Chronic Inflammatory Response Syndrome (CIRS)


What is Chronic Inflammatory Response Syndrome (CIRS)?


Chronic Inflammatory Response Syndrome (CIRS) is a multisystem, multi-symptom illness triggered by biotoxin exposure. A biotoxin is any living toxin. When exposed, the immune system can become stuck in an inflammatory state even when the exposure is removed.


24% of the population is genetically at risk to develop CIRS, due to alterations in their Human Leukocyte Antigen genes (HLA). There are specific HLA genes involved in CIRS and you only need to have one gene to be predisposed. For those genetically at risk for CIRS, chronic exposure to external infections, toxins, or inflammatory signals from within the body causes an ongoing innate immune response in the immune system.


The innate immune system, which is the non-specific first line of immune defense, turns on, as it should in response to any exposure. However, having one or more of the HLA genes will prevent a handover to the adaptive immune system. This means there is no antibody created and the innate immune system is never told to shutoff. As a result cytokines, the proteins produced by the immune system are over produced, and inflammation is triggered, regardless of whether the exposure is still there or not.


You have these genes your whole life, but they are only expressed when you have a combination of biotoxin exposures (one or many) and other stresses on the system, such as toxin exposures, stress, and food triggers. These environmental inputs will trigger the gene expression at different times – you can first be diagnosed as a child, or in your later years.


This dysregulation and inflammation can lead to damaged tissues and cells, alter gene expression, autoimmunity, and disrupt hypothalamic hormones (hormones produced in the brain), downstream hormones (hormones downstream from the brain), and peptides (small chains of amino acids). This causes many debilitating symptoms, which can affect every body system. Chronic Inflammatory Response Syndrome is a progressive illness that if left untreated can rob patients of their quality of life.


Triggers of Chronic Inflammatory Response Syndrome


CIRS is the result of downstream abnormalities that occur in the body from biotoxin exposure. A biotoxin is a toxic substance produced by living organisms.


A patient may be exposed to biotoxins from the mold and bacteria in water-damaged buildings, from diseases caused by tick bites, by consuming tropical fish, or even exposure to certain algae.


Knowing whether your Chronic Inflammatory Response Syndrome trigger is current is critical for proper recovery. That is why it is so important for physicians to get a thorough history from you before diagnosing or treating CIRS. In some cases we may not be able to figure out the exact trigger (or when it occurred), but we are most interested in ruling out current external exposures and internal infections.


CIRS triggers can be from any of the following:


  • Microbes, toxins and inflammagens from Water Damaged Buildings (WDB). The main 3 are mold, actinobacteria and endotoxin. We typically test for these inside the home.
  • Lyme disease and co-infections
  • Cyanobacteria (blue grey algae), often from freshwater exposures such as lakes
  • Apicomplexans like Babesia (parasite)
  • Pfiesteria, from exposure to ill fish – swimming
  • Ciguatera, from eating tropical fish
  • Red tide
  • Recluse spider bites
  • Mycobacteria
  • Traumatic brain injury can trigger similar downstream effects as CIRS


Symptoms of CIRS


Due to varied environmental stimuli and each individual’s unique genes, patients with Chronic Inflammatory Response Syndrome can present with wildly different symptoms. Because of the wide range of symptoms a CIRS diagnosis can be easily missed at family doctor visits, mostly because it is not looked for. Patients with CIRS are often misdiagnosed with allergies, anxiety, depression, PTSD, Alzheimer’s, Parkinsonism, Chronic Fatigue Syndrome, and many other conditions.


When CIRS is suspected, an easy screening symptom questionnaire & visual contrast sensitivity test can accurately delineate who may be at risk. This will then alert us to test further. Our Functional Medicine Physicians at Linden & Arc get to the root cause of your symptoms, so you can be sure you are receiving proper treatment.


CIRS is often suspected if:


  1. You have a complex multi system, multi symptom illness.
  2. You are not responding as expected to basic treatments, such as gut, hormone and nutrient treatments.
  3. You have atypical presentation of illness that may not necessarily fit into a clear diagnostic box in the conventional medical system
  4. You have multiple chemical sensitivities
  5. You have a known infective exposure, or home exposure


CIRS Symptoms:


  • Abdominal pain/diarrhea
  • Disorientation/confusion
  • Teary eyes
  • Metallic taste
  • Congested sinuses
  • Shortness of breath
  • Memory loss
  • Body aches/weakness
  • Headache/light Sensitivity
  • Brain fog/ difficulty concentrating
  • Skin sensitivities
  • Red eyes/blurred vision
  • Mood swings
  • Joint pain/cramps/stiffness
  • Numbness
  • Fatigue
  • Vertigo
  • Excessive thirst
  • Cough
  • Difficulty regulating body temperature
  • Increased urinary frequency
  • Appetite changes


Many Patients struggling with Chronic Inflammatory Response Syndrome may also deal with:


  • Histamine issues and Mast Cell Activation Syndrome (MCAS)
  • Electromagnetic / EMF sensitivity
  • Limbic system dysfunction
  • Over reactive nervous system (from Neuroinflammation)
  • Poor detoxification
  • Issues with gut health, hormones, nutrient imbalances, neurotransmitter imbalances


As discussed, CIRS is an inflammatory illness. However, we also now know that it causes significant disruption in the metabolism of the cell, including energy and protein production. It has transcriptomic effects, meaning it can also turn genes on and off. We see a specific pattern of gene dysregulation in CIRS at baseline, vs. after treatment. This is an extremely important part of correcting CIRS, as our goal is to prevent some of the complications that occur as a result of gene dysregulation.


Complications of Gene dysregulation include:


  • Insulin dysregulation
  • Metabolic acidosis
  • Low metabolism and energy production
  • Low protein production
  • Pulmonary hypertension
  • Effects on brain structure/ volume


Chronic Inflammatory Response Syndrome Diagnosis


The presentation of Chronic Inflammatory Response Syndrome varies between different people. That is why it is extremely important to have a thorough workup done when you are suffering with a wide range of symptoms. An in depth history of your entire ‘timeline”, your life story, your exposure history, and detailed lab investigations are needed. The various tests are necessary for a firm CIRS diagnosis and to properly track the success of treatments. We want to be sure we are on the right track and that you are responding to treatment and will continuously trouble shoot your individual illness. In complex illness, there is no room for guessing!


At Linden & Arc Vitality Institute the following Testing is done at baseline and repeatedly throughout the protocol:


1. Proteomic Lab Testing


Proteomic testing is how we make the diagnosis of CIRS, as per published literature. Below is a list of the labs, with short description of what they indicate:


  • Visual contrast sensitivity (VCS) test – this is an eye test measuring contrast, which decreases in people with CIRS
  • HLA testing tells us about your susceptibility to CIRS – are you one of the 24% of people with defective antigen presentation?
  • MSH – melanocyte stimulating hormone, is a key regulator of many important body functions
  • Capillary hypoperfusion: VEGF
  • Innate Inflammatory markers: MMP 9, C4a, C3a and TGF beta 1
  • Disruption of hormone feedback loops: ACTH/ cortisol; ADH or Copeptin/osmolality
  • Androgens and sex hormones
  • Leptin (leptin resistance)
  • Autoimmunity: Antigliadin antibodies and anti-cardiolipin antibodies
  • Abnormal clotting profiles: PAI I; vWF; D dimer; ESR
  • MARCONS nasal swabbing, for a resistant bacteria that sits in the sinus


2. GENIE (Genetic Expression, Inflammation Explained)


GENIE is a study of the transcriptome developed by James Ryan PhD at ProgeneX labs. Transcriptomic testing tells us how your genes are being expressed in response to environmental inputs. GENIE can tell us about your exposures, hypometabolism and insulin signaling, VIP (Vaso-Active Intestinal Peptide) and Ikaros function, coagulation risks, histamine production, brain and cognitive risks, and confirm a CIRS diagnosis. This test has proven to give us absolutely astonishing insights into your individual expression of the complex illness that is CIRS. It is used at baseline and in follow up to ensure resolution of the illness.


3. NeuroQuant Volumetric Brain MRI


Volumetric brain imaging is extremely useful in diagnosing the cause of CIRS and establishing the effect of CIRS on the brain. The function of the immune system is intricately linked with that of the nervous system, so we expect to see some changes in the brain in CIRS. Unlike a conventional MRI, it measures volumes of different brain areas with tremendous accuracy. The pattern of change in the volumes of different brain structures will vary depending on what the specific trigger is and if we can see a ‘fingerprint’ for CIRS on the brain. The volume changes, for example, will look very different if mold was your trigger, vs. endotoxin vs. Lyme disease. NeuroQuant will help to determine specifics of treatment and what the end point of treatment is for CIRS.


The combination of Proteomic labs, GENIE and NeuroQuant leaves us with solid objective data. You will know that you have a diagnosis of CIRS, without question. You will know what your individual trigger is, and you will have a baseline to track changes and evaluate the success of treatment using accurate data.


CIRS Treatment


Depending on how quickly we remove you from your exposures and how you respond to each treatment, it can take a year or more to show improvements. The goals of Chronic Inflammatory Response Syndrome treatment are to lower inflammagens, correct hormonal dysregulation, deal with autoimmunity, improve capillary hypoperfusion, eradicate commensal Staph in the nasal cavity, correct cellular immunity, and get you back to enjoying your life.


Once CIRS is diagnosed we follow the 12-step Shoemaker protocol as the core of therapy. It is important to follow this peer reviewed protocol for success of treatment. We may also suggest completing other therapies, which support your system and help with repair and possible side effects of the treatments. The most important part of the protocol initially is to remove you from the exposure/trigger for CIRS. This might involve referral to an Indoor Environmental Professional (IEP), who is the expert in home health as it relates to CIRS. They will individualize home testing and remediation based on your results and response to treatment. Removing from exposure also includes removing internal exposures, like infections. We treat Lyme and Lyme co-infections, virus, parasites for example, so that there is no ongoing trigger inside the system. This is individualized based on your testing.


Once we have ticked this first important box, we can begin to remove biotoxins from the system with binding therapy, which acts like an antibody and removes biotoxin from the system through the stool. The VCS test is used to track readiness for the next step, which is to eradicate MARCONS from the nasal cavity. Once we have done this we are able to assess progress through repeat testing and manage any ongoing inflammation where necessary.


The ultimate goal is to get you taking VIP, which is an important peptide used to calm inflammation, correct gene dysregulation and correct the brain changes associated with CIRS, amongst many other important functions. Management of other related issues and differential diagnoses occur alongside this core approach where needed. For example, Mast Cell Activation Syndrome can be treated, EMF remediation done and detoxification supported.


We have a strong focus on the limbic system, which is our emotional brain, as this is commonly an area affected by CIRS. In fact, many patients with CIRS suffer concomitantly with PTSD and other trauma related issues. As the brain-immune connection is so strong, it is important to manage both of these side by side.


We find the most successful healing journeys embrace a team approach that includes Indoor Environmental Professionals (IEP), a Health Coach, a Lymphatic Drainage Therapist, and a CIRS literate Physician. At Linden & Arc Vitality Institute, Dr. Murfin is a Chronic Inflammatory Response Syndrome Proficiency Diplomat. We encourage you to ask questions, get support where you can, and to trust that this evidence based treatment plan works, even though it may be challenging.


Contact Linden & Arc Vitality Institute


At the Institute we understand it can be very overwhelming to deal with the unpredictable and fluctuating symptoms caused by CIRS. That is why we are here to help you every step of the way. It’s time to break the cycle of unnecessary suffering with pro-active treatments that will change the arc of your life.


At Linden & Arc we can help you find freedom from pain, fatigue, memory loss, illness, and depression! If you are struggling with persistent health challenges contact us HERE to get started on your transformative health journey.



Dr. Michelle Van Der Westhuizen, MD & CIRS Proficiency Diplomat