1) What is a mast cell "mediator?"

Mast cell mediators are chemicals mast cells release when they're degranulating. This is how they say “Something's wrong over here! Send help!” Healthy, well-behaved mast cells degranulate for a variety reasons and play an important role in the healthy body's immune system. Mast cells degranulate when they see an invader like a virus or a bacteria or when there's an injury, releasing mediators like histamine, prostaglandins, heparin, leukotrienes, and others in order to cause inflammation and bring more blood and immune cells to the area to fight off the invader or to heal the injury. Unfortunately, with MCAS, your mast cells are prone to misbehaving or exercising poor judgment, setting off this alarm when they encounter things like pizza instead of things like the plague.

2) When you say treatment can prevent damage, what do you mean? Don't those medicines like H1 and H2 antagonists just work by stopping symptoms, and not by doing anything to the mediators themselves? (Is treatment really necessary if I can “live with” my symptoms?)

Mediators are only designed to "live" about long enough to call for more help to the area (that's why they're hard to catch!). They're kind of like throwing a little blood into the ocean to call over some sharks if you had a reason to call over some sharks to help you with something. You can see the color in the water for just a few seconds. Soon, it's invisible, but it's calling sharks. These mediators cause inflammation, but it's temporary and limited. It's when, inappropriately or for bad reasons, more mast cells can be called to the area to degranulate, and more alarms are set off telling mast cells in other parts of the body to degranulate, and this process goes on and on, that your little boat that can't stop dumping blood into the water accidentally attracts the Kraken. Histamine 1 and Histamine 2 are important pathways for calling in reinforcements. If you block enough of these to limit this "communication," if you will (What you want your mast cells to say is "We're fine over here. There's nothing wrong with this pizza." What you do not want to your mast cells to be able to say is "Pizza! Send in the Kraken!"), these mediators won't do much, and while you might attract some sharks nearby, they won't start a chain reaction that leads to calling in everything hungry in the entire ocean to come decimate your boat. Maybe you've heard of this process referred to as a "spiral," where you set off some mast cells here, which set off mast cells there, and there, and there, and...more alarms keep going off, more calls for reinforcements keep being placed, and your body is at war for days, weeks, months, or years, and doing a lot of collateral damage in the meantime, even though that war started with a very good slice of pizza that has long since exited the body.

3) But all the (real) people who have (actually) cured their symptoms without mast cell treatment. What else could they have possibly have had that could have been mistaken for this?

See this list. It's certainly not exhaustive.

4) What is a flare? How long can a flare last? Or how long can a trigger make me worse?

A flare is a period of increased symptoms. And this depends on so many factors, but indefinitely. There is no time limit on how long mast cells can keep setting off the body's alarm system and wrecking havoc long after any particular trigger that initially started these symptoms has been removed. This is something that characterizes a mast cell disorder.

5) All the things I might do in an allergist's office: allergy testing, shots, various low dose allergen therapies...why don't they work?

Regarding skin testing, it's inaccurate if you do happen to have a mast cell disorder, and if there's any reason to think that might be the case, it's also extremely dangerous. (Order an IgE blood panel, instead. Why? Because this can safely identify your actual allergens and help you distinguish them from triggers arising from a mast cell disorder.) Unfortunately, even the newest and greatest “allergy” approaches can do more harm than good in this population because the process by which mast cells react to various, often quickly changing triggers is not the process by which mast cells react to IgE, IgG...allergens or intolerances even though symptoms may initially look quite similar. Many therapies which resolve allergens successfully are about as likely to make the things you had a minor allergy to before a new, Kraken-like mast cell trigger. You can't train your misbehaving mast cells the same way you can desensitize an IgE or other sensitivity, because with a mast cell disorder, these kinds of low level exposure therapies will increase sensitivity rather than decrease it. It's kind of like the difference between training a dog and trying to train a wolverine. Your dog training techniques are just going to make the wolverine angry, and no matter how well-meaning you are, it will never learn to give good kisses. If you're dealing with a wolverine, you need the best fence you can build and not to poke the wolverine, and that's what treatment and trigger avoidance are.

6) I read a lot about people with these disorders having pain and also simultaneously not being able to take pain medications. Is this true?

With respect to pain, every patient is different, but bone pain can be a symptom of both Ehler Danlos and mast cell disorders in general, and neuropathic and other kinds of pain are also seen. Treating the mast cell disorder of course should come first, but other therapies, like low dose naltrexone, some non-opioid, non-NSAID pain and other classes of medications, and various alternative therapies may also be relevant depending on your continuing symptoms. It really is important to remember that every patient is different. You may not experience any discomfort, you may experience some discomfort during or after periods of increased mast cell activity until your condition becomes more stable (Remember that mast cells are calling inflammation to an area when they are degranulating. This is their job.), or you may need various treatment options to manage this symptom. It's important to note that pain is in no way indicative of disorder severity or type and also that a fair percentage of patients with these diagnoses have an uncommonly high tolerance to pain and have been living with what “ordinary” patients would identify as a “10” their entire lives. I've met many who experience things like regular joint dislocations, for example, whose first question is about the terrible pain they've read about in support groups that they're worried is coming with their new MCAD diagnosis. Every case is different, and I certainly would not want to diminish the experience of any patient with any mentally or physically challenging case to manage (and aren't they all?), but I would estimate that the percentage of patients I meet for whom debilitating, more challenging to manage pain is the primary concern seems quite low when compared to the percentage of patients I meet whose greatest fear is that they will unavoidably develop impossible-to-manage pain, irrespective of treatment and without options, because of the number of people they have encountered in support groups who appear to be experiencing this. Please see the page on support groups and, if you are struggling with pain, talk to your doctors about your best treatment plan.

7) I've heard some people have to get chemotherapy. Is this cancer?

Not exactly (unless you're here for a mast cell leukemia diagnosis, in which case I'm sorry that this is not the right website for you). But it is a white blood cell disorder, SM is myeloproliferative, MCAD specialists are most often hematologists/oncologists (and if you have SM, in particular, you will need to see one), and there are some cases for which “chemo” drugs like imantinib (Gleevec), Ayvakit, and others mentioned in this category on the treatment page are useful. If you’ve exhausted other therapies and your mast cell disorder specialist (specialist, not familiar provider) brings this up as an option for you, you should consider it, but this isn’t where you'd start.

8) I really don’t like everything I’m reading about cancer. Don’t something like one in three mast cell patients get cancer?

It’s true that about a third of the general population "gets" some form of cancer (In America, it’s over 40% of men and over 38% of women), so if you’re a human, yes, you run about this risk. But many cancers certainly do seem to be more common among mast cell patients. Why? Probably because mast cells acting badly sends inflammation running wild and does a great deal of damage in the body. This is just one reason why treatment is important.

9) I have a necessary surgery or dental procedure coming up. What do I need to know?

I recommend discussing your individual case with your specialist, who should discuss with your anesthesiologist and others involved in this, but in general, if this is a necessary procedure, the answers to the following questions are likely to be important for a mast cell disorder patient:

1) What kinds of medications need to be used in this procedure? Which options are best for me? Which needs to be avoided? If I'm in pain afterwards, what pain control options do I have? Are there risks of infection, and are there antibiotics I tolerate that will work to address this?

2) What materials will be used this procedure? Does it involve something left in the body? Topical surgical preps? Stitches? You may need to source alternatives for all of these things. For implants or dental materials, you can test your "biocompatibility" with various materials in blood (this will not identify mast cell triggers, but will narrow down your options to try yourself) and pick up samples to try of these materials, as well as of things like wound care products to help determine what you might best tolerate.

3) What does the procedure itself entail? How will my mast cells be managed during the procedure and with any other triggers I encounter afterwards as I'm recovering (and my mast cells are (correctly) fired up trying to help me heal)?

4) What premedication plan is right for me, and when and how should these medications be administered? Also, how will I be monitored and medications administered after the procedure?

10) How prevalent are these disorders?

Prevalence is most recently estimated as follows:

MCAS: up to 1 in 5 or 6 (2020)

Systemic Mastocytosis (all types): 1 in 10,000

Aggressive Systemic Mastocytosis: 1 in 1 or 2 million

Please note that SM is not a progression of MCAS, nor is MCAS is a progression of SM. Smouldering systemic mastocytosis (SSM), aggressive systemic masocytosis (ASM), and company are progressions of indolent systemic mastocytosis (ISM). There are treatment options for all of them. Studies have suggested that perhaps 3% (the newer data) with ISM will “progress” to other forms of SM, and roughly 1.2% (newer data) of these may eventually progress to ASM. (Most patients monitor elevated tryptase levels with periodic testing. Baseline tryptase over 200 is a minor criteria for SSM.) Many cases of ISM are also found in entirely asymptomatic patients for whom these biopsies are ordered for other reasons, however, and as such, ISM may well account for a much greater percentage than the roughly 90% of SM cases currently proposed and so these “progression” cases may be even lower than is estimated.

11) I must have aggressive systemic mastocytosis, because I have a really serious case/my organs are doing weird things or it's "in" my organs!/My spleen's enlarged!/I have a gene! (I’m hoping I have MCAS, right? Because SM’s bad? That’s what somebody told me.)

No. Not even a little. Mast cells are “in” everyone's organs, there is no way to distinguish SM from MCAS based on symptoms, and MOST serious/debilitating cases are MCAS. Cases are always individual, and there’s no “good” or “bad” here. Either can be life-threatening, a minor inconvenience, or anything in between (though some indolent systemic mastocytosis cases, which make up the majority of SM cases, are totally asymptomatic). MCAS is far more common, but keep in mind that in many cases, these diagnostic distinctions themselves make no difference at all in treatment. (What would suggest you may have ASM, pending the results of a bone marrow biopsy? If your baseline serum tryptase is over 200 (200, not 20), especially in the absence of HATS, this is one minor criteria for SSM, which is the stage before ASM. Enlarged spleens and other additional minor criteria for ASM (which are only relevant once previous criteria are met and when these symptoms are the result of mast cell proliferation, which is not typically why things like spleens become enlarged in the general population OR in this population) are extremely common among MCAS and ISM-diagnosed patients and also do not make ASM more likely.) See diagnostic criteria here.

12) I've been reading things about mortality rates. Is this disorder going to kill me?

First, I believe that many sources of information on mast cell disorder-specific mortality, usually for SM you've probably found online, are from largely outdated and/or extremely limited surveys from when both diagnosis and treatment and knowledge in general about these disorders were more limited, and so when only extremely unwell people were diagnosed, or else from pharmaceutical companies and based on nothing anyone recognizes at all. Of course, I can't answer this question for your individual case. Some people do die as a result of a mast cell disorder (Many more of these deaths are attributed to MCAS than to SM, in case you're still hung up on SM percentages.), some die as a result of complications of a mast cell disorder (things like infected ports or tubes, for example), some die of other conditions that were contributed to, or which may have arisen entirely because of their mast cell disorder (This is especially common with cancers and other conditions. Particularly untreated or under-treated mast cell disorders are correlated with several kinds of tumors, for example.), and many, many people with mast cell disorders live long and healthy lives.

Whatever your diagnosis, and even if you're a healthy dragon with impenetrable scales, there is no way to fully control all variables in your life to guarantee that you'll be in this latter group, but there are some questions you might think about to help make sure you're doing what you can to live your best, healthiest life. As hard as this may be right now, please try to remember that this is one of many potentially challenging diagnoses and is by no means the worst thing that you could learn you had today. EVERY form of MCAD offers treatment options and paths forward which could be right for you. Every patient has choices to make, and while no patient ever has control of everything, this means a lot. Consider the following:

1) Whatever your diagnosis, what are you doing to treat it?

A- to handle emergencies (rescue meds and plans with hospitals, loved ones, and so on)

B- to prevent these emergencies (regular treatment)

C- to prevent damage to the body from this disorder (regular treatment)

Are you comfortable with your plans? Have you reached out to other practitioners if yours have stalled out? Have you exhausted the treatment options that are appropriate for your case, in a reasonable order, to best manage your condition? Are you doing everything you can, in other words, medically, to keep your mast cell disorder in check and to prevent it from causing both short term risk and long term damage?

...Or have you tried some things and quit when they didn't work because this was so disappointing and you were overwhelmed at the time? Were you reactive to all the options you tried and haven't looked into things like excipients? Or did you try compounding, but only with cellulose and a few other things? Were you hoping for a one-and-done approach and went with something that wasn't mast cell treatment at all and might have been a little dangerous? Were you busy chasing "root causes," maybe a lot of them at once, and some of those “cures” made you worse? If so, can you acknowledge this now, and are you willing to try something different?

2) With the above, whatever your current triggers, are you doing what you can to avoid them to prevent any preventable worsening of this condition?

A- Are you still cleaning with the bleach, drinking the alcohol, spraying on the perfume, and insisting on making Grandma's Big Spicy Secret Recipe every year?

B- Are you dealing with attachment or addiction issues to some things that put you in danger or worsen your condition?

Are you willing to address these things, if needed with professional help?

3) Are you doing what you can to take care of your health in general?

A-Do you have some things that you could safely address, for instance nutritionally or with safe-for-you exercise, or at least work towards, that you're not willing to test or treat or work towards because it would be a lot of time and energy (and not how you like to or used to eat or exercise or whatever it is) since your mast cell disorder makes this more difficult?

B- Are there other conditions you're not addressing, unrelated to your mast cell diagnosis, because they would be a lot more effort to treat due to the diagnosis? Are you willing to consider ways around this?

4) Have you given up because you were exhausted and overwhelmed and then stayed in this pattern because it was more comfortable or because you've been so disappointed in the past when you have put in effort?

A- Have you stopped trying all meds in a class your familiar provider thinks you need when one caused an issue or didn't work for you?

B- Did you decide prematurely that a significant medical decision needed to be made that was not in your best interests? For example, did you find that discovering your triggers was too much work and consented a little early to a feeding tube or TPN because you were scared at the time? Are you working on doing what you can to make whatever the right choice is for you now, or are you only seeking opinions that confirm that you don't need to make any changes? (Many mast cell patients need different ways of getting nutrition, and this is essential for these cases. With the help of scared and unfamiliar practitioners, however, some patients jump to options like this before they've even thought about changes like getting a blender or not eating out.)

C- Have you accepted that your life's the way it is and stopped trying to make the little things any better or finding alternatives for things you used to enjoy? Are you doom scrolling and focused on only the "bad day" stories from your support group, or are you talking to a mental healthcare provider and doing other things trying to find new ways to improve your baseline and find joy in your current life

5) Given what you know and what's available to you, are you actively trying to make medical decisions that will benefit, or at least that will not unnecessarily endanger you?

A-Are you deciding not to make a fuss when a provider orders the CT with contrast when an MRI without contrast, or even an echo, would almost assuredly give you the same answer, or even when none of these are necessary? Do you sign up for the colonoscopy you haven't run by your specialist that's not medically necessary, maybe even without precautions, because it would take so many phone calls or discussions or an order for a non-invasive screening test?

B- Are you going for that beta blocker because it was the first medication suggested, or are you unwilling to try other classes or talk to a competent cardiologist because you've already been to this party?

C- Do you have suicidal thoughts or "what happens, happens," feelings sometimes that may not be in line with your conscious values and that you haven't evaluated and addressed?

D- Have you made some choices early on in this process, perhaps with a medication or with a whole treatment approach, that new information suggested might not have been the best for you, or that is no longer the best for you? Are you now rejecting this better information since you've been through so much and made the best choice you could at the time, or are you willing to change paths now?

I don't ask any of these questions with judgment. These are normal experiences for patients with any rare or challenging diagnosis, and MCAD is certainly among the most complicated to navigate, even more so than many "scary" but straightforward conditions that may cause this level of life shift. But I do think that it's important that patients are able to make the best-informed decisions they can, when they can. These decisions should not come from a place of fear, overwhelm, or disempowerment. So I recommend you talk with your providers, reach out for help when you need it, and try to focus on these things you can control.

13) My question isn't here or on any of the other pages. Can I contact you?

I'm really sorry for this, but...not really. I can't directly reply to you (This would be assumed medical advice outside of a patient-practitioner relationship.), but if you send your general question to this random-stranger-who-just-observes-mast-cell-patients-often at mastcellpsa@gmail.com and I can responsibly attempt to address it on the relevant FAQ page, I'll try my best to do this.