An August 2025 article by Dr. Ritchie R Shoemaker, Dr. Scott McMahon and colleagues reviews 30 years of research on how living or working in water‑damaged buildings can cause a chronic illness called Chronic Inflammatory Response Syndrome (CIRS).

The authors argue that these buildings contain a mix of harmful microbes and chemicals that can trigger long‑lasting inflammation in people who are genetically vulnerable, leading to multi‑system illness that is often missed by standard medical testing.

They wanted to pull together three decades of data to show that this pattern is real, measurable, and treatable. This paper (Part A) focuses on human health; Part B looks at buildings as ecosystems, and Part C covers treatment.

Their main message is that CIRS is a defined medical condition caused by environmental exposure, not simply anxiety, allergy, or “mystery illness.”

In the mid‑1990s, people on the Pocomoke River in Maryland became very sick after exposure to a toxic dinoflagellate (Pfiesteria) that killed fish. They had sudden fatigue, cough, diarrhea, pain, and brain fog, but routine blood tests were normal.

At the time, Dr. Shoemaker tried a bile‑binding drug called cholestyramine (CSM) to stop a patient’s diarrhea; to his surprise, the patient’s other symptoms and thinking also improved by the next day, and then returned with re‑exposure.

EPA scientist Ken Hudnell then showed that these patients had poorer visual contrast sensitivity (VCS)—a simple eye test—than healthy controls, and that both VCS and blood flow in the retina improved with CSM and worsened again with re‑exposure.

This pattern (sick → treatment → better → re‑exposure → sick again) supported the idea that a toxin was involved.

Over time, the same symptom pattern and response to CSM were seen after other algae toxins and then in people living in moldy, water‑damaged buildings.

The authors found that not everyone exposed to these environments gets sick; instead, certain HLA‑DR immune‑response genes make some people less able to clear toxins and more likely to develop chronic inflammation.

They measured many blood markers and found consistent changes: elevated matrix metalloproteinase‑9 (MMP‑9), complement components (C3a, C4a), and hormone imbalances such as low α‑MSH and disrupted ACTH/cortisol and ADH/osmolality.

These changes fit into what the authors call the “biotoxin pathway”—a chain of events where biotoxins and inflammatory molecules from the environment activate the innate immune system, damage tissues, and disturb hormonal and brain function.

They also show that patterns of symptoms and a failed VCS test can strongly predict CIRS, with a reported probability of about 98.5 percent in their data.

Microbes in water‑damaged buildings

The article explains that water‑damaged buildings are not just about “black mold.” They contain a complex mix of fungi, bacteria, and their toxic products:

Fungi like Stachybotrys, Chaetomium, Aspergillus, and Penicillium can make powerful mycotoxins that damage cells and suppress immunity.

Fungal cell‑wall pieces (beta‑glucans, mannans, chitin) strongly activate immune receptors even when mold is not easily seen.
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Actinobacteria (Streptomyces, Nocardia, Mycobacterium) grow in damp building materials, form tiny spores that reach deep into the lungs, and are hard for the body to clear.​

Gram‑negative bacteria release endotoxins that are known triggers of inflammation and fever.

Using new DNA‑based testing of dust, the authors estimate that about 42 percent of CIRS cases are driven by actinobacteria, 28 percent by endotoxin‑producing bacteria, only about 7 percent by fungi, and 6–10 percent by beta‑glucans. In other words, fungi are important but are not the whole story.

These microbes often live in biofilms—slimy communities on surfaces and in HVAC systems—that protect them from cleaning and allow them to release bursts of particles and toxins when disturbed. The authors say routine air sampling can miss these pulse exposures, which may explain why some “clean” buildings still make susceptible people sick.

What CIRS looks like in patients

People with CIRS typically have many symptoms in several body systems at the same time. Common complaints include:

Strong fatigue and weakness

Muscle and joint pain, headaches, odd “ice pick” pains

Shortness of breath, cough, chest tightness

Diarrhea, abdominal pain, appetite changes

Numbness, tingling, dizziness, temperature swings, thirst and urination changes

Brain fog, memory problems, trouble concentrating, word‑finding difficulty, feeling mentally “slowed”

When the authors compared different groups—people exposed to moldy buildings, cyanobacteria, dinoflagellates, ciguatera, and Lyme disease—they saw nearly the same pattern of symptoms, while healthy controls had very few of these issues. This led them to group these illnesses under the shared label CIRS.

The brain is often heavily affected. The authors point to cognitive symptoms, abnormal VCS tests, and, in other work, MRI brain volume changes (NeuroQuant) as objective signs of injury.

They suggest that mycotoxins, constant immune activation, and chemical signals from biofilms all play roles in damaging or disrupting brain cells.

To connect buildings to illness, the authors use dust‑based testing. They describe EPA scientist Stephen Vesper’s ERMI tool, which ranks homes by the types and amounts of mold DNA. Building on that, they developed the HERTSMI‑2 scoring system, which focuses on a set of high‑risk molds and assigns scores linked to relapse risk in CIRS patients.
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They report that patients who improved after treatment relapsed when returning to high‑score buildings and then improved again when moved to or remediated into low‑score buildings.

For legal and clinical purposes, they also describe a re‑exposure protocol (SAIIE) that measures symptoms and lab markers before and after going back into a suspect building to show specific causation.
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Treatment overview

Detailed treatment is covered in Part C, but this paper outlines the basic approach. Key steps include:

Removing the patient from ongoing exposure or remediating the building to safe levels.

Using non‑absorbable binders like cholestyramine to trap biotoxins in the gut and stop their recirculation.

Addressing nasal staph (MARCoNS), correcting hormone imbalances, and targeting complement and clotting problems.

Using a gene‑expression test (GENIE) to identify remaining inflammatory pathways and guide final treatment steps.

The authors state that, when this stepwise protocol is followed and re‑exposure is avoided, many patients recover, including improvements in brain imaging and function.

The authors note that CIRS and mold‑related illness have often been dismissed, and that legal battles (Daubert, Frye, “specific causation”) forced them to gather more rigorous data.

They credit careful listening to patients and repeating exposure‑treatment‑re‑exposure studies for revealing consistent patterns that could not easily be explained away.

They present CIRS as a real, measurable condition rooted in building science, immunology, and genetics, and they argue that recognizing it can help many people who are currently told their multi‑system illnesses are “all in their head.”

SOURCE:

https://esmed.org/MRA/index.php/mra/article/view/6769?utm_source=chatgpt.com

AUTHORS:

R Shoemaker
Progenedx, Pocomoke, MD
S McMahon
Whole World Health Care, Roswell, NM
A Heyman
School of Medicine and Health Sciences George Washington
E Dorninger
Roots and Branches, Boulder, Colorado
A Thacker
Moldco, Boston, Mass
D Lark
NSJ EnviroSciences Pty Ltd, Newcastle, Australia