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Tom had been sick for four years. Fatigue so severe he could barely work. Brain fog that made him forget his children's names. Sinus congestion that never cleared. Joint pain with no obvious cause. Three rheumatologists, two neurologists, a pulmonologist, and a psychiatrist couldn't figure it out. He'd been diagnosed with chronic fatigue syndrome, fibromyalgia, depression, and "possible MS" (ruled out by MRI). He was on five medications, none of which helped much. Then his basement flooded. He called a mold remediation company. They found Stachybotrys (black mold) and Aspergillus behind the drywall. Testing showed the ERMI (Environmental Relative Moldiness Index) was 18. Anything above 5 is concerning. Tom's urine mycotoxin test came back positive for ochratoxin A, aflatoxin, and gliotoxin. Four years of symptoms. Five medications. A dozen doctors. The answer was in his walls the entire time. Dr. Ritchie Shoemaker, who developed the CIRS (Chronic Inflammatory Response Syndrome) protocol, estimates that 25% of the population carries HLA-DR gene variants that impair mycotoxin clearance. These people can't detoxify mold effectively. Exposure that bothers most people for a few days makes them chronically ill.
Mold itself isn't the primary threat. Mycotoxins are.
Mycotoxins are secondary metabolites produced by certain mold species. They're toxic to humans at extraordinarily small concentrations. They're invisible, odorless (separate from the musty smell of mold itself), and can persist long after the mold that produced them is dead.
The most clinically relevant mycotoxins:
Ochratoxin A: Produced by Aspergillus and Penicillium species. Nephrotoxic (kidneys), neurotoxic (brain), and immunosuppressive. The most commonly detected mycotoxin in CIRS patients.
Aflatoxins: Produced by Aspergillus species. Hepatotoxic (liver) and carcinogenic. The International Agency for Research on Cancer classifies aflatoxin B1 as a Group 1 carcinogen.
Trichothecenes: Produced by Stachybotrys (black mold) and Fusarium. Potent immunosuppressants. Inhibit protein synthesis. Cause hemorrhaging in severe exposure.
Gliotoxin: Produced by Aspergillus fumigatus. Immunosuppressive. Suppresses T-cell and macrophage function. Makes you susceptible to secondary infections.
Zearalenone: Produced by Fusarium. Estrogenic activity. Acts as an endocrine disruptor.
These mycotoxins are fat-soluble. They accumulate in adipose tissue, brain, and organs. In genetically susceptible individuals (HLA-DR variants), the immune system doesn't recognize and clear them efficiently. They accumulate over months and years, causing progressive multi-system dysfunction.
Chronic Inflammatory Response Syndrome (CIRS) is the clinical condition that results from chronic mycotoxin exposure in genetically susceptible individuals. Dr. Ritchie Shoemaker described and named the condition and published the diagnostic criteria.
CIRS is not an allergy. It's an innate immune response. The body detects biotoxins (mycotoxins, in this case) and mounts an inflammatory response. In susceptible individuals, this response doesn't shut off because the immune system can't clear the toxins.
The result is chronic, systemic inflammation affecting virtually every organ system:
Neurological: Brain fog, memory loss, difficulty concentrating, word-finding problems, disorientation, headaches, light sensitivity, vertigo.
Musculoskeletal: Joint pain (not from arthritis), muscle aches, weakness, cramping.
Respiratory: Chronic sinus congestion, shortness of breath, cough, asthma-like symptoms.
Gastrointestinal: Abdominal pain, diarrhea, nausea, appetite changes.
Fatigue: Often severe and debilitating. Not improved by rest. Worsened by exertion.
Psychological: Anxiety, depression, mood swings, irritability.
Immune: Frequent infections. Slow wound healing. New food sensitivities.
Shoemaker and colleagues published diagnostic criteria in Neurotoxicology and Teratology (2005). The symptom cluster, combined with exposure history and biomarkers, distinguishes CIRS from other conditions.
Why do some people get sick from mold while others in the same building feel fine?
The answer is genetics. Specifically, HLA-DR (Human Leukocyte Antigen-DR) gene variants.
HLA genes code for proteins on the surface of immune cells that present antigens (foreign substances) to T-cells. If your HLA-DR configuration can recognize and present mycotoxin fragments to T-cells, your adaptive immune system mounts an effective response, creates antibodies, and clears the toxins.
If your HLA-DR configuration can't recognize mycotoxin fragments, your adaptive immune system never engages. The innate immune system keeps trying to fight the toxins with non-specific inflammation. But without the adaptive immune cleanup, the toxins aren't cleared. Inflammation becomes chronic.
Approximately 25% of the population carries "mold-susceptible" HLA-DR variants. These people can't clear mycotoxins efficiently.
Shoemaker identified specific HLA-DR haplotypes associated with susceptibility. The most susceptible variants are those that can't present biotoxin antigens, leaving the person reliant on innate immunity alone.
HLA-DR testing is a simple blood test, available through LabCorp or Quest. If you have a susceptible genotype and a history of water-damaged building exposure, CIRS should be investigated.
The other 75% of people can usually clear mycotoxins without chronic illness. They might feel unwell for a few days in a moldy building but recover when removed from exposure.
Diagnosing mold illness requires a combination of exposure assessment, symptom evaluation, and laboratory testing.
Environmental testing: Test your home or workplace for mold. - ERMI (Environmental Relative Moldiness Index): DNA-based test that identifies 36 mold species and produces a score. Score above 5 is concerning. Above 10 is significant. - HERTSMI-2: A simplified version using 5 key species. Score above 11 is problematic. - Air testing: Spore trap testing captures airborne mold counts. Less comprehensive than ERMI but useful for identifying active sporulation.
Urine mycotoxin testing: Tests for specific mycotoxins in urine. - RealTime Laboratories: Tests for aflatoxins, ochratoxin A, and trichothecenes. - Great Plains Laboratory (now Mosaic Diagnostics): Tests for additional mycotoxins including gliotoxin and zearalenone. - Some practitioners use a provocation challenge (glutathione or sauna before collection) to release mycotoxins from tissues, increasing sensitivity.
Blood biomarkers (Shoemaker panel): - hs-CRP: Often elevated. Non-specific inflammation marker. - MSH (Melanocyte Stimulating Hormone): Usually low in CIRS. MSH regulates inflammation, mood, sleep, and immune function. - VIP (Vasoactive Intestinal Peptide): Usually low. Regulates inflammation and GI function. - MMP-9 (Matrix Metalloproteinase-9): Elevated. Reflects immune activation and blood-brain barrier disruption. - TGF-beta 1: Elevated. Drives fibrosis and immune dysregulation. - ADH and osmolality: Dysregulated. Causes increased thirst and frequent urination. - VEGF: Usually low. Impairs oxygen delivery to tissues. - C4a: Elevated. Complement activation marker.
HLA-DR: Genetic susceptibility test.
VCS (Visual Contrast Sensitivity) test: A screening tool available online (free). Loss of visual contrast correlates with neurotoxicity. Not diagnostic alone but useful as a screening tool. Shoemaker found 92% of CIRS patients failed VCS testing.
Treatment follows a specific sequence. Shoemaker developed this protocol based on treating over 7,000 patients.
Step 1: Remove from exposure. This is the most critical step. If your home has mold, you must either remediate it properly (not just paint over it) or leave. No amount of supplementation or medication will overcome ongoing exposure.
Remediation must address the water source (fix the leak), remove affected materials (drywall, insulation, carpet), and professionally clean remaining surfaces. Simply killing mold with bleach doesn't remove mycotoxins. Dead mold is still toxic.
Step 2: Cholestyramine (CSM) or Welchol. Cholestyramine is a bile acid sequestrant (originally used for cholesterol) that binds mycotoxins in the gut, preventing reabsorption through enterohepatic circulation. Dose: 4g four times daily, taken away from food and medications.
Alternatives: Welchol (colesevelam) for those who can't tolerate CSM. Activated charcoal and bentonite clay as lower-potency binders.
Duration: 1-3 months, guided by repeat mycotoxin testing.
Step 3: Treat MARCoNS. Multiple Antibiotic Resistant Coagulase Negative Staphylococci colonize the deep nasal passages in 80% of CIRS patients. These bacteria produce biofilm that suppresses MSH production. Treatment: BEG nasal spray (Bactroban, EDTA, Gentamicin) for 30 days. Retest via deep nasal swab.
Step 4: Correct dysregulated biomarkers. Address low MSH, low VIP, high TGF-beta 1, and other abnormalities systematically. VIP nasal spray (requires compounding pharmacy) is one of the final steps: it regulates multiple CIRS biomarkers simultaneously.
Step 5: Support detoxification. Glutathione (liposomal, 500-1000 mg daily), infrared sauna (promotes mycotoxin excretion through sweat), liver support (NAC, milk thistle), and adequate hydration.
Water damage is the root cause. Preventing and addressing water intrusion prevents mold.
In your home: Fix leaks immediately. Any leak left for more than 48 hours can produce mold growth. Check under sinks, around windows, in basements, and in attics regularly.
Humidity control: Keep indoor humidity below 50%. Use dehumidifiers in basements and crawl spaces. Ensure bathroom exhaust fans vent to the outside (not into attics).
Workplace awareness: Office buildings, schools, and hospitals have some of the highest rates of water damage. If you work in a building with known water damage history and have chronic symptoms, consider environmental testing.
Post-remediation verification: After mold remediation, verify with clearance testing (ERMI or air samples). Many remediation jobs are done incorrectly. Visible mold is removed but mycotoxins remain in dust and materials.
Air filtration: HEPA air purifiers remove mold spores from indoor air. IQAir and Austin Air make medical-grade units effective for mold. Run them continuously in bedrooms.
For genetically susceptible individuals (HLA-DR positive for mold susceptibility): You need to be more vigilant than the general population. Regular ERMI testing of living spaces. Prompt attention to any water damage. Air filtration as standard practice.
Tom moved out of his house. Started cholestyramine. Treated MARCoNS. Took glutathione and did infrared sauna three times weekly. Six months later, his brain fog cleared. Energy returned. Joint pain resolved. He went from five medications to zero.
Four years of suffering. The cause was behind his basement wall.
Mold toxicity is real, documented, and treatable. It's also massively under-diagnosed because most conventional doctors don't think to test for it. If you have chronic fatigue, brain fog, pain, respiratory symptoms, and multiple system complaints that nobody can explain, and especially if you've lived or worked in a water-damaged building, investigate mold. Test your environment (ERMI). Test your body (urine mycotoxins, Shoemaker panel). Test your genes (HLA-DR). Remove from exposure. Bind the toxins. Treat the biofilm. Support detoxification. Monitor biomarkers. The answer to years of unexplained illness might be hiding in your walls, your workplace, or your previous home. Don't let it stay hidden.
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