CIRS Symptoms: Chronic Inflammatory Response Syndrome

CIRS Symptoms

At a prevalence of 7%, chronic inflammatory response syndrome is one of the greatest public health dilemmas in existence.

CIRS Symptoms: What Is CIRS?

To answer this question, let’s break down the term into two. 

Syndrome: This term is often given when an individual suffers from a group of specific symptoms that are known to go together but don’t have an established cause, trajectory, or treatment path. Think of Irritable Bowel Syndrome or Chronic Fatigue Syndrome as common examples. In the research, the cause is debated (partly because there are multiple causes). As a result, there is no single treatment that will have a high success rate (and let’s not forget that symptom improvement doesn’t necessarily mean successful treatment if you have to lead a sheltered life or consume a restrictive diet on an ongoing basis).

Chronic inflammatory response: This is what it says – someone is experiencing a chronic inflammatory response….to something!

It often gets described as a ‘multi-system and multi-symptom condition,’ meaning that there are a wide range of symptoms that may be connected to different bodily systems. For example, someone with CIRS might have bloating (which is associated with the digestive system) and headaches (associated with the nervous system)

But, and this is a big but, based on the work of Dr. Richie Shoemaker, we know that many people who receive a diagnosis of CIRS have been exposed to a biotoxin. 

What are biotoxins?

Biotoxins are defined as substances which are both toxic and have a biological origin. They include: 

  • Mycotoxins (made by fungi).
  • Zootoxins (made by animals) 
  • Phytotoxins (made by plants)

As a result, the three most common ways to develop CIRS are:

  • Exposure to a water-damaged, mouldy building
  • Being bitten by a tick, such as Lyme disease
  • Exposure to dinoflagellates (waterborne toxin producers) like Ciguatera or Pfiesteria

Once thought to be somewhat of a unique condition, recent research demonstrates that Alzheimer’s disease (5) and inflammatory bowel disease (3) may be connected with CIRS. It is likely many other conditions will be, too – essentially, a chronic inflammatory response driven by exposure to biotoxins might cause a long list of conditions.

In fact, experts in this field believe CIRS may likely be linked to a host of functional disorders – fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, functional abdominal pain syndrome, functional neurological disorders, chronic headaches, and chronic regional pain syndrome, among others.

“Many patients see 20-30 physicians before the proper diagnosis is made. Many unnecessary invasive procedures, lab tests, and imaging exams are performed, in futility, because they seek wrong diagnoses.” (1)

Specific Symptoms Of CIRS

While CIRS symptoms may appear random at first, Dr. Shoemaker’s analysis revealed that symptoms do have commonalities that allow them to be broken into 13 distinct clusters (3): 

  • Diarrhea, Abdominal pain, Numbness
  • Congested sinuses, Shortness of breath
  • Impaired memory, Difficulty with word finding
  • Heightened skin sensitivity, Tingling/Pins and needles
  • Disorientation, Metallic taste, Watery eyes
  • Weakness, Body aches, Headache, Sensitivity to light, Trouble learning new info
  • Blurry vision, Night sweats, Mood swings, Ice-pick pain, Red or bloodshot eyes
  • Joint pain, Morning stiffness, Muscle cramps
  • Deep, persistent fatigue
  • Trouble concentrating
  • Dizziness, static shocks,
  • Extreme thirst, cough, confusion
  • Trouble regulating body temperature, frequent urination

If a patient has symptoms present in 6 or more of the symptom clusters, biotoxin illness is possible, and further testing and evaluation must be done. Symptoms in 8 or more clusters are consistent with biotoxin illness (4). I’d argue further testing should still be done, even if 8 or more clusters are present. 

Other symptoms I have read about in the research include:

  • Bile acid reflux that occurs in over 66% of CIRS patients.
  • Thyroid illness frequently accompanies CIRS
  • Hyperflexibility
  • Inflamed sclerae
  • Pallor
  • Tremors
  • Facial rash 
  • weakness of the anti-gravity muscles of the dominant shoulder. 

There are two other considerations around symptoms of CIRS.

1. Symptoms of CIRS seem to be different based on age.

Practitioners specialising in this area describe how children under 5 often have only one bodily system involved, such as chronic headaches or gut issues.

Children 5-11 years old have one or more bodily systems affected and generally tend to have more of the above symptoms. 

Patients 11-19 years tend to present similarly to adults, i.e., they have a truly multi-system and multi-symptom condition (3).

2. Symptoms May Wax And Wane

Symptoms of CIRS vary from day to day and are subject to potentially unnoticed environmental exposures. It is, therefore, important to stay mindful of your schedule and what you might be being exposed to – patients should also log symptoms and schedule to look for connections (3).

What Is Required For Diagnosis

The case criteria simply include (4):

  • 1. Symptoms that are consistently associated with biotoxin illness. 6 of the symptom clusters listed above justify a more in-depth investigation (more below on this). 8 symptom clusters, and we can confidently consider biotoxin illness.
  • 2. History consistent with exposure to a water-damaged property, toxicogenic blue-green algae, tick bites, or consumption of reef fish.
  • 3. A positive Visual Contrast Sensitivity (VCS) test,
  • 4. Genetic predisposition as determined through testing.
  • 5. Presence of MARCoNS in the nasal cavity.
  • 6. An abnormal rise in pulmonary arterial systolic hypertension during exercise.
  • 7. Biomarkers consistent with CIRS: see biomarkers section below for more details.

Visual Contrast Test

The inflammation in response to biotoxin exposure has been shown to cause nerve dysfunction, resulting in various neurological symptoms. One of these symptoms is diminished visual contrast sensitivity (the ability to detect visual patterns). 

Dr. Shoemaker theorises this is due to the reduced velocity of flow of red blood cells reaching structures in the eye that are responsible for sending information via the optic nerve to the brain. 

However, as well as biotoxins being known to affect nerve dysfunction, there are numerous other things that can affect this test, including heavy metals such as mercury and lead, nutrient deficiencies, and parasites. 

What Is The Visual Contrast Test?

During the test, you are shown a series of images designed to measure your ability to detect visual patterns. When you have a biotoxin-related illness, you won’t do great during this test! (I failed it the first few times I did the test!) The test is thought to be very accurate and supports an accurate diagnosis of biotoxin-related illness. In fact, I have read that it will diagnose you correctly with 92 percent accuracy, meaning only 8 percent will get a false negative. 

The good news is that it is very cheap to do online and, so, can be used to assess improvement during your treatment. 

Biomarkers That Might Help Explain Symptoms

In the Shoemaker protocol, there are 10 standard biomarkers:

The lab tests used are (2):

  • HLA haplotypes – To determine if a patient is genetically susceptible.
  • VIP: a neuropeptide that helps regulate inflammation throughout the body
  • MSH is a hormone that helps regulate other hormones, such as aldosterone, and also regulates inflammatory and immune processes. What I find super interesting is that MSH controls tight junctions in the gut. Could this be a less well-known cause of leaky gut?
  • ADH, also known as vasopressin, is a hormone that influences hydration and helps control blood pressure.
  • ACTH with cortisol.
  • TGF-β1: a molecule that influences the immune system and inflammation.
  • MMP-9: a zinc-dependent enzyme involved in the breakdown of cell membranes in the blood vessel walls and involved in inflammatory processes.
  • C4a: involved in activating the innate immune systems complement cascade.
  • MARCoNS:. MARCoNS secrete toxins that decrease MSH.
  • The presence of significant ACLA or AGA antibodies. AGA is produced in response to gliadin found in gluten.

Two other key markers for CIRS are:

Leptin is well known as a “satiety hormone.” High levels of leptin increase the amount of fat stored in the body, causing weight gain. In biotoxin-related illness, inflammatory molecules called cytokines bind to leptin receptors and interfere with leptin signaling, creating leptin resistance.

VEGF: Vascular Endothelial Growth Factor stimulates the growth of new blood vessels when blood circulation is inadequate

Ignoring the CIRS epidemic will be disastrous. Researching CIRS and training practitioners will prevent an even larger epidemic than already exists.

CIRS patients routinely possess:

  • An HLA predisposition.
  • Depleted neuroimmuno-regulatory peptide levels (VIP and MSH).
  • Elevations of innate immune system markers (TGF-β1, MMP-9, and C4a), 
  • Dysregulation in hormones (such as dysregulated cortisol).
  • Abnormal VEGF levels
  • Presence of AGA antibodies
  • Nasal carriage of Marcons.


In summary, there are a lot of symptoms that have been associated with CIRS, and these can be put into clusters to help with the diagnosis. There are also several biomarkers that can be helpful in diagnosing CIRS, but also helpful in understanding what is creating the symptoms in the first place. 


  1. Scott W. McMahon An Evaluation of Alternate Means to Diagnose Chronic Inflammatory Response Syndrome and Determine Prevalence
  2. Natasha Thomas, Understanding Chronic Inflammatory Response Syndrome (CIRS)
  4. Werner Vosloo ND, Steps of the Shoemaker Protocol for treating Chronic Inflammatory Response Syndrome acquired following exposure to Water Damaged Buildings [CIRS-WDB].
  5. Bredesen, D. E. (2016). Inhalational Alzheimer’s disease: an unrecognized—and treatable—epidemic. Aging (Albany NY), 8(2), 304. Full text:
  6. Hope, J. (2013). A review of the mechanism of injury and treatment approaches for illness resulting from exposure to water-damaged buildings, mold, and mycotoxins. The Scientific World Journal, 2013. Full text:


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