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Tuesday, June 16, 2015

Mast cell activation disorder, MCAD: a new paradigm (for Lyme)

 Mast cells have long been a greatly under appreciated component of our immune system. These cells are located in all of our tissues and organs, including the brain. When stimulated by the immune system these cells may rupture and spew a wide array of substances into surrounding tissues; severe and varied consequences and symptoms may ensue.

I have discovered that many of my patients suffer with a form of mast cell activation disorder. It is my sense that most of my patients do not have primary MCAD described by Dr. Afrin and others. Typical MCAD patients have a genetic predisposition and suffer with symptoms which date to early childhood (in the absence of Lyme).  I see MCAD as a secondary phenomenon which appears as a consequence of Lyme. My patients did not seek out care for this disorder before becoming sick with Lyme/tickborne illness.  Only a subset of Lyme patients respond to MCAD therapy (I am not sure how big the subset is).  The therapy, which may not work, is cumbersome and hard to explain to patients. When the treatment works results can be very rewarding. The likelihood of response is tied to proper patient selection.  Likely candidates have a history of allergies of some sort and may have rhinitis or sinusitis. (Not required). Patients may report a history of itching and/or rashes which come and go for no apparent reason. A recent patient told me a rash which had been present for years dramatically vacated with MCAD therapy. Good patient candidates may be sensitive to many things including chemicals and scents and other environmental triggers. Other disorders, including POTS, may be closely tied to MCAD. Many other patients may respond to MCAD therapy. Sometime a therapeutic trial may be worthwhile. The great thing about the therapy is its safety. From my perspective, this is a very exciting and new therapy for many of my patients.

Lyme spirochetes are highly immunogenic. They stimulate exaggerated immune responses. These responses may cause mast cells to rupture and release numerous mediators contained within packets of granules. Mast cells are omnipresent, adjacent to blood vessels and heterogeneous, serving a variety of functions. Mast cells activation leads to dilation and increased permeability of blood vessels. A wide array of mediators may be released and cause toxic inflammation in surrounding tissues.

How do we intervene? We block the effects of mediators and do our best to stabilize the mast cells or keep them from rupturing. This is not an easy task. The best known mediator released by mast cells is histamine. Other mast cell mediators include: tryptase and other enzymes, leukotrienes, prostaglandins, cytokines, signaling molecules and there are many others. 

It takes a lot to counteract these noxious mediators and perhaps keep these cells from rupturing excessively. There is no magic bullet. Numerous medicines must be prescribed. This is what I do. 

I block histamine. There are 4 types of histamine receptor; we can only block two. Antihistamines, such as Zyrtec block H1 receptors and drugs like Pepcid block H2 receptors. Both are prescribed. I frequently prescribe a second antihistamine: Claritin. It is hard to harm a patient with too many antihistamines. Whereas Claritin is a weak antihistamine compared to many others such as Zyrtec, hydroxyzine, Benadryl and others, it appears to have mast cell stabilizing properties, a very desirable property. So there is synergy when Claritin is prescribed with Zyrtec.

I block leukotrienes, typically with Singulair.

I block prostaglandins, typically with a long acting agent such as Mobic or Celebrex. 

If a patient has trouble sleeping Benadryl, hydroxyzine or better yet, doxepin is prescribed. Doxepin has great affinity for histamine receptors.

Benzodiazepines like Klonopin have mast cell stabilizing effects and can be used judiciously in the right clinical circumstances.

Ketotifen is frequently prescribed. This drug is only available as an eye drop in this country. Compounding pharmacies however are able to provide capsules. Ketotifen has traditionally been used to treat allergic rhinitis and asthma. It causes drowsiness so it may be practical only to dose at night. Twice daily dosing is recommended. Many consider Ketotifen the primary mast cells stabilizer.

Cromolyn however, is the most effective mast cell stabilizer.  Cromolyn is available in nasal in oral inhaled forms which may not be terribly effective. In my experience, Gastrocrom, the oral form, is very effective. Only a small percent is adsorbed  systemically but this seems to be enough. The drug  comes in a liquid form needs to be dosed 4 times per day. Two ampules or 10 cc works best. 

This is a lot to throw at a Lyme patient, suddenly materializing form out in left field.

A patient should not attempt the treatment unless he or she has a working knowledge of the principals involved.

I do not like the approach of gradually adding agents incrementally because it probably won’t work and it will take a long time to reach an effective cocktail of drugs. 

I do not base decisions to treat based on laboratory results. 

Theoretically, the tryptase level should be elevated. This is rarely seen. This is only found in severe, generally genetic forms of disease. Elevated histamine levels, considered less specific are more likely to be present in my patients.

With everything on board good clinical responses are seen within a couple of months or sooner.  I am not sure how long to continue treating when it is not helping. I have to make sure my patient is taking everything and sometimes I add some more agents.

More serious forms of MCAD may respond only to chemotherapy or immune modulating drugs; this I leave in the hands of consulting hematologist.

MCAD is a great masquerader, like Lyme. It can be associated with myriad symptoms. If you are wondering what symptoms may be helped with MCAD therapy, the answer is almost any symptom, including fatigue, endurance, pain and brain fog.


G said...

thanks for the info! as usual, you are great!

Unknown said...

Thanks a lot for sharing this with us. I am "one of those" Lyme patients who despite huge improvements in major symptoms (cardiac, neurologic, etc), I am actually feeling worse (extra tired, LOADS of inflammation everywhere, POTS, sore and swollen eyes, asthma type coughing with a lot of abundant and sudden clear mucous pouring out of my nose, my eyes. I feel exhausted all the time, I have bouts of diarrhea, etc.
I am going to show your comments on this topic re mast cell activation and the various ways to counteract it to my very Lyme literate infectious disease specialist. Could you tell me more re dosages for eg gastrocrom, is it 4X5ml/day (total 20ml) or 4X2,5ml/day (total 10ml/day)?

Unknown said...

I'm one of these Lyme patients and I am treating exactly as specified by this article. I'm doing so well and feeling much better. My swelling is decreasing, energy increasing, and I'm having less allergic reactions. I'm so fortunate to have found you and this treatment protocol!

Bearhair said...

Kylie, how long did it take for you to notice the benefits of the treatment?

Razzle said...

Most who have too much histamine are undermethylating. MTHFR is only one tiny piece of the methylation puzzle, so other aspects must be considered as well (e.g., COMT, VDR, & CBS status, etc.).

Anonymous said...

Razzle: Methylation is part of B12's job, right?
And, pant. acid (b6) is necessary for DAO which breaks down histamine.

I know that once I began taking a B complex, (in addition to several other things I was doing: low-histamine diet, green smoothies 2x/day, quercetin, 2000mg C, ginger, turmeric, plenty of water, etc) it seemed to be the last piece in the puzzle. My hyperactive food reactions to just about EVERYTHING (as well as mold) virtually stopped after adding the ginkgo and the B's. I mean ... IMMEDIATELY, within minutes of taking a crushed B complex from Carlson, my "asthma" calmed down.

Zubi said...

I noted the comment that cromolyn is the most effective mast cell stabilizer. I've also read fairly recently that quercetin is better. Here's a link to the NIH article:

I've had a number of odd central nervous system issues since having surgery in May of 2015. Taking quercetin has moderated the symptoms somewhat, but Flagyl has done wonders. I took it for giardiasis and got two months of drastically reduced symptoms. After that time they got worse, which I attribute to the Borrelia recovering from the antibiotic. I've learned that most of my symptoms are consistent with late Lyme disease and will be working with an infectious disease doc to pursue a diagnosis.

Stan and Charlene said...

Is there a way to get more information on your protocol? I could not take all the drugs recommended here. Thanks

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