CIRS Testing and Treatment: What the Tests Measure and What the Evidence Shows

Last reviewed: October 2026 · 14 min read · 34 sources

The short answer

  • CIRS isn’t a recognized diagnosis in mainstream medicine. Allergy and immunology reviews call proposed mold illnesses like it unproven [1, 2].
  • There is no single CIRS test. Practitioners combine exposure history, symptoms, a vision test and a panel of blood markers [3].
  • The best-known treatment is the Shoemaker Protocol. It starts with removing exposure and moves through prescription and lab-guided steps [4].
  • Functional medicine practitioners add broader approaches, such as non-prescription binders, antioxidants, gut support, diet changes and sauna. Most of the research behind them comes from animal studies, small human studies or case reports [5].
  • The evidence is small and mostly from one group. Germany’s mold guideline lists both the vision test and cholestyramine among methods without sufficient evidence [6].

If you’ve searched “CIRS test” or “CIRS treatment,” you’ve probably found two very different pictures. One describes a clear, lab-guided illness with a step-by-step treatment plan. The other says the illness hasn’t been shown to exist. This post walks through both, test by test and step by step, so you can have a better conversation with your doctor.

For the basics of the illness model itself, start with our CIRS page. For symptoms people report, see our post on signs of mold toxicity and CIRS.

The mainstream view first

Chronic inflammatory response syndrome (CIRS) isn’t a recognized diagnosis in mainstream medicine. The American Academy of Allergy, Asthma & Immunology says many proposed mold-related illnesses “remain largely or completely unproved” [1]. A 2019 review in Clinical Reviews in Allergy & Immunology describes the symptoms usually blamed on mold as “vague and subjective” and says “the existence of toxic mold syndrome has been disproven” [2].

Germany’s 2023 medical guideline on indoor mold goes further. It lists the “visual contrast sensitivity test (VCS test)” and the “determination of cytokines” among diagnostic methods that shall not be used after indoor mold exposure “because there is insufficient scientific evidence” [6]. It also lists “Detoxification therapy, e.g., with cholestyramine (CSM therapy)” among “Treatment methods without sufficient scientific evidence” [6].

Even supporters agree that CIRS is rarely diagnosed. A 2024 review by authors who treat it calls CIRS “an under-recognized, underdiagnosed” illness [7].

None of this means your symptoms aren’t real. It means the CIRS explanation for them hasn’t been accepted, and it’s worth having other causes checked [2].

The functional and Shoemaker perspective

The rest of this post describes how CIRS practitioners, following Dr. Ritchie Shoemaker, test for and treat the illness. It’s attributed to them, with an “Evidence:” note on each part.

How CIRS practitioners diagnose it

A 2018 consensus statement from Dr. Shoemaker’s group sets out the case definition. There must be “the potential for exposure to a damp indoor space,” “a multisystem, multi-symptom illness,” and lab results similar to those in published studies [3]. In this model, people with CIRS have “reduced levels of regulatory neuropeptides MSH and VIP” and “elevated inflammatory markers of C4a, MMP9 and TGF beta-1” [3].

Evidence: a consensus statement from the group that developed the model [3]; we found no independent validation of the case definition.

The tests people ask about

These are the tests CIRS practitioners use [3, 4]. Most are real lab tests. What’s debated is using them together to diagnose CIRS.

  • VCS (visual contrast sensitivity) test. A vision test of how well you can see low-contrast patterns. In a 2006 study by Dr. Shoemaker and a colleague, VCS “was abnormally low in all participants” [8]. Evidence: small studies by the developers. In an independent NIOSH evaluation, VCS scores were lower among 95 employees of a water-damaged school than among 110 at a comparison school, but the investigators said “we do not recommend using it in evaluation of people exposed to mold” [9]. A 2026 study of 28 exposed people and 30 controls found that the standard handheld VCS chart “did not distinguish between groups,” while some digital versions did [10]. The German guideline says the VCS test shall not be used for indoor mold exposure [6].
  • HLA-DR. A genetic test for immune gene types. Dr. Shoemaker writes that about 95% of his cases have one of six gene types that “comprise 24% of the normal population,” and that “HLA research is in its infancy” [11]. Evidence: clinical observation; Dr. Shoemaker says a “very large prospective study” would be needed [11].
  • MSH (melanocyte-stimulating hormone). A regulatory hormone the model expects to be low. In a 2005 study, MSH levels were abnormally low in participants [12]. Evidence: small studies by the developers.
  • TGF-beta1, C4a and MMP-9. Inflammation markers the model expects to be high [3]. Evidence: these are real lab measurements, but the German guideline lists cytokine testing among methods with insufficient evidence after indoor mold exposure [6].
  • VIP (vasoactive intestinal polypeptide). Another regulatory hormone. Dr. Shoemaker’s group reports low MSH or VIP in “over 98%” of their patients [13]. Evidence: the developers’ own patient data.
  • NeuroQuant. MRI software that measures the volume of brain regions. A 2014 study compared 17 patients with 18 controls and reported differences in several areas [14]. Evidence: one small study by the developers.
  • ERMI and HERTSMI-2 home tests. Dust tests of a building, not of you. HERTSMI-2 is a scoring system based on ERMI results, meant to show whether a building “is safe for occupancy” for someone previously sickened [15]. EPA, which developed ERMI, says it “has not been validated for non-research purposes” and does not recommend routine public use [16]. Evidence: EPA treats ERMI as a research tool, and HERTSMI-2 comes from Dr. Shoemaker’s own scoring [15, 16]; more in our ERMI testing post.

Dr. Shoemaker’s own 2005 study listed its limits: “Exposure to specific agents was not demonstrated, study participants were not randomly selected, and double-blinding procedures were not used” [12].

The Shoemaker Protocol, step by step

As summarized by one Shoemaker-trained physician, the protocol works through these steps in order, each guided by lab results [4]. Every step should be supervised by a licensed clinician; several involve prescription medicines.

  • Step 1: Remove exposure. Test and fix the buildings you spend time in, or move. The summary calls this “the most critical, yet most difficult step” [4].
  • Step 2: Prescription binders. Cholestyramine or colesevelam [4]. Both are prescription cholesterol medicines called bile acid sequestrants, which bind bile acids in the intestines so they leave the body [17, 18]. The protocol uses them to help clear biotoxins and tracks progress with the VCS test [4].
  • Step 3: MARCoNS. Treat this nasal staph bacteria if a deep nasal swab finds it [4].
  • Step 4: Anti-gliadin antibodies (a gluten-related marker). Avoid gluten if positive [4].
  • Step 5: Androgens (sex hormones). Correct low levels [4].
  • Step 6: ADH and osmolality, which affect thirst and urination [4].
  • Steps 7–11: MMP-9, VEGF, C3a, C4a and TGF-beta1. Address each if abnormal, with diet changes or prescription medicines [4].
  • Step 12: VIP nasal spray. Used last, only if symptoms remain after the other steps, exposure is gone, VCS is normal and MARCoNS is cleared [4].

What the evidence shows. The physician’s summary calls it “the only peer reviewed published protocol shown to reverse the symptoms and laboratory findings” [4]. A 2024 review by supporters found 13 articles on CIRS treatment and said “the only treatment with documented clinical efficacy was the Shoemaker Protocol” [7]. The studies are small. The placebo-controlled cholestyramine trial had 13 participants: 7 got cholestyramine and 6 got placebo [8]. The VIP study was open-label, with 20 patients and no placebo group [13]. In an earlier study, all participants who went back into their water-damaged buildings became ill again within 1 to 7 days [12].

Evidence: small studies, mostly from Dr. Shoemaker’s group; the German guideline considers cholestyramine therapy unproven [6].

Practical limits. The 2024 review names cost, adherence and side effects as the main limitations, and says removing exposure “costs readily exceed tens of thousands of dollars” [7]. Binders can cause side effects such as constipation and bloating, and MedlinePlus advises spacing other medicines away from cholestyramine, so ask your pharmacist how to time them [17].

The functional medicine view: how integrative practitioners approach it

Some functional and integrative medicine practitioners use the Shoemaker Protocol; one integrative physician quoted below describes starting it after her own office flooded [19]. Their published material also frames mold illness more broadly and adds other approaches. This section describes that view as its practitioners present it, with the evidence for each approach.

How they frame it

The International Society for Environmentally Acquired Illness (ISEAI) uses “environmentally acquired illness” as an umbrella term covering CIRS, mold illness, mast cell activation syndrome (MCAS) and multiple chemical sensitivity [20]. In an article on ISEAI’s site, Dr. Jill Carnahan, an integrative physician and ISEAI board director, compares a person’s “toxic load” to a bucket. When exposures overflow it, she writes, inflammation can follow, and mold is one possible trigger alongside infections, chemicals, heavy metals and air pollution [20]. The Institute for Functional Medicine teaches clinicians to assess “total toxic load,” especially when a condition doesn’t respond to initial treatment [21].

A 2013 review by an environmental medicine physician names inflammation, oxidative stress, toxicity, infection, allergy and irritant effects as the ways water-damaged buildings make people ill [5]. It also describes glutathione and vitamin C working together to protect mitochondria, the cell’s energy centers, from oxidative damage, mostly citing animal research [5]. Dr. Carnahan’s article describes treatment as “eliminating ongoing toxin exposures, healing your body, resetting your immune system, repairing your gut, and restoring hormonal imbalances,” with the goal to “identify and treat the root causes” [20]. A 2022 functional medicine review argues that mycotoxin illness “does not resolve with current standards of care for conditions secondary to it” [22].

Evidence: these are organizing ideas, not tested diagnoses. The 2013 review itself notes that “many of the studies are limited to animals or are relatively small human studies or case reports” [5]. Germany’s mold guideline says there is no evidence linking indoor mold to conditions such as chronic fatigue syndrome and multiple chemical sensitivity [6].

The approaches they commonly use

  • Removing exposure and remediating first. Dr. Carnahan writes that it is “equally as important to address the environmental factors,” often with help from an indoor environmental professional who assesses the home and guides cleanup [20]. The 2013 review says complete removal from exposure “cannot be emphasized enough,” though it “is often not sufficient for some people to regain health” [5]. Evidence: the strongest of any approach here. Germany’s guideline calls finding the cause and proper remediation the most important measures [6], and a Cochrane review found that repairing damp, moldy houses decreased asthma-related symptoms in adults [23].
  • Binders beyond prescriptions. Besides the prescription binders in the protocol above, practitioners use non-prescription binders such as activated charcoal, clay and chlorella, a type of algae [5]. Binders can also bind medicines and nutrients, so they’re usually taken several hours apart from them [5]. Evidence: limited. Most research on these binders comes from lab and animal studies, and we found no controlled trials in people with mold-related illness [5]. Germany’s guideline considers even cholestyramine therapy unproven [6].
  • Glutathione and antioxidants. Glutathione is an antioxidant the body makes. The 2013 review says it “plays a large part in treatment” and describes forms given by IV, nebulizer, skin, mouth and nose [5]. Evidence: the review cites benefits in other conditions, such as cystic fibrosis, rather than trials in mold illness [5]. We found no controlled trials in mold-related illness.
  • Nasal and sinus treatment. Beyond the MARCoNS step in the protocol, some practitioners treat what they see as fungal infection or “symptomatic colonization,” including with antifungals [5]. Evidence: weak. A Cochrane review of 8 trials with 490 adults found it “uncertain” whether antifungals help chronic sinus inflammation, because the evidence was very low quality [24]. That review didn’t study mold illness specifically.
  • Gut and microbiome support. Approaches include probiotics, treating gut infections and avoiding identified food allergens [5]. Evidence: indirect. A 2018 review of mycotoxins in food and animal feed found they can disturb the gut lining and change gut bacteria [25]. We found no trials of gut treatments in people with mold-related illness.
  • Diet changes. The 2013 review discusses avoiding gluten, “even in those not found to have celiac disease” [5]. Some practitioners use a “low mold diet” that cuts sugar, processed foods and alcohol; one Houston functional medicine physician writes that she used it in her own recovery and prescribes it to patients [26]. Evidence: we found no studies testing these diets for mold-related illness.
  • Sauna and sweating. The 2013 review calls sauna and exercise “invaluable” and says sweating has “long been studied as a means of reducing the body burden of toxins” [5]. Evidence: no trials in mold illness. A 2018 systematic review of regular dry sauna use found 40 studies with 3,855 people, only 13 of them randomized, and said the medical evidence for claimed benefits “is not well established” [27]. It also noted a reversible drop in sperm production in one study [27], so ask your clinician before starting.
  • Calming the nervous system. Some practitioners add brain-retraining programs based on the idea that the brain keeps reacting to “perceived biological threats” and sending danger signals to the body [28]. Evidence: very limited. A survey of people who had bought one commercial program found self-reported improvement among 40 people with mold illness; among 19 people with CIRS, the change wasn’t statistically significant after correction [28]. The survey had no comparison group, and its author’s company consults for the program [28]. A randomized study of 134 people with mold illness was completed in 2025, but no results were posted on its trial registry as of October 2026 [29].
  • Treating overlapping conditions like MCAS. Dr. Carnahan writes that in her practice, “mold is probably the number one trigger of MCAS,” and recommends supplements she describes as “natural antihistamines and mast cell stabilizers” [19]. Evidence: the mold–MCAS link rests mainly on clinical experience. An allergy specialists’ work group wrote strict MCAS criteria to avoid “overdiagnosing the disorder in patients who likely have other conditions” [30]. If you have symptoms like hives, flushing or swelling, an allergist can evaluate them.

Working with a clinician. Supplements, binders, sauna and diet changes can all have side effects or interact with medicines [5, 27]. If you try any of them, do it with a licensed clinician who knows your full health history, and tell all your doctors what you’re taking.

What’s known and what’s debated

Generally accepted: cholestyramine and colesevelam are prescription medicines that bind bile acids [17, 18]. Even critics of CIRS agree that mold can cause allergies and trigger asthma [2]. A 2012 meta-analysis of 16 studies concluded that dampness and molds at home are “determinants of developing asthma” [31], and a Cochrane review found that repairing damp, moldy houses decreased asthma-related symptoms in adults, based on moderate-quality evidence [23].

Debated: whether CIRS exists as a distinct illness, whether the lab panel can diagnose it, whether the protocol works better than chance, and whether the wider functional medicine approaches help [1, 2, 5, 6, 7].

Questions to ask your doctor

  • Could something else explain my symptoms, and what should we rule out first?
  • If you order any of these tests, what would a result change about my care?
  • How reliable is this test, and is it covered by insurance?
  • What are the side effects of a binder, and how should I time my other medicines?
  • If you suggest a supplement, sauna or special diet, what evidence supports it for someone like me, and could it interact with my medicines?
  • If we try a treatment, how will we know whether it’s working?
  • Should I see a specialist, such as an allergist or a clinician experienced in environmental illness?

Our symptom checklist and doctor visit prep sheet can help you bring a clear summary.

When to get urgent help

Call 911 or your local emergency number for severe shortness of breath at rest, bluish lips or face, severe chest pain, or severe drowsiness or confusion with breathing trouble [32]. Swelling of the face, eyes or tongue with trouble breathing can be a severe allergic reaction; use epinephrine if your clinician has prescribed it [33]. If you are having thoughts of suicide, call or text 988 [34].

The bottom line

CIRS testing and treatment come from one well-defined model with a small evidence base, and mainstream medicine hasn’t accepted it. If you’re exploring it, go slowly, ask what each test will change, and keep your home environment at the center, since even critics agree mold can cause allergies and trigger asthma [2]. We’ve walked this road ourselves; you can read about it in our story, and our mold toxicity page covers the wider picture.

Sources

Numbers in brackets in the text link to these sources. Links were checked in October 2026. Some sources are written by people who support a particular approach; we've tried to say so in the text.

  1. Bush RK, Portnoy JM, Saxon A, Terr AI, Wood RA. The medical effects of mold exposure (AAAAI position paper). J Allergy Clin Immunol. 2006;117(2):326-333. PMID: 16514772. https://doi.org/10.1016/j.jaci.2005.12.001
  2. Chang C, Gershwin ME. The Myth of Mycotoxins and Mold Injury. Clin Rev Allergy Immunol. 2019;57(3):449-455. PMID: 31608429. https://doi.org/10.1007/s12016-019-08767-4
  3. Shoemaker R, Johnson K, Jim L, et al. Diagnostic Process for Chronic Inflammatory Response Syndrome (CIRS): A Consensus Statement. Report of the Consensus Committee of Surviving Mold. Internal Medicine Review. 2018;4(5). https://www.survivingmold.com/Publications/CIRS_diagnostic_protocol_final_5_1_2018.pdf
  4. Ou D. Steps of the Shoemaker Protocol (2014; hosted by Surviving Mold). https://www.survivingmold.com/STEPS_OF_THE_SHOEMAKER_PROTOCOL_3.PDF
  5. Hope J. A review of the mechanism of injury and treatment approaches for illness resulting from exposure to water-damaged buildings, mold, and mycotoxins. ScientificWorldJournal. 2013;2013:767482. PMID: 23710148. https://pmc.ncbi.nlm.nih.gov/articles/PMC3654247/
  6. Hurraß J, Heinzow B, Walser-Reichenbach S, et al. AWMF mold guideline "Medical clinical diagnostics for indoor mold exposure" - Update 2023. Allergol Select. 2024;8:90-198. PMID: 38756207. https://pmc.ncbi.nlm.nih.gov/articles/PMC11097193/
  7. Dooley M, Vukelic A, Jim L. Chronic inflammatory response syndrome: a review of the evidence of clinical efficacy of treatment. Ann Med Surg (Lond). 2024;86(12):7248-7254. PMID: 39649915. https://pmc.ncbi.nlm.nih.gov/articles/PMC11623837/
  8. Shoemaker RC, House DE. Sick building syndrome (SBS) and exposure to water-damaged buildings: time series study, clinical trial and mechanisms. Neurotoxicol Teratol. 2006;28(5):573-588. PMID: 17010568. https://doi.org/10.1016/j.ntt.2006.07.003
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  11. Surviving Mold. Bi-weekly member questions, week of February 5, 2024 (Dr. Ritchie Shoemaker). https://www.survivingmold.com/physicians/dashboard/faq/bi-weekly-member-questions/week-of-february-5-2024
  12. Shoemaker RC, House DE. A time-series study of sick building syndrome: chronic, biotoxin-associated illness from exposure to water-damaged buildings. Neurotoxicol Teratol. 2005;27(1):29-46. PMID: 15681119. https://doi.org/10.1016/j.ntt.2004.07.005
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  15. Surviving Mold (Shoemaker RC). HERTSMI-2 Scoring System (web page). Web page, accessed October 10, 2026. https://www.survivingmold.com/resources-for-patients/diagnosis/hertsmi-2
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  18. MedlinePlus (U.S. National Library of Medicine). Colesevelam (drug information). Web page, accessed October 19, 2026. https://medlineplus.gov/druginfo/meds/a699050.html
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  24. Head K, Sharp S, Chong LY, Hopkins C, Philpott C. Topical and systemic antifungal therapy for chronic rhinosinusitis. Cochrane Database Syst Rev. 2018;9:CD012453. PMID: 30199594. https://pmc.ncbi.nlm.nih.gov/articles/PMC6513454/
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This is educational information only. Always consult licensed healthcare providers for personal medical advice.

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