Many patients (and some doctors) wonder how to go about testing for mast cell activation syndrome (MCAS), a relatively newly recognized form of mast cell disease (MCD). In order to get a proper diagnosis, patients need to be properly evaluated.
Ruling in or out mastocytosis first.
While there are specific diagnostic tests and criteria approved by the World Health Organization (WHO) for the rarer forms of MCD, (skin mastocytosis, indolent systemic mastocytosis, systemic mastocytosis with an associated clonal hematologic non-mast cell disease, aggressive systemic mastocytosis, mast cell leukemia, mast cell sarcoma, extra cutaneous mastocytoma), MCAS still doesn’t have definitive diagnostic criteria that the WHO has approved.
Still, mastocytosis needs to be ruled in or out before considering MCAS and once that’s done, there are proposed criteria that the experts mostly agree upon. You can read them in detail at The Mastocytosis Society’s website here.
A simplified version can be found listed on Wikipedia:
- Although different diagnostic criteria are published, a commonly used strategy to diagnose patients is to use all three of the following:
- Symptoms consistent with chronic/recurrent mast cell release:
Recurrent abdominal pain, diarrhea, flushing, itching, nasal congestion, coughing, chest tightness, wheezing, lightheadedness (usually a combination of some of these symptoms is present)
- Laboratory evidence of mast cell mediator (elevated serum tryptase, N-methyl histamine, prostaglandin D2 or 11-beta- prostaglandin F2 alpha, leukotriene E4 and others)
- Improvement in symptoms with the use of medications that block or treat elevations in these mediators
I have MCAD and technically only fulfilled #1 and #3 of these criteria, which I’ll explain in a minute.
Why don’t the experts all agree on testing & diagnosing?
In an article published in 2013 by Nova Publishers, Dr. Afrin, a leading researcher and mast cell disease expert, had this to say about the proposed diagnostic criteria:
Given that MCAS has come to be recognized only recently, and given its heterogeneity , it is not surprising that there is not yet a definitive consensus regarding diagnostic criteria.
In late 2010 Akin et al. proposed the diagnosis be permitted if a patient met all of the following four criteria:
(1) symptoms consistent with aberrant mast cell mediator expression, (2) laboratory evidence of aberrant mast cell mediator expression, (3) absence of any other evident disease better explaining the full range of findings in the patient, and (4) at least partial response to therapy targeted controlling mast cells or blocking mast cell mediators.
In 2011 Molderings et al. proposed a set of two major and four minor criteria (modified from the World Health Organization 2008 consensus diagnostic criteria for systemic mastocytosis):
(1) Multifocal or disseminated dense infiltrates of mast cells in bone marrow biopsies and/or in sections of other extracutaneous organ (s) (CD117 – , tryptase – , and CD25 – stained)
(2) Unique constellation of clinical symptoms secondary to a pathological increase in mast cell activity (mast cell mediator release syndrome )
(1) Mast cells in bone marrow or other extracutaneous organ (s) show abnormal morphology (>25%) in bone marrow smears or on histological examination
(2) Mast cells in bone marrow express CD2 and/or CD25
(3) Detection of gene tic alteration s in mast cells from blood , bone marrow , or extracutaneous organs , which have been confirmed to result in an increase i n the activity of affected mast cells.
(4) Evidence of a pathological increase in mast cell activity through detection of an elevated level of at least one sensitive mast cell – derived mediator, i.e., tryptase, heparin, histamine , PGD 2 , chromogranin A, leukotrienes (and their assorted metabolites ) in blood and/or urine
Molderings et al. proposed that MCAS be diagnosed if both major criteria are present (with or without any minor criteria) or if the second major criterion and at least one minor criterion are present.
As you can see, because of the complex nature of this disease, the leading experts disagree somewhat on the criteria for testing for and diagnosing mast cell activation syndrome.
To complicate things further, the experts at the Mastocytosis Society also warn us that:
Some patients who present with typical and recurrent signs and symptoms of mast cell activation do not present with elevated levels of mediators for which we are currently able to test. Non-specialist physicians may most commonly use serum tryptase levels to exclude a mast cell disorder. However, some MCAS specialists have indicated that tryptase rises are not seen as often in patients with certain forms of MCAS, and that other changes in bloodwork and urine tests can sometimes be more reliable.
Dr. Afrin has this to say in conclusion in the article I referenced above:
Mast cell activation syndrome (MCAS) is a recently recognized, prevalent, relatively non – proliferative whose underlying mutational heterogeneity leads to marked clinical heterogeneity which can be quite confounding from diagnostic and therapeutic perspectives. While not diminished in duration compared to the general population, MCAS patients’ lives often are diminished in quality until the disease is diagnosed and treated.
With patience, persistence, and a methodical approach, most MCAS patients are able to eventually identify a therapeutic regimen which helps them feel significantly better most of the time. Although such efforts may require trials of many medications consuming months or even years, many MCAS patients have been ill for far longer periods of time prior to diagnosis and, in simply having finally identified a diagnosis and prognosis, are bolstered to willingly endure the present “trial-and-error” approach to identifying effective therapy.
He is (as always) absolutely spot on. Having a diagnosis changed everything for me.
As for my own testing and diagnosis, my doctor tested my tryptase (it was normal) and had me do a bone marrow biopsy based off of my long history and constellation of symptoms (I had 54 out of 58 symptoms listed here) and the fact that I had what appeared to be a urticaria pigmentosa skin lesion (UP).
We wanted to rule in/out mastocytosis right away.
By using Moldering’s criteria, having the symptoms alone fulfills one major criteria (#2).
My bone marrow biopsy showed my mast cells expressing CD25 which fulfills one minor criteria (#2).
I didn’t fulfill enough minor or major criteria for mastocytosis and I didn’t have any further mediator testing done which I’ll explain soon.
My c-kit test was negative for the mutation at codon D816V, but you can read why that may not mean much since other mutations may be found around that particular regulatory gene.
My white blood cell count is almost always elevated on my CBC tests, though, indicating systemic inflammation.
The fact that I respond so well to mast cell targeting therapies adds further evidence (according to #4 of Akin’s proposed criteria noted above) that I do, indeed, have some form of mast cell activation disease (MCAD).
But which type?
Just as there are several types of mastocytosis, there are variants of mast cell activation syndrome, too. According to The Mastocytosis Society:
Primary MCAS results from a clonal population of mast cells, where a genetic alteration in the cells exists, and may be due to mastocytosis or to monoclonal Mast Cell Activation Syndrome (MMAS).
Secondary MCAS is diagnosed when mast cell activation occurs as an indirect result of another disease or condition.
Idiopathic MCAS is proposed as a final diagnosis after proposed MCAS criteria have been fulfilled and a thorough evaluation has excluded the possibility of another known underlying cause for this activation.
Interestingly, according to this chart, I may actually have monoclonal mast cell activation syndrome (MMAS):
My doctors are unsure but because the testing process is costly, stresses me out badly and triggers me to get far worse, we are following this guideline for my own further testing and treatment at this time:
The important part is it’s working well for me. I am about 80% better than I was two years ago!
Good luck and don’t give up!!