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'Lyme' Is More than Lyme Alone
In the recently released book Why Can't I Get Better? Solving the Mystery of Lyme and Chronic Disease, by Richard I. Horowitz, MD, a compelling argument is made that there is much more to chronic Lyme disease than Lyme alone. In fact, Horowitz unveils his "16-Point Differential Diagnostic Map," which suggests numerous "nails" in the foot that must be explored in order to regain wellness. He further expands the concept of "chronic Lyme disease" by suggesting MSIDS, or multiple systemic infectious disease syndrome, as a more encompassing term for the multiple underlying factors involved in chronic illness.
In my personal experience recovering from Lyme disease after a tick bite in 1996 in Northern California, the journey has been one of uncovering many stones and addressing numerous layers of issues that were affecting my health. While borrelia, bartonella, babesia, ehrlichia, and many other microbial factors did play a role, it was not until I read the book Mold Warriors, by Ritchie C. Shoemaker, MD, in 2006 that I considered the possibility of mold as another key part of the systemic body burden that had without my awareness made me ill for so many years.
Upon further evaluation, it was determined that I had been living in an apartment for nearly 10 years that was contaminated with numerous molds, including Stachybotrys, better known as "toxic black mold." Removing myself from this constant, daily exposure to an environment that was not conducive to my recovery was an important step to take. Moving to a safer setting was one of the best things that I did as part of my journey back to health. I do not think I would be where I am today if I had not discovered and addressed this ongoing, toxic environmental factor that was contributing to my then poor state of health.
The connection between those struggling with chronic Lyme disease and ongoing exposure to toxic molds and mycotoxins is quite clear. Dr. Wayne Anderson has found that exposure to Lyme disease can make one more susceptible to mold illness, and vice versa; exposure to mold can make one more susceptible to Lyme disease. Both have the potential to affect the immune system and make the other more difficult to treat.
Dr. Neil Nathan has found mold toxicity to be a big piece of the puzzle in a very significant portion of patients with chronic Lyme disease. Lisa Nagy, MD, has suggested that many Lyme patients have a damaged immune system resulting from mold or pesticide exposures and that a focus on Lyme and coinfections may not always be the right focus.
One of the downsides of "chronic Lyme disease" is that Lyme often becomes the focus of treatment, when in fact it may not be the dominant stressor that the body is burdened by. The intent behind this article is to suggest a more expanded view of chronic Lyme disease and to consider that both environmental exposures to toxic molds and the production of mycotoxins resulting from fungal colonization in the body can be significant issues in terms of symptom presentation, as well as both the severity and duration of the illness.
What Are Molds and Mycotoxins?
Mold and yeast are both different types of fungi. Molds are multicellular fungi and grow in filamentous hyphae, or long threadlike branches. They produce airborne spores and are often quite colorful. In nature, molds are the recyclers of organic waste. While they are closer to plants than animals, they cannot undergo photosynthesis and thus rely on organic matter for nutrition. They reproduce using both sexual and asexual methods.
Yeasts are single-celled microscopic fungi that are round or oval in shape and are generally colorless in appearance. They reproduce asexually via mitosis or budding. Yeasts are often used in fermentation of alcoholic beverages such as wine and beer and as well as in baking. Some yeasts, such as Candida albicans, can be opportunistic infections in humans.
Mycotoxins are toxic chemicals produced by both molds and yeasts. They are believed to be used by fungal organisms as a protective mechanism, as a way to stake out their territory, and to allow for further proliferation of the fungi. Additionally, within a host, they may be used by the fungi to weaken host defenses in support of persistence of the fungal organisms.
The environment in which the fungi live may be directly correlated to the output of mycotoxins. The more threatened the fungi are by the surrounding environment, the more they may utilize mycotoxin production as a protective weapon. Mycotoxins are not essential for the fungi to maintain their existence, but they do provide a competitive advantage. In some cases, humans get caught in the crossfire.
Mycotoxins in the body may be the result of external exposure to molds or internal, colonizing fungal organisms. They are generally found intracellularly and may be stored in body fat, myelin, tissues, organs, and other body sites.
While there are hundreds of different mycotoxins that have been discovered, some of the more common ones include aflatoxin, ochratoxin, citrinin, ergot alkaloids, patulin, fumonisin, trichothecene, and zearalenone. The focus of this article will be on aflatoxin, ochratoxin A, and trichothecene, given that these can be readily measured via laboratory testing performed on a urine sample, providing a useful tool for practitioners working with patients with mold-associated illnesses.
Ongoing mold and mycotoxin exposure can be a very serious issue, creating illness in the genetically susceptible. Sadly, the importance of evaluating for the potential of mold illness and taking appropriate corrective actions is often overlooked by many practitioners and patients alike.
Shoemaker's Mold Contributions
Shoemaker deserves tremendous credit for being the voice that brought mold illness to our awareness. His "biotoxin pathway" and treatment protocol have been instrumental pieces of the puzzle for many struggling with chronic biotoxin illness. Biotoxins are toxins created by living organisms. Mycotoxins are a subset of biotoxins and are produced by fungal organisms.
Visual contrast sensitivity (VCS) testing is often a very useful biotoxin screening tool that can be performed online. Mycometrics ERMI (Environmental Relative Moldiness Index) is arguably one of the best evaluation tools for the presence of mold in an indoor environment. Numerous lab tests were brought to our attention by Shoemaker's work including HLA testing, which looks for genetic predispositions to various biotoxin illnesses, and markers such as TGF-b1, C4a, C3a, MSH, VIP, VEGF, and MMP-9. The information that a trained practitioner can ascertain from the results of these tests is significant in the work to guide a biotoxin-illness patient back to a higher level of health.
Cholestyramine is used in many with Lyme disease and mold illness as a direct result of Shoemaker's discoveries. Losartan, VIP nasal spray, and other useful therapeutic options have been introduced to biotoxin-illness sufferers through his work.
Shoemaker's approach has benefited and will continue to benefit many suffering with otherwise unexplained illnesses. No article on the topic of mold illness would be complete without a mention of his important contributions, and while not the focus of this article, his work has been life changing for many, myself included. More information about his protocol, his books (Mold Warriors, 2005; Surviving Mold, 2010), and the recently introduced doctor certification program can be found on his website. Several integrative practitioners now incorporate a combination of the Shoemaker Protocol with several of the other options discussed in this article.
Mold and Mycotoxin Symptoms and Associated Conditions
Symptoms produced in humans as a result of mold and mycotoxin exposure are widely varied and may range from no response or simple allergy to cancer or even death.
"Symptoms can be caused by mold allergy, mold colonization (or infection), or mold toxicity, or a combination of these," said Nathan. "Until Shoemaker raised awareness around the toxicity component, we had focused exclusively on allergy and infection. It is the understanding that mold toxicity, with its marked, uncontrolled outpouring of inflammatory cytokines, produces the same wide array of unusual symptoms that we see in Lyme disease and its coinfections that has dramatically improved our ability to diagnose and treat a large subset of patients that had been previously struggling to get better."
The symptoms may depend on the types of molds and mycotoxins, the duration of the exposure, and the overall health of the exposed person. Mycotoxins damage the immune system and may make one more sensitive to bacterial endotoxins found on the outer membrane of bacterial cell walls. With an increased sensitivity, the body's response to Borrelia burgdorferi, the causative agent of Lyme disease, and coinfections may be heightened and lead to a further exacerbation of overall symptoms.
Mycotoxins can cause coughing, wheezing, asthma, shortness of breath, sneezing, burning in the throat and lungs, and sinusitis. Memory loss, confusion, brain fog, and cognitive impairment may present. Vision problems, eye irritation, headaches, swollen lymph nodes, ringing in the ears, dizziness, hearing loss, fatigue, muscle weakness, multiple chemical sensitivities, joint pain, muscle pain, irregular heartbeat, seizures, depression, anxiety, irritability, psoriasis, skin irritation, fever, chills, sleep disorders, coagulation abnormalities, and numerous other symptoms have all been associated with mycotoxin exposures.
According to Dr. Joseph Brewer at the 2013 ILADS (International Lyme and Associated Diseases Society) annual meeting, mycotoxins bind to DNA and RNA, alter protein synthesis, increase oxidative stress, deplete antioxidants, alter cell membrane function, act as potent mitochondrial toxins, and alter apoptosis.
Molds and their mycotoxins may negatively affect the endocrine system, including sex hormones, thyroid function, and adrenal function. Mold exposure may lead to food allergies and chemical sensitivity. In some cases, POTS (postural orthostatic tachycardia syndrome) may be mold induced.
Fibromyalgia and chronic fatigue syndrome (CFS) have both been associated with mycotoxin exposure. Other conditions that may have a mycotoxin component include various cancers, diabetes, atherosclerosis, cardiovascular disease, hypertension, autism, rheumatoid arthritis, hyperlipidemia (elevated cholesterol), inflammatory bowel disease, lupus, Sjögren's syndrome, Crohn's disease, multiple sclerosis, Alzheimer's disease, Raynaud's disease, kidney stones, and vasculitis.
It has been suggested that elevated cholesterol may be a protective mechanism of the body as a response to mycotoxin exposure. Statin drugs have antifungal properties, and one of the mechanisms through which they may help to lower cholesterol is through the reduction of mycotoxins as systemic fungal populations are reduced.
In those with chronic Lyme disease, it is difficult to separate the symptoms associated with mold and mycotoxin exposure from those associated with Lyme disease or even with heavy metal toxicity. The overlap is significant, and as a result, all of these items must be explored as symptoms believed to be associated with Lyme disease may not be entirely the result of Lyme itself.
Mold and Mycotoxin Testing
The evaluation and treatment of mold- and mycotoxin-related illnesses has garnered attention from doctors who treat patients with chronic Lyme disease. New and evolving options for practitioners to diagnose and treat their patients have emerged over the past several years.
As an initial screening option, mold plate testing can be helpful in providing someone with visible proof that there may be an issue in the living environment. Mold plates are often available at local hardware stores or can be purchased through companies such as Tennessee Mold Consultants, Immunolytics, or EMLab P&K.
The Mycometrics ERMI has been a highly valuable tool for many practitioners and patients alike in evaluating the potential of ongoing mold exposure in the indoor environment. Several labs perform ERMI testing, but Shoemaker's work is based on the ERMI performed by Mycometrics. It analyzes a collected dust sample for the presence of molds associated with water-damaged buildings using quantitative PCR and compares these values with other common indoor molds to determine the ERMI score. The score is then evaluated to determine if the living environment is likely safe and conducive to one's recovery. If one has a mold-susceptible HLA DR type (discussed later), an ERMI score below 2 is generally desired. A more recent test called HERTSMI-2 is available from Mycometrics that is less extensive but may be helpful to determine if a previously contaminated environment is safe for one to reenter after remediation.
Air sample tests can be used when looking for molds, but Shoemaker has been very clear that these are of limited value. Air samples represent a snapshot in time and do not show the complete picture. It is not uncommon for air sample testing to return negative results in the same environment where an ERMI is highly positive. 99% of the toxic substances in a water-damaged building are carried by mold fragments too small to be detected by air testing or mold plates.
Stachybotrys is the most famous of the pathogenic molds. This "toxic black mold" produces a mycotoxin called trichothecene. Stachybotrys is rarely found outdoors. Given that it is not readily airborne, air sampling is generally not an effective tool for this particular mold; thus dust sample testing using the ERMI may be a better option.
While mold plates and ERMI testing are often helpful options for evaluating the indoor environment for the presence of mold, they do not consider the people living in the environment and whether they are affected.
Antibody testing for various molds can be performed. ALCAT offers a Molds Panel that looks for intolerances and sensitivities to about 20 different molds using a blood test. Nagy has discussed Alletess Medical Laboratory for IgG antibody testing to various molds. When these tests are positive, this could be explained by allergy or sensitivity response to exposures in the environment or could also potentially be the result of a colonization of fungal organisms in the body that the immune system is responding to.
RealTime Laboratories in Carrollton, Texas, introduced a panel in 2006 that evaluates a patient's urine for the presence of three different mycotoxins: aflatoxin, ochratoxin A, and trichothecene. This represents an exciting option for evaluating the mycotoxin burden in a patient. This will be discussed later in this article.
Recent Mold and Mycotoxin Publications
In April 2013, Brewer published "Detection of Mycotoxins in Patients with Chronic Fatigue Syndrome" in Toxins. The study looked at the CFS, or myalgic encephalomyelitis (ME), population to determine if there might be a connection between the condition and mycotoxin exposure from water-damaged buildings. Healthy controls with no known toxic mold exposures were compared with those with CFS/ME. Urine samples were evaluated for the presence of aflatoxin, ochratoxin A, and trichothecene. Of 112 samples assayed, 104 (93%) revealed the presence of at least one of the three mycotoxins. The most commonly identified was ochratoxin A (83%) followed by trichothecene (44%) and then the combination of ochratoxin A and trichothecene (23%). None of these were observed in the population of 55 healthy controls. Testing of the environment in many of the CFS patients revealed mold and mycotoxin exposure. The conclusion of the study was that mycotoxins could be a cause of mitochondrial dysfunction in the CFS population, which may explain fatigue and other symptoms.
A second publication titled "Chronic Illness Associated with Mold and Mycotoxins: Is Naso-Sinus Fungal Biofilm the Culprit?" was published in Toxins in December 2013 by the same lead author. This publication built on the earlier work by looking at potential sources of ongoing mycotoxin exposures that may be involved in chronic illness. It suggested that the sinuses were the most likely colonizing site for molds, leading to the ongoing production of internal mycotoxins. Essentially, once molds colonize in the body, even if one is removed from the environment where water damage may have led to ongoing mold and mycotoxin exposure, mycotoxins are produced internally, which serves as a constant source of additional toxic body burden. It is as if there is a mycotoxin factory open for business 24 hours a day, 7 days a week, with the end result being a toxic, polluted body.
It has been known for some time that people with chronic rhinosinusitis harbor numerous fungal organisms. Of the fungal organisms that have been observed such as Aspergillus, Chaetomium, Fusarium, Penicillium, and Trichoderma, many of these have the potential to produce mycotoxins. The publication notes that in one study, both those with sinusitis and controls had equal prevalence of fungal organisms and that essentially everyone has nasal fungi. However, mycotoxins were not found in nasal washing from healthy controls, though they were in those previously exposed to a moldy environment.
Fortunately, the publication continues to suggest approaches that have resulted in protocols which attempt to resolve the ongoing fungal organisms that may be at the core of the ongoing mycotoxin burden. Amphotericin B has been used intranasally with observed clinical improvements, and oral antifungals are often used concurrently. Intranasal therapy must also consider the likely presence of biofilms that protect the mycotoxin-producing organisms from antifungal therapies. In one study of 25 people with evidence of urinary mycotoxins, 90% had dramatic decreases in symptoms with targeted treatment.
As with many antimicrobial therapies, it has become more and more evident that the role of biofilms must be considered in order to maximize the therapeutic benefits. This polysaccharide sludge layer protects the organisms that live within it. Different types of organisms, such as fungi and bacteria, form a community within the biofilm that conveys considerable protection to these organisms and reduces the amount of an antimicrobial agent that actually makes it to the intended target. Biofilms make chronic infection more possible and treatment strategies more difficult. NAC and EDTA were mentioned in the article as potential tools for disrupting the biofilm layer, thus making the fungal organisms more susceptible to antifungal therapies.
At the ILADS 2013 annual meeting, Brewer shared that CSF consists of immune dysregulation, abnormal cytokine profiles, autoimmunity, and immune deficiency. Cognitive issues, central nervous system issues, endocrine abnormalities, oxidative stress, and mitochondrial dysfunction are common hallmarks of CFS. The overlap between the key issues in CFS and those that can be attributed to mycotoxins is notable.
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