My 24-year-old son has cutaneous mastocytosis. He is self-conscious. He has had spots since he was a little boy and continues to get more. Can he slow down additional skin “spots.” Is it triggers that add more? Or will he always get more for the rest of his life just because he has the disorder?

I’m sorry to hear of your son’s difficulties. In general, when the skin lesions of cutaneous mastocytosis become sufficiently bothersome (whether from a cosmetic or any other perspective), ultraviolet-light-based therapy (and there’s more than one specific approach to this which can be considered depending on the individual case) tends to be the most effective at reducing, at least for some time, the intensity and extent of the “spots.” Yes, it is possible that exposure to “triggers” of one sort or another may promote the progression of the lesions (i.e., the growth/reproduction of the mast cells comprising the lesions). Mastocytosis (whether cutaneous or systemic) is generally considered incurable with currently available treatments (though there is controversy whether allogeneic stem cell transplantation might have potential for curing occasional cases of the disease, and there are new drugs “coming down the pipe” which also might have some potential for bringing about a cure in some patients), so it’s most likely that it will be a situation in your son of managing his lesions for a long time to come – though I’ll also note that cutaneous mastocytosis (not systemic mastocytosis) occasionally undergoes spontaneous remission. Usually, when that’s seen, though, it happens by the end of adolescence, and it’s much less common to see spontaneous remission of cutaneous mastocytosis happen in adulthood.

I would love to see a blog post about the difference between MCAS and histamine intolerance.

“Histamine intolerance” is a state in which exposure to histamine brings about more symptoms of such (e.g., swelling, itching) than one would ordinarily see from the amount of histamine involved in the exposure. There are several potential root causes of histamine intolerance including a deficiency in the body’s production of diamine oxidase (DAO, the body’s natural enzyme for breaking down histamine ingested in the diet), a deficiency of (or mutation in) histidine N-methyltransferase (HNMT, the body’s natural enzyme for breaking down histamine produced internally by the body), or abnormalities of a wide variety of sorts in cells which have receptors for histamine on their surfaces. (There are many types of such receptors – H1, H2, H3, H4, and H5 – and various combinations of these receptors are present on a great many different types of cells all throughout the body (including mast cells).) Thus, having “histamine intolerance” does not necessarily imply that one has anything wrong at all with one’s mast cells.

“Mast cell activation syndrome” (MCAS) is a state in which the body’s mast cells are improperly “activated” – i.e., improperly producing and releasing into the body’s tissues (both at baseline and in reaction to various triggers) various subsets of the more than 200 “mediators” (potent intercellular signaling molecules) the mast cell is overall capable of producing. Current preliminary research suggests the vast majority of cases of MCAS are rooted in genetic mutations (usually not inherited but instead acquired, and usually relatively early in life at that) which, by and large, are present only in (some portion of) the body’s mast cells (plus, of course, the precursor “stem cells” or “progenitor cells” (mostly located in the marrow) which give rise to the mast cells when they come to be distributed all throughout the body, though dominantly sited at the body’s environmental interfaces). Different sets of these mutations in various genes and other regulatory elements in the mast cells in different MCAS patients drive their affected mast cells to improperly produce and release different sets of mediators, ultimately leading to not only different symptoms and findings in different MCAS patients but also different patterns of response to various treatments in different MCAS patients. Since mast cells do have histamine receptors on their surfaces and are naturally activated when histamine docks with those receptors, it’s not surprising that patients with “histamine intolerance” often demonstrate symptoms resulting from mast cell activation, but not every patient with MCAS demonstrates troubles tolerating excess loads of histamine (such as from the diet), and not every patient who demonstrates “histamine intolerance” necessarily has a mast cell activation syndrome at the root of that intolerance.

Nevertheless, distinguishing between histamine intolerance and MCAS can be challenging in some patients. In general, though, if there are symptoms and findings in the patient which are well beyond what would be expected from histamine alone but rather are more consistent with mast cell activation in general (i.e., consistent with not just histamine alone but rather histamine plus the vast array of other mediators the mast cell also produces), then it’s obviously much more likely the patient has MCAS than just histamine intolerance.

If DAO deficiency or HNMT mutations are suspected, though, specialized testing can be done to look specifically for those problems.

What histamine blocker works well for heartburn in patients with MCAS? Daughter on famotidine and montelukast for past year but now acid ingestion of heartburn is really bothering her. Would changing famotidine be more beneficial than adding omeprazole to help with heartburn systems?

I do not know of any method identified yet for predicting which drug is most likely to help any given symptom in any given MCAS patient. Heartburn sometimes can be helped by histamine H2 receptor blockers – drugs which also can be helpful with many other symptoms in MCAS, too, probably because they block not only the histamine H2 receptors on the stomach cells which make stomach acid but also because they block the histamine H2 receptors on the mast cells, wherever they may be scattered throughout the body. To my knowledge, there are four H2 blockers available on the U.S. market (famotidine (most familiarly known as Pepcid), ranitidine (most familiarly known as Zantac), cimetidine (most familiarly known as Tagamet), and nizatidine (most familiarly known as Axid)), but I do not know how to predict which one of these four is going to serve the individual MCAS patient better than the other three. Usually, though, trials (typically at standard over-the-counter doses, taken twice daily, for two to four weeks for each drug) of more than one lead to the patient discovering that one particular H2 blocker serves him/her better than the others which were tried. To understand which of the four will serve the patient best, all four need to be tried.

Beyond H2 blockers, proton pump inhibitors (e.g., omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Protonix), dexlansoprazole (Dexilant), and others) sometimes help with heartburn, and even simple old antacid interventions such as calcium carbonate (such as in Tums) can sometimes help, too. In some patients, too, it’s not even medication but rather simply elevating the head of the bed a bit which can best help patients with nighttime heartburn.

I think it’s important to mention the most important thing to be done with each case of heartburn is to figure out what’s causing that heartburn. Yes, mast cell activation disorders can cause heartburn, but many other processes/diseases, too, can cause heartburn. For example, heartburn might be a sign of an ulcer driven by infection with bacteria called “H. pylori” for which a pretty easy cure is readily available. And, though it doesn’t happen often, heartburn might even be a sign of cancer in the stomach or nearby tissues. Thus, I would strongly advise a patient who has heartburn which has not been evaluated by a physician to seek that evaluation in a timely fashion and not simply empirically treat the heartburn for months on end with various over-the-counter heartburn medications.

Can you tell me if there is a link to a burning mouth feeling and MCAS? I am on the good side of a long battle with Lyme disease and burnt mouth was one of the issues I had associated with Lyme. Now that I’m on the other side of my Lyme battle, I’m struggling with MCAS and I notice my burnt mouth issues are flaring up again.

Indeed, I have seen many patients who have complained of intermittent or chronic burning about various aspects of the oral tissues (sometimes, in fact, the burning extends throughout the entirety of the GI tract, “from stem to stern,” so to speak) and who have then been found to have MCAS likely at the root of it – and in many of those patients, treatments of various sorts targeted at the patient’s mast cells (or mast cell mediators) do often reduce or eliminate the burning.

It is not yet known which specific mediators released by the dysfunctional mast cells in an MCAS patient which result in the sensation of burning in the oral tissues, and it is not even known what the actual route/mechanism for that sensation is. Perhaps it’s a matter (in at least some patients) of oral tissue mast cells releasing inflammatory mediators which trigger oral tissue nerve cells to transmit signals to the brain which are interpreted as pain – or perhaps it’s a matter (again, in at least some patients) of mast cells elsewhere in the body releasing mediators which, through God knows what circuitous routes, result in the brain sensing pain in the mouth.

It should be noted, too, that there are a number of other diseases (for example, various infections such as Candida, or inflammatory diseases such as scleroderma) well established to be capable of causing a burning sensation in the mouth. Thus, it’s important that a patient suffering a burning mouth not assume the problem is due to misbehaving mast cells, and instead such patients should seek evaluations from appropriate specialists (for example, dentists, otolaryngologists, oral surgeons, or even internists looking for systemic diseases) before necessarily considering the diagnostic possibility of a mast cell activation disorder of one sort or another.

I am appreciating your Mast Cell articles and information. My most frustrating symptom is 24/7 derealization/Depersonalization which was started many years ago after taking an anti-malarial (there were some extreme sand flea histamine reactions and some trauma during that trip as well, but the dpdr started before that)
 Recently I’ve also gotten a CIRs diagnosis (mold/Lyme). Could the DP/DR simply be an unchecked MCAD reaction this whole time? Is dp/dr seen in many MCAD patients? I hear mostly about anxiety, which I do not have.

Although mast cells are present in every tissue in the body and can easily drive a wide variety of abnormalities in any given tissue, the neuropsychiatric issues of the disease are some of its most underappreciated issues. Neuropsychiatric effects from mast cell disease can arise not only from misbehavior of mast cells in the central and peripheral nervous systems but also from misbehavior of mast cells in other tissues/organs/systems which release assorted mediators which can easily come to impact, via a wide variety of mechanisms, the functioning of the central and peripheral nervous systems – and though anxiety and depression indeed are the most common neuropsychiatric symptoms I see in my MCAS patients, I also have seen a number of patients who have reported the “derealization/depersonalization” you have described (with or without concurrent anxiety/depression) and who then have been found to have a mast cell activation disorder (MCAD) of one sort or another (far more commonly a mast cell activation syndrome (MCAS) than mastocytosis) and who eventually find treatment of one sort or another which helps not only these neuropsychiatric symptoms but also a wide range of other symptoms.

To be sure, not every case of derealization/depersonalization is necessarily due to mast cell misbehavior, so it’s important that patients suffering this problem undergo careful evaluation to look for other causes, but if no other cause can be found, and especially if the patient additionally reports other symptoms also consistent with MCAS, then it’s completely reasonable to pursue an evaluation for MCAS and to consider – if MCAS indeed is proven to be present – the derealization/depersonalization to likely be driven by the MCAS. In those patients, of course, it would be reasonable to pursue not only “traditional” neuropsychiatric treatments but also treatments targeted at mast cells (or their mediators) to see if improvements in the neuropsychiatric symptoms can be realized.

Is there a link between MCAD and Amyloidosis (and other fibril disorders)? Apparently, it’s another one of those diseases that is very difficult to diagnose. I’m also curious to know what amyloid deposits “look” like when examined by a surgeon not experienced with the disease. For example, could it be mistaken for atherosclerosis? It’s ridiculous, the number of possible diagnosis’ that have been proposed. But the more we narrow down, the more I see that the treatment will likely be the same end result, regardless of which diagnosis we get.

Amyloidosis is one of the so-called plasma cell dyscrasias, a group of disorders in which the “plasma cells” of the immune system have turned malignant, and the specific effects seen from any given plasma cell dyscrasia depend on the specific role that was being played by the particular plasma cell which originally turned malignant (or, to be more precise, the particular plasma cell precursor cell which originally turned malignant). Different plasma cell dyscrasias can wind up causing very different symptoms and findings. Some of the more common plasma cell dyscrasias are multiple myeloma and its precursor condition “monoclonal gammopathy of undetermined significance” (MGUS), but the much less common amyloidosis is a plasma cell dyscrasia, too.

Although I’m not aware of any research having demonstrated a clear path by which mast cell disease (of any sort) can give rise specifically to amyloidosis, it has long been recognized that mast cell disease (likely via a variety of mechanisms) increases the patient’s risk for malignancies of all sorts, certainly including plasma cell dyscrasias.

There are many different types of amyloid fibrils, and they can have quite different appearances at the macroscopic level. Commonly, though, it can be difficult to distinguish – at eyeball level – a patch of amyloidosis from a simple scar, or even a glossy patch of connective tissue where there shouldn’t be such a patch. A biopsy is needed, and then under the microscope the difference between amyloidosis and other conditions becomes apparent – though usually additional special testing is then needed to pin down precisely which type of amyloidosis is present.

Even at the eyeball (“macroscopic”) level, amyloidosis and atherosclerosis usually are not confused for one another, if for no other reason than amyloidosis usually is initially found in non-arterial tissues where you just wouldn’t expect to find atherosclerosis.

Since atherosclerosis was brought up in this question, though, this is probably a good time to mention that mast cell disease has long been associated, too, with premature/accelerated atherosclerosis, so when a patient presents with consequences of such (for example, a heart attack at an early age), and particularly when such a patient also has other symptoms consistent with mast cell disease, then it would be completely reasonable to evaluate that patient for mast cell disease. Some of the basic research in this area is beginning to identify specific molecular mechanisms by which misbehaving mast cells can lead to the accumulation of cholesterol that’s at the heart (pardon the pun) of atherosclerosis, but much more research needs to be done before we have a good understanding of how much of the world’s atherosclerosis – a very common disease – is actually due to mast cell disease.

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