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You know that smell when you open a storage closet that has been closed for years, the sharp damp note that makes your throat tighten? In the CIRS world, that odor can be the start of a whole-body inflammatory spiral. Researchers studying water-damaged buildings have shown that symptoms can flare within days of reexposure, even after people feel recovered and their labs improve. That snap-back effect is one of the most surprising and validating findings in the CIRS literature, because it shows the trigger is real, repeatable, and measurable [Shoemaker 2005](https://pubmed.ncbi.nlm.nih.gov/15681119/).

Chronic Inflammatory Response Syndrome, or CIRS, is a multi-system, multi-symptom illness driven by an overactive innate immune response after exposure to biotoxins, most commonly from water-damaged buildings. The framework was developed by Dr. Ritchie Shoemaker and has since been expanded by research and clinical consensus. A recent review describes CIRS as an underrecognized condition that may affect a substantial portion of the population, with evidence supporting the structured treatment approach known as the Shoemaker Protocol [Dooley 2024](https://pubmed.ncbi.nlm.nih.gov/39649915/).

This guide is here to make the science feel understandable. You will see how genetics, exposure, and inflammation weave together, why your symptoms feel so scattered, and what a real diagnostic process looks like.

## What CIRS Actually Is

CIRS is not a single organ disease, it is a pattern of immune dysregulation that spills into many systems. Think of it like a smoke alarm that never turns off. Your innate immune system detects biotoxins but cannot clear them effectively, so inflammation stays on. That ongoing signal changes hormones, metabolism, neurologic function, and vascular regulation.

Shoemaker’s early studies in water-damaged buildings documented repeatable symptom patterns, abnormal lab findings, and rapid relapse when people reentered contaminated environments [Shoemaker 2005](https://pubmed.ncbi.nlm.nih.gov/15681119/) [Shoemaker 2006](https://pubmed.ncbi.nlm.nih.gov/17010568/). Those studies built the foundation for CIRS as a defined entity rather than a vague complaint.

## The Genetic Piece, HLA-DR and Why It Matters

About genetics. You do not have to be “weak” to develop CIRS. The key factor is HLA-DR, a set of immune genes that help your body tag and clear toxins. The 2024 review notes that CIRS can affect up to 25% of the population and highlights genetic susceptibility as a key part of the story [Dooley 2024](https://pubmed.ncbi.nlm.nih.gov/39649915/). In practical terms, some HLA-DR haplotypes do not recognize biotoxins well. When that happens, toxins linger, recirculate, and keep the immune system in a constant state of alert.

If you want a deeper dive on the genetics, see the dedicated guide: [HLA-DR Genetic Susceptibility](/vault/hla-dr-genetic-susceptibility).

## Why Symptoms Feel Everywhere

CIRS affects multiple body systems because inflammation touches multiple pathways at once. Shoemaker’s work documented changes in inflammatory markers, visual contrast sensitivity, hormones, and symptom burden in people exposed to water-damaged buildings [Shoemaker 2005](https://pubmed.ncbi.nlm.nih.gov/15681119/). The experience can feel confusing, because no single lab test explains everything. The pattern is the clue.

Common symptom clusters include:

– Brain fog, memory issues, word-finding problems
– Headaches, light sensitivity, dizziness
– Shortness of breath, chronic cough, air hunger
– Muscle aches, joint pain, weakness
– GI issues, nausea, abdominal discomfort
– Sleep disruption, anxiety, mood shifts
– Temperature dysregulation, unusual thirst, static shocks

## The Inflammatory Cascade, Simplified

Here is the short version of what happens in CIRS. You inhale biotoxins, your immune system recognizes them but does not clear them, then inflammation ramps up and stays on. That persistent signal affects multiple hormone and immune pathways, which is why you can feel “broken” in very different ways at once.

– Biotoxin exposure, often from water-damaged buildings
– Failure to tag and clear toxins in genetically susceptible people
– Cytokine and complement activation
– Hormone disruption, including MSH, ADH, VIP, and cortisol
– Neurologic effects such as reduced visual contrast sensitivity
– Ongoing tissue stress from chronic inflammation

## A Timeline of CIRS Progression

## Diagnostic Criteria, the CIRS Checklist

CIRS is not diagnosed by a single lab. The standard approach looks for a combination of exposure history, symptoms, and biomarkers. This is where many people get stuck, because they are told their labs look “normal” when in fact the right panels were never run.

If you want to see the full clinical pathway, this deeper guide walks through the standard diagnostic process step by step: [CIRS Shoemaker Protocol](/vault/cirs-shoemaker-protocol).

## CIRS vs. “Just Allergies”

This is where many people feel dismissed. Allergies and CIRS can overlap, but they are not the same. CIRS involves systemic immune activation and a pattern of biomarkers that do not show up in simple allergy testing.

## Evidence from Shoemaker Studies

The Shoemaker team conducted time-series and clinical trial work in water-damaged buildings that mapped symptoms, labs, and interventions. In one study, 18 of 21 participants had abnormal visual contrast sensitivity, and the average symptom count dropped dramatically after cholestyramine therapy and avoidance [Shoemaker 2005](https://pubmed.ncbi.nlm.nih.gov/15681119/). A follow-up clinical trial in 2006 also described multi-system illness and improvement with treatment strategies in occupants of water-damaged buildings [Shoemaker 2006](https://pubmed.ncbi.nlm.nih.gov/17010568/).

These studies have limitations, and they are not the final word. But they provide concrete, repeatable observations that line up with what many patients experience.

## Treatment, Why Sequence Matters

The Shoemaker Protocol is a stepwise plan. It works because it addresses the root cause first, then moves to downstream effects.

1. Remove from exposure
2. Bind biotoxins with cholestyramine or another binder
3. Address MARCoNS and ongoing nasal inflammation
4. Correct hormone and immune markers in order
5. Restore VIP signaling and stabilize recovery

If you want a detailed breakdown, visit: [CIRS Shoemaker Protocol](/vault/cirs-shoemaker-protocol).

## Finding a Practitioner Who Gets It

You deserve a clinician who understands CIRS and will not dismiss your symptoms. Mold-literate physicians, functional medicine doctors, and some integrative clinics follow the Shoemaker framework. This guide can help you find the right fit: [Finding a Mold-Literate Doctor](/vault/finding-mold-literate-doctor).

## The Bottom Line

CIRS is real, measurable, and treatable. The research from water-damaged building studies shows a repeatable pattern of symptoms, abnormal tests, and rapid relapse with reexposure [Shoemaker 2005](https://pubmed.ncbi.nlm.nih.gov/15681119/) [Shoemaker 2006](https://pubmed.ncbi.nlm.nih.gov/17010568/). A modern review confirms that CIRS is underrecognized, often misdiagnosed, and best treated with a stepwise protocol [Dooley 2024](https://pubmed.ncbi.nlm.nih.gov/39649915/).

If you are feeling stuck, remember this. You are not imagining it, and your body is not failing you. It is responding to a real trigger. With the right testing, the right sequence, and the right environment, many people find their way back to stability.