Wednesday, January 30, 2019

Mast Cell Activation Syndrome (MCAS) and ME/CFS

While Mast Cell Activation Disease (MCAD) is a well-known but rare condition, doctors have only just recently discovered that a related condition, Mast Cell Activation Syndrome (MCAS) is actually very common and behind many unexplained medical problems. Since mast cells are a part of the immune system (involved in allergic reactions), doctors and other medical professionals are discovering that many patients with immune disorders, like ME/CFS, or tick infections, which can affect the immune system, also have MCAS. Any kind of unexplained or new allergic-type reactions, rashes, pains, or weird symptoms that don't seem to fit anything else often point to MCAS.

The good news is that MCAS is often easily treated with readily available over-the-counter (OTC) medications and supplements. First-line treatments usually include OTC antihistamines and acid blockers, as well as other allergy treatments. Testing for MCAS is tricky because changes in the blood are often transient, so a single blood test may not catch them, but since the initial treatments are inexpensive and accessible, it can be worthwhile to try treating MCAS if your symptoms fit. Many of the parents in our Parents' support group have reported that their kids with ME/CFS, EDS, tick infections, and related conditions have responded well and improved--some dramatically--with some simple MCAS treatments.

Below is a bit more detail on MCAS, its diagnosis, and its treatment. Most of what I've learned about it has been from the book Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity by Dr. Lawrence B. Afrin, M.D., one of the main doctors responsible for identifying MCAS. His book contains many case studies of widely varying patients, including some information on diagnosis and treatment options, with a lengthy glossary (view the book on Amazon at the link). I also learned about MCAS from a few websites and from other patients and medical professionals.

Our Story
Our registered dietician (who also has an MS in biochemistry and is brilliant about ME/CFS and related conditions) mentioned the possibility of MCAS to me several years ago, but I didn't pay much attention. Then, I began to hear other patients talking about it, with more and more people diagnosed with MCAS and improving with treatment for it. Finally, when both our ME/CFS specialist and our Lyme specialist mentioned it to us within a month's time, I decided it was time to follow-up on it.

I have had annoying-level year-round allergies since we moved to Delaware in 1990--mainly to molds and dust--and developed a dairy intolerance when I got ME/CFS (as do 30% of ME/CFS patients). My older son, who also has ME/CFS plus 3 tick infections, also developed a dairy intolerance with ME/CFS but otherwise has only mild allergies and seldom even needs to take OTC antihistamines...which is why I didn't pay attention the first few times I heard about MCAS. He and his brother (who is recovered from ME/CFS but has fairly severe allergies) had both started reacting to certain fruits, vegetables, and nuts,  in the past few years (a condition known as Oral Allergy Syndrome), but again, for our older son, it's been mild.

Then, last spring, he had a random, unexplained anaphylactic reaction one day after playing soccer. He does carry Epi-Pens due to a bee sting allergy, but he definitely had not been stung that day. When he felt his throat start to close up, he walked to the nearby Urgent Care clinic (luckily, very close by), and phoned my husband, who rushed over there. Luckily, with the quick response and some Bendaryl (an OTC antihistamine) and a dose of steroids, he responded and didn't need the Epi-Pens, though he was wiped out for days afterward. But we still couldn't explain why it had happened.

A couple of weeks later, we were at a check-up with his Lyme doctor and just mentioned the weird, still-unexplained anaphylactic reaction. Our Lyme doctor said that it sounded like a mast cell problem, and finally, the light bulb went on for me! I started remembering all the disparate things I'd heard or read about MCAS and realized his strange reaction was a major sign. We took our ME/CFS specialist up on her offer to test us both for MCAS, and she ran a range of tests (see below, under diagnosis). Nothing showed up abnormal for me, but one test was way out of range for our son, so we began trying treatments. There hasn't been a huge change, but he did see a small improvement in his symptoms and how he felt overall. More importantly, he hasn't had another anaphylactic reaction since then, though he does still have a mild mouth-itching reaction to certain fruits. I didn't expect any major changes for me and didn't see any, though it has helped to better control my allergies, which are ever-present.

Diagnosis of MCAS is challenging. There are some blood tests that can be run, but none of them is foolproof: you can have perfectly "normal" results and still have MCAS. It is a condition that is mostly diagnosed clinically (that is, through symptoms, history, and physical exam), though lab tests might pick it up (very much like Lyme disease).

These lab tests (all for blood unless otherwise noted) might be helpful and can be requested to help determine if MCAS is present:

  • Tryptase
  • Chromogranin A
  • Histamine (plasma)
  • Immunoglobulin E (IgE)
  • IgE AB
  • Arginine Vasopressin
  • Osmolality (serum)
  • Osmolality (urine)
As I mentioned in the introduction, there are many problems with these tests. The tryptase test, for instance, has an inherent impracticality. It is most accurate when the blood sample is taken within 4 hours of the onset of a flare-up of symptoms ... but few patients are able to get to a lab and get it tested in that timeframe. Other MCAS/MCAD testing requires a sample that is kept chilled, which is also difficult to ensure once it is shipped off to a lab somewhere.

For us, my tests were all normal, as were most of my son's, but his IgE levels were more than 6 times higher than the normal range. IgE are the antibodies produced by your immune system when you've been exposed to an allergen, so this was an unusual result for someone who rarely has typical allergy symptoms.

There are more accurate and more complicated tests for MCAD and MCAS, but they are typically beyond the knowledge of most doctors or laboratories to request and/or correctly run.

Since the testing doesn't always (or even often) pick up MCAS, doctors must rely mainly on symptoms. Classic signs of MCAS include:
  • Typical allergic symptoms, like wheezing, congestion, flushing, rashes, throat swelling, or anaphylaxis.
  • Symptoms that are unexplained by the patient's existing diagnoses.
  • Any odd, strange, bizarre, weird, or mysterious symptoms. Dr. Afrin even suggests looking for these kinds of words in a patient's medical file: have previous doctors used these kinds of descriptors for unexplained symptoms?
This is where the title of Dr. Afrin's book comes from. He explains that Occam's Razor tells us that a multitude of problems (especially unusual problems) in a single patient is far more likely to be due to a single root cause than to multiple causes.

So, if you and your doctor suspect MCAS, based on symptoms and/or testing, the easiest way to confirm is not with more complex testing but to try some simple treatments.

First-line treatments for MCAS are usually various types of histamine blockers. There are four types of histamine receptors in the body:
  • H1 receptors, which cause much of what we typically think of as allergy symptoms and help to control our internal clocks.
  • H2 receptors are mainly located in the gastrointestinal tract, as well as the heart, uterus, and vascular smooth muscles.
  • H3 receptors are present throughout the nervous system and especially in the Central Nervous System.
  • H4 receptors have only been recently discovered and trigger the release of white blood cells from bone marrow.
So, accordingly, there are different types of histamine blockers you can try that might help with MCAS (note that I am using generic names here, with U.S. brand names in ( )--you can find these products simply by clicking the links to the generic names--generics are identical to the brand names but cheaper):
  • H1 blockers are typically sold as antihistamines, including all of the over-the-counter products, like the non-drowsy choices: loratadine (Claritin), fexofenadine hydrochloride (Allegra), cetirizine hydrochloride (Zyrtec), and levocetirizine dihydrochloride (Zyzal), a newer one. Diphenhydramine (Benadryl) is an older antihistamine that is an effective H1 blocker but can cause drowsiness (and contrary to popular belief and a lot of advertising, it is not a good choice as a regular sleep aid; see article on Correcting Sleep Dysfunction in ME/CFS). You can easily buy these online (see links) or in any drugstore without a prescription, and most are available as generics (so much less expensive). Note that most of them that are solid pills contain lactose as a filler (read the label for inactive ingredients to check); you can get lactose-free versions by buying gel caps, where available (click any of the links above and search for the name plus gel caps). That's what we do: we buy generic cetirizine (Zyrtec) gel caps on Amazon. Dr. Afrin sometimes uses twice-daily dosing, which is double the normal the dose. If one doesn't work for you, try another - everyone responds differently.
  • H2 blockers are usually sold over-the-counter as acid blockers, with brand names like famotidine (Pepcid AC), cimetadine (Tagamet) and others (note that ranitidine (Zantac) was recalled last year). Dr. Afrin recommends using the maximum strength products and beginning with once daily, but you can increase to twice daily.
  • Ketotifen is an anti-inflammatory that is also an H1 blocker. It is not currently sold in the US commercially, but you can easily get it through a compounding pharmacy.
  • Some drugs used for other purposes also have antihistamine effects, including doxepin, all tricyclic antidepressants (which are often used in low doses to correct sleep dysfunction in ME/CFS), certain anti-nausea drugs, and the anti-psychotic quetiapine.
  • Cromolyn has mast cell stabilizing activity and is available as a nasal spray, eye drop, or in liquid form for oral use. My son tried the oral liquid but couldn;t tolerate it, but I know it works well for some people.
  • Quecertin is an herbal supplement with antihistamine effects, which is naturally occurring in some fruits and vegetables and tea. We often use this brand, and our functional medicine specialist recommends Histaquel from Researched Nutritionals, which we buy directly from them. We've found Histaquel to be very effective.

Dr. Afrin's book covers other treatments, but these listed above are the most commonly used and readily available. He does sometimes use simple aspirin to treat MCAS (as one of several treatments), but it does have some potentially serious side effects when used regularly.

From this list, my son and I both take generic Zyrtec liquid gel caps (double dose for him) and Quecertin (2 pills twice a day) daily, as well as an acid blocker/H2 blocker. We started with Zantac and switched to  Pepcid-AC when Zantac was recalled. Note that there is no way to predict which particular medication in a category will work best for each individual. Everyone is different. So, some patients will respond well to Allegra, while other will have better success with Claritin or Zyrtec (and same with the H2 blockers and other categories) - it's a matter of trial and error. My son also tried ketotifen, 1mg daily, compounded, though he didn't see any change from that. He tried the liquid Cromolyn, but it gave him diarrhea, though I have heard that it works well for other patients.

As for results, my son reports that his food allergy symptoms (itchy mouth and throat with certain foods) have improved, and he hasn't had another anaphylactic reaction. My allergy symptoms are definitely better controlled now; I already took Zyrtec daily but adding Quecertin and famotidine has helped.

The bottom line with treating MCAS is that it comes down to trial and error, which means plenty of patience and persistence. You have to keep trying to find the combination of treatments that work best for you, and even within a single category, what works for you may not work as well for someone else.

Believe it or not, that's a brief summary! For more detailed information or to learn more about the science, check out the Mast Cell Action website or Dr. Afrin's book. MCAS is a complicated topic but one that is an exciting new development for many with immune disorders, including ME/CFS, and potentially a whole new avenue of treatments to try. We do think treating MCAS is helping our son, and I think it has helped to reduce my own allergy symptoms a bit more. I know of other patients who have improved dramatically with treatment for MCAS, so it is definitely worth looking into. Now, whenever someone tells me that they or their child has "a weird rash" or some other unexplained symptom, I always point them toward MCAS.

Have you looked into MCAS yet or tried any treatments for it? What has your experience been?

Note: This post contains affiliate links. Purchases from these links provide a small commission to me (pennies per purchase), to help offset the time I spend writing for this blog, at no extra cost to you.

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Anonymous said...

What about treatments for H3 and H4?

Interesting story.

Sue Jackson said...

What I've read so far in the book mentioned above mostly covered H1 and H2. You might try this website to see if there is more info:


Terry | said...

Great post, Sue. Full of helpful information! So glad that you seem to have your’s and your son’s MCAS at a controlled level. Is such a constant battle for many. Myself included. Would love to share some of your info in a blog post, then add my experiences, as well. Would you be up for a collaboration? Thank you, as always, for sharing your journey. Hugs from the desert.
—Terry xx

Anonymous said...

My son (16) was dx last year with Lyme and last month with MACS. Along with some of the meds you mention here, he was recommended to go on a strict histamine elimination diet. It’s pretty extensive and we aren’t sure it’s doable at his age. Any experience with diet? Did you see a difference?

Sue Jackson said...

Terry @ ColorMeLyme -

I don't know when you left your message - I have a feeling I missed it a while back! But, yes, I am always up for a collaboration! You can contact me at jacksonde at comcast dot net.


Sue Jackson said...

Anon -

Sorry to hear your son has been suffering, though it's good he is diagnosed! Before we get to your question re: MCAS, I would just like to encourage you to make sure he has been fully evaluated for ALL of the common tick infections (about a dozen or so) by an experienced Lyme specialist. My son was diagnosed with Lyme around 7th grade, but he didn't fully recover with treatment. It took us more than 3 years to finally realize he also had two other tick infections (his were babesia and bartonella) and by then, he was very, very sick. If so-called co-infections are present, you can't even get rid of the Lyme, so it's important to know what you're dealing with from the beginning. Ok, PSA over!

As for your question, I know many people who have tried the histamine-free diet, but we have not tried it. Just the treatments I described in this post worked (and continue to work) well for my son and I both.

Are you a member of the Parents' group I started on Facebook? This would be a great question to ask in the group - it's about 2000 parents from around the world whose "kids" (some like my son are adults now) have ME/CFS tick infections, MCAS, and related conditions. Great emotional support for parents, but they're also a very smart, experienced group with lots of great practical information to share! Here's the link - just answer the questions after you click the Join button so the current admins can quickly approve you - you can let them know I gave you the link!