by Jenny Lelwica Buttaccio
Updated 7/20/21

If your recovery from Lyme disease has been fraught with many twists and turns despite multiple trips to doctors, numerous treatments, and your best efforts — you might feel yourself becoming increasingly more frustrated. Thankfully, there are always new avenues to explore for finding relief, including a lesser-known condition you might not yet have heard of: Chronic Inflammatory Response Syndrome (CIRS).

Named by Dr. Richie Shoemaker, MD, a researcher and retired family physician from Pocomoke City, MD, CIRS is a biotoxin illness — meaning, an illness caused by chemical toxins released by certain living organisms — and it could play a critical role in why some patients remain ill despite months or years of treatment for chronic Lyme disease.

But because the symptoms associated with CIRS overlap with many other health conditions, including Lyme disease and other tick-borne diseases, it makes identifying the illness challenging for healthcare providers and adds layers to the problems that most patients already face when trying to obtain an accurate diagnosis.

Learn more about CIRS below, including its history, symptoms, testing, and treatment, to determine if this condition might be impeding your recovery and what to do about it.

The History of CIRS

The majority of our understanding of CIRS comes to the medical community by way of Dr. Shoemaker. He began his foray into the world of biotoxin illness in 1997 near an unincorporated community in Shelltown, MD. There, he linked a group of acutely ill individuals to water contaminated with a bacterial exotoxin (a biotoxin that damages cells in the body) from Pfiesteria, a dinoflagellate or single-cell aquatic organism.

Young black woman suffering from headache or migraine after waking up in morning. Stressed lady sitting in bed with painful face expression feeling terrible hangover, unpleasant weakness, dizziness

The affected individuals exhibited symptoms like headaches, memory loss, digestive disturbances, and skin lesions, according to a case report in the Maryland Medical Journal. The toxins produced by the dinoflagellate had been responsible for killing billions of fish in North Carolina’s estuaries, but whether or not it had contributed to illness in humans had largely remained controversial prior to Dr. Shoemaker’s findings.

Through his practice-based studies, a clinical picture of illness emerged, with the affected patients having a reduced capacity to clear biotoxins from their bodies, a heightened inflammatory response, and multi-systemic involvement. Dr. Shoemaker named the constellation of symptoms Chronic Inflammatory Response Syndrome. Through the years, he discovered other biotoxin illness in people who have had exposure to the following:

  1. Water-damaged buildings (WDB): WDBs are often hotspots for mold, even if you can’t see it or smell it. Though the exact prevalence of mold-infested buildings isn’t known, approximately 50% of homes and 85% of commercial buildings have sustained some water damage and mold.
  2. Organisms in the water: We already mentioned the discovery of the toxic dinoflagellate Pfiesteria, which laid the foundation for CIRS. However, another compound produced by dinoflagellates called ciguatera, as well as toxins from blue-green algae known as cyanobacteria, may be problematic for some people, too.
  3. Spiders: The poisonous venom from recluse spider bites, namely Mediterranean and brown, have been known to cause CIRS.

Of the above, mold is the most well-known biotoxin discussed in the chronic illness community. “Approximately, 25% of Americans carry a gene called HLA-DR (human leukocyte antigen) that makes it more difficult for them to excrete the toxic metabolites produced by a variety of different molds or other biotoxins,” says Dr. Bill Rawls, MD, Medical Director of RawlsMD and Vital Plan. Furthermore, the population of people with the genetic variant is more likely to develop CIRS because their bodies are unable to recognize toxins as foreign invaders, so they don’t produce the antibodies needed to remove these toxic substances.

But CIRS isn’t usually caused by one event alone, such as mold. Like many complex health conditions, there may be several components that overwhelm the body, such as multiple biotoxin exposures, untreated or stealth microbes, environmental toxins, and genetic variants.

Molecular level representation of virus, bacteria or disease.

For instance, if you’re already battling Lyme disease, your body is inundated with other kinds of toxins called endotoxins, which are pieces of dead bacteria that also cause an immune response, systemic inflammation, and can lead to a Herxheimer reaction. But unlike the exotoxin from Pfiesteria, endotoxins don’t damage cells directly.

Both exotoxins and endotoxins often get lumped together under the biotoxin umbrella, but they are quite different, notes Dr. Rawls, and they aren’t cleared from the body in the same manner. But ultimately, a body that is overrun with a multitude of toxins from various sources can reach a tipping point, and a person may encounter symptoms that don’t resolve with treatment.

The Primary Symptoms of CIRS

The symptoms of CIRS exist on a spectrum. Some individuals experience mild illness, while others are debilitated — which, as mentioned, is more likely to happen when Lyme disease is in the mix, burdening the immune system and stressing your cells.

Unhappy tired depressed mature woman sitting at home on the floor. Health problems of middle-aged women, mental health, covid coronavirus consequences

CIRS can affect several systems of the body, including neuroimmune, vascular, and endocrine systems. In addition to Lyme disease, the syndrome may mimic or overlap with other conditions, such as ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome), ulcerative colitis, fibromyalgia, and multiple sclerosis.

There are dozens of symptoms associated with CIRS, many of which will likely sound familiar to you. The most common ones include:

  • Cognitive problems with memory, concentration, and focus
  • Brain fog
  • Confusion
  • Headaches
  • Vertigo and dizziness
  • Fatigue and post-exertional malaise (PEM)
  • Muscle aches and joint pain
  • Abdominal cramping
  • Diarrhea
  • Shortness of breath
  • Sensitivity to light
  • Changes in mood
  • Sinus problems
  • Cough

How to Test for CIRS

Close up of female scientist sampling blood in test tubes while working on research in laboratory

Because the symptoms of CIRS are similar to those of other illnesses, your doctor will likely gather a detailed history of your potential exposure to mold or other biotoxins and perform a physical exam, as well as order tests to evaluate biomarkers that correlate with a mold and biotoxin illness.

Although many lab tests exist in the world of mold and biotoxin illness, is it a requirement to do all of them?

Not necessarily, says Dr. Rawls. It’s important to determine whether the information you might get from these labs will influence your decision-making. “Labs can provide valuable information, but in my opinion, about 75% of labs ordered by physicians probably won’t change the outcomes or management of the illness.”

Before allowing tests to be done, Dr. Rawls suggests always defining with your healthcare provider exactly how much a test will cost, whether it’s covered by insurance, and how the information obtained by a test will influence how you treat your condition. “Remember, you should always have the final say so.”

If you decide to move forward with testing, potential labs might include:

  1. HLA-DR: This genetic blood test determines whether a person has the genes that trigger the immune system to properly recognize and excrete mold and biotoxins from the body.
  2. VCS (Visual Contrast Sensitivity): A VCS test measures your ability to detect changes in visual contrast, a function that may be impaired in individuals who have been exposed to mold and biotoxins. The test is available online or can be completed in a doctor’s office.
  3. MSH (Melanocyte-Stimulating Hormone): The hormone MSH is produced in the hypothalamus and the pituitary gland. It regulates neuroimmune pathways, including melatonin, cortisol, cytokines, sex hormones, and the integrity of mucous membranes. Among CIRS-mold patients, 95% have decreased MSH functioning.
  4. TGF-beta-1 (Transforming Growth Factor Beta-1): TGF-beta-1 is an inflammatory cytokine marker that affects the functions of immune cells. It may be elevated in people with CIRS, causing a host of neurologic and autoimmune-type symptoms.
  5. VEGF (Vascular Endothelial Growth Factor): VEGF measures oxygen delivery capabilities throughout the body’s tissues. In the presence of CIRS, a state of low oxygen may ensue (hypoxia), resulting in increased fatigue, poor stamina, and PEM.
  6. C4a: C4a is a complement protein known as an anaphylatoxin, a substance that creates a response similar to an allergic reaction. It also executes tasks related to the immune system and inflammation. An elevated C4a may be present in individuals who have been exposed to mold or biotoxins. However, note that C4a levels aren’t exclusive to mold or biotoxins — levels may also be elevated in patients with Lyme disease and lupus.
  7. VIP (Vasoactive Intestinal Peptide): VIP is a peptide that regulates the immune response, inflammatory cytokines, and pulmonary arterial pressure. Low levels may be seen in people with mold and biotoxin illness. Symptoms of low VIP levels can include shortness of breath and exercise intolerance.
  8. MARCoNS (Multiple Antibiotic Resistant Coagulase Negative Staphylococcus): MARCoNs is a type of bacteria that resides deep in the nasal cavity and may pose a risk to people with mold and biotoxin illness. MARCoNs may suppress MSH levels, further hindering neuroimmune pathways. Testing for MARCoNs involves a nasal culture in the back of the nose.
  9. ADH (Antidiuretic Hormone): ADH manages the body’s fluid levels by balancing salt and water. ADH dysregulation may occur in people with mold and biotoxin illness, resulting in symptoms like excessive thirst, urinary frequency, fluid retention, and more.
  10. MMP-9 (Matrix Metalloproteinase-9): An enzyme, MMP-9, may increase in response to higher levels of cytokines in the body. A prolonged increase in MMP-9 may result in damage to certain tissues in the body.

Indeed, this is an expansive (and overwhelming) list of tests. “Labs can be extremely expensive,” says Dr. Rawls, “So your money might be better spent on therapies that have a high potential to help you feel better than labs that have a marginal impact on the outcomes or management of your illness.”

Thankfully, nowadays, most Lyme-literate medical doctors (LLMD) and many integrative physicians have at least a basic knowledge of mold and biotoxin illness and likely have established a set of biomarkers they prefer to use to evaluate for CIRS that might help trim the cost.

Top Treatment Options for CIRS

Treatment for CIRS requires an individualized, multi-faceted approach aimed at removing mold and biotoxins from the body, quieting inflammation, and assisting the body with cellular and tissue repair. Here are the best therapies to consider.

1. Remove or Remediate Biotoxins from Your Environment.

Woman holds ventilation grill with dust filter to clean it. Dirty and dusty white plastic, harmful for health. Cleaning lady with disguised expression, blurred, in protective rubber gloves and uniform

If you’ve been diagnosed with CIRS, a first key step is eliminating troublesome mold and biotoxins in your environment to nip the trigger for your symptoms in the bud. “The solution to a mold problem is avoiding it as best you can,” advises Dr. Rawls.

The reason? If someone living in a dwelling with mold issues is chronically ill with Lyme disease or another illness, then the likelihood that person is mold sensitive is quite high. “Though there is a higher incidence of mycotoxin sensitivity in HLA-DR positive individuals, it still occurs in individuals who are HLA-DR negative,” explains Dr. Rawls. “Either way, the solution is the same: Eliminate exposure to mold.”

If you know or suspect you’re contending with mold, the best course of action is to consult with a professional to safely remove or remediate it — tackling it on your own increases your exposure and often leads to a worsening of symptoms. In addition to selecting a professional you can trust, here are some things you can try:

  1. Use a HEPA air purifier in the areas of your home where you spend the most time. The bedroom is a good place to start.
  2. Use dehumidifiers and air conditioners to maintain low humidity levels. Mold flourishes when humidity is greater than 50%, so aim to keep levels between 30% and 50%.
  3. Heating and air conditioning units can contain hidden sources of mold. Regularly inspect them, and if mold is present, have them cleaned.
  4. Remove rugs or carpets in rooms known to contain high levels of moisture, such as bathrooms or the basement.
  5. Keep your kitchen, bathroom, and laundry rooms well ventilated.
  6. If you have an attic, make sure the space is dry and doesn’t contain moisture.

2. Use Binding Agents to Remove Biotoxins from Your Body.

“I must reiterate that with mold issues and mycotoxin sensitivity, the most important aspect of management is mitigating your exposure,” says Dr. Rawls. “In my clinical experience, symptoms generally start resolving within weeks of exposure elimination. With that said, binding agents may be helpful in severe cases for those who are not getting well after the threat has been removed.”

For this, Dr. Shoemaker uses medications like cholestyramine (CSM) or Welchol (for sensitive individuals). Though CSM and Welchol are cholesterol-lowering medications, they have a unique structure that binds to biotoxins and removes them via the digestive tract.

image split into four sections. Okra pepsin, bentonite clay, activated charcoal, chlorella

Some healthcare providers may also recommend gentler, natural binders like okra pepsin, bentonite clay, activated charcoal, and chlorella, depending on the type of mold or biotoxin you’ve come in contact with. But it’s important to know that binders absorb more than biotoxins — they’ll also mop up supplements, medications, and herbal therapies. To avoid this, you’ll generally want to take binders two hours before or after the other elements of your treatment protocol.

Typically, binders are taken until you have an improvement in test results like VCS, MSH, or a negative MARCoNS culture. Note that some people may experience constipation when taking activated charcoal or other toxin binders. If this happens to you, increasing your intake of magnesium, especially magnesium glycinate or citrate, can be useful to keep the digestive tract moving.

3. Eat a Healthy Diet

A nutritious diet is a mainstay of any smart recovery plan, but knowing what to eat can be a challenge. One simple rule of thumb: “The majority of your diet should be plant-based foods, especially vegetables,” says Dr. Rawls. “Vegetables contain nutrients and antioxidants to feed the beneficial flora of your gut and reduce inflammation, as well as crucial fiber to aid in toxin removal.”

Healthy food background, spinach, quinoa, apple, blueberry, asparagus, turmeric, red currant, broccoli, mung bean, walnuts, grapefruit, ginger, avocado, almond, green peas and goji, top view

To combat runaway inflammation, be sure to eliminate sugar, gluten, processed carbohydrates, or foods you have a known allergy to. Instead, you’ll want to stock up on healthy fats and proteins — foods like eggs, wild-caught salmon, chicken, olive oil, avocados, and ghee. In general, “If you pick up a food package and can’t pronounce the ingredients listed on the label, that product is better left on the shelf,” says Dr. Rawls.

Finally, if you’re taking certain binders, they may come with specific dietary requirements for maximum effectiveness. For instance, a low-amylose diet is recommended when taking CSM or Welchol; amylose is a digestion-resistant polysaccharide found in legumes, starchy fruits and vegetables, and whole grains.

4. Include Beneficial Adjunct Therapies.

CIRS therapy sauna yoga supplements outside

Various therapies can support the body’s efforts to eliminate biotoxins and reduce symptoms. There’s no one-size-fits-all approach to healing, but options that are often beneficial to patients include:

  • Herbal therapy: Herbal remedies like allicin (from garlic), curcumin, and glutathione help to lessen inflammation and normalize immune function. Antimicrobial herbs like cat’s claw, andrographis, and Japanese knotweed can help suppress stealth microbes that might be overtaxing your immune system.
  • Heat therapy: Infrared sauna use increases circulation, quells inflammation, and oxygenates tissues.
  • Time outdoors: Going outside offers breaks from continuous exposure to indoor mold and access to some fresh air. Some patients with mold or biotoxin illness practice extreme mold avoidance where they live or spend a substantial amount of time in drier climates such as the desert. For many people, this may not be a viable option, but spending extra time outside whenever possible can greatly benefit you as you heal.
  • Mind-body exercises: Yoga, Pilates, and tai chi can dial down an overactive sympathetic nervous system. These therapeutic movements help set the stage for more healing without pushing yourself to the max — which can leave your body more vulnerable to illness, not less.

The Bottom Line

Healing from CIRS takes time because, like Lyme disease, there are many layers to peel away. The good news is that as you sort through the different areas of dysfunction and take a comprehensive approach to recovery, you’ll begin to notice an increase in energy, clearer thinking, less pain, and a reduction in other debilitating symptoms. With time and patience, most people reach a state of better health — and that’s worth waiting for!

Dr. Rawls is a physician who overcame Lyme disease through natural herbal therapy. You can learn more about Lyme disease in Dr. Rawls’ new best selling book, Unlocking Lyme.

You can also learn about Dr. Rawls’ personal journey in overcoming Lyme disease and fibromyalgia in his popular blog post, My Chronic Lyme Journey.

1. Berndtson K. Chronic Inflammatory Response Syndrome: Overview, Diagnosis, and Treatment. 2013. Available at
2. Gunn SR, Gunn GG, Mueller FW. Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLA-DR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures. Am J Case Rep. 2016;17:320-325. Published 2016 May 11. doi: 10.12659/ajcr.896949
3. Prevalence of Building Dampness. Indoor Air Quality Scientific Findings Resource Bank website.
4. Shoemaker RC. Diagnosis of Pfiesteria-human illness syndrome. Md Med J. 1997;46(10):521-523.
5. Shoemaker RC. Surviving Mold: Life in the Era of Dangerous Buildings. Otter Bay Books; 2011.
6. Stricker RB, Savely VR, Motanya NC, Giclas PC. Complement split products c3a and c4a in chronic lyme disease. Scand J Immunol. 2009;69(1):64-69. doi: 10.1111/j.1365-3083.2008.02191.x