What is the likelihood of inheriting Mast Cell Activation Disorder (MCAD)?

As best as we presently understand, the likelihood of inheriting mastocytosis is extremely slim. As for inheriting MCAS, all that can be said at present, based on very limited available peer-reviewed, published data, is that that likelihood appears to be 50%, but when it happens, the affected child usually begins demonstrating symptoms at an earlier age than was seen in the affected parent, plus the affected child usually comes to be generally more severely afflicted by the disease than was seen in the affected parent. To be crystal clear, though, that estimate of 50% means that there are plenty of children of MCAS-afflicted parents who appear healthy or, at worst, only mildly afflicted by MCAS. We are many years (actually, more likely decades) away from being able to more precisely predict (during fetal development or shortly after birth) whether, and how, a given child of an MCAS-afflicted parent will be afflicted by the disease.

I am a 24 year old with MCAS, EDS, POTS, and possible Chiari malformation. I have been experiencing a gradual decline in vision/blurred vision since 2016, my eyesight is very blurred and I can no longer read it is so bad. I have tried Ketotifen drops and steroid drops that have not helped. Do you see any MCAS patients with vision issues or vision loss? Have you seen a progressive loss of vision? If so, what is often the cause and treatment?

Although brief episodes of blurred vision are common in MCAS patients, progressive loss of vision is uncommon, and patients experience such a problem must undergo careful ophthalmologic evaluation to look for any other (hopefully treatable) cause.

Other than systemic MCAS-directed treatments which might be able to impact MCAS-driven eye problems in some MCAS patients, direct eye treatments for MCAS-driven eye problems are somewhat limited. Beyond the ketotifen and steroid treatments you noted, there also are antihistamine eyedrops and cromolyn eye drops as well as eye drops containing certain other immunosuppressants (such as cyclosporine). With the caveat that I’m a hematologist/oncologist, not an ophthalmologist, I’ll admit I’m unaware of any other direct eye treatments for MCAS-driven eye problems. Again, though, it’s always possible that *systemic* treatments for MCAS might come to bear positive influences on MCAS-driven eye problems (just as they might come to bear positive influences on MCAS-driven problems in other organs). For example, not too long ago I saw a patient who had been known for some time to have MCAS and who unfortunately had fairly rapidly developed blindness of uncertain cause. As you might imagine, she was intensively evaluated and was tried by her ophthalmologists on a variety of treatments (including various medications taken by eyedrop and orally), all of which modestly improved her vision, but it wasn’t until oral (i.e., systemic) imatinib was started that her vision dramatically improved and nearly fully recovered. Still, though, as imatinib was *added* to the other drugs she was trying rather than being tried in isolation, it’s not possible to say with much confidence whether imatinib truly had any impact on recovery of her vision, since it’s also possible that her other treatments were primarily responsible for her recovery but just took an unexpectedly long time to work and it might just have been pure coincidence that her other treatments really started kicking in around the same time imatinib was started.

Unfortunately, the true cause of the blindness this patient suffered (and fortunately largely recovered from) is still quite unclear.

What are your thoughts on abnormally low hormone levels after diagnosis of SM/MCAS/MMAS (ex: testosterone, estrogen, progesterone) Should they be adjusted to within normal range (if too low), is there another range that is beneficial or should they be left alone? 

The issue here is a classic chicken-and-egg puzzle: which came first, the low hormone levels (developing independently of the mast cell disease) or the mast cell disease (driving the low hormone levels)? Different clues in different patients might lead that thinking in different directions. In general, if hormone levels are low to such a degree as to be thought to be driving significant symptoms (i.e., beyond what the mast cell disease itself is driving), and if one cannot wait to see whether mast-cell-targeted treatments might help the symptoms (and the hormone levels), then it’s probably reasonable (in most such patients; there are always exceptions) to try hormonal supplementation to see whether those symptoms thought to be consequential to hormone deficiency improve significantly. However, if those symptoms don’t improve significantly with such trials of hormone supplements, then either the hormone deficiency is not as significant as first thought or there is another factor present (whether the mast cell disease or something else) which is *impeding* the ability of the hormone supplements to bring about benefit.

What bearing do they have on symptoms and potential treatment modalities? I had my first Xolair injections with no problems until 3 weeks post-injection. Very swollen face and wheezing. Is this normal. Should I get my second round of injections?

I’m not sure what this question is asking about. What bearing does *what* have on symptoms and potential treatment modalities? If this is a follow-up to the prior question regarding hormone deficiencies vis-à-vis MCAS, the only answer I can think of is that the symptoms of some hormone deficiencies (for example, fatigue from severe testosterone deficiency) can mimic some of the symptoms sometimes seen in MCAS, and thus in a patient who has both demonstrable MCAS and demonstrable severe testosterone deficiency, it’s fundamentally impossible to say how much of that patient’s fatigue is due to one condition vs. the other until one corrects one condition or the other – and, in general, it’s far easier to correct testosterone deficiency than to correct MCAS.

As to the question of whether it is “normal” to get a “very swollen face and wheezing” three weeks after a Xolair injection, I’m sure the doctor who provided the Xolair was able to tell you this is not an expected result of Xolair treatment, and I would be far more suspicious that some other exposure or event (far more proximate to the onset of the swelling and wheezing than the Xolair injection three weeks earlier) was the cause of the swelling and wheezing than that Xolair was the cause. Although I obviously can’t provide personalized medical treatment recommendations to a patient I’ve never seen (the full range of details present in any case can easily sway decisions one way or another, and there’s no way any case is as simple as “got Xolair and swelled three weeks later”), I feel that *in general* it would not be unreasonable to try at least a second, modestly dosed injection of Xolair when a flaring of mast cell activation didn’t come on until three weeks after the first injection was given.

Most doctors who give Xolair know to caution their patients getting the shot that, according to the manufacturer and the studies conducted in the drug’s initial development, there is a 0.1% (i.e., 1 in a 1000) chance of fatal anaphylaxis from the drug.

What is the relationship between MCAS and the HPA axis, or more specifically, Cortisol levels?

As can be said about most other systems in the body, too, the relationship between MCAS and the hypothalamus-pituitary-adrenal axis (at least, that is what I am assuming is meant by the reference to “the HPA axis” in this question) is quite unclear. I have seen plenty of patients in whom cortisol levels are low (usually, in such cases, just mildly low and just occasionally low, i.e., not low on every check), and I also have seen plenty of patients in whom cortisol levels are high (again, usually just mildly high and just occasionally high), and I’ve also seen plenty of MCAS patients in whom cortisol levels are just persistently plain normal. Given the tremendous assortment mediators produced by the mast cell and the great range of effects that each mediator can have on various tissues and organs and systems, I expect there are many different mechanisms by which different patterns of abnormal mast cell activation in different MCAS patients can drive different patterns of abnormalities in a system as complicated as the HPA axis, involving function of two different parts of the brain (hypothalamus and pituitary) and another organ, too (the adrenal glands).

I’m sorry, I recognize this is a fairly wishy-washy answer, but I just am not aware of any peer-reviewed published studies giving me data for a more specifically informative response.

For those of us who’s menstrual cycle seems to be a trigger, what is recommended to help avoid being triggered?

Menstrual-cycle-driven worsening of MCAS symptoms is common, and I think it’s not unreasonable to suspect that MCAS might be the underlying issue in some fractions of the female populations diagnosed with various menstrual disorders such as premenstrual syndrome, premenstrual dysphoric disorder, and dysfunctional uterine bleeding. In addition to commonly tried (and commonly successful) interventions with hormonal contraceptives (oral and otherwise), and beyond the rather radical solutions of removal of the ovaries +/- uterus, it is quite possible that any other mast-cell-targeted treatments (for example, systemic antihistamines) might prove helpful in controlling any particular symptoms of MCAS, including menstrual-cycle-related symptoms. In addition, I have been hearing increasingly in the last few years from women with MCAS who have begun finding that topical application (by douching) of mast-cell-targeted medications such as diphenhydramine and cromolyn sometimes can be helpful for genital tract inflammation and bleeding which seems likely to be driven by their MCAS. (Some colleagues and I are writing a paper about this.) To be clear, though, I can’t possibly responsibly provide personalized treatment recommendations for a patient I haven’t seen, and the above statements should not be construed as a recommendation for any woman (diagnosed with MCAS or not) who is afflicted by bothersome menstrual-cycle-related symptoms to try these treatments.

If you have additional questions on Mast Cell Activation Syndrome (MCAS), be sure to leave them on our MCAS Facebook page here. We will be putting out a new blog post every Friday answering a batch of randomly selected questions posted on our Facebook page.

If you would like to see a NY Mast Cell Activation Disorder specialist, Dr. Lawrence Afrin is now seeing patients in a private practice setting at our office in Armonk, NY. To make an appointment with Dr. Afrin, please call the office or contact us here