It’s well known among patients and doctors familiar with mast cell disease that adverse reactions to medication products are commonly experienced by such patients, regardless of whether the mast cell disease present in the specific patient is the very rare cancer of the mast cell called mastocytosis or the far more common mast cell disease known as mast cell activation syndrome (MCAS).

To be clear, most adverse medication product reactions (and we should take care to keep in mind that all foreign substances taken into, or otherwise applied to, our bodies are essentially “medications,” i.e., the disease certainly doesn’t care whether a given product is labeled as a “medication” or a “supplement”) in mast cell disease patients are matters of one or more of the product’s excipients (i.e., the so-called “inactive ingredients” in the product, such as fillers, binders, dyes, preservatives, etc.) triggering the patient’s dysfunctional mast cells to further inappropriately activate and release their assorted mediators (which are what’s actually causing most or all of the symptoms of the reaction).

However, there are a few classes of drugs which just naturally trigger activation of mast cells in some people — sometimes even triggering the activation of normal mast cells in healthy people.  Narcotics (“opioids”) are an example of such a class.  Almost all opioids are intrinsic triggers of mast cell activation, though some opioids (e.g., morphine, codeine, hydrocodone, oxycodone, meperidine) tend to be much more egregious triggers than other opioids (e.g., tramadol, hydromorphone, fentanyl, buprenorphine).  Only opioid is known to not be a trigger — piritramide — and though this drug is available in some countries in Europe and elsewhere, it’s not available in the U.S. or Canada.

Another drug class which triggers mast cell activation in a small subset of mast cell disease patients is the “non-steroidal anti-inflammatory drug” (NSAID) class.  As the name of the class implies, the principal use of these drugs is to combat inflammation, whose cardinal symptoms are pain, swelling (“edema”), temperature (i.e., fever), and redness (“erythema”).  There are many drugs in the NSAID class.  Commonly used NSAIDs include ibuprofen, naproxen, diclofenac, and meloxicam, and aspirin (a.k.a. acetylsalicylic acid), but there are many others, too.  Most NSAIDs are available at least orally, and many are available in other forms, too, such as ointments for topical application.  Ketorolac is the NSAID most commonly used when the doctor thinks an NSAID needs to be given intravenously.

Virtually all NSAIDs work by inhibiting two key enzymes, found in many types of cells all throughout the body, named cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2).  Normally functioning COX-1 and COX-2 enzymes molecules are crucial for the manufacturing (again, by many types of cells all throughout the body) of “prostaglandin”-type mediators which are intimately involved in producing inflammatory symptoms/effects.  (There also are a very few NSAIDs which are selective COX-2 inhibitors, largely leaving COX-1 alone, a feature which seems to maintain significant extents of anti-inflammatory activity but greatly reduce the troubles which sustained use of a COX-1 inhibitor can bring about, such as stomach ulcers, ringing in the ears (tinnitus), kidney dysfunction (“renal insufficiency”), and inhibition of platelet function (leading to excessive bleeding and bruising.  Celecoxib is the most widely used selective COX-2 inhibitor.)

As such, by their inhibition of COX-1 and COX-2 and thus their inhibition of production (again, by many types of cells all throughout the body (certainly including the mast cells)) of pro-inflammatory prostaglandin mediators, the NSAIDs can deliver helpful anti-inflammatory activity to patients beset by inflammation.

It’s important to recognize, though, that almost all NSAIDs (including the selective COX-2 inhibitors) provide only *reversible* inhibition of the COX enzyme molecules they target.  Therefore, during the few hours the drug is present in the patient’s body following administration of a dose, prostaglandin production will be inhibited.  But all drugs are (sooner or later, by one or more molecular pathways) metabolized (broken down) and excreted from the body.  Therefore, once the majority of a given dose of an NSAID providing reversible inhibition of COX enzyme molecules has been metabolized and excreted and is no longer present in the body to continue inhibiting the COX enzyme molecules, then those COX enzyme molecules jump right back into business, so to speak, resuming production of prostaglandin mediators.

Aspirin is fairly unique among the NSAIDs, though, in providing *irreversible* inhibition of the COX enzyme molecules.  A dose of aspirin essentially renders all of the COX enzyme molecules in the body permanently inoperative.  Therefore, after a dose of aspirin has been taken, the only way a human being can resume making more prostaglandin mediators is if the various types of cells which can make COX enzyme molecules start making more of those molecules after the dose of aspirin has been metabolized and excreted.  But it takes time to make more COX enzyme molecules.  And — of course — if the patient takes *another* dose of aspirin just about the time the prior dose of aspirin is losing its effectiveness, then all of the new COX enzyme molecules being manufactured will themselves be immediately irreversibly inhibited, too.  This is why aspirin is probably a better NSAID than the other NSAIDs for regular use in the treatment of the chronic inflammatory disease that is mast cell disease.

Although a small subpopulation of people naturally suffer mast cell activation upon exposure to just about any NSAID, there’s an even smaller subset who tolerate most NSAIDs fine but clearly are triggered by aspirin.  And in those patients, it’s clear that it’s not just aspirin that’s triggering such reactivity but rather all chemical compounds in the “salicylate” (or “salicylic acid”) class.  Aspirin is the salicylate known as acetylsalicylic acid, but there are plenty of other salicylates, too — and they’re found in many foods and household products (especially household cleaning products and personal hygiene products).  For example, salicylate of one sort or another (though typically methylsalicylate) is at the core of almost all products which taste or smell “minty.”

It would be relatively easy for a salicylate-reactive MCAS patient to avoid offensive, salicylate-containing foods and products if the salicylate ingredient in the food or product were clearly labeled on the ingredient list with the term “salicylate” (or “salicylic acid”).  Unfortunately, that’s not the case, and salicylates actually are known, and shown in ingredient lists, by a wide variety of other names, too.  For example, a salicylate is at the core of the “aloe vera” commonly used in personal hygiene and cosmetic products.  Certain (but certainly not all!) food and medication dyes — such as red dye #40 and yellow dyes #5 and #6 — are, in truth, salicylates.  Some mast cell disease patients who turn out to be salicylate-reactive can gain remarkable improvements in their health — even before starting to try any mast cell-targeting drugs! — simply by coming to recognize their salicylate reactivity and then rigorously removing all salicylates from their presence (i.e., not only removing them from their diets and their medication regimens but even physically removing all salicylate-containing materials from their households, as sometimes even the subtle odor of salicylate escaping from a medication bottle or a cosmetic product or a household cleaning product (such as a laundry detergent) can be a trigger).

Lists of NSAID drugs are readily findable on-line.  (Note: acetaminophen (e.g., brand-name Tylenol), also known in some other countries as paracetamol, provides anti-inflammatory benefits but is *not* in the class of NSAIDs, and when it’s taken within standard dosing recommendations, it virtually never provokes any adverse reactions, meaning an adverse reaction to an acetaminophen/paracetamol product virtually certainly is an excipient-driven reactivity, not a drug-driven reactivity.)  There are many sources of information on-line about foods and products which contain salicylates, but many years ago I came to feel that the website salicylatesensitivity.com provided the most comprehensive lists of such foods and products that I could find in one place.  That website unfortunately “went dark” in 2021, but we were able to obtain a copy of the content from the site shortly before it went dark.  We’re happy to continue making this useful information available to the public (at no charge, as was the case at salicylatesensitivity.com) on our practice’s website here.

As noted above, NSAIDs, including salicylates, can induce reactions in some (certainly not all) mast cell disease patients, and such reactions can range from quite mild symptoms of a wide variety of sorts to much more severe reactions, occasionally even life-threatening anaphylaxis. Unless they can be successfully taken by an allergist through a salicylate desensitization treatment protocol, salicylate-reactive mast cell disease patients are strongly advised to *learn* the foods which tend to contain higher vs. lower salicylate content, and also learn the different monikers used to describe the salicylate components of various household and personal hygiene products, so that they can avoid future exposures to such foods and ingredients and thereby avoid any flarings of their disease’s symptoms which further salicylate exposures would have triggered.  And patients who are reactive to NSAIDs in general of course need to avoid not only all salicylates but also all the other NSAID drugs (again, medications such as ibuprofen and naproxen).

Patients who still have questions about their suspected or known NSAID or salicylate reactivity even after reading the available on-line information are encouraged to consult with their physicians.  Knowledge is power.  Whether the diagnosis is MCAS or anything else, and whether the treatments in question are NSAIDs or otherwise, it’s a general truism that the more a patient and his/her doctors understand how the patient’s disease operates and behaves, the better the patient and his/her doctors will be able to make decisions which will result in the patient suffering less trouble from the disease.