The incredible thrill of a doctor who is kind, inquisitive, understands MCAS, and isn't afraid to admit what he doesn't know
**Note: The biology nerd in me was PUMPED to be a talk where the language was full of science jargon. I've tried to define things as I go, but plan to read this one with google definitions handy.
The Mast Cell Specialist
One of the challenges of having a rare, or newly discovered, disease is that no one in your area will likely specialize in it. I've traveled to Baltimore to find geneticists who know about EDS, to Providence, RI to see a physical therapist known for their EDS protocol, and to Boston for a GI specialist who works with MCAS (although I learned less from that visit than from google). The last stop on my list is NYC to see Dr. Afrin. He is a hematologist -- someone who treats blood disorders. It seems an odd choice, since my bloodwork always comes back great (one of the reasons my doctors always exclaimed "you're so healthy!"). Dr. Afrin, however, was one of the first people to explore MCAS as a possible diagnosis for his confusing patients. He has been studying the disease for almost a decade, making Afrin one of the most MCAS-knowledgeable practitioners in the country. He has written a detailed book on the subject -- Never Bet Against Occam -- that has helped me more than most doctor visits.
I was lucky enough to see him speak in person a few weeks ago, and to chat with him afterwards. Here are my thoughts from that day:
Psychiatry and MCAS
First of all, the talk was hosted by the Psychiatric department of the hospital. Dr. Afrin noted that this was the first psychiatric invitation he'd received and how important it was to reach out to psychiatrists. Many MCAS patients are dismissed as crazy hypochondriacs when seeking medical treatment. Our labs often come back fine, or at least mild enough and confusing enough to not show any concerning patterns. Other times, our symptoms mimic those of other diseases, so we're incorrectly diagnosed and treated. When we still complain of symptoms after we've been deemed cured or at least significantly treated, it's assumed yet again that we are just crazy. The number of doctors who have told me I'm "just anxious" still haunts me. I find myself involuntarily adding "but I might just be crazy" at the end of my symptoms list every time I see a new doctor. It has been deeply ingrained into my self-image at this point. You're told you're crazy enough times since childhood, you deeply internalize it, and you end up in therapy, likely medicated. Welcome to my adult life.
So, the beauty of this talk was that the psychiatric department had recognized they were misdiagnosing -- and therefore mistreating -- a group of bizarre patients, and wanted help navigating the world of MCAS. They told stories (with patient consent, of course) that were so freakishly similar to my own experience, it made me tear up multiple times before Afrin even began. Patients would come in with symptoms that looked like depression (fatigue, inability to get out of bed, mood swings...), anxiety (weird heart rate, difficulty breathing, insomnia, GI symptoms...), or even ADD/ADHD (difficulty focusing on simple tasks, decreased memory recall...), but would act super motivated to get better. They would take their meds, do all their therapy homework, read books and consult experts, and yet see no improvement. The psychiatrist described one patient in particular (diagnosed with anxiety, depression, fatigue, and ADHD) who was clearly working so hard to improve that you could tell how heartbroken he was when she could not "achieve sustained response." She was in her 30s, had always been high-functioning in the past, and just couldn't keep it together anymore. Then one day she came in and he described that she looked like a new person. She said she felt "great" for the first time since he'd seen her, "like she was 20 again." She had found the right key for the lock -- an expression used again later by Afrin -- and it had come from a diagnosis of MCAS. After a few short weeks of treatment for the correct disease, she had energy, could think clearly, and was able to go back to work.
This psychiatrist called Dr. Afrin to see if he could learn more about this mysterious disease that had now been the key for multiple patients. Afrin told him he was "one of three psychiatrists in America who know abut this, and one of them is my wife." So, they set up the talk to create a larger community of informed practitioners.
Medicine by Trial and Error
At this point in the talk, Dr. Afrin took the stage. He was a warm, personable man. Despite what we know of the benefits of bedside manner, this was refreshingly different than what I've experienced of specialists throughout my life. He began much like the first speaker, with three case studies to show the extreme heterogeneity with which MCAS can present. As a hematologist, he was dealing with patients who seemed to have blood disorders. The first two were definitively "diagnosed" and treated, only to become significantly worse, at which point they were brought to him. The first had low red blood cells and was being kept alive by constant transfusions, the other had extreme high red blood cells. Neither, however, matched the criteria he would have looked for to give their diagnosis.
He looked into other possibilities and stumbled upon cases of what seemed to be atypical mastocytosis -- a very rare disease caused by too many mast cells. On a whim, he tried some treatments and found something that immediately and drastically improved both patients' symptoms. After this seemingly miraculous discovery, he was forwarded other patients with unexplained symptoms. The third case study was a woman with something called Burning Mouth Syndrome (yes, that is actually a thing). Her mouth and esophagus were in constant pain, yet her blood and urine tests came back completely normal, even when tested for mast cell issues. He tried treating her anyway, just to see what would happen, and once again she immediately improved. He then suggested to other doctors dealing with BMS that they try similar treatments, and found widespread success. These patients had been told their entire lives that it was all in their head until it turned out there were others like them, and yet had no treatment until Dr. Afrin's wild guess led them to mast cells.
Discovering Mast Cell Activation
Despite treating these patients, however, no one yet knew what the disease they were treating actually was. The first case report was written in 2007, but much of it was conjecture and later revised once more evidence came out contradicting their first attempts. It was classified as a strange type of mastocytosis, but it turned out that these patients didn't actually have too many mast cells, but rather the few that they had were over active. Thus, when in 2010 it was finally named in an official proposal, the disease was called Mast Cell Activation Syndrome. What shocked me at this point in the talk was just how new and under-researched this all was. I knew that it wasn't much more than a decade old, but I didn't quite grasp that literally a decade ago they had no idea what it was, had no name for it, and didn't even really understand how to diagnose or treat it. Sure, a lot can be done in ten years of research, but not if immunologists, you know the doctors who study mast cells, largely deny that it exists (a problem I've run into multiple times), and especially not if the vast majority of patients/test subjects are operating under a false diagnosis.
Crossover With Other Unexplained Diseases?
This next part of the talk was fascinating to me. While mastocytosis and most other mast cell issues are extremely rare, researchers estimate that potentially 17% of the population could have MCAS. This is based on the statistics of other unsolved inflammatory issues that have the same symptoms, like Chronic Fatigue Syndrome (ME/CFS), Fibromyalsia, IBS... In fact, thinking back to my friends who have been diagnosed with (and unsuccessfully treated for) ME/CFS or Fibromyalsia, the similarities are staggering. I myself was assumed to have IBS and hypochondriasis/anxiety.
So if these diseases are all caused by overactive mast cells and so many people are affected by these diseases (17% is HUGE!), then we should be able to quickly research, educate, and treat huge populations, right? Well, unfortunately not only is the presentation of MCAS symptoms incredibly heterogenious (varied), but so are the testing methods and treatments. Why should the testing be so complicated for a genetic disease? It turns out that, although MCAS seems to be inherited, it's not actually one specific mutation that gets passed down. Rather, the propensity for mutation in that particular locus (trait/location in your DNA) is what's passed down, but each individual, even within the same family, might have wildly different mutations and genetic coding for their mast cells. So, there's no one genetic marker that they can test for to see if you have this disease. **This is all according to the research Afrin presented; other research may have a different take, and since it's all so new, no one actually knows much for certain.
Testing
Sure, genetic testing may be out. But with mastocytosis you can easily test for increased mast cells. Is there a way to check out mast cells for MCAS? Yes and no -- it's somewhat easy to look under a microscope and see if someone has too many mast cells. MCAS patients don't have too many though, so those stains may look normal. It's tough to tell in a snapshot how often something reacts. They've tried isolating what chemicals are released during mast cell reactions, and those they can test for. BUT there are literally hundreds of them. Of those hundreds, some are also released by other white blood cells, so you couldn't isolate that the results were solely from mast cells. Of those that are only released by mast cells, some we do not yet have the capacity to test for. We're now down to only dozens, rather than hundreds, of substances to test for. One person with MCAS might have some elevated but not others, and a different MCAS patient could have totally different combinations elevated. So sure, if you test positive for high levels of one of those chemicals, then yeah, you have a definitive diagnosis. But what are the odds, that of hundreds of options, the three or so that your body produces happen to be in the few that we can actually test for? Then added to that, some people only show an increase in reactivity when they are actively sick. For an explanation of why it's difficult to get results when sick, see my post Just Another Wednesday. Due to these many complications, the majority of negative test results received are likely to be inaccurate.
So how else can you diagnose someone? Through symptoms, but the symptoms of MCAS are so varied, it's almost impossible to feel confident just on that, and new symptoms linked to MCAS are still being discovered. The last possibility is to put a patient on medication and simply see if symptoms improve. This is what doctors seem to do most often, but the problem is that MCAS patients often react to medication, so if they don't improve, how do you know if it's because they don't actually have MCAS, or if they're allergic to something in the medication itself? MCAS can cause severe anaphylaxis, and patients have actually died from being put on medication. Not only that, but there are several options for medication, and it seems like what is a miracle drug for one MCAS patient is completely ineffective for another. Dr. Afrin has so far found no correlations between which patience seem to respond to which drugs, even by matching up symptoms, genetic mutations, test results, etc. Thus, they may need to try multiple expensive and difficult to acquire meds before finding something that works.
Final Thoughts
In an upcoming post, Seeing the Big Picture, I show this image, that I actually got from Dr. Afrin's slides. He urged us to not get lost in each symptom, but to see the whole elephant (or zebra :-P) for what it is. I will go more into Occam's Razor later, but it's always more likely to have one disease causing 15 problems than to have 15 separate diseases. When we see several specialists rather than one doctor interested in our whole self, we often end up with segmented information. Afrin is hoping that the practitioners in the room would begin looking for what else may be in the picture. He also preached compassion and working to reduce shame. As he put it, people will "stop reporting their troubles" if they are made to feel crazy or stupid. In fact, the chief complaint he has found is cognitive dysfunction, which often goes unreported or is explained away with anxiety.
This ending brought me full circle to the beginning of the talk -- tearing up at how real it felt to me. I remembered how it felt to be in a fast-paced educational environment with a highly-intellectual family and to feel that some days I just couldn't keep up. I could feel, sitting in the hospital lecture hall, the shame and fear that I was just somehow stupid, despite knowing I had a lot of good days. The heart-racing moments when I'm teaching and suddenly can't remember anything on the subject that I prepped for (effortlessly) the night before, or getting halfway through a sentence and having no clue where the other half went, or staring at the simple addition problem on the board and not knowing how to solve it. It is terrifying to not be able to rely on your own brain and to have to force your way through the thickening brain fog at age 26. Or even younger, as I remembered the shame of being nicknamed "Airhead" in freshman year of high school.
Solidarity and Hope
This was my favorite takeaway of meeting doctor Afrin. Yes, it was an absolute BLAST to be in a room of doctors using medical jargon and be able to use my college science knowledge to actually keep up. Yes, it was awesome to finally learn the nitty gritty details of my own body's disease. Yes, it was unbelievably liberating to hear an expert specialist actually say "we honestly don't know yet." But the best part for me, and what I later spilled in that week's therapy session, was how cathartic it was to hear stories of other people like me. Stories of people who had Master's degrees and careers, businesses they started on their own, vibrant lives and families, only to crash sometime in their mid-twenties. I cried over and over again, hearing the specific symptoms they felt, knowing how real each one feels, knowing what no psychiatrist in that room could truly understand without having MCAS. The fears and sticking points for each patient were so familiar, and made me feel less alone and ashamed in feeling that way. And then the successes! Yes, there were plenty of stories of unemployment, having to go on disability, losing that business that they worked so hard to build. But given the correct treatment, whether diet/lifestyle or medication, they improved! They got back into having friends, a job, a life. Somehow, I'm not less terrified by the notion that I might not be able to sustain my current lifestyle forever, because I have hope that as more research comes out, I can find a way to turn it around and rebuild a life that works for me.