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Lisa
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First, letīs go back to the umbrella term: Mast Cell Disorders. This umbrella term has to do with any kind of proven disorder of the mast cell. The original umbrella term was Mastocytosis. Yet the CYTOSIS part of this means the invasion of mast cells within the tissues. However, in the 80s Drs. Roberts and Oates from Vanderbilt studied patients and found that there was not just the issue of proliferation but also that of activation. However, from what seems apparent, the researchers, because they could not genetically prove anything wrong with the mast cells other than with those patients who had the proliferation form, the WHO criteria was established based upon this pathological proof, thus the strict criteria of those patients.
What they only learned with Dr. Akinīs landmark finding of the genetic defect upon the MCs of 1/3 of the patients in his study group while he was at the NIH is what totally undermined those previous beliefs. When that WHO concensus was held in 2001, those authorities believed at that time that the only real form of a mast cell disorder was that of the proliferation form and that with a proven genetic defect upon the MC. This neatly explained why the tryptase was so elevated and why there was proven MC degranulation thus activation. Dr. Akinīs finding was in 2006 I believe, the very same year that the WHO met again and made the SM criteria even stricter. This is why it rocked all of the researchers for there was a group of these doctors who were looking back at their patients who had been tossed out with the SM criteria of 2001 and began seeing inconsistencies! A number of them whom they would have sworn were SM didnīt make it under the wire and yet they responded to the same medical treatment. It didnīt make any sense. This is why they began to reevaluate the situation. They could not deny that those who had SM certainly had all of these specific criteria, but then were they catching these other patients too early in their disease process or was there another form out there? Was there an activation form instead? What was the missing link in all of this?
Dr. Akinīs findings rocked the boat!! Yet why werenīt doctors able to find this before? TECHNOLOGY!!! In order to find the defective MCs on those patients the bone marrow had to be especially purified in order to find the rare number of mast cells within their marrow. This is a process which is only now become more known and there are still only perhaps 3 or 4 labs in the world who can do this. This is not readily available and itīs expensive!! So for those patients with a very low or normal tryptase, the number of MCs within the marrow are so rare that itīs very difficult to the MCs in the first place to test them. Once they were tested, then they found the genetic defect. But even with these IA patients, their MCs appear totally normal in view - not misshappened nor aggregated!!! Yet there was no denying the genetic defect, it was there! Yet these patients remarkably broke the rules for they have no elevated histamines, tryptase or prostaglandins!! This is why the researchers have begun looking for other markers for obviously the MC is defective, but not defective enough to be putting out chronic levels of mediators, it only puts it out accutely it seems or perhaps there is another mediator which is behind the anaphylaxis. These are things theyīve yet to figure out.
With this discovery was born the theories of MCAS and they began looking at the other patients differently, those who didnīt fit into the classic mastocytosis form. This finding also reinforced the convictions of doctors like Dr. Castells and the others who believed in an activation form. Thus began the controversial unofficial diagnosis of MCAS/MCAD. Some called it a disorder others a syndrome others called it IA depending upon who your diagnostic doctor was. At the NIH they still favor IA at least up until the MCAS/D consensus of last year. Those patients who had some kind of proven chronic (constant) MC mediator release, be it histamines, tryptase or prostaglandins were put into this category when they could not fulfill the SM criteria.
What next shook up the masto researchers was the next patient group to be found, the MMAS group around 2008. This was a much smaller group it seems. They had proven MC mediator release, but low tryptase, or borderline elevated. They had pathological damage which coincided with the SM patients but could not be given the SM diagnosis because the MC aggregates were nowhere to be found. They had all the activation of SM patients, but lacked the proof of the same degree of proliferation. They seemed to be the missing link group tying the SM patients with the MCAS patients. Dr. Escribano made a profile of these patients last year and his study revealed specific characteristics amongst these petints. First it runs more among men than women. They have very severe cardiovascular reactions with syncope being one of them. They do not present with angioedema nor with urticaria when in crisis. They have the pathological damage shown that an SM patient can show, but their trytpase is remarkedly low and yet they have some kind of proven MC mediator release in high histamines or prostaglandins.
So, this group is what cinched the theories of those doctors convicted that MCAS was indeed another form of Mast Cell Disorder. They are different from the MCAS patients in that when they can find the MCs they are found to be clonal and aggregated, but finding them is the trick. The fact that there is the same pathological damage seen in the proliferative SM patients reinforces that this group straddles the fence. They have the same damage going on as the SM patients, however, the neoplasm is so very slow in itīs growth that these patients do not seem to be in any serious danger from the disease.
Yet due to the research going on, they feel that this group proves that there are different forms of mast cell disorders based upon the DNA defect of the production of the MC and that depending upon that defect the patients are going to show one of the various forms. I suspect that they are going to find that those patients who have their disease come out of hiding in the aggressive form are themselves another form of the defect, that they too are in their own patient group. Those SM patients who have their disease progress into a smouldering form and perhaps progress into an aggressive form also have a specific difference upon their MC genetic makeup which caused them to go into this form.
You see, all of this depends upon finding the MC genome! Once they can find the origin of the DNA defect, from that point on they can see what the differences are between the other forms and what role each persons genes have in influencing these changes. Once they can pinpoint these things, they can find A CURE!!!!
So, just to return to the original question, MMAS is a clonal form of mast cell disorder, but it is different from MCAS/D just as much as it is different from SM. It may be that this group will progress into SM, but at this point in time they just donīt know. More study is necessary.
Lisa
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