01 Apr Chronic Inflammatory Response Syndrome (CIRS)
Chronic Inflammatory Response Syndrome is the result of persistent biotoxicity in genetically susceptible patients. Chronic fatigue syndrome and fibromyalgia are subsets of CIRS.
One in three homes in Australia is potentially water damaged and can be a source of CIRS. There are over 24% of individuals who are genetically predisposed to biotoxin illness via HLA genes.
Individuals predisposed via genetics to CIRS exhibit disruptions in their adaptive and innate immune mechanisms when exposed to certain biotoxins.
These biotoxins include mould, vector born bacteria such as Borrelia burgdorferi, ciguatera from fish and cyanobacteria from still water such as ponds. 80% of CIRS patients have been exposed to mould. CIRS now explains why 20% of Lymes patients do not recover and it reframes our understanding of chronic fatigue and fibromyalgia.
There is a submission for CIRS recognition as a disease with the health department of Australia now pending. Accepted in the US as a diagnosis following many Daubert & Frye decisions in courts across the US. Dr Shoemaker has received US Patent number US 9,770, 170 B 2 on diagnosis and treatment of CIRS.
It was first identified over twenty years ago by Dr Richard Shoemaker an American general physician in Florida, who lived in an area where ciguatera had infected the local fish and thus humans. By coincidence, he prescribed cholestyramine for high cholesterol in an infected patient and the patient’s inflammatory symptoms improved. He thus discovered a useful binding agent for the biotoxins from the ciguatera.
Common Signs and Symptoms
- Chronic and unexplained pain
- Migraines that last longer than 25 hours (Due to low ADH)
- Sudden weight gain (Leptin resistance resulting in weight gain that will not respond adequately to diet and exercise.)
- Push – Crash – After overexcretion, two or more bad days usually follow.
- Abdominal pain (66% of CIRS patients have bile acid reflux. It sounds typical of acid reflux but never responds to acid, It will be diagnosed as ‘functional’)
- Joint stiffness, shoulders and knees ‘gelling’ (The aching that won’t respond to medications often coming from tendon/epicondylitis and patellar tendinitis.)
- Muscle cramping
- Susceptibility to electric/static shocks
- Long and fourth finger make a v shape.
- Arching MCP and MTP joints.
- Decreased capillary perfusion and inflammation
- Long and fourth finger make a v shape.
CIRS diagnosis and treatment is often complex so working closely with a qualified health professional with experience in CIRS treatment is recommended. If you, or someone you know is suffering from any of the symptoms mentioned above, fibromyalgia, chronic fatigue or unexplained pain and fatigue, get in touch for a FREE 15-minute scoping session.
The Science Behind CIRS
- CIRS WDB: CIRS post-water-damaged building
- CIRS Post Ciguatera
- CIRS Post Lymes
Fragments of amplified mould, filamentous bacteria, antimocytes and mycobacteria may possess toxins. Once inhaled they are detected by the innate immune system starting the CIRS process in the genetically predisposed
Biotoxins bind to certain cell surface markers such as Toll, mannose and L-type Lectin.
Recognition and binding of the biotoxin at these receptors leads to specific upregulation of inflammatory pathways, resulting in an abnormal rise in inflammatory markers such as cytokines, TGF-beta 1 and split products of complement.
In addition to triggering systemic inflammation, biotoxins can also have a neurotoxic effect. In most patients, VCS testing (https://www.vcstest.com/) can detect deficits caused by biotoxicity affecting the neurologic function in the visual system.
Persistent innate inflammation leads to
- Abnormal T cell response (TH1, TH2, TH 17)
- Dysregulation of the complement cascade. C4a, C3a + dysregulation of cytokines and hormones.
Each mature T cell has a specific function in the immune system. In CIRS, we see a dysregulation of TH 1, TH 17 (as seen in autoimmune disease) and in TH2 as seen in allergies. Thus there may be patients diagnosed with other diseases in these categories such as rheumatoid arthritis (especially seronegative), treatment-resistant asthma and eczema that may also have CIRS and CIRS may offer a treatment option for such.
Stage One: There is a deficiency of Neuropeptides
- Melanocyte stimulating hormone (MSH) and or
- Vasoactive polypeptide. VIP
VIP: Vasoactive Intestinal Polypeptide. Is deficient in >90% CIRS patients. VIP receptors are intimately tied to a family of nuclear transcription factors. A vasoactive intestinal polypeptide (VIP) is a neuropeptide that functions as a neuromodulator and neurotransmitter. It is a potent vasodilator, regulates smooth muscle activity, epithelial cell secretion, and blood flow in the gastrointestinal tract.
MSH: A crucial neuroregulatory peptide is best known for influencing skin pigment however it is a central hormone with anti-inflammatory actions through numerous signalling pathways.
Chronic inflammation + low MSH = loss of cortisol regulation = ACTH + CORTISOL high.
- Hypothalmic Leptin resistance = ACTH + Cortisol Low.
- Low ACTH causes a reduction in androgens.
- Low VIP = ^ aromatase enzyme = causes DHEA and testosterone to convert to oestrogen.
(low VIP causes shortness of breath with exercise and pulmonary hypertension.)
Exogenous administration of VIP will remedy the VIP deficient symptoms. VIP can downregulate the cytokines make it invaluable in the treatment of CIRS. Do not use VIP spray until the patient clears the VC test.
MSH excerpts a regulatory influence on other hormones especially gonadotropins. Thus, androgens and estrogens are affected. MSH controls tight junctions in the gut.
MSH interacts with ADH in the hypothalamus to regulate other hormone activities.
MSH when normal:
- Induces cyclic adenosine monophosphate (cAMP)
- Inhibits or regulates peripheral and intracerebral inflammation via regulation of interferon-gamma, NF- KB, TNF-a (when MSH is low dysregulation in TNF a causes capillary hypoperfusion resulting in microvascular perfusion. IL6, IL-1 beta. ( a plasminogen activator/inhibitor (PAI). When MSH low= dysregulation = coagulopathies + Von Willenbrands factor.
LOW MSH = ^ CYTOKINES = symptoms: thermal dysregulation, headaches, brain fog and muscle ache.
Stage 2: Cytokine effects. An up-regulation in the innate immune system
Increase in inflammatory markers: C4a, C3a, MMP9, TGF-beta 1, Leptin.
This leads to hypoperfusion of capillaries and coagulopathies.
^ Innate immune system = ^ cytokines = cytokines bind to receptors on White blood cells = signals release of MMP9 into the bloodstream.
MMP-9 enzymatically degrades the proteins found in the protective extracellular matrix of blood vessel walls (endothelium).
Inflammation from the bloodstream thus penetrates sensitive tissues such as the brain.
Known for vasodilation, angiogenesis & neuroprotection. It can be too high or too low in CIRS patients. Low VEGF = ^ permeability of blood-brain barrier + hypoperfusion = dyspnoea, brain fog, fatigue and cramps.
Serum osmolality regulates sodium and water concentrations. When too much salt osmoreceptors act on the hypothalamus to signal the posterior pituitary to secrete ADH. = signals kidneys to reabsorb free water diluting the blood.
60 % of CIRS patients have dysregulation in serum osmolality resulting in excessive thirst. Because osmolality is high (blood is too high in salt) the conductivity of the physiology increases resulting in static shock type symptoms.
If the osmolality is not stabilising due to low ADH then you will feel thirsty and suffer from frequent urination.
Multiple antibiotic-resistant coagulase-negative staph infections of the nose. Marcons evade host defences through biofilm formation.
Low MSH = ^ susceptibility to bacterial infection = MARCONS – these staph secrete toxins A + B (=splits MSH molecules = reducing MSH further) + Heamolysins = ^ inflammation )
You can treat Marcons at any stage to avoid the further reduction in MSH but will need to keep treating it until > 1 month after commencing cholestyramine.
CIRS Diagnosis checklist for practitioners
- Review of past medical records. All test results. Accurate collection of a medical history remains the single most important aspect of differential diagnoses.
- Identify exposure. 80% of CIRS patients is due to exposure to a water-damaged building. See the WHO 2009 statement on mould and WDB health risks. http://www.euro.who.int/__data/assets/pdf_file/0017/43325/E92645.pdf. However, a patient may be unfortunate enough to be suffering from multiple exposures and or ongoing exposure which can make an assessment of the aetiology or source of biotoxin illness challenges. EG a post Lyme patient living in a WDB!
- Is it a horse or a zebra? Ruling out all other causes of cytokine and complement response via thorough testing, clinical assessment and history.
- Biotoxin Questionnaire. An adult must answer yes to a minimum of one (or more) symptom in each cluster over a total of 8 clusters or more. A child must be positive or answer yes to a minimum of one question over at least 6 clusters. This does not mean a positive for every question in each cluster found. Rather a minimum of one affirmative answer in each cluster. Statistically, according to Dr Shoemaker’s research, there is a 95% likelihood of CIRS if a patient is positive to 8 or more clusters and if a child is positive for 6 or more.
- VCS testing. https://www.vcstest.com/. Statistically, according to Dr Shoemaker’s research, there is a 98.5% likelihood of CIRS if a patient is positive to 8 or more clusters and if a child is positive for 6 or more and if the patient tests positive for the VC test.
- HLA genotyping female hormones, androgens, DHEA, fasting cortisol, serum osmolality, Autoimmune markers Anti gliadin (Tg IgAb, Anticardiolipin (ACLA) , Antineutrophil cytoplasmic antibodies. (ANCA), TSH T 3 T4 via clinipath.
- Viral load tests: EBV, Herpes, CMV, RRV, HIV, HPV (any lab)
- Proteomics via Nutripath.
- A brain scan that demonstrates differential between biotoxin exposure and correlating cognitive dysfunction. Available (NatMed is currently working with radiologists to discern access to MRI using neuroquant analysis.
- Transcriptomics, not currently available in Australia.
- VC test monthly at the clinic prior to the consultation.
*Urinary mycotoxin testing has now been demonstrated as uncompromisingly unreliable by the CDC in the US. (kawamoto M, Page E. Notes from the field: use of Nonvalidated urine mycotoxin tests for the clinical diagnosis of illness-US 2014. MMWR 2015; 64 (6) 157-158)
In the face of infectious disease, cells become hypometabolic to prevent viral take over of cellular function. Hypometabolic immune cells activate primordial mechanisms: innate immunity, compliment & defensins. These protective inflammatory elements do not require the participation of cells.
When cells begin to recover from the illness-induced hypometabolic state, the protective mechanisms of innate immunity begin to wane. Cells then up-regulate protein production, energy production and begin to use sugar properly.
Abnormalities in glycolysis and ribosomal and nuclear-encoded mitochondrial genes that reduce the availability of energy.
VIP receptors are intimately tied to a family of nuclear transcription factors. Patients naïve to treatment have profound suppression of these genes.
Microbial toxins attack protein production at the level of the ribosome & energy production in the mitochondria.
Inflammation reduces responsiveness to GP130 cytokine receptor which reduces receptivity to leptin.
Hypometabolic immune cells activate primordial mechanisms: innate immunity, compliment & defensins. These protective inflammatory elements do not require participation of cells. The sequence of hypometabolism and recovery are shown in transcriptomics and demonstrate a ‘synchronised reboot of cellular systems’.
A distinctive molecular pattern marking gene activation by Trichothecenes and Actinomycetes and clusters of differentiation for endotoxin exposure and beta-glucans.
^ Regulation hypoxia-inducible factor (HIF genes) = promotes the production of VEGF & transforming growth factor-beta (TGF-beta)
Here is a testimonial from one of our patients who was treated for CIRS at our clinic
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