Chronic inflammatory response syndrome - What is it?
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Chronic Inflammatory Response Syndrome (CIRS) is a complex, multi-system illness associated with exposure to biotoxins. The primary cause of CIRS is exposure to a water-damaged building (WDB). Elevated moisture levels within a building foster the growth of microorganisms, including mould and gram-negative and -positive bacteria. While mould's role is the most well-understood and the easiest to test for, health effects stem not solely from any single contaminant but from the toxic combination of microbes, their metabolites, microbial fragments, and VOCs/mVOCs. These microorganisms continuously produce toxins (including mycotoxins) that, individually and collectively, can activate immune system responses. In fact, studies have indicated that the combination of toxins elicits a more robust immune response than any single microbe alone [1], and there are a variety of theories as to why these microbes may be becoming more potent or prevalent. Around 20% of CIRS cases have a trigger other than a WDB, and include tick-borne infections (such as chronic Lyme disease), cyanobacteria from toxic blue-green algae, ciguatera from reef fish and recluse spider bites [2]. These conditions are collectively recognised as "biotoxin illnesses”, and biotoxin illness resulting from a WDB is termed "CIRS-WDB”. To date, there are over 1700 scientific articles on this condition[3], which is commonly referred to as "Mould Illness”.
Cho, J. Water damage building biochemical stew, Nutrition with Judy, n.d.https://www.nutritionwithjudy.com/cirs. Accessed 27 Nov 2023.
While the public are well aware of the dangers of consuming mouldy food, a concern globally regulated through food standards and limits on mycotoxin contamination [4], there is significantly less awareness regarding the health effects of inhaling these toxins. CIRS is caused by repeatedly breathing in biotoxins (like mould and mycotoxins) while in a WDB [5]. In most individuals, removing these biotoxins from the body relies on the interaction between the innate and adaptive immune systems. The innate system acts as the 'first responder,' mobilising immune cells to deal with the threat. It then communicates with the adaptive immune system, often referred to as the 'second line of defence,' guiding it to neutralise the toxins. When this system functions optimally, the body should effectively eliminate these foreign invaders.
However, in up to 24% of the population (including myself), the 'second line of defence' remains inactive due to a faulty HLA-DR/DQ gene, impeding the body's ability to clear the toxins efficiently [6]. The innate immune system will stay chronically activated, generating persistent inflammation through inflammatory cytokines, while the adaptive system fails to signal an endpoint. As a result, biotoxins persist within the body, inducing toxicity and contributing to a significantly dysregulated immune response and ongoing inflammation [5]. In time, this can eventually impact every organ in the body, manifesting in a diverse array of symptoms.
"Understanding Chronic Inflammatory Response Syndrome (CIRS)." Surviving Mold, https://www.survivingmold.com/docs/UNDERSTANDING_CIRS_EDITV2A.PDF. Accessed 27 Nov 2023.
"Understanding Chronic Inflammatory Response Syndrome (CIRS)." Surviving Mold, https://www.survivingmold.com/docs/UNDERSTANDING_CIRS_EDITV2A.PDF. Accessed 27 Nov 2023.
While individuals without a genetic predisposition to CIRS may also fall ill with significant exposure to mould and water damage [7], their health problems typically resolve upon leaving the source of exposure. In contrast, for CIRS patients, the issues will persist even after relocating from the affected environment. This means that an individual with susceptibility may endure ongoing illness from having lived in a mouldy home decades earlier due to their inability to effectively clear the acquired toxins and the persistent activation of their immune system. CIRS can be confused with mould allergy, but it's crucial to differentiate between the two as they represent distinct immune issues. CIRS and mould allergies are separate conditions, and while it is possible, it is rare for an individual to have both [8].
There are 35 common symptoms of CIRS that have been systematically separated into 13 clusters, based on the implications of the biotoxin pathway [9]. While there are additional symptoms that may be experienced by sufferers beyond these, statistically, these clusters of symptoms provide a diagnostic capability to distinguish CIRS from other diseases [10]. Each cluster requires only one symptom for it to be considered positive. Individuals who have symptoms in eight or more of the 13 clusters (or six if younger than 11 years old [11]) and a history of exposure should complete a Visual Contrast Sensitivity (VCS) test online. Individuals with a biotoxin-related illness typically exhibit poor performance on this test (which measures the ability to detect visual patterns) due to optic nerve dysfunction [12]. A positive result is determined when the test is failed in either eye. Where a person has 8+ positive clusters and fails a VCS test, the likelihood of CIRS is over 98.5% [10]. The next step is working with a provider to run blood work to confirm a diagnosis.
"Mold Illness in Children (CIRS Kids)." Mold Illness Made Simple, https://moldillnessmadesimple.com/mold-illness-in-children-cirs-kids-dr-scott-mcmahon/. Accessed 28 Nov 2023.
Another aspect of the condition involves the abrupt reactivity observed in many CIRS patients when exposed to contaminated environments, including buildings and cars, and items contaminated by these environments, like bedding, clothing, and personal items. Affected air-conditioning units can also trigger an immune response and produce symptoms. The responses are partially mediated by mast cells, which release histamine and pro-inflammatory cytokines, causing symptoms [13]. Navigating the concept of "mould avoidance" can be incredibly daunting due to the widespread occurrence of water-damaged homes, offices, cars, and commercial buildings. One might question the frequency of damp buildings, but the reality is that they are exceedingly common. Estimates suggest that approximately 45% of buildings in Europe, 40% in the USA, 30% in Canada, and up to 50% in Australia are affected by mould [14]. Other estimates are even higher, with the US EPA’s BASE study finding that 85% of office buildings in the USA had been damaged by water at some time [15].
“In damp conditions, hundreds of species of bacteria and fungi grow indoors and emit spores, cell fragments and chemicals into the air. Exposure to these contaminants is associated with the incidence or worsening of respiratory symptoms, allergies, asthma and immunological reactions. Children are particularly susceptible.”
Most biotoxins consist of extremely small molecules that can easily move from cell to cell through cell membranes without relying on the bloodstream for transportation [3]. This characteristic makes biotoxins challenging or nearly impossible to detect through standard medical practice (i.e., sedimentation rate, c-reactive protein, lipid profiles, thyroid studies, immunoglobulin studies, metabolic profiles and complete blood counts), which are nearly always normal in CIRS-WDB [5]. Additionally, symptoms may vary day-to-day and often go unnoticed by general practitioners who lack specialised training in screening for mould-related illnesses.
Patients with CIRS frequently face misdiagnosis with other debilitating illnesses [16]. This misidentification can result in years of suffering as patients navigate from one doctor to another in search of an accurate diagnosis and appropriate treatment. Common misdiagnoses of CIRS include:
Chronic Fatigue Syndrome
Irritable Bowel Syndrome (IBS)
Fibromyalgia
Depression and Anxiety
Allergies
Hypochondria (Somatisation)
Attention Deficit Hyperactivity Disorder (ADD/ADHD)
Stress/Post-traumatic Stress Disorder (PTSD)
Multiple Sclerosis
PANS (in children) [17]
These conditions, when genuinely present, will not improve with therapies used in treating CIRS-WDB. In contrast, when the cause of the illness is CIRS, the patient will experience recovery [5].
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CIRS treatment is mainly centred on the avoidance of further exposure to water-damaged environments and items contaminated by those environments, as well as the use of Cholestyramine and Colesevelam (Welchol). Antifungal drugs may also be used to address fungal colonisation. Cholestyramine and Welchol function by attracting and binding biotoxins, aiding in their elimination [18]. This mechanism enables the removal of toxins in a way comparable to how a non-genetically susceptible individual would eliminate them. A comprehensive treatment approach, often devised by an Integrative Medicine doctor or specialist, should also incorporate nutritional and detoxification strategies to enhance effectiveness.
If you suspect you may be suffering from CIRS, remember that treatment is available and most patients will experience a full recovery with medication and lifestyle changes. The following are some useful resources to explore further:
Moldy movie - https://moldymovie.com/
Change The Air Foundation - changetheairfoundation.org
9News, "National inquiry launched into mould-related illnesses", https://www.9news.com.au/national/parliament-committee-launch-inquiry-into-mould/b434f3f4-f27a-4b8b-919a-beac36cf9bb5
Hoffman Centre for Integrative & Functional Medicine, "CIRS Evaluation and Treatment", https://hoffmancentre.com/chronic-inflammatory-response-syndrome-cirs-evaluation-and-treatment/
Dr Todd Maderis, Mold Illness is more than a Chronic Inflammatory Response Syndrome, https://drtoddmaderis.com/chronic-inflammatory-response-syndrome
The Jordan Peterson Podcast, Worse than Asbestos? Dr Scott McMahon & Dr Richie Shoemaker, Ep. 415, https://www.youtube.com/watch?v=LGG7om1hHcU
Biotoxin.com, "Scientific Articles", https://biotoxin.com/scientific-articles/
References
1. Morris G, Berk M, Walder K, Maes M. The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability. Mol Neurobiol. 2016;53(4).
2. Cho J. "CIRS." Nutrition With Judy, 30 Mar. 2023, www.nutritionwithjudy.com/cirs. Accessed 28 Nov 2023.
3. Hoffman B. "Mold Exposure." Hoffman Centre, 5 Sept. 2023, www.hoffmancentre.com/tag/mold-exposure. Accessed 29 Nov 2023.
4. van Egmond H, Schothorst R, Jonker A. "Regulations Relating to Mycotoxins in Food." Analytical and Bioanalytical Chemistry. 389. 2007.
5. Shoemaker R. Research Committee Report on Diagnosis and Treatment of Chronic Inflammatory Response Syndrome Caused by Exposure to the Interior Environment of Water-Damaged Buildings. Policyholders of America, 2010.
6. Shoemaker R, Rash J, Simon E. Sick Building syndrome in water damaged buildings: generalisation of the chronic biotoxin associated illness paradigm to indoor toxigenic fungi. Bioaerosols, fungi, bacteria, mycotoxins and human health. 2006.
7. World Health Organisation. WHO Guidelines for Indoor Air Quality: Dampness and Mould. Geneva. 2009. Available from: https://www.ncbi.nlm.nih.gov/books/NBK143943/
8. "Chronic Inflammatory Response Syndrome versus Allergy." Integrative Functional Medicine and Acupuncture Centre, n.d., https://www.drionelahubbard.com/article/chronic-inflammatory-response-syndrome-versus-allergy. Accessed 30 Nov 2023.
9. Shoemaker R, House D. Sick building syndrome (SBS) and exposure to water-damaged buildings: time series study, clinical trial and mechanisms. Neurotoxicol Teratol. 2006;28(5).
10. Surviving Mold. "CIRS Diagnostic Protocol." Surviving Mold, 2018, www.survivingmold.com/Publications/CIRS_diagnostic_protocol_final_5_1_2018.pdf. Accessed 26 Nov 2023.
11. McMahon S, Gupta S. "Mold Illness Made Simple." YouTube, uploaded by Dr Sandeep Gupta, 3 Dec 2018, https://www.youtube.com/watch?v=oWzKCCw_Xg4. Accessed 26 Nov 2023. Webinar.
12. Hudnell H, House D, Schmid J, Koltai D, Stopford W, Wilkins J, Savitz D, Swinker M, Music S. Human visual function in the North Carolina clinical study on possible estuary-associated syndrome. J Toxicol Environ Health A. 2001. 20;62(8).
13. Kritas S, Gallenga C, Ovidio C, Ronconi G, Caraffa A, Toniato E, Lauritano D, Conti P. Impact of mold on mast cell-cytokine immune response. J Biol Regul Homeost Agents. 2018;32(4).
14. Brambilla A, Sangiorgio A. Mould growth in energy efficient buildings: Causes, health implications and strategies to mitigate the risk. Renewable and Sustainable Energy Reviews. 2020;132.
15. United States Environmental Protection Agency. "Building Assessment Survey and Evaluation Study." Available online: https://www.epa.gov/indoor-air-quality-iaq/summarized-data-building-assessment-survey-and-evaluation-study. Accessed 28 Nov 2023.
16. Thomas, N. "Understanding Chronic Inflammatory Response Syndrome (CIRS)." n.d., https://www.survivingmold.com/docs/UNDERSTANDING_CIRS_EDITV2A.PDF. Accessed 27 Nov 2023.
17. Crista J, Seymour K. "PANDAS, PANS, and Environmental Toxins." YouTube, uploaded by Change The Air Foundation, 8 Feb 2023, https://www.youtube.com/watch?v=jEZ8uLj_VjY. Accessed 29 Nov 2023. Podcast.
18. “Cholestyramine Uses.” Park Compounding Pharmacy, n.d., https://www.parkcompounding.com/cholestyramine-uses/. Accessed 30 Nov 2023.