Background

A chronic inflammatory illness caused by insufficient clearance of biotoxins affects as many as one in four people in the United States and elsewhere. The poor clearance of biotoxins associates with ten separate genotypes. Genes simply load the gun. It takes exposures to pull the trigger. It appears that exposure alone is not enough to cause chronic inflammation in everyone with a genetic susceptibility. For some, becoming ill from this condition requires a priming of the pump, so to speak. A priming event appears to be anything that results in high or moderately sustained levels of stress caused by infection, autoimmune activity, toxicity from other causes, physical or psychological trauma, immune suppression, or a severely depleted state.

Several peer-reviewed controlled studies have appeared on this condition, also know as Chronic Inflammatory Response Syndrome (CIRS). Much of what we know about CIRS is a consequence of ongoing practice-based outcome studies done by a physician researcher, Ritchie Shoemaker, and his colleagues over the past seventeen years. In a series of studies going back to 1998, Shoemaker developed an increasingly thorough description of an illness caused by poor clearance of toxins produced by dinoflagellates (eg, Pfiesteria and Ciguatera). He subsequently associated the condition with certain molds known to grow in water-damaged buildings. Chief among these toxin-forming molds are species of Aspergillus, Chaetomium, Penicillinium, Stachybotrys, Trichoderma, and Wallemia.


Mold Inspection, Remediation, and Cleaning

Toxin-producing molds grow under conditions of sustained or recurrent moisture combined with access to cellulose. The moisture might be the result of water intrusion from flooding, roof leaks, burst pipes, plumbing leaks, or from chronic recurrent condensation. Steady cellulose sources include drywall, wood, paneling, carpet padding, paper, and dust. Predisposing factors include poor building site choices, inattention to groundwater drainage and diversion, compromised cement foundations, crawl spaces, sloppy roof flashing, too many roof angles, ice dams, inadequate insulation of water pipes from sub-zero temperatures, pinhole roof, sink, or shower leaks, and lack of adequate ventilation in bathrooms and basements.

Should significant amounts of water come into contact with cellulose in any of its forms, only forty-eight hours are needed for the mix to foster the growth of molds. Molds with the ability to produce toxins usually do so when their colonies make contact with man-made chemicals, including formaldehyde, adhesives, paints, and stains. Toxin production by such molds is thought to be a defense against our industrial chemicals. If residents, workers, or students with genetic susceptibilities are sufficiently exposed to the toxins and other inflammagens found in the air of water-damaged buildings, they are prone to developing CIRS. The inflammagens include diverse bacterial and fungal fragments as well as volatile organic compounds released by microbial species and/or building materials. This toxic admixture makes the genetically vulnerable sick with a chronic inflammation that cannot subside without removal from ongoing exposure.

A mold inspector should be state-licensed as a building inspector with additional certification as an indoor environmental consultant. It makes sense to use an independent mold inspector who can draft a detailed remediation plan who is also familiar with the medical reasons for doing ERMI and HERTSMI testing. ERMI stands for Environmental Relative Moldiness Index. It was developed by the Environmental Protection Agency to identify the presence of specific molds by DNA analysis. ERMI separates common molds from toxin producing molds and comes up with a score between -10 and 20. Data shows that patients fare well with treatment in spaces with a score of 1 or below. HERTSMI tests for the top five nasty toxin producers. Patients tend to fare well in spaces that score 10 or below.

Mold toxins are classified as nanoparticles. They are far too small to be filtered by HEPA systems. Mold remediation involves replacing water-damaged structural elements and cleaning HVAC systems such that the building in question no longer supports the growth of toxin-producing molds. Once remediation is complete, the all-important task of small particle cleaning remains.

Like VOCs, nanoparticles are suspended in air and are subject to Brownian motion. Mold toxins can settle into porous surfaces including clothes, carpets, rugs, upholstery, drapes, stuffed animals, etc. Special techniques are required to clean porous materials. Clothes can be dry-cleaned or washed in a Borax solution but clothes cleaned in these ways will be re-contaminated until toxin counts in the living space become negligible and, thus far, we have no technological means to count toxin levels in ambient spaces.

Non-porous surfaces can be wiped down with cleaning agents that contain quaternary ammonium. Such agents include Clorox (though not regular bleach), Windex, Formula 409, and Borax. Wipes should be placed into plastic bags that are then sealed and disposed. Small particle cleaning is important because a remediated but uncleaned living space can continue to trigger inflammation due to ambient exposure to airborne toxins.


Pandora’s Box

It is the sad duty of the reality-based clinician to inform CIRS patients that they have three options: 1) move from your residence, change jobs, or switch schools, 2) remediate and clean the residence, workplace, or school, or 3) get worse. A fourth option is to pretend that none of prior three options are real. Lots of luck to the genetically susceptible who choose to ignore the first step of treatment, which is to remove yourself from ongoing exposure to air made toxic by the colonization of building materials by toxic molds and sundry inflammagens.

Homeowners, landlords, employers, and school districts are aware of the Pandora’s box that could be opened by testing a building for toxic molds. A common strategy for these parties is to contract with a mold inspection service that does air testing. Air testing is unlikely to find evidence for toxin producing molds in the air because thy settle on horizontal and slanted surfaces. They are happy to brandish air sample results that show no evidence for toxin producing molds.

Should a lawsuit commence, the defendant will hire attorneys to argue that the test of specific causation has failed and that, therefore, the defendant is not liable for damages. The plaintiff will argue that when it comes to biomarkers of inflammation caused by a variable admixture of particles found in the toxic air of water damaged buildings, that the specific causation precedent is wholly inadequate to the complexity of the problem when it comes to the genetically susceptible. In other words, various mixes of toxin burden cause the disease, not a proven exposure to any toxin in particular.


Diagnosis

If the patient does not present with a multi-symptom illness, the patient does not have CIRS. Shoemaker’s data found that untreated CIRS cases averaged 22 of 38 symptoms whereas health controls averaged 3 of 38 symptoms. History alone is not reliable enough to make the diagnosis. History plus multiple symptoms is enough to warrant diagnostic testing to include vision testing, genetic screening, and evaluation to see if characteristic patterns of abnormality are seen

A typical first step in the diagnosis of CIRS is to check visual contrast sensitivity (VCS). This test assesses the patient’s ability to detect whether increasingly thin and light gray lines are tilted toward the right or the left. This depends on an ability to detect the edges of the lines, also known as contrast sensitivity. Department of Defense research has determined criteria for passing or failing this test. Those who failed this test in one or both eyes likely have a neurotoxic burden that is affecting their optic nerves. Eight percent of neurotoxic patients will pass the test.

The next steps in diagnosing CIRS require confirmation of genetic susceptibility and biomarkers that confirm exposure. CIRS susceptibility genes are found roughly one in four people. Genes load the gun but it takes exposure to toxic indoor air to pull the trigger on CIRS. Several biomarkers abnormalities are needed to diagnose CIRS. Key examples are described below:

C4a responds to microbial toxins and tends to rise quickly following exposure to biotoxins from any source. The most common cause of elevated C4a appears to be the toxin-producing molds known to grow in water-damaged buildings.

TGFbeta-1 acts in the bloodstream and in the mucous membranes. In the bloodstream, white blood cellsrelease TGFbeta-1 as a way to suppress an overactive immune system. In CIRS, the innate immune system stays activated because microbial toxins aren’t effectively being processed and cleared by the host. The result is non-stop detection of toxic invasion resulting in chronic inflammation. In the mucous membranes, lymphocytes release TGFbeta-1 as a way to kill microbial intruders. Once the patient is removed from ongoing exposure and MRCoNS is no longer present, the majority of the TGFbeta-1 level in the bloodstream likely reflects immune suppression activity.

MMP-9 is an enzyme associated with inflammation. Levels above 500 are associated with multiple symptoms whatever the cause. MMP-9 is a gelatinase that breaks down perivascular and perineural matrix tissue—the loose connective tissue that surrounds every vessel and nerve in the body.

VEGF (vascular endothelial growth factor) is released in response to poor oxygenation of peripheral tissue beds. VEGF stimulate the formation of new capillaries as a way to compensate for lower levels of oxygen and nutrition reaching tissue beds. Unfortunately VEGF is not the solution to the underlying problem. As a result, blood testing may find the VEGF level to be high at first, a sign that it is trying to compensate for low oxygen levels. Over time the level passes will pass through the reference range to undetectable levels. The only treatment likely to normalize this picture is to reduce inflammation by lowering toxin carriage.

MSH is currently viewed in the peer-reviewed immunological literature as a field general coordinating immune defenses in the skin and in the mucous membranes of the body. CIRS lowers MSH. Another way to lower your MSH is to host a multi-drug resistant coagulase-negative staph known as MRCoNS in the deep nasal space. MRCoNS can release an exotoxin that splits MSH, thus assassinating the field general coordinating mucous membrane defenses against it. If MRCoNS is present, a compounded nasal formula known as BEG spray. After four to six weeks of BEG spray, a repeat swab for MRCoNS will be negative over 80% of the time.

VIP is known by the same literature as an important regulator of immune function and as a regulator blood flow in micro-circulatory tissue beds. ADH tells the kidneys to conserve water.

ADH notifies the kidneys to conserve water. Low levels lead to chronic thirst. Despite frequent water intake, patients with a low ADH level will frequently urinate. These patients often report dry skin, mouth, and eyes. If the serum osmolality runs high, such patients may experience frequent static shocks due to high sweat electrolyte levels.


Treatment

The absolutely necessary first step for treating CIRS is for the patient to remove him- or herself from ongoing exposure to toxic indoor air, since the ingress of mold toxins and inflammagens from breathing that air may cancel out the egress achieved by the binders.

Reducing toxin carriage is accomplished using agents known to bind biotoxins. The only binding agents shown to do so in controlled studies are cholestyramine (CSM) and Welchol. They may also bind certain drugs and dietary supplement ingredients. For this reason, they must be taken a full hour after any drugs or dietary supplements. Both of these binding agents contain quaternary ammonium groups. The nitrogen atom in this chemical group carries a positive charge about the same size as the negative charge carried by most mold toxins. CSM and/or Welchol will remove biotoxins from the body provided the bowels keep moving.

CSM is a large double-decker bus with many seats waiting to be filled by toxins. Welchol is a smaller bus with fewer seats and it is more user-friendly in that it comes as a tablet that can be taken with meals three times daily. CSM is a gritty powder that is best taken 30 minutes before a meal that contains a small amount of healthy fat. This properly positions CSM as toxin-containing bile enters gut space. Compared to Welchol, CSM is more prone to causing constipation or reflux. Because CSM is roughly three times as potent as Welchol, it can reduce toxin carriage at a much faster rate.

CSM also has a stronger effect on the flow gradient of toxins in the body. When toxins are being bound and exported from the body, toxins lightly to cell membranes free up more readily. This results in a higher bloodstream concentration of toxins, which in turn leads to a heightened inflammatory response. This toxin mobilization phenomenon results in symptom flares. In a clean environment, these flares often settle down within three to four weeks as toxin levels fall below the threshold needed to flare symptoms. At this stage, symptoms begin to improve.

Welchol may be the better choice for patients with extreme sensitivities or severe neural excitability. Such patients have little reserves left to withstand symptom flares. Advancing Welchol up to three tablets with meals three times daily would result in roughly seventy-five percent of the binding power of CSM at four times a day.

It is truly amazing to see patients with twenty or more symptoms improve over time by following the diagnosis and treatment protocol developed by Dr. Shoemaker. By conservative calculation, the estimated number of patients with CIRS outnumbers the physicians who know how to manage the condition by roughly a million to one. There’s a health alert worth broadcasting to the public.