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It can be difficult to watch your spouse suffer with a complex chronic illness, especially when it seems that no one can figure out what is going on. And by difficult I mean sad, frustrating, terrifying, maddening, and creates a sense of helplessness. What’s worse is when their illness doesn’t fit the standard medical framework. Then they are ostracized and abandoned by the very ones tasked to help them. They become what I call medical refugees, people left wandering from provider to provider, looking for the help they truly need.
I’m sure you’ve heard many of the following statements before:
“Your labs are all normal.” What labs are they running? Are they searching like an investigator or someone out of time and knowledge to deal with a complex problem.
“It sounds like you may just be sad or depressed [you can insert any mood disorder or emotion here such as anxiety].” Having a complex chronic illness will make you sad, depressed, and anxious. Too bad the typical psychoactive drugs never seem to fix this issue in the long run.
“You are stressed out and need to relax, take a break.” Most chronically ill patients can do nothing but take breaks. Stress plays a role in all disease so it’s an easy scapegoat.
As the support person for your ill spouse, you may latch onto some of these statements because you're not getting any other answers. Neither you nor your spouse know what’s going on, so maybe the doctors are right, maybe it really is just stress or depression. Maybe it really is all in their head. But they aren’t coming to these conclusions after careful examination, they come up with these responses because they don’t know what else to do…
This is when we have to look deeper, when we have to don our Sherlock Holmes style hat and borrow his investigative skills. Doing this becomes a necessity when working with mysterious, complex chronic illnesses. If the standard lab tests such as CBCs, CMPs, or hormone panels reveal nothing, then we must explore other options. With many of my cases this means looking at things such as tick-borne infections, environmental exposures like mold and mycotoxins, and how they impact our body systems, especially the immune system and central nervous system.
Many of these mysterious cases fall into a category called Chronic Inflammatory Response Syndrome. This syndrome, well documented at this point to be caused by biotoxins such as Lyme disease and mold exposure, often ties all of the disparate symptoms these patients have together into a unified whole1. Is it Lyme, chronic viruses, toxicity, allergies, environmental exposure??? YES!
These all funnel into the biotoxin pathways to create a common inflammatory cascade that can be measured via laboratory tests. What’s even better is these tests can be performed by major medical labs such as Labcorp or Quest Diagnostics. Before we look at these labs, let’s talk about how Chronic Inflammatory Response Syndrome explains so many of these complex chronic cases.
Biotoxins can come from many sources such as fungus, Borrelia species (Lyme Disease), algae, but also water damaged buildings2. Once they have been introduced into the body, the immune system and detoxification pathways begin trying to clear them quickly. But with a large enough exposure, poor health, or a genetic susceptibility these body systems quickly get overwhelmed and result in a predictable inflammatory event. These biotoxins bind to nearly every type of cell, creating a cytokine event and affecting nerve function. They release high levels of TGF beta-1 and complement proteins from the immune system. Nerve function can be easily and accurately measured via a test known as the Visual Contrast Sensitivity test3.
These next parts get a bit technical but I believe they are important to review. These cytokines bind to cells and release MMP-9 (releasing more inflammation) but also go on to the brain where they affect leptin receptors. Leptin is vital for maintaining healthy weight and appetite regulation. Suddenly balancing your weight and food cravings seems more difficult than ever. With this leptin resistance comes a decrease in melanocyte stimulating hormone (MSH). These negatively impacts skin, sleep, sex hormones, endorphins, immune suppression, pain regulation, inflammation, leaky gut, and much more. Not only that, but this dysregulation impacts blood clotting and can lead to frequent and even life threatening nose bleeds. Can you see how quickly this spirals out of control but is easily missed if you don’t know what to look for?
As the biotoxin pathway continues, it begins to decrease blood flow and oxygen delivery to the cells (capillary hypoperfusion) and decreasing vascular endothelial growth factors. These looks like chronic fatigue, poor circulation, muscle cramps, and shortness of breath.
Because all of this dysregulates the immune system (and it’s worse in people with genetic susceptibility with HLA DR haplotypes), you can develop antibodies to things like gluten, muscle tissue, cardiolipins, and other tissues in your body. Ever hear doctors talk about odd autoimmune conditions? Bingo…
Because the immune system is suppressed due to low MSH, your spouse may have frequent sinus infections, catch every cold that comes their way, or chronic Lyme. This is the strep throat that lasts a month despite antibiotics, the cold that just seems to linger on, it’s due to immune suppression. Their immune system just can’t fight off these invaders anymore. As this progresses, ADH (antidiuretic hormone: which keeps you hydrated) can get drastically lowered, leading to chronic urination and dehydration. Low blood pressure, low blood volume, POTS, salt cravings, static shocks, muscle cramps, can all result from low ADH.
If you are thoroughly confused, let me break it down into a simple list so you can see all that is affected by biotoxins and Chronic Inflammatory Response Syndrome.
Allergies
Asthma
Shortness of Breath
Prolonged illnesses
Inflammation
Unstable temperature
Poor Concentration
Brain fog
Memory issues
Flu-like symptoms
Body aches
Pain syndromes
Low endorphins
Low sex hormones/hormone imbalances
GI issues/Irritable bowel syndromes
Sleep disturbances
Disrupted circadian rhythms
Dehydration
Frequent urination
Frequent thirst
Easily shocks things or people (static shocks)
Chronic sinus infections (especially staph)
Gluten sensitivity
Chronic fatigue syndrome
Poor circulation
Skin rashes
Hives
Autoimmune markers in blood (various)
Poor vision/visual changes
Difficulty losing weight
Difficulty maintaining weight
Muscle cramps
Multiple chemical sensitivities
Nose bleeds
Poor skin pigmentation/sun sensitivity
Anxiety
Depression
There may even be more that I’m missing from that list. Can you imagine someone walking into your office with all of those symptoms? Most doctors don’t know what to do with that, especially when the standard lab tests are normal. Here are the lab tests that have been shown, in research studies and clinical settings, to give better answers.
HLA DR Genetic Testing (HLA DR1,3,4,5, DQ): genetic testing looking at mold susceptibility.
Vasoactive Intestinal Polypeptide: neuroregulatory hormone for inflammation, digestion, and lung function, among other pathways. Low in CIRS.
Melanocyte Stimulating Hormone (MSH): anti-inflammatory, regulates hormones, endorphins, and sleep cycles. Important for neuroregulation and the immune response. Low in CIRS.
Transforming Growth Factor Beta-1 (TGF Beta-1): Regulates the innate immune system, controls growth of cells, cell movement, and cell death. Can cause lungs to “remodel” or change to become more reactive. Often elevated in CIRS.
Complete C3a and C4a: Inflammation marker for the innate immune system. Will be raised when exposed to water damaged buildings. Often elevated in CIRS.
Anti-Gliadin Antibodies (IgA/IgG): Produced in response to gluten, such as wheat, barley, or rye. Sometimes elevated in CIRS.
ACTH/Cortisol: Signaling and steroid hormones that are produced in response to stress. Can be imbalanced, but often elevated in CIRS.
Vascular Endothelial Growth Factor (VEGF): stimulates new blood vessel formation and growth, stimulates blood flow to the capillary beds (tiny blood vessels near cells). When decreased it lowers blood flow to cells and starves them. Often low in CIRS.
Autoantibodies IgA/IgG/IgM (anticardiolipins and antiphospholipids): Parts of the immune system that attack our own cells/tissues. Sometimes elevated in CIRS.
Antidiuretic Hormone (ADH)/Osmolarity: Also known as vasopressin, controls the amount of water the body keeps or releases. ADH is often low in CIRS while Osmolarity is often high. (Signaling dehydration despite drinking plenty of fluids).
Matrix Metallopeptidase-9 (MMP-9): enzyme that breaks down the extracellular matrix. Plays a role in COPD, RA, cardiovascular disease, and other tissue breakdown processes. Also moves inflammatory elements into smaller areas in the body. Often elevated in CIRS.
Leptin: Regulates how the body holds onto fatty acids. When Leptin is high, one holds onto fatty acids and stores them in fat. This leads to rapid weight gain, and because of the high Leptin, standard approaches to weight loss like eating less and exercising more will fail. Often elevated in CIRS.
*It is vitally important that when running these tests, you use the ranges from the research. The standard lab values are based on populations known to be unhealthy and therefore skewing the ranges.
Additional Labs Found to be Clinically Relevant
Urine Mycotoxins: Measures the amount of mold toxins in a person’s urine. Often helpful to do deep tissue massage before testing to ensure adequate drainage.
Environmental Relative Moldiness Index (ERMI): A DNA test developed by the US-EPA to measure mold in homes. This has been the gold-standard for measuring wet building mold levels and clinically out performs air sampling/air quality tests consistently.
Visual Contrast Sensitivity Testing: An online test used to measure the effect of biotoxins on the nervous system and monitor treatment.
Organic Acids Test: A urine test which measures the metabolites associated with some of the effects of biotoxin illness.
A Call to Action
Husbands, family members, friends, we can not sit idly by and take pat answers as the truth when we have research-verified tests and solutions for these issues. It’s up to us to be protectors, providers, and leaders. It’s up to the wives and women to help us see the forest when all we can focus on is the trees. They help us see the connections, the intuitive knowings, and the relationships when we want to focus on the big vision. Here I’m asking you to take your spouse's concerns seriously and don’t stop searching until you have answers that truly make sense.
Read the research articles and papers below completely. Highlight them, look up definitions when needed, take notes, ASK THE HARD QUESTIONS. But please don’t give up just because it’s hard or overwhelming. I know it’s scary to have your home feel compromised. I know it’s infuriating to think that your belongings may be making your family sick. It’s ok to grieve that loss. But this can consume your whole life if you focus on the frustration and you may want to go back to “normal.” But normal is what got you here and so now we need something extraordinary. We need a coordinated approach to find the problem, provide solutions, and create a safe place for healing.
1. Policy Holders of America: Research Committee Report on Diagnosis and Treatment of Chronic Inflammatory Response Syndrome Caused by Exposure to the Interior Environment of Water-Damaged Buildings (2010)
2. Shoemaker R, Hudnell K, House D. Sick Building Syndrome in Water Damaged Buildings: Generalization of the Chronic Biotoxin-Associated Illness Paradigm to Indoor Toxigenic-Fungi Exposure. 9/2003 5th International conference on bioaerosols (conference peer review)
3. Shoemaker RC, House DE. Sick building syndrome (SBS) and exposure to water-damaged buildings: time series study, clinical trial and mechanisms. Neurotoxicol Teratol. 2006 Sep-Oct;28(5):573-88. doi: 10.1016/j.ntt.2006.07.003. Epub 2006 Aug 7. PMID: 17010568.
Additional Resources/Research Articles
Shoemaker R. Diagnosis of Pfiesteria-human illness syndrome. Maryland Medical Journal 1997; 521-523.
Shoemaker R. Treatment of persistent Pfiesteria-human illness syndrome. Maryland Medical Journal 1998; 47: 64-66.
Grattan L, Oldach D, Perl T, Lowitt M, Matuszak D, Dickson C, Parrott C, Shoemaker R, Kauffman L, Wasserman M, Hebel R, Charache P, Morris G. Learning and memory difficulties after environmental exposure to waterways containing toxin-producing Pfiesteria or Pfiesteria-like dinoflagellates. The Lancet 1998; 352: 532-539.
Shoemaker R, Bullano K. Use of pioglitazone to prevent intensification of persistent symptoms following cholestyramine treatment of patients with Post-Lyme syndrome. 2000; American Diabetes Association Annual Meeting. (conference peer review)
Friedman M. 2000 Maryland Family Doctor of the Year, RC Shoemaker MD.
Shoemaker R. Endocrine Society 6/2001. Use of rosiglitazone in treatment of hyperinsulinemic obesity in non-diabetics (conference peer review).
Shoemaker R, Hudnell K. Possible Estuary-Associated Syndrome: Symptoms, vision, and treatment. Environmental Health Perspectives 2001; 109: 539-545.
Shoemaker R. Residential and recreational acquisition of possible estuary-associated syndrome: A new approach to successful diagnosis and treatment. Environmental Health Perspectives 2001; 109: 791-796.
Shoemaker R. Linkage disequilibrium in alleles of HLA DR: differential association with susceptibility to chronic illness following exposure to biologically produced neurotoxins. American Society of Microbiology 2003. (conference peer review).
Shoemaker R, Hudnell K, House D. Sick Building Syndrome in Water Damaged Buildings: Generalization of the Chronic Biotoxin-Associated Illness Paradigm to Indoor Toxigenic-Fungi Exposure. 9/2003 5th International conference on bioaerosols (conference peer review)
Shoemaker R. Use of visual contrast sensitivity and cholestyramine in diagnosis and treatment of indoor air acquired, chronic, neurotoxin-mediated illness. 9/2003 (conference peer review)
Shoemaker R, Hudnell K, House D, Domenico P. Association of nasal carriage of methicillin resistant and multiple antibiotic resistant coagulase negative staphylococci species with deficiency of alpha melanocyte stimulating hormone in Chronic Fatigue Syndrome: implication for expanded treatment options. American Society of Microbiology 2003. (conference peer review)
Shoemaker R, Hudnell D. A time-series study of sick building syndrome: chronic, biotoxin-associated illness from exposure to water-damaged buildings. Neurotoxicology and Teratology 2004; 1-18.
Shoemaker R, Rash J, Simon E. Sick Building syndrome in water damaged buildings: generalization of the chronic biotoxin associated illness paradigm to indoor toxigenic fungi. Bioaerosols, fungi, bacteria, mycotoxins and human health. Dr med Eckardt Johanning MD editor 2006.
Shoemaker R, Hudnell, House D, Kempen A, Pakes G. Atovaquone plus cholestyramine in patients coinfected with Babesia microti and Borrelia burgdorferi refractory to other treatment. Advances in Therapy 2006; 23: 1-11.
Shoemaker R, Lipsey R. Results of health screening and visual contrast testing. St. Bernard’s Parish, Louisiana. 2006. published on-line
Shoemaker R, House D. Sick building syndrome (SBS) and exposure to water-damaged buildings: Time series study, clinical trial and mechanisms. Neurotoxicology and Teratology 2006; 573-588.
Shoemaker R, Lawson W. Pfiesteria in Estuarine Waters: The question of health risks. Environmental Health Perspectives 2007; 115: A2-A3.
Shoemaker R, Lin K. Inside Indoor Air Quality: Environmental Relative Moldiness Index (ERMI). Filtration News 2007; 32-36.
Shoemaker R, Maizel M. Treatment of elevated C4a in patients with CFS using low doses of erythropoietin safely reduces symptoms and lowers C4a: a prospective clinical trial 2007, IACFS (conference peer review).
Shoemaker R, Giclas P, Crowder C, House D. Complement split products C3a and C4a are early markers of acute Lyme disease in tick bite patients in the United States. International Archives of Allergy Immunol 2008; 146: 255-261.
Shoemaker R, Maizel M. Innate immunity, MR spectroscopy, HLA DR, TGF beta-1, VIP and capillary hypoperfusion define acute and chronic human illness acquired following exposure to water-damaged buildings. 2008. International Healthy Buildings (conference peer review)
Shoemaker R, Maizel M. Exposure to interior environments of water-damaged buildings causes a CFS-like illness in pediatric patients: a case/control study. 2009 bulletin of the IACFS
Shoemaker R, House D. Characterization of chronic human illness associated with exposure to cyanobacterial harmful algal blooms predominated by Microcystis. 2009 Cyanobacterial harmful algal blooms pg 653.
Shoemaker R, Exposure to water damaged buildings causes a readily identifiable chronic inflammatory response syndrome successfully treated by a sequential intervention protocol. Biology of Fungi, International Mycology Congress 2009 (conference peer review)
Shoemaker R, House D, Ryan J. Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: A case/control study. Neurotoxicology and Teratology 2010; 633-639.
Shoemaker R. ACOEM position statements on mold: ploys and lies. Published on line 2011.
Shoemaker R, House D, Ryan J. Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health 2013; 3: 396-401.
Shoemaker R. House D, Ryan J Structural Brain Abnormalities in Patients with Inflamatory Illness acquired Following Exposure to Water Damaged Buildings A Volumetric MRI Study Using Neuroquant. June 17, 2014
Ryan J. Wu Q. Shoemaker R. Transcriptomic Signatures in Whole Blood of Patients Who Acquire CIRS Following an Exposure to the Marine Toxin Ciguatoxin. August 8 2015
Medically sound investigation and remediation of water-damaged buildings in cases of chronic inflammatory response syndrome.Berndtson K, McMahon S, Ackerley M, Rapaport S, Gupta S, Shoemaker R, January 19, 2016
Indoor Environmental Professionals Panel of Surviving Mold CONSENSUS STATEMENT Medically sound investigation and remediation of water-damaged Buildings in cases of CIRS-WDB; Larry Schwartz CIEC, BSME, MBA, Greg Weatherman CMC, Michael Schrantz CIEC, CMI, BPI-BA/EP, Will Spates CIAQP, CIEC, Jeff Charlton, ACIEC, AACIEH, Keith Berndtson MD, Ritchie Shoemaker MD April 12, 2016
Reduction in Forebrain Parenchymal and Cortical Grey Matter Swelling across Treatment Groups in Patients with Inflammatory Illness Acquired Following Exposure to Water-Damaged Buildings. McMahon SW, Shoemaker RC, and Ryan, JC April 12, 2016
Internal Medicine Review- Intranasal VIP safely restores volume to multiple grey matter nuclei
in patients with CIRS- April 2017 Shoemaker, R., Katz, D., Ackerley, M., Rapaport, S., McMahon, S., Berndtson, K., Ryan, J.
Shoemaker, RC and Lark, D - 2016, HERTSMI-2 and ERMI: “Correlating Human Health Risk with Mold Specific qPCR in Water-Damaged Buildings” #658 in Proceedings of the 14th International Conference on Indoor Air Quality and Climate, International Society for Indoor Air Quality and Climate, Ghent, Belguim.
2018 Diagnostic Process for Chronic Inflammatory Response Syndrome (CIRS): A Consensus Statement Report of the Consensus Committee of Surviving Mold
Urinary Mycotoxins: A Review of Contaminated Buildings and Food in Search of a Biomarker Separating Sick Patients from Controls; Shoemaker, Ritchie; Lark, David
Shoemaker, R. Ryan, J. Medical Research Archives, Volume 4, Issue 7. RNA-Seq on patients with chronic inflammatory response syndrome (CIRS) treated with vasoactive intestinal peptide (VIP) shows a shift in metabolic state and innate immune functions that coincide with healing