Chronic Inflammatory Response Syndrome

CIRS – What is it and How is it treated?

Teresa Birkmeier-Fredal MD

CIRS is short for Chronic Inflammatory Response Syndrome and is essentially a biotoxin triggered immune dysfunction disorder. This syndrome was originally characterized by Ritchie Shoemaker MD, a Family Physician in Pocomoke, Maryland. He first published a study in this syndrome in 1998, and has published over 20 papers validating the physiology of this syndrome as well as the step wise protocol that he created to treat it. The official definition of CIRS is a complex, multi-system, multi-symptom illness following exposure to either internal or external biotoxins. A biotoxin is defined as a harmful substance produced by a living organism and we are exposed to them on a daily basis. For the majority of the population, the body’s detoxification process is able to clear these substances with minimal long term consequences.

However, approximately 24% of the population possesses a genetic determinant, known as their HLA type, that leaves them susceptible to this biotoxin triggered immune dysfunction. So when an individual with one of the susceptible HLA types is exposed to large amounts of biotoxins from either environmental mold, Lyme, Babesia or even Candida, the immune dysfunction that is triggered results in seemingly unrelated symptoms that are often misdiagnosed as conditions such as Fibromyalgia, Chronic Fatigue Syndrome, Anxiety, Depression, Leaky Gut, POTS and even Chronic Lyme Disease.  The reason for this diverse presentation of symptoms is due to the fact that the immune dysfunction can manifest in the following ways:
1) Increased Autoimmune processes such as lupus, MS and Interstitial Cystitis. These autoimmune processes often triggered by microbes in the body that are common and nonpathogenic.

2) Allergies to foods and environmental triggers

3) Excessive cytokine production leading to multiple issues including “illness behaviors” such as loss of appetite and fatigue, sleep disturbance, as well as hormone receptor resistance affecting nearly every hormone system in the body.

4) Immune suppression often leading to persistent infections or frequent acute infections.

How is CIRS diagnosed?
First, CIRS is diagnosed by meeting all three of the following Tier One Criteria:

Criteria 1) Confirm internal or external biotoxin exposure.
Biotoxin exposure is quite common as approximately 50% of buildings in the US have been found to have some degree of water intrusion with the resultant mold and bacterial growth. Internal toxigenic organisms are also common and include Borrelia, Babesia and as well as Candida species.

Criteria 2) Rule out other causes for symptoms.
This includes non-symptom based illnesses and other exposures, which can include chemical toxins and even heavy metal exposure. Although the presence of multiple classes of toxins simultaneously is quite common, so additional exposures do not necessarily rule out Biotoxin Associated Illness.

Criteria 3) Screen for characteristic symptoms
These symptoms must be multi-system and include at least 6 of the following:

Fatigue                                                 Abdominal Pain                                 Temperature Regulations

Weakness                                           Diarrhea                                               Excessive Thirst

Aches                                                    Joint Pain                                            Increased Urination

Muscle Cramps                                 Morning Stiffness                               Excessive Static Shock

Unusual Pain                                      Memory Issues                                  Numbness

Ice Pick Pain                                       Focus/Concentration Issues          Tingling

Headache                                            Word Recollection Issues               Vertigo

Light Sensitivity                                Impaired Learning                            Metallic Taste

Red Eyes                                              Confusion                                           Tremors

Blurred Vision                                    Disorientation                                   Tearing

Skin Sensitivity                                  Sinus Problems                                 Mood Swings/ Anxiety/Depression

Cough                                                   Appetite Swings                                Shortness of Breath

Sweats (especially night sweats)

Other common symptoms include post-exertional malaise, sleep disturbance and skin rashes.

Then, three of the following six Tier 2 Criteria must also be met:

1) Abnormal VCS
Elevation of biotoxins in the brain will affect the optic nerve’s ability to see edges clearly. This can be assessed either online here, or can be done in office.

2) Susceptible HLA DR Genotype
HLA stands for Human Leukocytic Antigen and there are several genotypes that result in a dysfunctional immune response to biotoxins leading to a persistent inflammatory process. The HLA type will determine which biotoxins had been shown to trigger CIRS – although further research is needed as some HLA types also seem to be more likely to result in autoimmune processes vs. allergies vs. chronic infections.
Multi susceptible                         Mold Susceptible                                 Lyme Susceptible
4-3-53                                                     7-2/3-53                                                 15-6/5-51
11-3-52B                                              13-6-52A/B/C                                           16-5/6-51
14-5-52B                                                 17-2-52A

3) Elevated MMP-9
Matrix Metalloproteinase 9 is a marker of inflammation.
Normal ranges are 85-322.

4) Dysregulation of ACTH/Cortisol
ACTH (Adrenocorticotropin Hormone) and cortisol are both hormones and are used to assess hypothalamic and adrenal function. Early on in CIRS, ACTH and cortisol levels are typically elevated. This is often followed by a drop in ACTH and cortisol resulting in multiple symptoms. Ideally, these labs need to be drawn simultaneously at 8 AM in the morning.

Cortisol is considered abnormal at levels of >19 or <8.
ACTH is considered abnormal at levels of >60 or <10
Values are also abnormal when ACTH is >15 with a Cortisol of >15
Or when ACTH is <40 and Cortisol is <8

5) Dysregulation of ADH/Osmolality
ADH (Anti Diuretic Hormone) and Osmolality assess hormonal control of fluid retention in the kidneys. ADH is the hormone that controls fluid retention and Osmolality measures the degree of fluid hydration within the serum. Dysregulation of this system can lead to chronic dehydration with increased urinary frequency and
excessive thirst.

Osmolality is abnormal at levels of >295 or <275
ADH is abnormal at levels of <1.3 or >8
Values are also abnormal when ADH is <2.3 with an Osmolality of 292-295
Or when ADH >4.0 with an Osmolality of 275-278

6) Low MSH
Alpha Melanocyte Stimulating Hormone (MSH) regulates production of endorphins and melatonin in the hypothalamus. Low MSH also results in dysfunction in pituitary hormone release leading to multiple hormonal imbalances. MSH levels have also been shown to be affected by sunlight exposure.
Normal values for Lab Corp are 35-81 and >10 for Quest Labs.

Additional prognostic and confirmatory testing:
NeuroQuant of Brain MRI – $150
An analysis of a brain MRI that precisely quantifies the size of different regions of the brain.
There are certain areas of the brain that with either enlarge or shrink when CIRS is triggered
by mold or yeast, and other areas that are affected when CIRS is triggered by Lyme. Dr. Shoemaker has shown that this test alone can be used to diagnose Mold or Lyme triggered CIRS and that CIRS treatment will lead to a resolution of the abnormalities found on the NeuroQuant. So we use it as both a diagnostic tool as well as a tool to assess whether or not treatment has successfully resolved the immune dysfunction and inflammation associated with CIRS.

Urine mycotoxin testing – $699
Able to quantify the levels of four common biotoxins in the urine –
This test work better when the urine sample is collected after either one week of oral glutathione at 500 mg
twice daily and/or a 10-30 minutes Far IR sauna.

Nasal fungal culture – $85
Can identify persistent fungal sinusitis and identify optimal treatment option

TGFB1 – Covered by insurance
A marker of inflammation used to assess immune dysfunction during treatment. Values can shift rapidly with exposure to biotoxins so it can also be used indirectly to assess recent biotoxin exposure.

Environmental Assessment and Remediation:
Ultimately treatment will only be successful when a patient has confirmed that they live, work and go to school in environments that are free from biotoxin-forming molds. It will not be necessary to completely mold free forever, as this is very close to impossible. But healing will really only be successful if biotin exposure is minimized during the healing process.

An environmental assessment should begin with a HERTSMI test from The swiffer version seems to work best. Be sure to take samples from all rooms in the main living area while avoiding the basement and garage areas. The HERTSMI will quantify the levels of 5 pathogenic mold species from the dust that is collected utilizing PCR testing. These levels are used to compute a score for the HERTSMI per the scorecard on

A HERTSMI score of <11 is considered ideal.
A score of 11-15 will require the addition of an air purifier – Air Oasis is the best option.
A score of >15 will necessitate an inspection of your home or work place for the source of the mold and an appropriate remediation plan will need to be created and carried out. Mark Banner of MJB is a good option for this inspection. Terry Wright or Wright Way Environmental can also be helpful in this capacity, and he is also able to assist with the remediation process.

Many physicians who treat CIRS insist that this step be completed prior to staring any CIRS treatment. While I agree that this would be ideal, I typically start with at least a few aspects of the treatment process even while the environmental assessment and remediation are still underway as my goal is to get my patient better as quickly as possible. However, it cannot be overstated that a mostly biotoxin-free environment will be necessary for long term healing to occur.

Inflammatory Response Syndrome Treatment
Clinical experience has shown that the most important aspects of treating CIRS to reduce symptoms and overcome immune dysfunction on a permanent basis include the following “Big Three” Interventions outlined below:

1) Take Toxin Binders

Can utilize 1-3 binders from the list below
Cholestyramine 1 packet 1-4 times daily 30 minutes before a meal
Welchol 2 tablets 1-3 times daily before meals
Chlorella 5 tablets 1-3 times daily taken at any time (Mercola Fermented Chlorella)
Activated Charcoal 1-3 capsules once daily on a mostly empty stomach (Nature’s Way)
Bentonite Clay 1-3 capsules once daily on a mostly empty stomach (MediClay)
While Cholestyramine and Welchol are the most powerful of the toxin binders they bind a somewhat narrower range of toxins than Activated Charcoal. My preference is to start with Welchol or Cholestyrmne for the first several months and eventually add in Activated Charcoal in combination wth Bentonite Clay long term as this combination has been shown to bind all potential biotoxins contributing to CIRS. When on toxin binders long term it is important to add in a mineral supplement to prevent depletion, and to monitor Magnesium, Zinc and iron levels to be sure that levels remain normal.

2) Treat Toxin-producing Infections – Lyme, Babesia, Candida
Lyme, Babesia and Candida will need to be tested and treated when positive. The best way to test for Lyme is with a Nano Trap test from Ceres Labs as it has been shown to be 98%  sensitive and specific. Candida can be assessed using a Quest titer, as well as from stool or Organic Acid testing. Babesia can be difficult to diagnose definitively, and the best test available at this point in time is from Igenex using a combination of a FISH and antibody titers. Treatment for each infection is variable and beyond the scope of this article.

3) Reverse Immune Dysfunction – increase Treg cells with immune modulators

Option 1 – LDI/LDA – Low Dose Immunotherapy typically given for 3 years and possibly longer

Sublingual treatments every 7-8 weeks
Need to identify antigen trigger for it to work
Also treats allergies and Multiple Chemical Sensitivity

Option 2 – VIP – Vasoactive Intestinal Polypeptide at 1 spray in each nostril four times daily
Will be used for at least 3 months and possibly forever
Can start with 1:100 or 1:10 dilution for sensitive patients
Need to meet the following criteria before it can be started – which can be difficult to do:
Normal VCS
Normal ERMI <2 or HERTSMI-2 <11
Normal Lipase
Negative MARCoNS culture

Option 3 – LDN – Low Dose Naltrexone at 0.5-4.5 mg taken at bedtime

Option 4 – Specific Transfer Factors – Enviro, L Plus and Plas-Myc typically taken for 18 months

Additional treatment options to speed healing -
1) If AGA (Anti-Gliadin Antibody) positive – avoid gluten. Most patients do better off of  gluten while healing.
2) If MMP-9 elevated – Fish Oil 3-4 grams or SPM Actives 2-8 capsules
3) If TGFB1 elevated – Curcumin 1000-1500mg (Curcuplex 95, Meriva SR, Enhansa)
4) If GI dysfunction is present – Restore for Gut Health at 1 teaspoon three times daily