Lyme and mast cells

I have been asked to provide more feedback regarding mast cell therapies for Lyme disease. I present a brief, recent patient case. 

A 46 year-old woman sought my help this past March. She suffered with a multisystem disorder which had ultimately led to disability. She suffered with severe fatigue making it a struggle to get out of bed each morning. She had trouble thinking clearly and experienced significant memory loss. She found it difficult to communicate with others and because of this withdrew from a church social group, because of embarrassment. (Severe fatigue was also a factor). At the time I met her she felt helpless and hopeless. She complained prominently of facial pressure and headache. Additional symptoms included: episodic fevers and chills; mild night sweats; insomnia; sudden hearing and writing; episodes of confusion and disorientation; weakness, numbness and tingling, dropping things and an overall inability to think and other cognitive and psychological symptoms. Severe pain was a major disabling symptom. 

She recalled finding an embedded tick in her back one year prior to our visit. She believed the tick was removed shortly after attachment and had no concerns at that time. Over time, she has found numerous ticks crawling on her body. She lives in a wooded area. Her back yard backs into Rock Creek Park in Montgomery County Maryland.  She sees groups of deer in her back yard daily. She has three dogs, all diagnosed with Lyme.

Additional history: She suffered with severe childhood asthma treated with and iron lung. She has experienced severe, recurring respiratory infections causing scarring in her lungs. She has chronic sinusitis and congestion causing permanent hearing loss. She reports a history of random itching and rashes on her skin. She has dermatographia: when you write on her skin the letters remain visible.

A standard Lyme test was negative.  A Lyme test from Stony Brook was negative.  Coinfection testing was positive for Bartonella (MDL) and a blood smear failed to show any Red blood cell parasites. 

Prior to our visit a rheumatologist diagnosed fibromyalgia. She told me she learned about Lyme from a movie “Punk Singer”; I have not looked it up. 

Her illness forced her to sell her business: dog boarding and walking. 

Treatment: I treated her for Lyme and coinfections with standard therapies. (I have modified my regimens – cannot discus here). I also treated her for excessive mast cell degranulation. 

See previous post: Treatment is difficult and comprehensive. 

Three months later she states she is incredibly better in all areas. She is functioning well with a good quality of life and is now able to exercise. Memory loss has remained impaired but brain fog has cleared significantly.

Comments:  When anti-mast cell therapy works it seems to do so quickly (if patient on correct regimen) and results can be dramatic.

She presents with many clues suggesting that this therapy might work, especially dermatographism which is a mast cell mediated phenomenon.

I am not diagnosing my patients with true MCAD or with any other formal diagnosis. Rather I view my patients as experiencing hyper- stimulation and degranulation of mast cells, as a complication of Lyme disease, especially if symptoms only started with the Lyme diagnosis.

Lyme in a test tube and ILADS' Guidelines validation

Recent test tube studies demonstrate that Lyme is hard to kill. A lab in Johns Hopkins found that over 1500 different antibiotics could not kill Lyme. Viable persisters were found in each case. (1500 different drugs). These persisters were comprised of round body, pleomorphic forms and biofilm-like colonies, as previously described by Sapi.  The study informs us that Lyme does not persist because of antibiotic resistance as it is generally known. For example, bacteria can produce penicillinase, an enzyme witch inactivates the drug. Other bacteria develop pumps wish recognize the antibiotics as toxic and expel the drugs.  Lyme resistance is different, resistance is based on its ability to change its appearance and secure a foot hold within protected colonies. Some antibiotics were found to be more effective against persisters while others were more effective against rapidly dividing spirochete forms. The Hopkins’ lab tried combination therapy and found a single 3 drug combination (cocktail) that completely eradicated the spirochetes (test tube only). The first drug is daptomycin: expensive with limited access; one month of therapy, 30, 0000 dollars. The second drug, cefoperazone, is currently unavailable from the manufacturer. The third drug is doxycycline. Many other combinations of antibiotics using 2 or 3 agents were tested and found to be inadequate. The ingredients of the cocktail are 2 bactericidal drugs and one bacteriostatic drug. In theory these two types of antibiotics can cancel one another out. In clinical practice this is completely untrue.

A newer test tube study shows that the Lyme bacteria may be eradicated with pulsed therapy with a single agent, Rocephin.

Test tube studies cannot be used as a basis for clinical use. But, there is proof of principal. Lyme spirochetes are hard to kill; three drug cocktails and pulsed therapy -- already in clinical use, are vindicated in contradistinction to IDSA recommendations. (Easy to kill, 2 weeks of doxycycline).

What else do we learn? Flagyl is not a “cyst buster.” In the studies it was no more active against persisters than amoxicillin of doxycycline.  Rifampin may convert non-cyst busting drugs, like doxycycline or amoxicillin and confer some anti-cyst capability. By itself Rifampin has no activity against Lyme. Rifampin is added to Lyme culture growth media (ALS new Lyme culture test) to kill non-lyme bacteria.

A major dogma, long bandied about in Lyme circles, a sacred cow, may be incorrect. Flagyl is not a “cyst buster.” Other drugs in cocktails, for example Ceftin, may be doing the cyst-busting, based on published data.

There are other interesting odds and ends. Antifungal drugs, including amphotericin B are active against Lyme. Quinine kills Lyme.  In context, we do not know if these drugs kill Lyme in living systems and this info should not be used as a sole basis for any therapy. 

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.