Wednesday, March 25, 2015

Mast cells and Lyme



Lyme can be thought of as a disease of inflammation. It has been established that small numbers of spirochetes can cause inflammation and symptoms referable to the infected organ. Usually when we talk about immune reactions to infection we are talking about innate immune responses and acquired immune responses. The innate immune system, innately recognizes foreign, unwanted antigens and attacks them with ready-made defenses which include killer T cells and complement fixation. The acquired immune responses process involves an elegant system which “reads” the antigens (histocompatibility molecules/ antigen presenting cells) leading to the production of specific antibodies which mark the antigen, with laser like precision, for destruction. This process involves chemical mediators: chemokines and cytokines, helper T cells, killer T cells, B cells, macrophages and a host of other blood cells which partake in this incredibly complex process. But alas, I have been missing something all along. Mast cells?

We know that the related eosinophils, basophils along with mast cells cause allergic symptoms and participate in the killing worms and parasites. But they do much more. 

I recently met with a patient in my office. When I met this young woman several years ago she looked terrified. She had made the rounds, been to countless doctors who had been unable to help her. She was doubtful that I would be able to offer any help. She suffered with a complex multisystem disorder, as do many of my patients. She presented with evidence of Lyme and coinfections and was treated accordingly. She suffered with severe weakness and dizziness. Additional testing revealed she suffered with POTS syndrome, postural orthostatic tachycardia syndrome. This disorder has been discussed elsewhere. This condition presents as an “autonomic neuropathy.” The cardiac manifestation are well known. This disorder can have protean other effects which include dysfunction of the gastrointestinal system. In her case she was intolerant of nearly all foods. She developed poor motility affecting her entire digestive tract. She experienced terrible pain and bloating with each meal.  She struggle to maintain her weight and a marginally acceptable nutritional status. The most aggressive Lyme and POTS therapy failed to quell the severely dysfunctional gastrointestinal system. This went on for years.  Each day brought indescribable misery. I was at a loss for what to do. But something remarkable happened the other day. With a broad smile she said she was tolerating and enjoying many foods, all because she had started a new medicine, ketotifen. This had been added for a suspected mast cell disorder.

Mast cell activation disorder relates to a different kind of inflammation, one that can cause chronic, multisystem disease which remits and relapses displaying unpredictable and diverse symptoms. This disorder is discussed in detail by Dr. Afrin, a hematologist in 2013. His treatise was describing something that sounded like Lyme disease. This disorder presents as a “mystery diagnosis” which takes 10 years or more on average to diagnose. Patients are typically diagnosed with a psychiatric disorder rather than a physical one. These patients, like Lyme patients report bizarre symptoms and unusual constellations of symptoms. The author describes repetitious patterns which he learned to recognize over time.

When we look at a CBC, the most commonly ordered routine test, we find that white blood cells are broken down into various types. We usually pay no attention no basophils which may be seen in 0-2% of circulating blood cells. Eosinophils, which we associate with allergies and parasitic diseases may draw our attention.

Basophil and eosinophils are part of a category of blood cells are granulocytes. When these cells rupture histamine, heparin and many other immune-active, vasoactive and inflammatory substances are released into the blood stream. Mast cells are essentially stationary, tissue basophils found in all the tissues of our bodies to varying degrees. These cells may rupture inappropriately, in a wide range of tissues causing the diverse symptoms alluded to.  These cells play an important role in our immune system when things are functioning properly.  These cells participate in the killing of an array of pathogens, not just worms, as we may have thought. A published study suggests that Borrelia burgdorferi is a good activator of mast cells.  It is probably unrelated, but tick bites have a unique property of attracting large numbers of mast cells.

Histamine is the substance of greatest clinical importance. 

Ketotifen, the above mentioned drug, is both an antihistamine and a mast cell stabilizer. Mast cell stabilizers are sometimes used for the treatment of typical allergies. These agents stop mast cells from rupturing and releasing their toxic granules. Ketotifen, alluded to above, is not available in the U.S. but can be obtained via compounding pharmacies. Treatment of “mast cell activation disorder” can be challenging. What works for one patient may not work for another.  Drugs which may be effective include antihistamines. There are two types of histamine receptors, H1 and H2. H1 is associated with typical seasonal allergies and H2 receptors stimulate the production as gastric acid. Common H1 blockers include Benadryl, Claritin, Allegra and Zyrtec. Common H2 blockers include Zantac and Pepcid. One drug from each category is used in combination. Benzodiazepine sedatives like Xanax and Ativan are also used for mast cell stabilization. NSAIDS may be helpful. Cromolyn is the best known mast stabilizer and it is available in a number of forms including oral Gastrocrom. Ketotifen is a valuable agent. Numerous other treatments exist.  Patients are not cured but their symptoms are managed.  As with Lyme, laboratory tests for the disorder have limited value.  Positive results are more likely to be found during a flare-up. The most common test ordered is a measurement of serum tryptase and histamine levels.

In summary, mast cell activation disorder, MCAD and Lyme can appear identical and Lyme may be a cause of MCAD.  Diagnosing and treating this disorder can be invaluable.

4 comments:

Lori Reilly said...

How interesting!! Thank you.

Lymemom3 said...

Do you recommend xolair / omalizumab to your mast cell or EoE patients that also have Lyme disease or coinfections?

I have inhalant allergies to purfume so bad that I can not drive in cars that have had shampoo aplied during detailing ever. I also can not be in buildings that have had the carpets shampooed ever. My lungs just burn and I am down to 3 "safe" foods.

I believe that MCS multiple chemical sensitivites is really esophageal eosinophilia / esophageal mastocytosis.
Do you have an opinion on this theory?

Lymemom3 said...

Do you recommend xolair / omalizumab to your mast cell or EoE patients that also have Lyme disease or coinfections?

I have inhalant allergies to purfume so bad that I can not drive in cars that have had shampoo aplied during detailing ever. I also can not be in buildings that have had the carpets shampooed ever. My lungs just burn and I am down to 3 "safe" foods.

Do you believe Lyme can cause mast cell acivation or EoE?

I believe that MCS multiple chemical sensitivites is really esophageal eosinophilia / esophageal mastocytosis.
Do you have an opinion on this theory of MCS?

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