Tryptase. The mere mention of it makes Mastie’s cringe. Physicians and patients alike seem to have a great deal of difficulty sorting to out. A recent discussion came up after patients had been to see Dr Vadas, the most well known Canadian MCAS expert. It seemed that he was giving contradictory advice. He had told one patient that to get a confirmed diagnosis of MCAS, you need a positive tryptase. He told another (the same week) that a positive tryptase wasn’t needed for a diagnosis of MCAS. Those two statements are both correct, but incomplete. I don’t know Dr Vadas, nor would I speak for him, but I hope I can help clarify by giving a bit more info.
What is Tryptase?
Tryptase is a cell mediator hormone. Mast cells schlep around many different molecules, in little packets called granules, there are hundreds of cell mediators in the body, and the job of mast cells is to apwarehouse many of these chemicals, releasing them when told to. Most people know about histamine and tryptase. When mast cells go nuts (de-granulate), they release these hormones. They can slowly release selective mediators, or it can be a spectacular blast and release all their mediators at once.
Mast cell mediators are hard to ‘catch’. A cell mediator cascade reminds me of one of those marble toys, the gigantic ones where a ton of things happen at once. You know the ones, little steel balls going and hitting bells, ramps and other things, some balls being pulled out, some going around again. The mediators set off other cells, there are positive and negative feedback loops, etc. Medical science has only begun to scratch the surface of this highly complex system.
False Negatives
Mast cell mediator tests are notorious for false negatives. If you have elevated tryptase or other mediators, you almost certainly have something going on with your mast cells, but the opposite is NOT true. Many people with MCAS have normal, or even below normal tryptase. Self included. I believe I know why, but I don’t want to go down that rabbit hole right now.
The ‘Consensus Criterion.’
Recently, several mast cell specialists from around the world established a ‘consensus criterion’ to diagnose MCAS. Specialists who know about MCAS seem to widely accept them for ‘confirmed’ diagnosis. (If you want to read more about the criteria, here’s a place to get started.).
For now, let’s focus on Criteria number 2. To paraphrase, it says that you have to have a urine or blood test that indicates atypical mast cell mediator release. Tryptase is the most common test, and can be done at several labs across Canada. The problem is that most people with MCAS don’t have elevated tryptase. In fact, some studies show that 80% of people with MCAS have normal tryptase levelsn that’s one in five. Clearly, you can have MCAS without having an elevated tryptase.
The testing challenge.
There are very few labs around the world that can analyze for those other mast cell mediators- (leukotrienes, prostaglandin, nmethyl histamine, etc.) as in two or three labs in the world, depending on the test. The samples are very sensitive to temperature, they need to stay between freezing and 5 degrees Celsius. Can you imagine how hard that is to do? It has to be shipped to Ontario, then sent to Minneapolis, New York or California. All while staying in that temperature range. To continue with the marble run analogy, you have to capture a freeze frame of all those little marbles whizzing around. You can imagine that if you took a photo of the marble maze you could easily miss several marbles, and if you’re five minutes too late, nothing is moving at all. The temperature is what makes a mediator chemical ‘freeze frame’ possible, and it’s hard to do. The cost of the transportation and the tests themselves are expensive.
The Spectre of False Negatives
I had a nightmare to deal with when it come to those tests. The first set of tests I had done (in 2015) came back negative. A physician (who should have know better), said that if the tests were negative, I didn’t have MCAS. Since there isn’t any other explanation for my being ill, it had to be a mental illness. I was immediately denied care, told to see a psychiatrist. I was discharged from hospital with no follow up care. I ended up having to go to the states (to Minneapolis to see Dr Afrin) and get the tests done at the Mayo Clinic lab there. My being nearby, and having the samples treated properly seemed to make the difference, several were positive.
When I returned to BC, it was insinuated that I rigged the positive tests, and several allergists continued to insist that I didn’t have MCAS, despite clear evidence to the contrary. SO many times I have had a team of docs really on board, only to see derailed with one phone call. Unfortunately they are the same people who everybody in BC calls for advice, and they are woefully misinformed (willfully so?). Slowly, slowly the awareness of MCAS is growing, with younger physicians being willing to look at allergy and Immunology as a much broader practice than doing skin prick tests and telling patients how to reduce dust in their home. I’m pegging my hopes on this new generation who understand that you can’t look at one system at a time, and that how we function is more important that test numbers.
There is no doubt. I do not have elevated tryptase. In fact, it’s usually below normal. I have had negative mediator tests and then positive ones. I have MCAS, and it is confirmed. It is unbelievably annoying to be told I don’t fit the criteria by people who haven’t read them. (A huge pet peeve). If I don’t have MCAS, it doesn’t exist. It exists.
My current advice
If you’re getting the care you need, consider if you need a confirmed diagnosis, or if a presumptive/clinical diagnosis is enough. If you’re getting the care you need, is the benefit worth the risk?
A clinical diagnosis of MCAS from a knowledgeable doctor ‘should’ be sufficient to begin treating for MCAS. There are a few things to rule out, but once that’s done, there are two explanations- you have some form of mast cell disease, whether it be mastocytosis, MCAS, TEMP, etc., or you’re crazy. You’re not crazy.
I often tell other Canadians to consider very carefully before getting the full mast cell mediators tests done. They’re expensive and unreliable, adding a border crossing adds more chances it will spoil. Perhaps more importantly, a false negative can toss your care off the rails. When confronted with something that they have never seen, too many physicians fall back to a ‘it must be in their head’ explanation. Once that label is stuck on it is excruciatingly difficult to shake. It’s better to have a ‘clinical’ or ‘presumptive’ diagnosis than to be accused of a psychiatric illness by someone who isn’t knowledgeable about the tests.
Do you need a confirmed diagnosis?
No. This is where the Canadian factor comes in on the positive side. You don’t need a diagnostic code to get treated here. We’re much less fussed about covering our butts, which makes things much more flexible (which is changing, unfortunately). If a patient isn’t suspected of having MCAS, a few rare possibilities have to be ruled out, then the thing that’s left is MCAS. If it walks like a duck, quacks like a duck, flies like a duck, looks like a duck, swims like a duck, you don’t need a DNA test to know that IT’S A DUCK!
Dr Vadas’ team at St Mike’s appear to be aware how detrimental those false negative results can be. (Again, I don’t presume to speak for him or his team, I’m basing this on patient reports.) They seem to be comfortable recommending treatment when the MCAS isn’t ‘confirmed’, but pretty obvious clinically. For heaven sake, I can pick Masties out of a crowd, he’s met scores of us, it must be quite obvious for most of the patients he meets if their profile fits.
Confirming a Diagnosis- other mediators count!
So, to get a confirmed diagnosis of MCAS in Canada, patients need to have elevated tryptase- not because the other tests aren’t valid, but because they are extremely expensive, notoriously negative (especially from anywhere outside Toronto) and you don’t need ‘confirmation’ to get treated for MCAS. That is NOT the same as saying that a negative tryptase rules out MCAS. It also doesn’t indicate that other tests are not valid. If you have positive mediator tests from the specialist labs, that aren’t tryptase, they count! A positive tryptase is the most commonly accepted test, perhaps the only one many would recommend in the current situation in Canada, but certainly not the only one that can confirm MCAS.
The landscape is changing quickly, and the specialists here are definitely becoming more knowledgeable about MCAS. I believe it will all get sorted out, but in the meantime, I plan to stay pragmatic, focus on getting the care I need and save the validation for another day. (I did say ‘plan’, right?). I REALLY want to stop telling patients to play medical politics, but until we’re there, do what works.
So far, most physicians who become aware of MCAS are pretty happy to find something that not only explains their patients symptoms, but points to treatment possibilities. If we, as patients, have a good understanding of what is going on, we can help our physicians see how MCAS affects each of us so very differently. Undoubtedly, being able to clarify the tryptase thang can help us and other patients.