body become unbalanced due to chronically abnormal levels of the mediators that affect the homeostasis of those systems. Virtually every body system can be affected with this “silent” disease that often “looks normal to the eye” and is very difficult to diagnose.

Border Patrol, Soldiers & Earthquakes

Dr. Anne Maitland uses some wonderful analogies for mast cells in her work. In a 2017 webinar she described mast cells as “border patrol.” She explained that they provide ongoing surveillance and protection in addition to coordination a response for repair, depending upon what they “see.”


She added, “Mast cells can become dangerous if a subset of them ‘goes rogue or mast cells are being great soldiers, but following bad orders.’” (Li & Ehrlich 2016) In this analogy, going rogue refers to Mastocytosis, and the soldiers that follow bad orders refers to MCAS.


Dr. Maitland likens the anaphylaxis triggered by mast cells to a spectrum of danger signals, similar to a grading system used for earthquakes.  And when describing the effects of chemical mediators released, she quotes Dr. Theoharides, “Tryptase is tissue tenderizer.” Tryptase is just one of the hundreds of chemical mediators potentially released by mast cells! It’s easy to see why the subsequent symptoms associated with MCAD are so widespread and devastating.

The Family Reunion

Some researchers break MCAS down into three sub-categories: primary, secondary and idiopathic MCAS.


Primary MCAD includes Mastocytosis and Monoclonal MCAS (abbreviated MMCAS). Specifically, to have Primary MCAD most experts agree that you must have the presence of an inherent genetic defect in the mast cells or their progenitors that presumably results in a reduction in their activation threshold. (Soderberg 2015) These patients have evidence of both MCAS criteria and mast cell monoclonality proven via the c-KIT and CD25 analysis. MMCAS typically presents with one or two minor criteria, such as the c-KIT mutation or CD25 expression on bone marrow analysis, but not the complete criteria for diagnosis of Mastocytosis. Patients who have MMCAS often have normal baseline tryptase levels that may raise to abnormal levels in symptomatic episodes. According to Soderberg, another hallmark is that patients with MMCAS present with less than 15 mast cells per high powered field and the mast cells are hypo granulated and spindle-shaped, whereas patients with Mastocytosis will have numbers greater than 15 per high powered field.


In other words, MMCAS is in-between Mastocytosis and MCAS. They may have problems with both quantity and quality.  These patients have signs of Mastocytosis, but not enough concrete evidence to clinch the clinical diagnosis of Mastocytosis. Both MMCAS and Mastocytosis are considered “primary” disease because they show fundamental signs that the disease is genetically inherent and not caused by an outside factor.


I like to think of MMCAS as Mastocytosis’ baby sister – many things look alike and they both have the same “clonal” background, but there are some fundamental differences in the laboratory findings that distinguish the two.


Secondary MCAD includes allergic disorders, mast cell activation associated with chronic inflammatory or neo-plastic conditions, and urticarias (physical or chronic autoimmune urticarias). These patients meet the criteria for diagnosis of MCAS and also have clinical diagnoses for an underlying type I allergy or other medical condition that can induce mast cell activation. This category covers a broad range of root causes and there are many descriptions of Secondary MCAD in the literature. (Soderberg 2015) Some argue that other conditions such as the Epstein Barr virus, mold exposure, or chemical toxicity (to name a few) may be responsible as the underlying root cause that is triggering the mast cells inappropriately.


I consider Secondary MCAD to be the cousin of Primary MCAD. They are related and some things look alike, but they were raised in a different household and the Secondary folks have some unique factors from their environment that are the true root of the symptoms.


Idiopathic MCAD includes sub-groups of anaphylaxis, angioedema, urticaria, and MCAS. Idiopathic (or “without a known origin”) is a more puzzling subgroup from a clinical diagnostic perspective. These patients also meet the criteria for MCAS, but there is no discernable clonality or secondary cause found. In other words, the idiopathic group is where patients are placed if they display no type I allergy, no underlying disease that can explain the symptoms, and no monoclonal mast cells or skin Mastocytosis detected. Patients with Idiopathic MCAS have an absence of clonal markers (like the c-KIT mutation or CD25 expression). (Soderberg 2015)


To me, Idiopathic MCAD is my favorite wild aunt who shows up to family events unexpectedly. Unpredictable, often unexplainable, and still very much a real and powerful presence.

Hopefully these analogies help make some sense of the little nuances within the lingo. Do you know other ones that may be useful? Please comment and share your ideas below!


Molderings et al. Mast Cell Activation Disease: A Concise Practical Guide for Diagnostic Workup and Therapeutic Options. J Hematol & Oncol. 2011.

Maitland, Anne. EDS Awareness Webinar: Mast Cell Activation Update. Aired September 19, 2017.

Webinar: Mast Cell Activation Disorder

Li XM, Ehrlich H. Traditional Chinese Medicine, Western Science, and the Fight Against Allergic Disease. World Scientific. 2016.

Soderberg, ML. The Mast Cell Activation Syndrome: A Mini Review. MOJ Immunology. 2015.



This content is Copyright © Mast Cells United and is not intended to diagnose or treat anyone. Always consult your medical professional for any health guidance or advice.

Get Free Email Updates!

Signup now and receive an email once I publish new content.

I agree to have my personal information transfered to MailChimp ( more information )

I will never give away, trade or sell your email address. You can unsubscribe at any time.

%d bloggers like this: