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Once exposure has been verified, symptoms must be elucidated in a systemic rubric called a Cluster Analysis.
Melanocyte Stimulating Hormone (MSH) is a master regulator in the hypothalamus. The downward regulatory effects of low MSH results in CIRS symptoms spiraling out of control. MSH is related to melatonin production and circadian rhythms, disrupting sleep. Endorphin production is suppressed-resulting in loss of pain control; this is commonly described by patients as Fibromyalgia type pain.
HLA Genetic Testing
Human Leukocyte Antigens (HLAs), are located on the surface membranes of almost every cell in the body. Their purpose is to assist the immune system in identifying self versus non-self or said another way, determine what is you verses what is not you.
Visual Contrast Sensitivity (VCS): This test is highly sensitive for neurotoxins effects on the brain. 92% of those with CIRS fail the test, 8% with CIRS will still pass it, and 1% without CIRS will fail the VCS. This is a test to detect the eye's ability to differentiate the contrast between grey and white lines of variable thickness.
MMP-9 can be used to measure T Helper 1 cells and if low, this arm of the innate immune system is disputed. Elevation is seen in cytokine mediated inflammation where MMP-9 delivers inflammatory elements from the blood into the subintimal spaces. Elevation has been associated with diseases ranging from COPD, Rheumatoid Arthritis, Atherosclerosis, Aneurisms, Cardiomyopathy and CIRS.
Vasoactive Intestinal Peptide (VIP) is a neuroregulatory hormone with receptors in the hypothalamus. Low levels of VIP are found in 98% of patients with CIRS and only 10% on controls.
C4a levels refers to part of a system known as the complement system — a group of proteins that move freely through your bloodstream and works with the immune system playing a vital role in inflammation. In CIRS, C4a is used to measure an excessive innate immune response to biotoxins and has become the inflammatory marker of greatest significance looking at innate immune responses in those with exposure to Water-Damaged Buildings (WDBs).
Alpha melanocyte stimulating hormone (MSH) is neuropeptide that controls many functions not only in the central nervous system but also throughout the body. ... In CIRS, MSH will be too low in over 95% of patients resulting in increased susceptibility to mold-related illness, hormone irregularities, mood swings and chronic pain.
TGF Beta-1 (TGFB1) is a protein that has important regulatory effects throughout innate immune pathways. This molecule occurs throughout the body and plays an important role in prenatal development, blood vessel formation, wound healing, formation of blood vessels, cell movement, cell self-destruction (aka apoptosis) and immune system regulation especially that affected by regulatory T-cells. Elevations of TGFB1 have been seen with a litany of fibrosing and autoimmune diseases.
Antigliadin (AGA) antibodies are a marker for increased gastrointestinal permeability (i.e. Leaky Gut) and increased risk for autoimmunity. When MSH is low, there is increased intestinal permeability which can lead to a loss of the gut integrity and increased autoimmunity. When this occurs, multiple autoantibodies can be observed which include AGA and ACLA.
Multiple Antibiotic Resistant Staphylococcus Aureus (MARCoNS) is a slow growing bacterium that creates a sticky mucous like biofilm allowing it to stay undetected and resistant to antibiotics. It colonizes the nasal passage ways of those who have suppressed immune systems—specifically, those with a low MSH. It's a vicious circle, MARCoNS releases endotoxin A and B which break down MSH and lower its levels and a low MSH can cause susceptibility to MARCoNS.
Antidiuretic Hormone (ADH) is a peptide produced by the hypothalamus and released by the pituitary gland. The primary purpose of ADH is to maintain the concentration of the blood, as measured by osmolality, and maintain the bodies water balance. ADH also affects VIP and MSH levels in the hypothalamus, so hypothalamic regulation is tightly dependent on these three substances. Around 80% of those with CIRS will have dysregulation of the ADH/Osmolality balance.
Adrenocorticophic Hormone (ACTH) is produced in the anterior pituitary gland of the brain and controls production of cortisol, a steroid hormone, by the adrenal cortex. Cortisol naturally is increased in the morning in a circadian fashion upon awakening, utilizing glucose for brain alertness. Cortisol at 4am may be up to 1/10 that of normal at 8am. ACTH production increase in response to stressors allows for an appropriate physiological response. Excessive stress can result in sleep/wake disorders of the circadian rhythm with result of a 'wired but tired' feeling.
1. Removal from ongoing exposure
To remove the ongoing exposure, it must be identified. This is the first and most crucial step of this process.
2. Treat with Cholestyramine or Other Binder
Biotoxins from water damaged building must be removed from the body, this is especially true for those with a genetic predisposition to CIRS. This can be accomplished using cholestyramine (CSM), a bile acid sequestrant. The structure of CSM is such that it binds negatively charged ionophores resulting in their excretion in the bile. Biotoxins are ionophores that are difficult to excrete and CSM facilitates their removal from the body.
3. Treat Multiple Antibiotic Resistant Staphylococcus Aureus (aka MARCoNS Treatment)
MARCoNS treatment consists of using an antimicrobial biofilm reducing compounded nasal spray.
4. Correct Anti-Gliadin Antibodies
If someone has a positive anti-gliadin antibody, then they need to be 100% gluten free. If an individual is found either on lab testing or endoscopic biopsy to have Celiac Disease, then all gluten containing foods must be removed.
5. Correct Androgens
Ideally, the dysregulated gonadotropins, ACTH, cortisol and testosterone will be corrected as the biotoxin treatment is implemented in a stepwise process. However, this does not always occur. A low MSH will disrupt the typical fluctuations of LH and FSH and the androgens.
6. Correct ADH/osmolality
Antidiuretic hormone is crucial in regulating the bodies blood concentration of electrolytes, known as osmolality. If at this stage in CIRS treatment, there remains a degree of ADH/Osmolality dysregulation, DDAVP support may temporarily be provided.
7. Correct MMP-9 Levels
Biotoxins can cause cytokines to become elevated resulting in the release of MMP-9 from neutrophils and macrophages. Using CSM to remove the biotoxins starts this process but at times additional therapies are needed.
8. Correct VEGF
If still elevated, additional CIRS treatments begin with graded exercise. Graded exercise pushes the cells capacity to utilize oxygen for production of energy, but it must be done without exceeding the anaerobic threshold, if this occurs a patient will get the 'push/crash phenomena,' meaning it can take days to recover from a simple exercise regimen or increase in activity levels.
9. Correct C3a
Retest levels of C3a and if still elevated, treat. Levels of C3a aren't often elevated in CIRS-WDB because bacterial cell membranes are required for its elevation. If high, consider Lyme Disease.
10. Correct C4a
C4a levels are used to assess the overall severity of CIRS. For many, by the time they reach Step 10, after removing from exposure and walking through the previous steps, the C4a level has normalized.
11. Lower TGF beta 1
High levels of TGFB1 are associated with hard to treat asthma attacks, fibrosis in organs such as the liver/kidney/lungs and autoimmunity. The level of TGFB1 can be lowered with a blood pressure medication called losartan. This angiotensin receptor blocker has a metabolite EXP 3179 that is associated with its effects in CIRS.
12. Vasoactive Intestinal Peptide (VIP)
Vasoactive Intestinal Peptide is the crown jewel of the Biotoxin Pathway treatment. Its actions allow it to lower the pulmonary artery systolic pressure associated with shortness of breath, elevated VEGF, restore the sleep/wake cycle, regulate Th17 function and autoimmunity and even improve the brain volumes seen on NeuroQuant.