By Jennifer L. Gaudiani, MD, CEDS-S, FAED
As a reminder, the Gaudiani Clinic blog is medical information and not medical advice or professional consultation. The Gaudiani Clinic is unable to provide medical advice to individuals who are not our patients. If you have questions or concerns about your health, please reach out to your medical provider or schedule a consultation with our team.
It was really exciting to hear back from so many of you after posting Part One of this blog series (What is MCAS, and why should people with eating disorders care?). People replied from all over the world having realized this pertains to them or their loved ones. Most people’s outreach ended with, “So how do you diagnose it, and how do you treat it?” Part Two will address key issues in MCAS diagnosis, and Part Three will start to consider treatment. As the blog series continues, I’ll try to address specific crossover populations, like those with postural orthostatic tachycardia syndrome (POTS) and MCAS, those with median arcuate ligament syndrome (MALS) or superior mesenteric artery (SMA) syndrome and MCAS, and more.
There are of course many other vital patient populations affected by MCAS, but I’m going to hold myself to the ones that also pertain to those with disordered eating/eating disorders. My new goal is to try and ensure that every eating disorder provider—especially the wonderful dietitians in the field, but not limited to them—screens every patient they encounter for MCAS. Please help me with this goal by passing along the social media posts or blog links to anyone you think might benefit! Parents are the most amazing advocates of all, so the more they share this information among their support circles, the more they can bring it to the attention of care teams. Let’s try to reduce the typical time from symptom onset to diagnosis from decades to months!
Let’s come back to Melinda.
Melinda is pretty excited at her initial consultation that there might be a “one ring to rule them all” type diagnosis to link her severe and mysterious symptoms. (Sorry: Tolkien nerd here.) Her first question of course is how we actually solidify this MCAS diagnosis.
I start by telling her that perhaps the majority of doctors and healthcare providers either haven’t heard of MCAS or don’t believe it exists. There are famous clinics, renowned for figuring out complicated and mysterious medical problems, that explicitly refuse to see someone who believes they have MCAS. Allergists specifically, the folks many patients turn to because of their reactivity to so many seemingly innocuous exposures, still as a whole tend to wave off this diagnosis. Because of this lack of awareness or denial of its existence, most patients who do receive a diagnosis of MCAS suffer for decades before they are identified and started on treatment.
“But why,” Melinda asks, bewildered. “If this is a problem that might affect up to 17% of the population, why would doctors not want to believe it exists?”
I tell her there are probably a couple reasons:
1) Doctors still have a really hard time believing something they cannot measure by a blood test, vital sign, or scan. This is important to some extent, of course. But I’d say it’s necessary but not sufficient: it captures those who will have measurable illnesses whose course can be clearly tracked along peer-reviewed literature. But it misses and harms all those whose illness does not (yet) have a readily-available measurement. Not infrequently, doctors have to admit that what they had deemed psychological in origin/made up/not “real” ends up being very physiological once a test appears that validates it. For instance, a slew of people who were bit by a tick (often unbeknownst to them) and then started having allergic reactions to red meat were pooh-poohed by the medical world. Then doctors discovered an antibody that proved this is Alpha-gal syndrome! Another recent example is the dawning realization more broadly across the medical field with the onslaught of Long Covid (especially as physicians themselves got it) that oh…chronic fatigue/myalgic encephalomyelitis/dysautonomia are in fact real! Maybe all those other people before Covid weren’t just making it up/malingering/being overly sensitive and anxious. It turns out that MCAS blood tests are notoriously finicky due to specific handling requirements as well as lack of coverage or unavailability of a lab to run them.
2) Doctors didn’t learn about it in medical school or residency training, and they’re too tired to learn it now. Actual awareness of MCAS didn’t really start to bloom until around 2010. Like I said in Part One, I didn’t know about it until around 2017 myself. With an astonishing amount of information to process, learning about new diagnoses may not come easy to doctors and frankly often isn’t welcome. Plus, doctors are operating within a broken system, especially since Covid started. Burnout invariably reduces one’s curiosity, delight, passion for learning, and openness to novelty.
3) Patients with MCAS symptoms are felt to be too complicated. This is the toughest one, but I’ve never minced words about the failures of the medical system—my own care for sure not excluded—and I won’t start now. Much like the medical care of those with eating disorders, those with complicated, mind-body symptomatic, less measurable chronic diseases just aren’t that welcome in medical practices. They take too much time and they have this “annoying habit” of not promptly responding to treatment. They need to be seen more than once a year. I think whether it’s conscious or subconscious, the medical field would rather pretend MCAS doesn’t exist, or is a figment of the “difficult patient’s imagination,” than really jump in, name it, treat it, validate it, and walk with the patient through the coming years of managing it.
But there are medical providers and allied clinicians all over the world who are in fact passionate about MCAS. They have dedicated their entire careers to its care, have published amazing articles while seeing wonderful individuals whose stories encompass years of suffering, gaslighting by clinicians, and finally proper diagnosis followed by what may yet be complicated years of titrating medications and avoiding triggers. These MCAS providers, many of whom I’ve been immensely lucky to learn from directly and through their published work, show up with huge respect for the patient narrative, understand the vitality of a thorough history that includes awareness of traumatic or stressful life events, and are ready to believe the patient even when the numbers don’t completely corroborate the story (due to laboratory issues and complexities of the disease, not due to the patient!).
I tell Melinda all this as well as an abbreviated version of the following:
The History of MCAS Diagnosis
Consensus 1
In short, there are two camps of clinicians who treat MCAS. One follows “Consensus (1)” criteria outlined by Valent and others with the most recent set of criteria released in 2019. The patient must show all three of these:
· Flushing, pruritus, urticaria, angioedema, nasal congestion, nasal pruritus, wheezing, throat swelling, headache, hypotension, diarrhea (2 or more)
· Increase in serum total tryptase by at least 20% above an asymptomatic baseline plus 2 ng/ml during or within 4 hours after a symptomatic period
· Response of clinical symptoms to histamine receptor blockers or “MC-targeting” agents, e.g., cromolyn
There are lots of problems with this approach, mainly that it may miss 85% of patients who actually have MCAS! That tryptase lab value is not only hard to draw (race to the lab 4 hours after a reaction?), but experts who have seen thousands of patients who clearly have MCAS can attest that tryptase is often just normal. (It’s more often elevated in those with mastocytosis.) Plus that’s a very limited set of symptoms that may not capture everyone. Those who follow this however are deeply dismissive of the following diagnostic model.
Consensus 2
This is the model I follow, as do those who have been my teachers. Realizing how many get missed by Consensus 1, a group of highly experienced MCAS experts offered an alternative diagnostic framework. Here’s a fabulous article that has free full text access that goes into all the details.
Major criterion (must have this):
Constellation of symptoms that could arise from pathologically increased MC activity in 5 or more organ systems
Minor criteria (≥ 1 of these, but optimally including at least one or two of the measurable laboratory tests)
Evidence of high numbers of mast cells in marrow and/or gastrointestinal or genitourinary tract; ≥20 mast cells/high power field (e.g., you ask your GI doctor to send your upper endoscopy/colonoscopy biopsy for CD117 staining, and the pathologist should report out how many mast cells are present per high power field. But remember, this isn’t necessarily a problem of number of mast cells but rather overreaction of the ones that are there.
Abnormal spindle-shaped morphology in >25% of mast cells in tissue
Abnormal MC expression of CD2 and/or CD25 (i.e., co-expression of CD117/CD25 or CD117/CD2)…honestly, I’ve never seen this test run
Mast cell genetic changes (e.g., activating KIT codon 419, 509, or 560 mutations) shown to increase MC activity
Lab evidence in blood or urine of high levels of mediators that mast cells release (after being off proton pump inhibitor medications for at least a week): prostaglandin D2, histamine, chromogranin, leukotriene E4, N-methylhistamine, heparin, tryptase, chromogranin A (although other issues can cause this too), and 11-β-PGF2α (don’t ask). Note: Unless your doctor really orders these right, where the samples of both blood and urine have to be kept properly cold at all times including using a cold centrifuge, these labs will look normal. Plus, by no means are these available around the world! A negative set of lab tests does not mean you don’t have MCAS.
Improved symptoms while taking mast cell stabilizing and/or mast cell mediator mitigating medications
No alternative diagnosis that accounts for all symptoms and laboratory findings
My practice to date
Here’s what I’ve used for the past five years, because I was “treating in the wild” and doing my best without a lot of guidance at first! I’ve gotten more sophisticated in my approach over the past 1-2 years for sure, and since going to the MCAS conference in 2022, I’m gearing up to offer laboratory testing to my patients in order to be more in line with full Consensus 2 guidelines.
Fundamentally, if one of my patients has multiple symptoms that can be associated with MCAS, across multiple organ systems, I will strongly consider that MCAS may be involved and offer to start treatment. If treatment makes the patient feel better and reduces symptoms, I am content that we are managing some sort of mast cell issue.
There’s no standardized set of screening questions for MCAS, although there is a validated tool created by Consensus 2 physician Dr. Molderings in Germany that is used productively in academic studies and at times in clinical practice, called the Mast Cell Mediator Release Syndrome Questionnaire (MCMRS). It has 57 questions, with symptoms potentially contributing 37 points, where ≥ 14 is consistent with some sort of mast cell mediator release syndrome. By no means is the MCMRS symptom list exhaustive.
Any one of the following symptoms may be nonspecific (i.e. could be related to a wide variety of causes), but a whole bouquet of them across organ systems is highly suggestive. I’ll share with you the questions I’ve found to be highest yield for my population of patients with eating disorders. I haven’t published this or validated it yet. And to be clear, I have been deeply humbled by realizing after five years of working with a patient that they in fact have MCAS, and I’ve missed it all along (because I wasn’t screening every patient), or even better…when the RD on the team who shares other MCAS patients with me suggests, “Um, I think she has MCAS too.”
Gaudiani Clinic MCAS Review of Classic Symptoms
· Reaction to alcohol (topical or ingested) that includes flushing, itching, rash, sweating, digestive distress like pain/nausea/bloating, and/or surge in depression/suicidality in the days following consumption.
· Reaction to heat/sunlight that includes extreme fatigue compared with peers, edema formation especially in hands/feet but sometimes also in abdomen, skin sensitivity that can include redness, hives (juicy, lacy welts that appear and may or may not stay long), rash, and sometimes brain fog. People with MCAS often say that they feel best overall in the cooler months of the year. Patients emerge from showers and hot tubs with a tingly scalp, lacy red rash over their body, etc.
· Reaction to artificial dyes that includes flushing, itching, digestive distress, worsening of rapid heart rate or dizziness upon standing, mouth sores. I know this one sounds orthorexic. When a terrific clinician in Denver taught me this, I pushed back! But it’s real. Some of my patients muse, “Oh, so this is why when I eat M&Ms I feel like crap, but I can eat a bar of chocolate no problem.” Others realize in dismay, “Every time I’ve drunk a brightly colored sports drink thinking I was helping my POTS, I’ve been fueling the flames of my MCAS.” I feel every person should eat in the least restrictive way possible, so for this one I remind patients it’s totally fine to eat gummy bears still…just buy ones that aren’t artificially dyed (e.g. organic ones). This actually holds true for medication dyes as well; I’ll discuss in Part Three how a simple change in a generic prescription from a white to a blue pill may throw a person with reasonably controlled MCAS into a flare.
· Sensitive skin with a history of unexplained skin reactions, rashes, hives, since childhood usually, often worsening over the years. Many describe flushing on their chest, neck, and face when they experience heightened emotion. Some don’t even realize it’s atypical to shampoo one’s hair or emerge from getting one’s hair dyed and having an itchy or tingly scalp. Many have already found the hypoallergenic skin care line their skin tolerates best. Some may have dermatographia (where a light scratch as with a fingernail turns into a red welt that persists).
· Digestive distress after eating which may or may not have any clear trigger or food type. This includes nausea, fullness, burning/crampy/spastic pain, bloating soon after eating, diarrhea or constipation, joint pains that land in different joints at different times, a sense of general unwellness or feverishness without an actual fever, achiness, “like I’m coming down with something.” To be clear: many of these symptoms could describe anyone with irritable bowel syndrome, inflammatory bowel disease, small intestinal bacterial overgrowth, etc. It’s taken in the context of multiple body systems being affected that they are likelier to be associated with MCAS.
· Regularly gets headaches and sinus issues/stuffiness that are so much a part of the person’s life that they may not even mention it to their doctor. Patients may get a drippy nose after eating and have a history of multiple bouts of sinusitis that don’t really respond to antibiotics (because they’re due to mast cell mediator release/inflammation, not bacterial infection).
· Has a history of cyst formation which can show up as cystic acne, cystic ovaries (yes, I have seen many cases of so-called polycystic ovarian syndrome, PCOS, turn out to be MCAS…where ovaries and menstrual function totally normalize just with MCAS treatment), cystic breasts, skin cysts, cartilaginous cysts. MCAS is a cyst-making disease.
· An asthma-like history that may indeed have been diagnosed as asthma, but turns out at least somewhat to be fueled by overactive mast cells in the lungs. Triggered by any of the above exposures. Sometimes pulmonary function testing hasn’t shown classic findings of asthma, but the symptoms are so classic that they are treated with inhalers anyway. Scents/chemical exposures are a major trigger (of breathing issues as well as any of these symptoms).
· For those who menstruate, a feeling that one is allergic to their period and is a heavy bleeder. Very often, patients describe heavy, extremely crampy periods and severe worsening of mood the week before and week of the period. Periods may be irregular (worsened by nutritional inadequacy of course) or absent. These two weeks of the month may in fact be associated with worsening of all MCAS symptoms because mast cells have lots of estrogen receptors, and hormone shifts can meaningfully worsen MCAS symptoms. Patients of all genders with MCAS may find they are particularly “bleedy” (unexplained nosebleeds, easy bruising) due in part to the mediator heparin that’s released from mast cells.
· Pain syndromes that may have been misdiagnosed as fibromyalgia, seronegative arthritis, or “oversensitivity.” Pelvic/bladder pain is very common. (In fact, interstitial cystitis may well reflect hyperactive mast cells in the bladder.) When these patients get injured or go through surgery or have concurrent IBS, they feel more pain than others do and are again often shamed as being oversensitive or even drug-seeking.
· Brain fog, nerve issues, or bipolar 2-like mood disorders which represent neuroinflammation. I say to patients that having your brain full of bee stings all the time isn’t good for it. I regularly find that when those with MCAS are treated, anxiety, OCD symptoms, depression, and especially bipolar-2 like mood disorders meaningfully improve.
· Unexplained edema or retention of fluid in the body tissues. Edema may worsen whenever MCAS is triggered
· Unexplained changes in weight that can be either up or down. It’s more understandable to people when food reactivity leads to reduced intake which leads to weight loss and classic complications of malnutrition, but it’s less expected when these same symptoms lead to weight gain, oftentimes quite rapid. This may follow a toxically stressful/traumatic life event and can precipitate an eating disorder or make recovery work vastly harder. It turns out that mast cells contain mediators that stimulate adipose tissue growth. I am a weight-inclusive provider all the way, and I have seen individuals who are simply confounded by rising weight ultimately see their weight settle back toward a genetically-anticipated set point range with MCAS treatment.
· Worse gum health than expected based on oral hygiene habits: Fascinatingly, most of my patients with MCAS when asked agree that their dentist has been lamenting for years how inflamed their gums are, even when they take really good care of their teeth. Then of course they are prescribed dyed/alcohol-containing/chemical-containing mouthwash and flavored floss that only worsens what is in fact MCAS of the gums!
· All of these symptoms worsen with stress that is either physical or emotional, and no other disease process better explains the symptom.
The above are the most common ones I see. You don’t have to have all of them by any means to have a suspected diagnosis of MCAS, but five or more organ systems with symptoms is pretty indicative. While some people’s symptoms are really mild (maybe only worse during times of intense stress), others’ is pretty severe all the time. Dr. Afrin, a world-famous expert on this topic, talks about a disease course that may be characterized by little ups and downs in symptoms followed by a marked worsening (usually around a stressful life event, medical or psychological), then little ups and downs followed by another marked worsening. There are many more symptoms, some of them detailed in Melinda’s initial consultation.
Melinda has a tendency to doubt anything that’s not clearly measurable herself. She always fears that someone will think she’s making up a symptom or overexaggerating it, in part due to eating disorder distortions. However, she’s pretty bought in that she likely has MCAS.
So, she says: How do we treat this?
Stay tuned for Part Three: MCAS Treatment!