Lyme Disease

Lyme Disease Management-Immune Health

Part One

By Peter J Muran, MD, ABIHM

The immune system of each individual must ultimately assume the management of infections like Lyme disease. In my experience, antibiotics level the playing field by reducing the abundance of bacteria leaving the work of sustained recovery to our own immune system. Without the body’s own immune vigilance there is a slow progression to health.

Our understanding of the immune system is ever evolving and the most recent 2010 research casts the spot light on the impact of gastro-intestinal health on the ability of the immune system to function effectively.

In this Part One of a three part series we will explore the most recent understanding of the enormous role the gut plays in the health of the immune system. Part Two will discuss evaluation and testing of immune dysfunction caused by the GI tract. Part Three will be putting it all together discussing how to strengthen the immune system.

Immune Triggers

There are approximately 100 Trillion bacteria in the human gut. Astoundingly, this represents 10 times more cells then what makes up the body. The presence of these bacteria has an immunological effect on the rest of the body. Under most circumstances, this immunological effect is greatly beneficial. However, disruption of this normal flora, if not tolerated, is inflammatory and can be significantly harmful.

Intestinal bacterial disruption and inflammatory conditions are seen in the association of Klebsiella with ankylosing spondylitis; Citrobacter and Klebsiella with rheumatoid arthritis; Yersinia with thyroiditis; Escherichia coli and Proteus with autoimmune disorders. These examples may not reflect a direct cause by the bacteria, but rather molecular mimicry taking hold and eliciting an autoimmune response.

In addition to disruption of the normal flora, diet is the other major contributor to overall health of the GI tract. Diet has a direct response of an important component of the immune system within the “gut associated lymphoid tissue,” or GALT. The GALT is a chain of lymph glands attached to the intestines. These lymph glands are very similar to the lymph glands located at the neck under the jaw. When one has a throat infection, these glands become swollen and inflamed – as when the gut has inflammation, the GALT becomes swollen and inflamed.

Food sensitivities have a direct insult on the GALT. The response to this assault is more complex than just formation of antibodies. Thus, the measuring of the typical immunoglobulin titers for food allergies does not suffice in uncovering the source of this inflammatory component.

Most foods contain lectins, specialized proteins, which may be inflammatory for that individual without causing the classic antibody response. Studied food groups which include high levels of lectins are grains, legumes (that is beans, including peanuts), dairy, and plants in the nightshade family. Many other foods contain lectins but are less well studied and the amounts of lectins present are not thought to be as high or as potentially toxic.

Other inflammatory triggers of the immune response are pathogen associated molecular patterns (PAMPs-typical structures of non-vertebrate pathogens); damage associated molecular patterns (DAMPS- intracellular components); advanced glycation end products (AGES- produced when food is fried, grilled, dried, smoked or pasteurized); free radicals; trauma; and toxins.

The culmination of these inflammatory triggers occurs within the GI tract leads to a measurable systemic inflammatory response. The integrity of the cellular lining of the gut, epithelium mucosa, changes because of this inflammation leading to what is known as leaky gut syndrome. Leaky gut syndrome is the central antecedent of a wide range of disorders associated with chronic inflammatory condition.

This is best described by Dr Alessio Fasano in the article, “Mechanisms of Disease: The role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune disease.” He states, “Together with the gut-associated lymphoid tissue and the neuro-endocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self-antigens. When the finely tuned trafficking of macromolecules is dysregulated in genetically susceptible individuals, both intestinal and extra-intestinal autoimmune disorders can occur. This review is timely given the increased interest in the role of leaky gut in the pathogenesis of gastrointestinal diseases and the advent of novel treatment strategies, such as probiotics.” (Nature Clinical Practice Gastroenterology and Hepatology, Sept. 2005, Vol 2 No 9).

The Immune System

Briefly, the body's immune system is divided into the innate and adaptive response. The innate response is usually within 0-96 hours. It is divided into 2 groups. One group is non-induced and/or nonspecific. The second group is broadly specific.

This broadly specific group contains a large list of immune responders including macrophages, mast cells, cytokines, complement system, polymorphonuclear leukocyte (PMN), antimicrobial peptide, natural killer cells and dendritic cells.

Current research shows that if there is a modulator of the innate and adaptive immune system, it would be the dendritic cells. Dendritic cells are throughout the entire body. Dendritic cells “sample” everything and determine if it is a friendly or a danger-stranger to the body. This sampling sets up a priming of the dendritic cells, which will then communicate with the remainder of the cells of the immune system, and respond accordingly.

The adaptive response system is usually activated within 4-5 days. The adapted system characteristically gives a sustained response to the offending agent or establishes antibodies to react to and prevent re-infection. It is a highly evolved specific system which specializes in effectors T and B lymphocytes cells. The information which the T and B cell lymphocytes use to differentiate is derived from the dendritic cell.

The B cell response is known as the humoral (circulating in our bodily fluids) mediated system. It is in this system where the anti-bodies for specific protein or infection are formed. The T-cell lymphocyte response is also known as the cell-mediated system. The T-cell lymphocytes can have many different responses, including triggering a B-cell response.

The dendritic cell is primed for response by the previously described triggers. This dendritic priming will derive differing sets of T-cell instructions resulting in conversion of naïve Th0 cells into Th1, Th2, Th17 and T-regulatory cells. Depending on the signaling, a pathway can be redirected to express a healthier response.

This is most dramatic for the person with significant allergies and an underlying infection impacting the efficacy of the immune system to handle the infection. By modulating or balancing the pathways, an excessive response and it’s draining complications is decreased, thus allowing the immune system to focus on the more critical problem at the time.

Th1 cells produce cytokines that are involved in many types of cell-mediated immunity and delayed hypersensitivity response. It does this by increasing cell mediated activation macrophages and neutrophiles. The more predominant diseases seen with Th1 are rheumatoid arthritis, multiple sclerosis, thyroiditis, Lyme arthritis and Crohn's disease.

Th2 cells produce cytokines which are involved with further B cell activation and consequent allergy anti-body response. It does this with the recruitment of mast cells, basophils and eosinophils. The more predominant diseases seen with Th2 are allergic diseases, asthma, contact dermatitis, scleroderma, ulcerative colitis and systemic lupus erythematosus.

Th17 cells mediate mucosal immunity to GI and pulmonary pathogens (especially Candida and gram-negative). This is a primary driver of chronic inflammation. It is the predominant driver to initiate inflammation of tissues and organs in Lyme arthritis, allergy, tumorigenesis, transplant rejection and autoimmune diseases (multiple sclerosis, Crohn's disease, ulcerative colitis, systemic lupus erythematosus, rheumatoid arthritis, scleroderma, alkylosing spondylitis).

As mentioned earlier, the gastrointestinal tract is full of potential immune triggers. For the most part, the immune system is able to recognize and tolerate non-harmful triggers. It does this by the means of the innate immune response. It is when there is a trigger (such as a harmful bacteria or fungus) causing the inflammatory response, that cannot be completely removed, resulting in continued inflammation. If this continued inflammatory response is not switched off, then there is a move to the next level of chronic inflammation.

This next level of chronic inflammation has many facets. It includes leaky gut syndrome and dysregulation of the immune system’s inflammatory profile. One can also develop an autoimmune response where there is a decrease in self recognition; a continued imbalance in the TH1/TH2/TH17 lymphocytes; and depletion of the natural killer cells, which could lead to an increase in chronic disease and cancer.

Most chronic diseases have been linked to excessive or persistent inflammation. This chronic inflammation is a systemic phenomena with local manifestations. Chronic inflammation occurs when the injury is ongoing or a predisposed immune system fails at counter-regulation. Unaddressed chronic inflammation can completely obstruct the path to recovery from an infection such as Lyme disease. In order to properly manage Lyme disease the immune system needs to be optimized. The first area of optimization is the GI tract.

For any further information please visit our website page on Lyme disease: http://www.alternativemedicinehealthcare.com/immune-health/lyme-disease. Peter J. Muran, MD, practices Integrative Medicine in San Luis Obispo, CA, specializing in immune conditions such as Lyme disease.

www.longevityhealthcare.com

Tel: (888) 315-4777

Lyme Disease Management-Immune Health

Part Two

By Peter J Muran, MD, ABIHM

Lyme disease management requires a healthy immune system. A healthy immune system requires a healthy gastro-intestinal (GI) tract. To summarize the first article on this topic the GI tract significantly affects the immunological system. The gastrointestinal tract is full of potential immune triggers. For the most part the body is able to recognize and tolerate most non-harmful triggers. It is when an immunological response occurs and the inflammatory response is uncontrolled then the next level of inflammation is stepped-up. This next level of inflammation includes:

• Continued deregulation of the immune system

• Leaky gut syndrome

• Continued imbalance in the TH1/TH2/TH 17 lymphocyte profile

• Depletion of the natural killer cells

• Disruption of the hormonal system

• Increased sensitivity or allergic response to a wider spectrum of agents

This Part Two of a three-part series will discuss evaluation and testing of the immune dysfunction caused by the GI tract.

What's Living in You

Throughout all the information on Lyme disease, antibiotics are used without the appreciation of the bacterial flora except for the administration of probiotics. Yet, analysis of the GI flora is rarely examined to determine the extent of the dysbiosis that is occurring within the intestine. Although the short-term use of antibiotics with the use of probiotics might not require such an examination, the long-term use of antibiotics could have detrimental effects which would affect the innate immune system generating a profile of chronic inflammation. This chronic inflammation profile could complicate the symptoms and compromise improvement resulting in a confused issue in health management.

There are two methods to evaluate the small intestine for harmful bacteria overgrowth; one method that is specific to leaky gut syndrome, which occurs in the small intestines; and secondly, a test for the evaluation of the large intestine. All of these tests have their benefits and drawbacks. In essence what is being evaluated is the total antigenic burden in the intestine resulting in altered GI permeability and over activation of the immune system.

Small Intestine

One method that is available to evaluate internal ecology of the small intestine is with a urine analysis for organic acids, Clostridia species, D-Lactate and D-arabinitol. These measurements could indicate if the patient has small intestinal bacterial overgrowth (SIBO) and or yeast overgrowth. This test gives specific quantitative results of the type of bacteria. The urine analysis can usually be expanded to include additional metabolic products which would provide clues on deficiencies which would affect detoxification, neurotransmitters, energy production cycles and oxidative stress. The drawback of these tests is the expense.

The second method of measuring bacterial overgrowth is an abnormal hydrogen breath test. Abnormal bacterial overgrowth is usually the result of low stomach acid, maldigestion or stasis. In some cases Helicobacter pylori may be the causative bacteria. The main destruction is done by the enzymatic action of the bacteria destroying the integrity of the protective coating of the small bowel permitting digestive enzymes to further breakdown the lining cells of the intestines. The drawback with this test is the lack of identifying a quantifiable result of other bacteria that may be present.

The measurement of leaky gut syndrome is, at first, pretty straight forward. Two sugars, lactulose and mannitol, which are minimally metabolized, are given at the same time. Mannitol is passively transported through the intestinal wall while lactulose is impermeable in a healthy gut. The ratios of the two sugars are measured in a urine analysis. The ratio in a healthy gut is less 0.03. If the lactulose level is high then there is in increase intestinal permeability, whereas, if the mannitol level is low then there is an absorption problem. The lactulose/mannitol challenge test is done fasting and with a meal. The complicated part comes with trying to determine the exact causative agent through an elimination rotational diet. Allergy testing will not always identify the causative agent. The underlying bacterial dysbiosis also needs to be considered in this evaluation.

Large Intestine

Evaluation of the internal ecology of the large intestine can be done in one or two methods. The first method, which has been more established, is done with cultures and microscopic evaluation. The advantages are the standardized care-culture technique and the microscopy and enzyme-linked immuno-assay technology and techniques which are well established and validated. This method also has many shortcomings. One of the most obvious is the difficulty in collecting and growing an anaerobic strain of bacteria, which happens to be the predominant organism of the GI tract. Of the bacteria that can be grown, it requires 1,000 to 5,000 cells to culture. The second drawback is the microscopic detection for parasites which require 25,000 cells per gram.

The other method to detect and measure what bacteria is in the large intestine by DNA strand identification, PCR, and chemical analysis. This has a higher sensitivity for discovering the organisms present in the GI tract and identification. There is an ease of collection and transport. It only requires 1 to 5 cells for identification of bacteria and only 5 cells per gram for parasites. This method has its shortcomings in that PCR techniques and reference ranges are not clinically validated. Correlation between quantification of pathogen or resistance genes based on PCR is not fully known. Ability to determine bacterial strains and specific species depends on limited availability and cost of commercial probes (especially for anaerobes). There are a few human studies on clinical significance of using PCR evidence of a protozoan pathogen.

(Reader Caveat: The following section is detailed and technical. If you find this a bit overwhelming, advance to the summary paragraph to obtain the pertinent concepts)

Identification of GI inflammation

Both lactoferrin and calprotectin are proven markers of intestinal inflammation. They distinguish inflammatory bowel disease from irritable bowel syndrome.

Fecal lactoferrin is in iron-binding glycoprotein which is expressed by a white blood cell seen in acute inflammation or infection, the neutrophil. Elevated levels of lactoferrin indicate neutrophil infiltration of the inner layer of the intestines, the mucosa. Lactoferrin is 90% specific for active inflammatory bowel disease versus irritable bowel syndrome, thereby lactoferrin uniquely discriminates an inflammation from infection.

Fecal calprotectin plays a regulatory role in inflammatory process. It is a reliable marker for the presence of infectious, inflammatory or malignant disease. It is released by mobilized and activated neutrophils in the gut in response to cell or tissue damage, increased permeability of the mucosa, or infectious processes.

What About Your Immune System

An over expression of the immune system caused by gut inflammation normally responds as a systemic inflammatory response of the cytokines. This results in inflammation messaging throughout the whole body. These over-expressions of an inflammatory response through cytokine chemical messengers are imitated by the dendritic cells. Upon a dendritic cell encountering a pathogen, cytokines or specific tissues, it will process that information and either engulf it; facilitate antibody production through another lymphocyte the B cells; cause an oxidative burst of the substance; deliver cytokines to the foreign substance; or lead to further cytokine production by means of activating T- lymphocytes. T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity.

The immature T lymphocyte is activated and the T lymphocyte activation begins at an immature T lymphocyte or Th-naive cells (Th0 cells). The Th0 cells are transformed into Th1, Th2 or Th17 lymphocytes, which have different levels of interaction. For those without an immunology background, mainly get the idea that Th1, Th2, and Th17 will respond to a stimulus differently, as outlined below. Please refer to the first article to clarify cellular versus humoral immunity.

The dendritic cells can also signal the Th0 cells to produce T-regulatory cells. The T-regulatory cells net effect in the gut is to maintain tolerance by dampening immune responses to ingested antigens. The T-regulatory cells also modulate and balance TH1, TH2 and TH17 lymphocyte subsets. It is the modulation lymphocyte subsets which maintain balance throughout the whole body.

• Th1 produces mostly cellular immunity and is measured by IFN-gamma, IL-6, and TNF-alpha.

• TH2 produces mostly humoral immunity and is measured by IL-4, IL-5, IL-6, IL-10

• Th17 produces chronic inflammatory immunity and is measured by IL-17

• Tregulatory for example CD4+CD25+ and is measured by IL-10 and TGF-beta

Th17 is the primary driver of chronic inflammation by producing interleukin 17 cytokines, IL-17. IL-17 further stimulates NFkB (COX-2) and MAP kinases production, which initiate inflammation in Lyme arthritis. NFkB is a measurable unit and can be used to determine the degree of inflammatory response the body is undergoing.

Another inflammatory marker of the innate immune system are complements, c3a and c4a. These will guide to determine whether the inflammation is an autoimmune versus infectious process. The Inflammatory markers of the erythrocyte sedimentation rate, anti-nuclear antibody, C reactive protein and the immunoglobin subclasses may also be of assistance.

A measure of a healthy and responsive innate immune system is the level of the functional natural killer cell activity. These cells are depleted in response to chronic inflammation and the imbalance of excessive Th1 expression. The NK cells can be monitored to reflect the improvement of the immune system.

Summary

The foundational testing associated with both Lyme disease and gastrointestinal inflammation are many. If the situation occurs when the use of antibiotics are not giving the symptomatic relief expected and it appears that the Lyme is still prevailing; look at other regions which can interfere with a healthy immune response. Of importance is the possible inflammation harbored in the GI tract. This can be investigated by exploring the function and possible bacterial overgrowth of the small intestine. The intestinal permeability or leaky gut syndrome should be reviewed. There could be a possible harmful bacteria or parasites in the large intestine. All of these interactions should be compared to the current presentation of possible decline in immune status as fatigue, skin rashes, diarrhea, toxic feelings, shortness of breath, joint and muscle pain, fevers of unknown origin, food intolerance, abdominal discomforts and cognitive changes. To determine the immune directed pathway for the symptoms, utilize laboratory measurements of immune activation and immune tolerance, as described above.

Next article will present a case study and treatment.

For any further information please visit our website page on Lyme disease: http://www.alternativemedicinehealthcare.com/immune-health/lyme-disease. Peter J. Muran, MD, practices Integrative Medicine in San Luis Obispo, CA, specializing in immune conditions such as Lyme disease.

www.longevityhealthcare.com

Tel: (888) 315-4777

Lyme Disease Management – Immune Health

Part Three

By Peter J. Muran, MD, ABIHM

Let’s summarize our prior two articles before launching into the final in this series on the extraordinary immune and gut relationship. The immune system is the most powerful means the body has to fight infection and its central role applies to Lyme disease as well.

Part one discussed how the immune system is divided into two types of subsystems, the innate and the adaptive immune system. The innate system is a more primitive type of system and is seen in most life forms. The innate system is more generalized in its detection of a foreign substance. Its immediate response would be to destroy the substance by exposing harsh chemical to the foreign substance. Major components of the innate system are dendritic cells, macrophages and natural killer cells. The adaptive immune system is seen in higher life forms and is more sophisticated in its specific reaction to an offending agent. The two major pathways of the adaptive pathways involve two different types of white blood cells or lymphocytes. These lymphocytes are known as B-cells and T-cells. The B-cells form antibodies. The T-cells can develop into a variety of forms depending on how they are programmed. The adaptive immune system is mostly programmed by the dendritic cells, a major component of the innate immune system.

Part two discussed how the gastrointestinal track, GI track, is a major contributor to the response of the immune system. Something foreign or irritating to the cells of the GI tract will trigger the innate immune system, causing a localized inflammatory response. If the localized inflammation is not kept under control it will progress to cause an inflammatory response throughout the whole body. This whole body or systemic response is caused by the innate immune system’s programming the T-cell lymphocytes to release pro-inflammatory chemical messengers called cytokines. The pro-inflammatory cytokines are managed by another type of programmed T-cell know as T regulatory cells. It is when our immune system cannot be controlled or it gets “stuck” in an expression of a repeating inflammatory response that tissue destruction occurs and it is felt as pain. The messengers for this chronic inflammatory response are certain cytokine expressions from specific T lymphocytes, Th1/Th17. An example of the over expression of Th1/Th17 is the joint pain and destruction seen in Lyme disease.

In view of the importance of the immune system and its intricacy it is clear that the management of a complicated disease such as Lyme requires utilization of a healthy immune system. A healthy immune system is dependent on a healthy gut. A healthy gut is dependent on a healthy bacterial flora and consumption of foods that are not inflammatory. An over stimulated inflammatory response as a result of poor GI health can result in the immune system getting “stuck” in a pro-inflammatory mode. The healthy immune system would benefit in balancing out the pro-inflammatory mode to a non-inflammatory mode through regulation or modulation of the immune system.

The over usage of antibiotics will change the normal GI bacterial flora, which can lead to dysregulation of the immune system as described above. The dysregulation of the immune system will cause symptoms that are sometimes confused with that of Lyme disease. While antibiotics should be considered as a part of the treatment program for Lyme disease, it is important to maintain the delicate balance between the use of antibiotics and a healthy gut bacterial flora. Development of bacterial strains that are optimal for an individual’s GI tract and immunity is one of the hottest topics undergoing investigational research. Today, we can only guess that we are improving the healthy flora in the selection of the specific probiotics selected for an individual. As research develops we look forward to being able to select the exact strains required by an individual.

What we eat has a great influence on our immune system response. Inflammatory foods or food sensitivities greatly change the internal milieu or environment of the GI tract. It can lead to severe dysregulation of the immune system. While a proper diet will lead to proper regulation of immune modulation by supporting and promoting regulatory T cells.

Note that food sensitivities are not the same as food allergies. Not all food sensitivities develop antibodies. As described above the innate immune system, the pro-inflammatory T-cell lymphocytes can be triggered off without developing antibodies. This response covers many situations where a person is just not getting better because of their diet. The problem is the reliance on a food to antibody test result. The test results could be negative yet the food sensitivity persists. Unfortunately, this misunderstanding leads to the mismanagement of individuals who have treatment directed only at inflammatory response and not the causes of the inflammation.

An example of this misguided treatment is similar to someone who develops an intermittent autoimmune response. This person has a sensitivity to dairy and gluten but does not show an antibody response. Frequently, the main focus of treatment is a disease-modifying anti-rheumatic drugs, DMARDs (e.g. CellCept or Mobic), which are pro-inflammatory, initiated by Th1/Th17, immune blocking drugs. There is no direction by the physician to tell the person to stop their routine consumption of dairy and foods which are contributing to the flare up their T-cell response.

It is important to reduce the cause of an out of control T cell response in tandem with immune regulation which reduces the recurrence of auto-immune flare-ups. The use of such medications should be considered a secondary aid in treatment of an out of control immune system. The primary treatment should be the elimination of the irritant to the GI tract, in this case dairy and gluten, while supporting the competency of the digestive capacity.

A large portion of the immune system is affected by the GI tract. The management of Lyme disease is best directed at increasing the natural anti-body/antigen response, the adaptive immune system, while preventing an out of control inflammatory T cell response. Reducing a misdirected immune response sourced at the GI tract improves the directed immune response to management of Lyme disease.

Case Study

Toni was a 37-year-old top commercial banking executive with a specialty in acquisitions. She has a past medical history of progressive joint pain, which started approximately 2 years prior and was left untreated. The joint pains were debilitating and migratory with associated fatigue. She had developed significant fatigue to where she could not get out of bed four days out of the week. She also had associated with her illness significant muscle pain, insomnia and cognitive changes.

The noticeable cognitive changes include difficulty in thinking and concentrating, short-term memory loss, disorientation, reversing numbers, word finding problems, and depression. The patient also states that she has had fever and night sweats; swollen and tender neck lymph glands; unexplained menstrual irregularity, PMS and loss of libido; stomach discomfort associated with bloating and daily diarrhea; heart palpitations with severe swollen ankles and feet; neck discomfort which includes stiffness, cracks and pain; and headaches with a slight dizziness similar to vertigo type symptoms. Her past medical history includes ongoing sinusitis and human herpetic viral infections with prior increased liver enzymes and a history of asthma, which was triggered off by mold and pollution.

Skin problems included mild acne on the face with long standing history of treatment with doxycycline; bumps on the upper arms; increased cellulite; moderate amount of dark circles under her eyes; easy bruising; lackluster pale skin; sensitivity to bites; strong body order and thick calluses on feet.

She has noticed an intolerance to milk and gluten products associated with nausea and severe upper abdominal pain.

She went to several top specialists and although some of the tests were positive for Lyme disease she did not fit the exact criteria and Lyme disease was excluded from her diagnosis.

She did start treatment with a Lyme literate physician who began treatment with Neurontin and Trileptal for joint and muscle pain; Trazadone for insomnia and Claritin for sinuses. She was to begin the antibiotic therapy in 2 weeks with the use of three antibiotics (Omnicef, azithromycin and minocycline) to be stepped up quickly with the inclusion of Flagyl in two weeks. She was having difficulty in managing the above medication treatment and sought other medical advice.

Prior positive labs included:

2009 - Elisa and Western blot IgM for positive for Bb; total porphyrin elevated 173

August 2010 - CD57 @ 20/ul ; human herpetic viruses (HHV) #1, #2, #3 and #6; D3@ 34 ; and C4a elevated at 4285.

Recent positive labs were as follows:

Infectious disease - Borrelia burgdorferi, HHV 1,2,3 and 6. Negative for typical co-infections and Chlamydia pneumonia

Gastrointestinal tract - The GI tract with small intestinal bacterial overgrowth (SIBO). Large intestine with Helicobacter pylori, yeast 2+/4+ and gluten sensitivity.

Immune system - The IL-6, C4a and the erythrocyte sedimentation rate (ESR) was mildly elevated. The fibrinogen, CCP antibodies and vascular endothelial growth factor were normal, CD57 @ 16/ul.

Coagulation profile - Plasminogen activator inhibitor type I (PAI-1) gene heterozygous for the 4G/5G.

This signifies a decrease in fibrinolytic activity leading to persistent clot formation which could be associated with increased difficulty in breaking down Lyme’s biofilm. Intermittent porphyuria when physiologically stressed

Endocrine system - T3 (total) 77 ng/dl: T3 (reverse) 52.5 ng/dl; cortisol saliva test (showing an 18 hour cyclic pattern -6am through 12am) was below the lower limits of normal throughout the whole day; estrogen levels were sufficient for the luteal phase of the cycle yet progesterone deficiency levels were suggestive of anovulatory menstrual cycles.

General working diagnosis is composed of:

1. Infectious disease

2. GI dysbiosis with inflammation and leaky gut syndrome resulting in over stimulation of the Th1/Th17 response with over production of pro-inflammatory cytokines

3. Difficulties with hepatic and cellular detoxification

4. Biotoxin histocompatability

5. Genetically impaired fibrin or clot break down, which increased difficulty with the Lyme biofilm breakdown

6. Hormonal imbalance

7. Euthyroid sick syndrome, poor metabolism of T4 to T3(active) secondary to inflammation

8. Adrenal fatigue resulting from a chronic inflammatory state

9. Dysregulation of sex hormones, including estrogen, testosterone and progesterone.

The approach to such a complicated patient is to begin with correcting the GI tract at the same time balancing out the hormones. The GI tract had several variables which needed to be addressed. Gluten sensitivity treatment would be to stop all gluten products including food and personal hygiene products.

Toni has a propensity for high yeast growth in the large intestine, Candida albicans. This factor needs to be brought under control prior to starting any antibiotics. If ignored, a bloom of the Candida with its subsequent toxic release would confuse the infectious profile. Treatment with nystatin, diet change, and probiotics were instituted immediately. Zinc carnosine was used to eliminate H. pylori. There is significant research out of Japan showing that this is an effective method without causing additional imbalance of the GI flora.

Properly balancing the hormones increased her resilience and management of immunological stress. The immune system was balanced by first addressing the cortisol levels. Hydrocortisone was utilized to maintain physiologic levels of cortisol throughout the day. After one week of supplementing hydrocortisone, Cytomel, T3 active, was also introduced taking care that the patient was not symptomatic of the T3 active excess in view of possible low cortisol levels. The hormonal balancing helped to improve her fatigue in conjunction with the length and quality of sleep.

The pain and depression medications, Neurontin and Trazadone, were transitioned to Lyrica and a serotonin based SSRI, Zoloft. 5-HTP was added to help increase the serotonin production. The depression resolved, and the muscle and joint pain started to lessen, shortly thereafter.

After the GI tract was staged for control of an exacerbation of a possible fungal overgrowth, antibiotics were introduced. She had significant difficulty with the antibiotics, which required them to be slowly introduced. This was accomplished over 2.5 month progression until tolerating a therapeutic daily intake of antibiotics, Azithromycin and minocycline. With the antibiotics in place and the GI tract and hormonal system supported it was time to add the fibrolytic, lumbrokinase, to start breaking down any fibrin encasement protecting the Bb.

During this time metronidazole, Flagyl, was introduced. After one month of using metronidazole she developed thrush, nausea and vomiting, and ankle swelling. The liver enzymes started to elevate slightly out of normal range. The metronidazole was discontinued and her symptoms improved. Focus was directed towards improving her phase 1 and 2 liver detoxification and elimination while maintaining proper GI balance. Once accomplished, the Flagyl was reintroduced without any problem.

After four months she was taking daily walks and saunas with drinking plenty of water. The swelling in the legs were gone. The pain medication was reduced as the discomfort subsided. Muscle weakness improved. Cognitive improvements continued with “feeling better to almost being back to “herself”.

She had continued improvement of the muscle and joint pain yet the fatigue remained a continued problem. Using a scale of 1 to 10, with 10 representing the most severe joint pain, dental pain, and muscle pain completely resolved from a 9 to a 3 out of 10. The antibiotics were then pulsed and she continued to improve.

The swelling resolved and the fatigue had improved from a score of 9 to a 5 out of 10. She only felt a little achy with excess activity. The pulsing the antibiotics revealed an associated cyclical pattern of increased cognitive difficulties would worsen to an 8 out of 10 with diarrhea, and without the antibiotics, cognitive difficulties improved to a 3 out 10 without diarrhea. The antibiotics were discontinued. The antibiotics leveled the playing field. It was time to move from the antibiotics to a more naturopathic regimen.

The antibiotics were transitioned to an herbal and homeopathic program while continuing to maintain GI balance and immune modulation.

Currently, the patient is off all pain medications; she is exercising to the level of not causing fatigue; the cognitive changes have improved, her menstrual cycles have returned to normal w/o any PMS symptoms and no GI issues. She remains on primarily a naturopathic regimen and is improving every day, without any GI problems. The only symptoms are a little fatigue at the end of the day, which she contributes to spending 60% of her day in helping her elderly parents relocate to their new home. The fatigue continually improves.

The success in the Lyme treatment of for Toni was based on optimizing the immune system, balancing the major hormones and removing inflammation in the GI tract. The GI tract is the most forgotten yet most influential in absorption of nutrients, improvement of immune response and the pathway to health.

For any further information please visit our website page on Lyme disease: http://www.alternativemedicinehealthcare.com/immune-health/lyme-disease. Peter J. Muran, MD, practices Integrative Medicine in San Luis Obispo, CA, specializing in immune conditions such as Lyme disease.

www.longevityhealthcare.com

Tel: (888) 315-4777