It can be concerning to suspect that mold exposure might be causing your health symptoms. If you suspect mold exposure might be at the root of your health symptoms, you are not alone, as many buildings in Western countries have some water damage. In this article, I am discussing chronic inflammatory response syndrome, or CIRS. CIRS is most commonly known to be caused by exposure to mold or mycotoxins, but it's not just mold that can cause CIRS. A long list of other "bad actors" can contribute to CIRS.
What is Chronic Inflammatory Response Syndrome, (CIRS)?
CIRS has been described as a chronic, progressive, multisystem, multi-symptom syndrome characterized by exposure to biotoxins, HLA genetic predisposition, altered innate and adaptive immunity, peripheral hypoperfusion at multiple sites, and multiple hypothalamic-pituitary-end organ dysregulations. I know, say what? Let me explain this in a little more detail.
The symptoms associated with CIRS can vary widely. Some common symptoms may include fatigue, difficulty concentrating, memory issues, muscle aches, joint pain, gastrointestinal problems, sensitivity to light and sound, respiratory issues, and neurological symptoms such as headaches and dizziness. These symptoms may overlap with other conditions, making diagnosis and treatment complex; however, CIRS is a legitimate medical diagnosis that requires specific lab testing and patient history analysis to verify.
When people with an HLA genetic predisposition (more on this later) are exposed to biotoxins from water-damaged buildings, their immune and inflammatory response may not be appropriate, as their immune system does not recognize the biotoxins and fails to remove them. Consequently, the biotoxins can circulate in the body indefinitely, leading to a multi-symptom, multisystem illness called CIRS.
What Exactly are Biotoxins?
Biotoxins (or neurotoxins derived from a biological source), are tiny molecules that can penetrate the cell membrane and move between cells without traveling through the bloodstream, making them very difficult to detect through standard blood tests. They can enter the body through inhalation, direct contact with contaminated water, ingestion, and insect bites.
When biotoxins enter the body, they can wreak havoc, especially on individuals genetically predisposed to biotoxin illness and dealing with CIRS. In such cases, the immune system struggles to recognize and eliminate these biotoxins effectively, leading to the attachment of biotoxins to specific surface receptors, particularly those found on white blood cells known as antigen-presenting cells. This can lead to pervasive inflammation and disrupt normal cell health and function, compounding the burden on an already overworked innate immune system driven by CIRS.
Biotoxins can also affect the integrity and function of cell membranes, which are essential for the healthy functioning of cells. They compromise the protective function of cell membranes, which are crucial for regulating substance passage in and out of cells and facilitating cell signaling and communication. Additionally, biotoxins, with their unique polar and nonpolar regions, possess hydrophilic (fat-loving) and lipophilic (water-loving) properties, allowing them to create ion channels that disrupt cell electrodynamics. Consequently, the disruption inhibits the cell from carrying out its energy-producing (ATP) functions and interferes with cell signaling, triggering a defensive response and the production of inflammatory cytokines.
Biotoxins exhibit an affinity for fatty tissues, particularly the brain, especially in cases where the blood-brain barrier is compromised. Because biotoxins love fat, they also gravitate towards the nervous tissue, the autonomic nervous system, and the cardiovascular and GI systems. In fact, many of the symptoms people with CIRS experience lie within the gut-brain-immune axis.
Encountering Biotoxins
While CIRS is most commonly associated with inhaling mold or mycotoxins in water-damaged buildings (WDB), other factors can also contribute to biotoxin illness and CIRS.
Inhalation: Water-damaged buildings can contain a harmful combination of fungi (mold and its fragments), bacteria (and its fragments), actinomycetes, mycobacteria, volatile organic compounds, and substances that cause inflammation, such as endotoxins, beta glucans, mannans, hemolysins, and proteinases. Mold species that are particularly linked to CIRS include Aspergillus penicillins, Aspergillus versicolor, Chaetomium globosum, Stachybotrys chartarum, and Wallemia sebi, accounting for 80% of the CIRS-related illness burden.
Bites: Ticks can carry Borrelia burgdorferi (Lyme disease), Babesia microti (Babesiosis), and other infections (Bartonella, Anaplasma, Ehrlichia). The Brown Recluse and Mediterranean Recluse spiders can also cause biotoxin illnesses.
Ingestion: Reef fish such as barracuda, grouper, and snapper often ingest toxin-producing dinoflagellates by consuming smaller fish, which leads to Ciguatera, the most common fish poisoning globally. Ciguatera can cause symptoms such as nausea, vomiting, diarrhea, and neurological effects, including tingling sensations, numbness, and temperature reversal. These symptoms can persist for weeks to months and sometimes become chronic, thus potentially leading to CIRS.
Direct contact with contaminated water: Certain invertebrate species in water, such as Pfisteria and Cyanobacteria (Cylindrospermopsis and Microstysis), produce neurotoxins. People can be exposed to these toxins through direct contact with water contaminated by toxins in areas of fish kills or by inhaling airborne toxins from this source. Exposure to water contaminated with neurotoxins from invertebrate species such as Pfisteria and Cyanobacteria can lead to various health consequences, including skin irritation, respiratory problems, neurological issues, and gastrointestinal disturbances. Additionally, exposure to these toxins can have long-term effects on human health, including potential impacts on the nervous system and liver.
Other Sources: Additional triggers for CIRS include certain vaccines and certain viruses.
Symptoms:
Often, people dealing with CIRS have tried all of the conventional and functional medicine approaches and still do not get better. These same people have usually been previously diagnosed or misdiagnosed with a list of other symptoms from depression, anxiety, and PTSD to Alzheimer's or Parkinsonism, allergies, ADD/ DHD, Fibromyalgia, and Chronic Fatigue Syndrome and have seen or felt a slight improvement in their health based on previous treatments. The reason for the lack of progress in their health is that they did not address the underlying condition—CIRS.
A global set of symptoms, specific lab tests, and biomarkers associated with CIRS are critical components in CIRS diagnosis. As outlined by Dr. Shoemaker, 37 specific symptoms are associated with CIRS, which are then grouped into 8 organ categories. These categories make up the Symptom Cluster Analysis. For adults, if symptoms present in at least 8 of the 13 symptom clusters, this is considered consistent with biotoxin illness. It is considered positive for children if symptoms are in 6 out of 13 symptom clusters. When there is a positive symptom cluster analysis, it would be a great idea to move on to the next stage in CIRS analysis, which can include a VCS test, MARCoNS test, and CIRS biomarkers; more on this to come in a separate blog, Part II of Understanding CIRS.
The symptom clusters include:
HLA genetic predisposition
HLA stands for Human Leukocyte Antigen (HLA). HLA's are found on the surface of nearly every cell in the human body and provide instructions for making a group of related proteins known as the HLA complex, which help the immune system distinguish between the body's own proteins and those created by foreign invaders (insert Biotoxins). A haplotype is a grouping of inherited genes from a single parent, consisting of multiple SNPs on a single gene. There are nearly 50 different HLA haplotypes, and variations in the HLA genes can lead to differences in the cell surface proteins, affecting immune responses and potentially contributing to susceptibility or resistance to certain diseases.
The HLA DR test identifies one's susceptibility to CIRS and other diseases, and in relation to CIRS, people are divided into two groups:
Those with the genetic ability to produce an immune response that effectively eliminates biotoxins from the body (76% of people)
The remaining 24% of the population have HLA gene types that make them susceptible to biotoxin illness, meaning they lack the genetic capability to clear biotoxins. This susceptible population makes up 95% of the CIRS patients.
Innate and Adaptive Immune Systems
Understanding how the innate immune system works is essential. Our immune system has two main parts: the innate (or nonspecific) and the adaptive (acquired or specific) immune systems. We're born with innate immune responses, and the adaptive immune system develops over time as we encounter pathogens.
Innate Immune System
Once an antigen gets past our physical immune barriers, such as the skin, the nasal passage, and the stomach, the innate system is the first responder. It acts almost immediately in response to infection. The innate immune system is not specific to a particular antigen, an invading microbe or pathogen, and reacts consistently to various invading microbes or pathogens. The innate immune system also activates the complement system, which works to identify foreign substances/ antigens, recruit immune cells to the site of infection, and trigger inflammation.
While the innate immune system doesn't provide long-lasting immunity, it plays a crucial role in communicating with the adaptive immune system. The innate immune response does not involve antibodies; instead, it uses antigen-presenting cells that display an antigen to the adaptive immune system.
Adaptive Immune System
The adaptive immune response is more complex than the innate immune response. This response is unique to our third line of defense and is called adaptive, or specific, immunity. Adaptive immunity is activated by (or should be activated by) the innate immune system and requires the development of highly specialized cells involved in specific immune responses. Upon exposure to an antigen, the adaptive immune system processes and recognizes the antigen. Once it recognizes an antigen, the adaptive immune system creates an army of immune cells d signed to attack. Its primary job is to protect us against reinfection by creating an immunological memory" that makes future responses against a specific antigen more efficient and provides long-term immunity by creating immunological memory after the initial exposure to a particular pathogen or biotoxin.
Due to specific genetic HLA susceptibilities, the innate immune system's presentation of biotoxins is flawed, so the adaptive system doesn't get the message to kick into action. The toxin is not recognized as foreign, so the innate immune system becomes overactive, and the adaptive immune system does not appropriately respond and produce antibodies to neutralize it. The innate immune system continues to create inflammatory cytokines, leading to dysregulation of multiple systems and can lead to CIRS.
Summary
Understanding biotoxin illness and its relationship to CIRS is crucial for effectively managing and treating these conditions. If you suspect you may have CIRS or mold/ biotoxin exposure, it is vital to work with a practitioner who is CIRS-literate and can help manage the treatment so that healing can occur.
In the next part of this blog series, I will explore the criteria for a proper diagnosis* and treatment of biotoxin illness and CIRS. Stay tuned for more valuable information.
*NOTE: While I am trained and knowledgeable about restoring balance in the body through functional nutrition, it's essential to understand that I'm not qualified to provide diagnoses. For a proper diagnosis, seeking guidance from a healthcare professional who can diagnose is necessary.
Resources:
Chronic Inflammatory Response Syndrome (CIRS): Everything You Need To Know. https://hoffmancentre.com/chronic-inflammatory-response-syndrome-cirs-evaluation-and-treatment/
Tanio, C. P. (2017). Chronic Inflammatory Response Syndrome (CIRS): Overview, Diagnosis, and Treatment. Rezilir Health.
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