• Dr. Lawrence Afrin, Dr. Tania Dempsey

The Difference Between MCAD and MCAS

We recently received a very interesting question asking us the difference between Mast Cell Activation Syndrome (MCAS) vs. Mast Cell Activation Disorder (MCAD). Our answer was quite long for this one so we thought it deserved an entire post.

"Mast cell activation disease" (or "mast cell activation disorder") -- MCAD -- is the new term (since late 2010, when it was proposed in a publication by Drs. Cem Akin, Dean Metcalfe, and Peter Valent, all luminaries in the world of mast cell disease) for the full spectrum of mast cell disease based on the new understanding that *all* mast cell diseases first and foremost feature inappropriate mast cell activation, and inclusion of the term "activation" (rather than just calling it "mast cell disease") helps everyone remember that it's the activation that's causing the lion's share of the problems in the great majority of patients with *any* form of mast cell disease. Of course, the forms of MCAD which *also* feature cancerous proliferation of mast cells are known as the various established types of "mastocytosis," but mastocytosis (of any type) is a rare disease. "Mast cell activation syndrome" (MCAS), then, is the new term (also first proposed in that publication in late 2010) to refer to mast cell diseases which feature chronic inappropriate mast cell *activation* with little to no inappropriate *proliferation* of mast cells. MCAS is then further divided into primary MCAS (in which it's proven that the mast cell activation in the patient is truly the root problem), secondary MCAS (in which the mast cell activation clearly is coming about as a reaction to some other disease in the patient), and idiopathic MCAS (in which it just isn't clear whether it's primary MCAS or secondary MCAS). At present, it seems that most patients have idiopathic MCAS, but there have been a few research studies done suggesting that most MCAS patients probably have primary MCAS. Nevertheless, the testing done in those research studies to prove that isn't yet available in clinical laboratories, so it will be quite some time yet before we can routinely distinguish whether a given case of idiopathic MCAS is truly primary MCAS vs. secondary MCAS. Note that this new "umbrella" term of MCAD does *not* say that proliferation of mast cells (as in mastocytosis) isn't a problem. It just acknowledges that activation, not proliferation, is the *principal* problem in *most* patients with mast cell disease (there will always be exceptions, of course). And, to be sure, there remain yet other diseases of chronic inappropriate mast cell activation, too (i.e., beyond mastocytosis and MCAS), such as angioedema, urticaria, and anaphylaxis, and when the patient's *only* mast-cell-driven problem is one of these other diseases, it's probably simpler to just label that problem with the traditional name/diagnosis for that problem (e.g., "chronic idiopathic urticaria"). However, if the range of problems the patient has been suffering goes beyond one of these relatively narrow labels to include the broader spectrum of findings usually seen in "MCAS," then it's probably easier/simpler to just label it as "MCAS" and understand that the "chronic idiopathic urticaria" also seen in such a patient likely is "just another consequence" of the underlying MCAS which probably is causing most or all of the patient's other problems, too. It's easy to see that there remain semantic/labeling/terminology issues here, and this imprecision is a direct product of our poor understanding of what's precisely going on (at molecular and genetic levels) in each MCAD patient's mast cells. In time (i.e., likely over many decades to come), as we improve our scientific understanding of precisely what's going on at the root of the mast cell misbehavior in each MCAD patient, our terminology likely will (slowly but steadily) get more precise -- "oh, Patient A has variant XY123 of MCAD according to the database of MCAD variants we've been building, whereas Patient B has variant JK456 of MCAD," and that improved precision in diagnostic labeling likely will lead to improved therapeutic decision-making, too (i.e., we'll come to understand that different variants (of course!) respond to different treatments) -- but until then, calling a given MCAD either mastocytosis or MCAS (or one of the other "traditional" forms of MCAD) is the best we're going to be able to do on a routine basis. Patients need to be patient with their doctors about all of this. *Everybody* -- doctors and patients alike -- is learning about this together, and we all have a long way to go to get to a truly satisfactory level of understanding of it all. (Heck, every time we answer one question about what makes this disease tick, the answer actually reveals to us a hundred more questions we couldn't even think of before, so imagine how much research remains to be done and how long it's going to take to get to a "satisfactory" level of understanding of all of this.) But, hey, at least we're now able to *recognize* that MCAS exists, and we've learned pretty well how to diagnose it (yes, I know there remain controversies, and obviously, our diagnostic techniques will continue improving with time), and at least we're now able to *do* something about it, at least in most MCAS patients (and even though our methods for figuring out *what* to do about it in the individual patient remain quite crude). So that's a good bit of progress -- in merely the one decade that's now passed since the first case reports of the disease were published, and it's all the more impressive a bit of progress when one additionally considers just how complicated MCAD is. (If it were simpler, we probably would have "figured it out" -- as we did with most other diseases -- a long time ago, right?)

#mcad #mcas #mastcellactivationdisorder #mastcellactivationsyndrome #madvsmcas #mastcelldisease

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