You walk out of your house and your body starts to breathe again. Your head clears on day two of a trip, then the fog slams back in the minute you return. It feels like your home is the problem, but it is also the place you are supposed to heal.
If you have been told this is just stress, it makes sense if you feel angry and tired. You are not imagining it. There is a body of research that describes this exact pattern, and it has a name.
Chronic Inflammatory Response Syndrome, or CIRS, is a multi system illness triggered by biotoxins from water damaged buildings. Dr. Ritchie Shoemaker is the physician who built the most studied clinical framework for diagnosing and treating it. This article is a research overview, not medical advice. Think of it as a map that shows you how the science fits together.
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Abnormal VCS
Participants exposed to water damaged buildings had visual contrast deficits that improved with treatment
2005–2006
Key trials
Time series and clinical trial data established the early evidence base
## What CIRS Is, In Plain Language
CIRS starts with exposure. Biotoxins from water damaged buildings can trigger an innate immune response that does not shut off. In susceptible people, the immune system stays on high alert even after the exposure ends. That ongoing signal can disrupt hormones, blood flow, and brain function. It is why symptoms can feel scattered and relentless.
The Shoemaker framework describes a pattern that is measurable. People with suspected CIRS often show a combination of abnormal symptoms, impaired visual contrast sensitivity, and immune markers that point to inflammation and immune dysregulation. The research is not perfect, but it is specific and reproducible enough to guide a structured treatment sequence.
If you want a gentle primer before diving into research, start here: [Understanding CIRS](/vault/understanding-cirs).
If your symptoms jump between systems, that does not mean they are unrelated. CIRS describes a whole body response that can show up in many places at once.
## The Research Foundations
Two early studies are cited often because they established a clear sequence: exposure, abnormal findings, treatment, and relapse with re exposure. In a time series of people exposed to water damaged buildings, investigators documented multi system symptoms plus abnormal visual contrast sensitivity. Symptoms and VCS improved after cholestyramine therapy and avoidance, then returned with re exposure [Shoemaker 2005](https://doi.org/10.1016/j.ntt.2004.07.005).
A later clinical trial focused on cholestyramine as a bile acid binder that can capture biotoxins in the gut for elimination. Participants again showed improvement when exposure control and binders were used together [Shoemaker 2006](https://doi.org/10.1016/j.ntt.2006.07.003). A more recent review summarizes the clinical evidence and highlights how often CIRS is missed in mainstream practice [Dooley 2024](https://pubmed.ncbi.nlm.nih.gov/39649915/).
This is not a cure in a bottle. It is a sequence that acknowledges how the immune system behaves when it is stuck in a loop.
## Key Biomarkers in the Shoemaker Model
The Shoemaker Protocol uses lab markers to confirm the inflammatory pattern and guide treatment order. The exact labs vary by clinician, but the core set often includes immune and hormone markers such as:
MSH
Often low, linked to sleep, mood, and immune regulation
C4a and C3a
Complement activation markers that reflect immune overdrive
TGF beta 1
Cytokine involved in inflammation and tissue remodeling
ADH and osmolality
Hydration regulation that can drive thirst and lightheadedness
These markers are not a diagnosis by themselves. They are a pattern. The protocol treats the pattern in a specific order to reduce inflammation without forcing the body to compensate too early.
If this is new to you, you might want a broader overview of mold illness first: [What Is Mold Illness](/vault/what-is-mold-illness).
## Why the Sequence Matters
This protocol is intentionally linear. You do not correct hormones while you are still being exposed. You do not use the final step until upstream markers are stable. It is a conservative approach designed to prevent the immune system from relapsing.
That matters because the Shoemaker studies showed relapse with re exposure, even after improvement [Shoemaker 2005](https://doi.org/10.1016/j.ntt.2004.07.005). The clinical reality is that many people feel better while away from their home, then regress when they return. This is not failure. It is the expected result of ongoing exposure.
✅ CIRS pattern
- Multi system symptoms that shift and cluster
- Worse indoors, better away
- Abnormal VCS or inflammatory markers
❌ Simple allergy pattern
- Primarily respiratory or seasonal
- Improves with antihistamines alone
- No clear relapse pattern tied to buildings
If you are trying to untangle your own pattern, this guide can help: [Mold Illness vs Mold Allergy](/vault/mold-illness-vs-mold-allergy).
## The Shoemaker Protocol, Step by Step
Below is the research based sequence in plain language. Your clinician might personalize it, but the order is the core idea.
Remediate, relocate, or create a safe room. If exposure continues, the immune response continues. This is the foundation.
Cholestyramine or colesevelam bind biotoxins in the gut for elimination. This is the most studied treatment step [Shoemaker 2006](https://doi.org/10.1016/j.ntt.2006.07.003).
Resistant staph colonization in the sinuses can keep inflammation active. Targeted treatment may be used if testing is positive.
If markers suggest gluten driven inflammation, diet and gut repair are addressed here.
DHEA and testosterone can be low or dysregulated, affecting energy, mood, and recovery.
Hydration and electrolyte regulation are often off balance in CIRS and can drive dizziness and frequent urination.
MMP 9 reflects ongoing inflammation and vascular stress. It is addressed after biotoxin clearance.
VEGF supports blood flow and oxygen delivery. Low levels can contribute to fatigue and pain.
Complement activation is another sign of immune overdrive. This step helps settle it.
This complements the previous step and supports immune balance.
TGF beta 1 is involved in tissue remodeling and immune signaling. It often stays high in CIRS.
VIP is considered the final step and is typically used only after labs and exposure are stable.
Skipping steps or starting VIP early can backfire. The protocol is built to reduce inflammation in a controlled order.
If you want practical help with exposure control, these guides are helpful: [Testing Your Home for Mold](/vault/testing-your-home-for-mold) and [Creating a Safe Room](/vault/creating-a-safe-room).
## What the Criticism Gets Right
It is fair to say this approach is not universally accepted. Some clinicians view the protocol as too rigid. Insurance often does not cover testing. Some biomarkers are specialized and not available everywhere. Treatment can be long and expensive.
Those critiques are real, and they are part of your decision process. You deserve a clinician who can explain why each step matters, not just insist on it.
If a practitioner cannot explain the logic of each step, it is okay to seek a second opinion. You are allowed to understand your plan.
## Practical Steps You Can Take Now
You do not need to do everything today. You do need a starting point that is grounded.
- Track symptoms with dates, places, and exposures
- Run a VCS test as a low cost screening tool
- Schedule a professional inspection or ERMI test
- Gather past labs and imaging for a future consult
- Reduce exposure in the room where you sleep
If you want help finding a clinician who understands this framework, see: [Finding a Mold Literate Doctor](/vault/finding-mold-literate-doctor).
## Encouragement for the Long Haul
It sounds like you have been trying to recover in the same place that made you sick. That is exhausting. The Shoemaker Protocol is not a judgment of how you got here. It is a map out.
You do not have to believe in everything at once. You just need the next right step. If you can control exposure and document your pattern, you are already doing real work that your future clinician can use.
The Shoemaker research describes a measurable pattern of illness and a stepwise sequence for recovery. The order matters because exposure control and toxin binding come first.
### Read next
– [Understanding CIRS](/vault/understanding-cirs)
– [What Is Mold Illness](/vault/what-is-mold-illness)
– [Testing Your Home for Mold](/vault/testing-your-home-for-mold)
– [Detox Binders Explained](/vault/detox-binders-explained)
– [Finding a Mold Literate Doctor](/vault/finding-mold-literate-doctor)
## Sources
– [Shoemaker 2005](https://doi.org/10.1016/j.ntt.2004.07.005) Time series study of symptoms, VCS, and treatment response after exposure to water damaged buildings
– [Shoemaker 2006](https://doi.org/10.1016/j.ntt.2006.07.003) Clinical trial of cholestyramine in water damaged building exposure
– [Dooley 2024](https://pubmed.ncbi.nlm.nih.gov/39649915/) Review of evidence for CIRS treatment efficacy