What Is CIRS?
A Plain-Language Guide to Chronic Inflammatory Response Syndrome
*Note: this blog was written by me, Mark Volmer. All spelling mistakes, misquotes, errors, and omissions are my own doing. It is not AI generated.*
I want to start with something I hear almost every week in my clinic.
My doctor says my labs are normal. But I feel like I’m dying.
The person sitting across from me (or, more likely, on the other end of a video call) has usually been sick for years. They are exhausted in a way that sleep doesn’t fix. This is not the “I have a small child and a full-time job type tired”. It is a tiredness that I struggle to articulate. A bone-deep tiredness. A tiredness that has a component of pain to it. A tiredness that is unrelenting. A tiredness that engulfs and overwhelms every part of your being. A tiredness that steals from you the person you were and leaves nothing but a faint remembering of who you used to be. Those who know this type of tiredness, know.
I see you.
If that wasn’t enough, those with CIRS also experience a brain that feels foggy, slow, and entirely unreliable. They have joint pain, headaches, gut problems, and a creeping sense of anxiety they can’t explain. For some, anxiety is too kind of a word. Terror is more apt.
They have seen specialists. They have had tests. And they have been told, repeatedly, that nothing is wrong. They have been gaslit time and time again by well-meaning professionals and loved ones.
Something is wrong.
In a significant number of these cases, what I’m looking at is CIRS: Chronic Inflammatory Response Syndrome. And once we give it that name, everything starts to make sense.
So…What Is CIRS?
CIRS stands for Chronic Inflammatory Response Syndrome. It is a complex, multi-system, multi-symptom illness caused by chronic dysregulation of the immune system following exposure to biotoxins. Multi-system meaning it affects many different body systems. Think, cardiovascular symptoms, respiratory symptoms, neurological symptoms, and more. Multi-symptom meaning multiple symptoms, often across body systems. More on this later.
The definition that matters most comes from Dr. Ritchie Shoemaker, the physician-researcher who spent decades developing both the diagnostic framework and treatment protocol for this condition. He describes CIRS as an acquired, chronic illness involving innate immune dysregulation triggered by exposure to a water-damaged building and the organisms within it: mold, bacteria, actinomycetes, mycobacteria, and their byproducts like endotoxins and beta glucans.
What makes CIRS distinct from a typical mold reaction is that simple word: chronic. Check out this article I wrote that differentiates CIRS from a mold allergy.
In most people, the immune system reacts to a threat and then resolves. Inflammation switches on, does its job, and switches off. In CIRS, that off-switch stops working. The inflammatory state becomes self-perpetuating, running long after the original exposure has ended, spreading through virtually every body system, generating a cascade of symptoms that looks different in every patient.
This is why CIRS gets missed so often. There is no single symptom, no obvious lab marker, no obvious explanation. Just a person who feels terrible and doesn’t know why.
What Causes CIRS?
Short answer: biotoxin exposure in a genetically susceptible individual.
Let me break both of those parts down.
Biotoxin Exposure
A biotoxin is any toxic substance produced by a living organism. The most common trigger for CIRS is exposure to a water-damaged building: a home, office, school, or any structure where moisture has allowed mold and/or bacteria to grow. This doesn’t require visible mold. The toxins produced by mold colonies can circulate through HVAC systems, settle in walls, and contaminate an entire building long before anyone sees a single dark spot.
Common sources of biotoxin exposure that can trigger CIRS include:
- Mold and mycotoxins from water-damaged buildings
- Endotoxins from gram negative bacteria
- Actinomycetes
- Tick bites carrying Borrelia burgdorferi (Lyme disease) or other tick-borne co-infections
- Cyanobacteria (blue-green algae) from contaminated water sources
- Toxic dinoflagellates in certain marine environments
The EPA estimates that up to 50% of US buildings have experienced water damage significant enough to support mold growth. I would argue the real number is significantly higher than 50%. More importantly, it’s not just water damage that facilitates mold growth, humidity levels alone can provide enough moisture to facilitate the growth of mold. So the more likely percentage of homes with microbial contamination is likely closer to 90%.
Genetic Susceptibility
Here is the part that explains why not everyone in the same moldy building gets sick.
Approximately 24–25% of the population carries specific HLA-DR gene variations: variants of the Human Leukocyte Antigen system, that impair the body’s ability to recognize and clear mycotoxins. Dr. Shoemaker’s research on HLA-DR linkage disequilibrium established that people with these susceptible haplotypes cannot mount the normal immune response required to tag, neutralize, and eliminate mycotoxins from their system.
The toxins keep circulating. The innate immune system keeps firing. And the inflammatory state becomes chronic.
Meet Christine (name changed to honour patient confidentiality) who lived with her husband in the same house for eleven years. Her husband had zero health problems. Christine, meanwhile, had spent the last four of those years acquiring acronyms from specialists: IBS, PMDD, CFS, and MCAS. Initially Christine knew there was something seriously wrong. But after multiple providers told her she just needed to focus on stress management, had started to wonder if she was just someone who didn’t handle stress well.
When we ran her HLA-DR genetics, she had two susceptible haplotypes. Her husband had none. Christine wasn’t weak. She wasn’t anxious. And no amount of stress management was ever going to be a solution for her. She had a genetic profile that made her body unable to clear the mycotoxins from the mold hidden in their basement crawl space.
Understanding this matters enormously. Not just clinically but for the way patients feel about themselves. I often tell patients, it’s not you, it’s your mitochondria.
How CIRS Affects Your Immune System
Your immune system operates in two main divisions, and understanding both helps explain why CIRS is so hard to shake.
The innate immune system:
- This your first responder. It acts fast, broadly, and without specificity (hence why it is also called the non-specific immune system). It uses inflammation as its primary tool. When you encounter a pathogen, the innate system fires up immediately to contain the threat.
The adaptive immune system
- This the intelligence arm. It analyzes the threat, develops a targeted response, and creates immunological memory. This is why you only get chickenpox once (hopefully); your adaptive system remembers the virus and eliminates it before it can take hold again.
In a healthy immune response, the innate system buys time while the adaptive system generates a specific solution. Then both stand down.
In CIRS, the handoff from innate immune system to adaptive immune system never happens. Because of the HLA-DR gene variation, the adaptive immune system fails to recognize mycotoxins as a target. It never generates a specific response. This leaves the innate system running entirely on inflammation stuck in an endless loop, fighting something it cannot properly identify and cannot resolve on its own.
The result is systemic, multi-organ inflammation that affects the brain, lungs, endocrine system, cardiovascular system, and gut simultaneously and persistently.
What Does CIRS Feel Like?
This is where CIRS becomes genuinely difficult for both patients and clinicians because it can feel like almost anything. A CIRS case will often rhyme with another CIRS case. But it never presents in the same ways.
Dr. Shoemaker’s research has documented 37 symptoms associated with CIRS, spanning nearly every body system. No two patients present identically. One person’s CIRS might look like crushing fatigue and brain fog. Another person’s might look like joint pain, gut issues, and anxiety. A third might have headaches, light sensitivity, and temperature dysregulation as their dominant picture.
The breadth of that list is exactly the problem. A rheumatologist sees joint pain. A gastroenterologist sees IBS. A neurologist sees headaches and cognitive symptoms. A psychiatrist sees anxiety and depression. No one sees CIRS. Because CIRS requires someone to look at all of it together.
Unfortunately, our medical system is siloed. Meaning that you get a specialist for each system of your body. A GI for your gut, a cardiologist for your heart, a neurologist for your brain etc. CIRS has the potential to affect every body system. When the system is designed to identify an illness that transcends systems, you’re never going to get the care you need from said system.
What CIRS Gets Mistaken For
I want to name this explicitly, because I think it’s one of the most important things someone searching for answers needs to hear.
The conditions that CIRS most commonly gets misdiagnosed as include:
- Fibromyalgia
- Chronic Fatigue Syndrome (ME/CFS)
- Irritable Bowel Syndrome (IBS)
- Mast Cell Activation Syndrome (MCAS)
- Multiple Chemical Sensitivity (MCS)
- Multiple Sclerosis (MS)
- Post-Traumatic Stress Disorder (PTSD)
- Depression and anxiety disorders
- Attention Deficit Disorder (ADD and ADHD)
- Somatization disorder
The critical difference between CIRS and all of these is this: CIRS has a cause, a diagnostic pathway, and a treatment that works.
Fibromyalgia is a description of a symptom pattern. CIRS is an explanation for why that pattern exists. When CIRS is properly treated, fibromyalgia symptoms frequently disappear. Why? Because people don’t actually have fibromyalgia. Fibromyalgia is just a word used to describe a set of symptoms.
I think about a patient I’ll call James. He had a fibromyalgia diagnosis for six years. He had been through physiotherapy, two rheumatology consults, and a chronic pain program. Nothing did anything to improve his symptoms. He came to me as a last resort, skeptical and exhausted. He met every diagnostic criterion for CIRS.
We started by testing his apartment, a basement suite he’d lived in for eight years. HERTSMI2 testing revealed a score of 29 – a number that put it firmly in unsafe territory. Looking back through the lens of CIRS, James recounted that all his fibromyalgia symptoms began shortly after moving into that apartment.
How Is CIRS Diagnosed?
Diagnosing CIRS requires a systematic approach that combines symptom history, objective testing, and clinical judgment. There is no single test that confirms it. Instead, you are building a picture from multiple data points.
The Shoemaker consensus diagnostic criteria require that a patient meet all of the following:
- History of biotoxin exposure:
- typically a water-damaged building, though tick bites or algae exposure can also qualify. This can be established through visible mold, musty odors, or environmental testing (ERMI or HERTSMI-2).
- A multi-symptom, multi-system illness
- symptoms spanning at least three body systems from the Shoemaker symptom cluster.
- Positive Visual Contrast Sensitivity (VCS) testing
- CIRS affects a specific nerve pathway in the eye that governs contrast perception. This simple, validated screen has been shown in Shoemaker’s research to be positive in the majority of CIRS patients and can be completed online.
- Abnormal biomarker patterns
- a panel of blood markers that reflect the downstream effects of chronic innate immune activation. Key markers include elevated TGF-β1, elevated C4a, elevated MMP-9, low MSH (melanocyte-stimulating hormone), low VEGF, and ADH/osmolality dysregulation, among others.
- HLA-DR genetic testing
- confirming the presence of a susceptible haplotype, which explains the mechanism of illness and guides treatment expectations.
- Treatment response
- symptom improvement following the sequential Shoemaker Protocol is itself a diagnostic criterion.
The diagnosis is not quick. It requires a knowledgeable clinician and a willingness to look at the full picture rather than one symptom at a time. This is exactly the kind of work we do at Flourish Clinic.
How Is CIRS Treated?
The only peer-reviewed, published treatment protocol for CIRS is the Shoemaker Protocol. A sequential, 12-step intervention that addresses the causes and downstream consequences of chronic innate immune dysregulation.
I want to be clear about that word: sequential. The order matters. Each step addresses a specific part of the disruption and creates the conditions for the next step to work. Jumping ahead, or treating symptoms in isolation, is one of the most common reasons patients plateau or don’t respond.
Here is the framework of how treatment works:
- Remove exposure first.
- No protocol works in an ongoing toxic environment. Environmental testing (ERMI/HERTSMI-2) establishes safety before anything else begins.
- Bind the toxins.
- Binders intercept mycotoxins in the gastrointestinal tract before they can be reabsorbed through enterohepatic recirculation. For patients with susceptible HLA-DR genetics, this step provides the toxin clearance their bodies cannot achieve on their own.
- Eradicate MARCoNS.
- Multiple Antibiotic-Resistant Coagulase-Negative Staphylococci (MARCoNS) colonize the deep nasal passages of most CIRS patients. They form protective biofilms and release toxins that cleave alpha-MSH.
- Correct downstream dysregulation.
- CIRS disrupts a cascade of hormones and immune signals throughout the body. The protocol systematically corrects anti-gliadin antibody responses, androgen imbalance, ADH/osmolality dysregulation, elevated MMP-9 (treated with a low-amylose diet and high-dose omega-3s), low VEGF, and HPA-axis dysregulation.
- Restore VIP as the final step.
- Vasoactive Intestinal Polypeptide (VIP) nasal spray is the capstone of the protocol. Research has shown it corrects persistent inflammatory gene expression, restores neuroendocrine balance, and consolidates recovery. VIP therapy only works when all prior steps have been completed and the patient is in a safe environment. Used too early, it doesn’t hold.
Treatment takes time. Most patients begin to feel meaningful improvement within the first few months. Full recovery can take a year or more depending on how long the illness has been active and how complex the patient’s picture is.
But recovery happens. I have watched it enough times to say that with confidence.
You’re Not Imagining This
I want to close with that, because I know it’s what so many people reading this need to hear.
CIRS is a real, scientifically validated condition. It has a known cause, an objective diagnostic pathway, and a treatment with documented clinical outcomes. The mystery is solvable.
If your symptoms have been dismissed, misdiagnosed, or explained away, if you have been told your labs are normal while your body is telling you something is very wrong, please don’t stop looking.
You can start with our free mold illness quiz to see if your symptom pattern fits CIRS. You can also book a discovery call with our team at Flourish Clinic. We don’t rush this process. We take the time to understand your full history before we make any recommendations.
You have spent long enough being sick and not knowing why. Let’s change that.
