Description:　
Idiopathic environmental intolerance (IEI), formerly called multiple chemical sensitivity (MCS), is a subjective condition characterized by recurrent, nonspecific symptoms attributed to low levels of chemical, biologic, or physical agents in the absence of consistent objective diagnostic physical findings or laboratory tests that define an illness (AAAAI, 1999; ACOEM, 1999; Black & Temple, 2021).

Policy:
Application of coverage criteria is dependent upon an individual’s benefit coverage at the time of the request.

The following does not meet coverage criteria due to a lack of available published scientific literature confirming that the test(s) is/are required and beneficial for the diagnosis and treatment of a patient’s illness.

1. In all circumstances, laboratory tests designed to confirm the diagnosis of idiopathic environmental intolerance is considered NOT MEDICALLY NECESSARY. 
2. In all circumstances, the screening of blood, saliva, serum, plasma, urine, and/or stool samples for volatile solvents, organic acids, and organophosphates is considered NOT MEDICALLY NECESSARY. 
3. In all circumstances, profiling of phthalates and parabens using a blood, serum, plasma, saliva, urine, and/or stool sample is considered NOT MEDICALLY NECESSARY. 
4. For asymptomatic individuals, profiling of chlorinated pesticides, including DDE and DDT, using a blood, serum, plasma, saliva, urine, and/or stool sample is considered NOT MEDICALLY NECESSARY. 
5. In asymptomatic individuals and/or during general encounters without abnormal findings, testing of blood, serum, plasma, saliva, urine, and/or stool samples for carnitine sufficiency, oxidative stress and antioxidant sufficiency, detoxification adequacy, methylation sufficiency status, lipoic acid and CoQ10 sufficiency, and/or intestinal hyperpermeability is considered NOT MEDICALLY NECESSARY.  
6. In asymptomatic individuals and/or during general encounters without abnormal findings, testing of blood, serum, plasma, saliva, urine, and/or stool samples for vitamin sufficiency, mineral sufficiency, and/or nutritional analysis is considered NOT MEDICALLY NECESSARY.  
7. The use of a breath hydrogen and/or breath methane test to assess or diagnose the following conditions is considered NOT MEDICALLY NECESSARY:
   1. Idiopathic environmental intolerance
   2. Food allergies and sensitivities
   3. Carbohydrate sensitivity or intolerance
   4. Bacterial overgrowth, including but not limited to, small intestinal bacterial overgrowth [SIBO]
   5. Digestive disorders
   6. Constipation, diarrhea, or flatulence
   7. Neurological/neuromuscular disorders
   8. Rosacea
   9. Obesity
   10. As part of a wellness visit and/or general encounter without abnormal findings
8. In asymptomatic individuals and/or during general encounters without abnormal findings, testing of blood, serum, urine, cerebrospinal fluid, fingernails, hair, and/or stool sample for metals is considered NOT MEDICALLY NECESSARY.

Reimbursement Policy

1. For 83918 (Organic acids; total, quantitative, each specimen), a maximum of 2 units per date of service is ALLOWED.
2. For 83919 (Organic acids; qualitative, each specimen), a maximum of 1 unit per date of service is ALLOWED. 
3. For 83921 (Organic acid, single, quantitative), a maximum of 2 units per date of service is ALLOWED.
4. For 82127 (Amino acids; single, qualitative, each specimen), a maximum of 1 unit per date of service is ALLOWED. 
5. For 82136 (Amino acids, 2 to 5 amino acids, quantitative, each specimen), a maximum of 2 units per date of service is ALLOWED.
6. For 82139 (Amino acids, 6 or more amino acids, quantitative, each specimen), a maximum of 2 units per date of service is ALLOWED.
7. For 84585 (Vanillylmandelic acid (VMA), urine), a maximum of 1 unit per date of service is ALLOWED. 
8. For 83150 (Homovanillic acid (HVA)), a maximum of 1 unit per date of service is ALLOWED.
9. For 83497 (Hydroxyindolacetic acid, 5-(HIAA)), a maximum of 1 unit per date of service is ALLOWED.
10. For 82656 (Elastase, pancreatic (EL-1), fecal, qualitative or semi-quantitative), a maximum of 1 unit per date of service is ALLOWED. 

Regulatory Status
No specific U.S. Food and Drug Administration (FDA) approval or clearance of a test for idiopathic environmental intolerance was found. Additionally, many labs have developed specific tests that they must validate and perform in house. These laboratory-developed tests (LDTs) are regulated by the Centers for Medicare & Medicaid Services (CMS) as high-complexity tests under the Clinical Laboratory Improvement Amendments of 1988 (CLIA ’88). As an LDT, the U.S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use.

Rationale 
Patients with idiopathic environmental intolerance (IEI) typically report sensitivity to multiple, chemically unrelated substances and become ill due to a wide range of nonspecific symptoms when exposed. Symptoms may include anxiety, shortness of breath, chest pain, and more. Psychiatric disorders may also be at the core of the IEI patient (Black & Temple, 2021). The mean age of patients reporting IEI is between 30 and 40 years, women are diagnosed more than men, and individuals who are married are significantly more likely to be diagnosed with IEI than those who are not (Black & Temple, 2021). IEI also occurs in 40% of people with chronic fatigue syndrome and in 16% of people with fibromyalgia (Black et al., 2020). 

The symptoms of IEI are nonspecific, ambiguous and common in the general population. There is no characteristic set of symptoms and ultimately no major differences between patients self-reporting IEI and those that do not. Virtually any symptom can be considered a symptom of IEI (Black & Temple, 2021). Within the definition of multiple chemical sensitivity (MCS), identified symptoms included “asthmatic-like, skin irritation, dermatitis, migraine, dysuria, dyspepsia, symptoms of supposed sensitization to food, persistent arthromial pain, vertigo, vestibular impairment,” with 80% of patients experiencing “asthenia, arthromial pain, dyspepsia, coriza, eructation, chest pain, insomnia” (Quarato et al., 2020). The classification of IEI as a distinct medical disorder is also in question, as a lack of reliable case reports, lack of consistent findings or laboratory results, and reliance on surveys or self-reporting all cloud the condition and understanding of this disorder (Black & Temple, 2021). 

Recently, many articles have been published suggesting a relationship between electromagnetic fields and IEI. Electromagnetic fields may include radiofrequencies from telecommunication devices (Eltiti et al., 2018; Huang et al., 2018), Wi-Fi and base stations (ANSES, 2018). For an unknown reason, these individuals claim to react to the exposure of certain electromagnetic triggers that most people can tolerate without issues; these triggers are below established toxicological and hazardous thresholds. ANSES (2018) researched the relationship between electric field exposure and IEI symptoms and stated that “either the symptoms experienced by EHS [electromagnetic hypersensitivity] individuals are not caused by exposure to electromagnetic fields and there are no quantifiable biological and/or physiological abnormalities when they are exposed to electromagnetic fields (assumption 1) or the absence of results is due to the methodological limitations of the provocation studies (subject selection, sample size, exposure type, etc.) (assumption 2).” These findings were corroborated by Schmiedchen et al. (2019), who, in their systematic review of articles pertaining to EHS, stated, “limitations in design, conduct and analysis could therefore have given rise to either false positive for false negative results,” and that the “nocebo effect or medical/mental disorders may explain the complaints in many individuals.” Characteristic symptoms of EHS include sleep and circadian rhythm disorders, migraines and headaches, hypersensitivity, and other related syndromes and disorders such as fibromyalgia, tinnitus and MCS (ANSES, 2018).

Tests such as elimination diets, food challenges, and provocation-neutralization tests have been used to test for food or chemical sensitivities. Immunological tests or tests measuring the amount of various chemicals in body tissues have also been performed (Black & Temple, 2021). In fact, testing for a wide range of autoantibodies is generally discouraged, as “pretest probability is low, and false-positive results are far more likely than true-positive results; a weakly positive ANA [antinuclear antibodies] is present in about 20% of the population” (Black et al., 2020). However, these assessments are typically not rigorous enough to provide strong evidence; for example, these tests are often not performed blinded or with placebo controls. No unusual laboratory findings have been reliably linked to IEI (Black & Temple, 2021). Due to the vast number of causes, symptoms, responses, and general heterogeneity of this condition, it may be very difficult to provide a scientifically valid or useful test. Worse, testing may even exacerbate or increase the number of symptoms of a patient. Physicians should use caution in testing for reassurance of patients as negative findings may increase anxiety instead (Barsky & Borus, 1999; Black & Temple, 2021).

Proprietary Testing 
Due to the number of symptoms that may be considered part of IEI, there are a corresponding amount of tests performed. These tests are generally unnecessary as the condition itself is far too ambiguous to reliably test for and any test can be ordered under the guise of IEI. For example, assessment of factors such as elastase, stool culturing, or fat differentiation may all be done for the sake of IEI treatment. These tests may have legitimate medical purposes (for instance a stool culture may be useful for numerous conditions) but their use for IEI is essentially none, as IEI itself carries no reliable characteristics to test for. Other tests that evaluate a tangentially relevant analyte, such as micronutrient panels or a lactose intolerance breath test (BT), may be done for IEI’s sake as well. Since virtually any symptom or sign can be called IEI, these tests are sometimes ordered for nonspecific or subjective symptoms such as fatigue or pain. However, these tests cannot provide any useful results because of the dubious nature of IEI itself. 

Another commonly used test for IEI are panels that test multiple factors in one. For example, the Triad Bloodspot Profile offered by Genova Diagnostics measures organic acid levels, “the level of IgG4 reactions for 30 common foods,” and “essential amino acid imbalances” (Genova, 2021d). Genova offers several similar panels, such as the Organix Comprehensive Profile (which tests 46 analytes for subjective symptoms such as depression, weight issues and chemical sensitivities) (Genova, 2021c), the NutrEval FMV [first morning void] (which tests 118 analytes for symptoms such as fatigue, weight issues, and sports fitness optimization) (Genova, 2021a) and the Allergix IgG4 Food Antibodies (which tests 90 foods for sensitivity). Genova Diagnostics also offers the GI Effects Profile (advanced stool tests for the management of gastrointestinal [GI] health), a full line of allergy testing and assessment tests (measuring IgG and IgE food antibodies, inhalants, molds and spices), the Ion Profile (which evaluates various types of organic, amino and fatty acids as well as nutrient and toxic elements), the Comprehensive Digestive Stool Analysis (CDSA) 2.0 Profile with Parasitology (evaluates the microbiome, digestion and absorption), and SIBO Profile tests (breath tests which measure methane gases and exhaled hydrogen) (Genova, 2020).

An evaluation of symptoms of IEI patients includes a history, physical examination, and laboratory tests (complete blood count, serum electrolytes and glucose, urine analysis) with further testing guided by reported symptoms. An occupational or environmental history is also useful as patients typically report problems from chemical exposure (Black & Temple, 2021). A questionnaire such as the “Environmental Exposure and Sensitivity Intolerance” (EESI) may be used for an initial screening (Rossi & Pitidis, 2018). A psychiatric history is also recommended as psychiatric disorders are often co-morbid with IEI. A screening questionnaire such as the Patient Health Questionnaire (PHQ-9) can be used to identify psychiatric conditions in an IEI patient (Black & Temple, 2021; Gilbody et al., 2007).

Micronutrients are the essential vitamins and minerals required by the body for proper functioning. Panels have been developed which evaluate intracellular levels of essential vitamins and minerals. These panels may also be used on IEI patients. This may help to identify nutritional deficiencies in otherwise healthy patients or in patients suffering from some type of disease. SpectraCell Laboratories have developed the Micronutrient Test Panel, which is able to measure 31 vitamins, minerals, metabolites, amino acids, fatty acids and antioxidants; this test also measures how these micronutrients affect cellular functioning in an individual (SpectaCell, 2021). SpectraCell Laboratories have also developed the SPECTROX™, claiming it measures total antioxidant function in an individual, reporting on the repair mechanisms and net ability of each individual’s cells (SpectraCell, 2008). As noted above, Genova Diagnostics has developed the NutrEval FMV that measures 118 markers, including amino acids, fatty acids and organic acids (Genova, 2021a). ONE (Optimal Nutritional Evaluation) FMV, also by Genova Diagnostics, is a urine-based nutritional test which assesses “the functional need for antioxidants, B-vitamins, minerals, digestive support and amino acids” (Genova, 2021b). The company notes that the ONE FMV test may be used for patients with mood disorders, fatigue, digestive issues, weight problems, general health, dietary guidance and fitness. Another nutrient panel blood test, developed by Life Extension, measures vitamin B12, folate, vitamin D 25-hydroxy, vitamin A, vitamin C, selenium, zinc, CoQ10 (coenzyme Q10) and magnesium (LifeExtension, 2020). Finally, Vibrant America provides a test which measures approximately 40 intracellular and extracellular vitamins, minerals, fatty acids, amino acids and antioxidants (Vibrant, 2017).

Clinical Utility and Validity 
Very little information suggests that the intracellular micronutrient analysis assists with positive health outcomes. Houston (2013) published an article on the role of vitamins, minerals and overall nutrition in the prevention and treatment of hypertension. This article reviewed hypertension-related clinical trials that include information on the “efficacy of nutrition, weight loss, exercise, and nutritional supplements, vitamins, minerals, and antioxidants” (Houston, 2013). Approximately 3338 patients were treated with micronutrient testing over a five-year period, with 20% of these patients exhibiting abnormally high blood pressure. After six months, 62% of the hypertensive patients reached lower blood pressure goals. Hence, the author states that the diagnosis and treatment of various nutritional deficiencies can decrease the number of cardiac events as well as reduce blood pressure and improve vascular biology. However, data for the control group not treated with micronutrients was not provided for comparison.

Another technique that has been used to assess nutritional status is the measurement of the hepatic proteins prealbumin and albumin. However, it seems that a physical examination has evolved as the main technique to diagnose malnutrition in a clinical setting. “The current consensus is that laboratory markers are not reliable by themselves but could be used as a complement to a thorough physical examination” in a malnutrition diagnosis (Bharadwaj et al., 2016). The Academy of Nutrition and Dietetics (AND) also do not accept albumin and prealbumin as a diagnostic tool for malnutrition and state that “There is no laboratory test that is both sensitive to and specific for protein-calorie malnutrition” (AND, 2017).

IEI patients may also report bowel irritability. Small intestinal bacterial overgrowth (SIBO) occurs when excessive aerobic and anaerobic bacteria colonize the small intestine; these bacteria are not typically found in the colon and can cause chronic diarrhea and malabsorption (Pimentel, 2022). SIBO may be diagnosed by a breath test. However, a validated gold standard method for diagnosing SIBO has not been indicated (Rezaie et al., 2017). The SIBO breath test uses carbohydrates in a simple, non-invasive and widely available testing method. A carbohydrate substrate (such as lactulose or glucose) is administered to the patient, which leads to the production of an analyte such as hydrogen or methane. “In individuals without SIBO, the administration of lactulose results in a single peak in breath hydrogen/methane within two to three hours due to the metabolism of lactulose by colonic flora. In patients with SIBO, administration of lactulose results in an early peak in breath hydrogen/methane levels due to metabolism by small bowel bacteria” (Pimentel, 2022). As noted above, Genova Diagnostics has developed the SIBO Profile test which is a two or three hour breath test that measures methane gases and exhaled hydrogen (Genova, 2020). This test requires the patient to ingest a lactulose solution.

Bratten et al. (2008) completed a study with 224 patients with irritable bowel syndrome (IBS) and 40 controls. A lactulose breath test (LBT) was used to measure methane and hydrogen production to identify patients with IBS. Results showed that “The majority of patients with IBS and healthy subjects meet criteria for an "abnormal" LBT using previously published test criteria, and groups are not discriminated using this diagnostic method” (Bratten et al., 2008). The authors then questioned the utility of an LBT to diagnose IBS as the testing did not discriminate between IBS patients and healthy controls. A more recent study by Ghoshal et al. (2014) evaluated 80 patients with IBS for SIBO. Culture had previously diagnosed 15/80 patients with SIBO. Both lactulose and glucose hydrogen breath tests (LHBT and GHBT, respectively) were used to measure SIBO. The authors conclude that “The specificity of GHBT was 100%, but the sensitivity of this test and the diagnostic performances of LHBT and breath methane were all very poor” (Ghoshal et al., 2014).

Speck and Witthöft (2022) included 410 patients in a cross-sectional study design to investigate the relationship between IEI symptoms associated with chemicals and schizotypy spectrum. They found that “schizotypal traits were found to be significantly positively associated with [modern health worries], [chemical odor sensitivity]…, and showed significant positive associations with hallucination proneness. Magical thinking was found to exhibit a significant positive relationship with both [modern health worries] and [chemical odor sensitivity].” This demonstrates how the principles surrounding IEI may need to consider associated psychiatric differential diagnoses to properly evaluate symptoms and testing. Finding that patients have symptoms of chemical odor sensitivity and modern health worries can also conversely encourage further insight into the mental wellness of a patient. 

Madigan et al. (2022) investigated the relationship between SIBO caused by Archaea and certain clinical symptoms. Archaea are anaerobic bacteria that produce methane specifically. Through a retrospective cross-sectional study, the researchers used glucose breath tests conducted for SIBO to correlate the bacteria to their phenotypic manifestations. From 1461 patients, they found that 33.1% were SIBO positive, with 38.8% producing only methane, 11.4% producing both methane and hydrogen, and 49.8% with hydrogen only producing organisms. Methane-producing SIBO patients had an increased odds of experiencing constipation and gassiness in comparison to SIBO(-) patients. On the other hand, hydrogen-producing SIBO patients had several “significant factors”: “vitamin B12 deficiency (odds ratio, 1.44; CI, 1.01 – 2.06; P = .046), [Roux-en-Y Bypass] (odds ratio, 2.14; CI, 1.09 – 4.18; P = .027), cholecystectomy(odds ratio, 1.42; CI, 1.06 – 1.91; P = .020), , and diabetes (odds ratio, 1.59; CI, 1.13 – 2.24; P = .008).” However, when comparing methane-producing SIBO versus hydrogen-producing SIBO patients, “vitamin B12 deficiency was the only factor that reached significant (OR 0.57; CI, 0.34-0.97; P = 0.038), indicating that [methane-producing SIBO] patients were almost half as likely to report cobalamin deficiency.” This study demonstrated the implications of varying gas producing organisms in SIBO and the clinical symptoms that can affect treatment and prognosis, solely by extrapolating data from breath tests (Madigan et al., 2022).

Rangan et al. (2022) conducted a review to investigate the clinical utility and drawbacks of SIBO breath testing. They identified that the “variability in oral-cecal transit time” was the biggest limitation in breath testing, and that it greatly contributed to common false-positive test results. This theoretically results from lactulose fermentation by normal colonic flora versus invasive microbial flora. In comparing the specificity and sensitivity for lactulose breath testing versus glucose breath testing, it was found that the former had a sensitivity of 42.0% and specificity of 70.6%, whereas the latter had a sensitivity of 54.5% and a specificity of 83.2%. However, those with a positive lactulose breath test result were more likely to respond to rifaximin therapy, thereby implying greater clinical utility. Despite the controversies in the substrates for testing, the researchers state that “notably, however, clinical symptoms have also been shown to be nonspecific for diagnosing SIBO, and thus breath testing remains a useful diagnostic tool in managing those patients with compatible symptoms and an absence of another diagnosis on endoscopy or imaging, particularly if there are other underlying conditions that could predispose to SIBO” (Rangan et al., 2022). 

Bushyhead and Quigley (2022) corroborates the technical difficulties and clinical utility of SIBO breath testing discussed in the two studies mentioned above. In their review, they state that breath testing is less invasive and inexpensive relative to small bowel culture-based diagnoses. However, there is no solidified association between methanogenic overgrowth and gastrointestinal symptoms like constipation, as the “positive breath test for methane may be due to methane production by resident anaerobic colonic methanogens rather than small bowel flora.” They also concur on the idea that “an important factor that may confound the interpretation of lactulose breath tests… is orocecal transit time…It is also possible that glucose malabsorption, which may be more prevalent than previously considered, could lead to a positive glucose breath test… Prior upper GI surgery could also contribute to accelerated orocecal transit of glucose; conversely, those with constipation and preformed gas can confound more test results.” The variability and contamination limit the diagnostic utility of breath testing in the setting of SIBO (Bushyhead & Quigley, 2022).

Due to the dubious nature of this condition, several prominent medical studies have regarded this condition with suspicion. In 1992, the American Medical Association (AMA) stated that multiple chemical sensitivity (now IEI) should not be recognized as a syndrome until accurate, reproducible, and well-controlled studies can be done (AMA, 1992). Other societies such as the American College of Physicians and the American Academy of Allergy and Immunology hold similar views (AAAAI, 1986; ACP, 1989).

American Academy of Allergy, Asthma and Immunology (AAAAI) 
In 2006, AAAAI referenced IEI in their position statement on the medical effects of mold stating that testing many nonvalidated immune based tests, as had been done to suggest an immunologic basis for IEI (MCS), is expensive, not useful or valid, and should be discouraged (Bush et al., 2006).

American College of Occupational and Environmental Medicine (ACOEM) 
In 1999, the ACOEM published a position statement that stated there have been no consistent physical findings or laboratory abnormalities in IEI (then called MCS) patients and recommended that a generalized clinical approach, such as establishing a therapeutic alliance and avoiding unnecessary tests, would be useful in the management of other nonspecific medical syndromes (ACOEM, 1999).

French Agency for Food, Environmental and Occupational Health & Safety (ANSES) Appraisal-Collective Expertise Report 
An ANSES expert committee published an opinion piece regarding the expert appraisal on EHS or IEI due to electromagnetic fields. This committee did not find any conclusive results regarding IEI and therefore does not recommend any specific testing methods for this ailment, other than the psychological testing of patients. 

Consensus Document (1999) 
An international document, created by 89 clinicians and researchers with broad experience in the field, aimed to establish consensus criteria for MCS. The recognition criteria of MCS set forth by this expert panel are as follows:

• Chronic condition
• Reproducible symptoms with repeated chemical exposure
• Low exposure levels cause syndrome to occur
• Removal of offending agents cause symptoms to subside
• There are responses to chemically unrelated substances ("Multiple chemical sensitivity: a 1999 consensus," 1999)

The 1999 Consensus Document is the most widely used criteria for recognition of MCS (Martini et al., 2013).

North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 
The NASPGHAN and ESPGHAN have stated that “Clinicians should familiarize themselves with the limitations of nutritional biomarkers in the context of chronic liver disease” but do not give specific recommendations regarding nutritional laboratory testing (Mouzaki et al., 2019).

World Health Organization 
The WHO published guidelines on the micronutrient intake in children with severe acute malnutrition. The guidelines recommend that the weight-for-height/weight-for-length status should be measured by clinicians to determine malnutrition. Micronutrient laboratory testing is not mentioned by the WHO.

The North American Expert Consensus Guidelines 
A team of experts have published guidelines on breath tests including their use for a SIBO diagnosis. The authors have provided the following recommendations:

• “Current small bowel culture techniques are not satisfactory for the assessment of SIBO. [Quality of evidence: Low]
• If culture is considered for diagnosis of SIBO, based on the current evidence, we suggest the threshold of > 10 3 c.f.u./ml for the definition of SIBO [Quality of evidence: Low].
• We suggest breath testing in the diagnosis of small intestinal bacterial overgrowth [Quality of evidence: Moderate].
• Until a true gold standard is established, we suggest breath testing in assessing the presence of antibiotic responsive microbial colonization of the gastrointestinal tract [Quality of evidence: Moderate].
• We suggest to evaluate for excessive methane excretion on breath test in association with clinical constipation and slowing of gastrointestinal transit [Quality of evidence: Moderate].
• We suggest that breath testing should not be used for assessment of orocecal transit time [Quality of evidence: Moderate].
• We suggest breath testing for the diagnosis of carbohydrate maldigestion syndromes [Quality of evidence: Moderate].
• We suggest breath testing in the assessment of conditions with bloating [Quality of evidence: Low].
• We suggest that fructose and lactose breath test should be performed for at least 3 hours [Quality of evidence: Moderate].
• We suggest that the presence of bacterial overgrowth should be ruled out before performing lactose or fructose breath testing [Quality of evidence: Moderate]” (Rezaie et al., 2017).

It may be worth noting that the above recommendation of LHBT testing for SIBO was publicly criticized by Usai-Satta et al. (2018) due to high false positive rates and a low sensitivity. The authors state that “in our opinion, LHBT should be neither recommended nor suggested to detect SIBO in the clinical practice. Despite a low sensitivity, Glucose BT [breath test] remains the most accurate BT for non-invasive diagnosis of SIBO (Usai-Satta et al., 2018).” In contrast, an article published in Gastroenterology by Baker et al. (2021) did a retroactive study, examining how these 2017 guidelines for glucose breath testing for SIBO compared to the older, modified Rome Consensus protocols. The authors found that the more recent North American Consensus protocol showed a higher percent of individuals with SIBO because of more prevalent positive methane excretion. Another article published by Pitcher et al. (2022) provide further support for the North American Consensus protocol for SIBO testing. 

The Academy of Nutrition and Dietetics 
The AND note that “serum proteins such as albumin and prealbumin are not included as defining characteristics of malnutrition because evidence analysis shows that serum levels of these proteins do not change in response to changes in nutrient intake. Hepatic proteins are not indicators of nutritional status, but are rather indicators of morbidity and mortality, and recovery from acute and chronic disease (AND, 2017).”

American College of Gastroenterology (ACG)
The ACG published an update on SIBO (Small Intestinal Bacterial Overgrowth). This guideline addresses diagnostic testing and treatment options for SIBO. Their recommendations include:

• “We suggest the use of breath testing (glucose hydrogen or lactulose hydrogen) for the diagnosis of SIBO in patients with IBS (conditional (weak) recommendation, very low level of evidence).”
• “We suggest using glucose hydrogen or lactulose hydrogen breath testing for the diagnosis of SIBO in symptomatic patients with suspected motility disorders (conditional (weak) recommendation, very low level of evidence).”
• “We suggest testing for SIBO using glucose hydrogen or lactulose hydrogen breath testing in symptomatic patients (abdominal pain, gas, bloating, and/or diarrhea) with previous luminal abdominal surgery (conditional (weak) recommendation, very low level of evidence).”
• “We suggest testing for methane using glucose or lactulose breath tests to diagnose the overgrowth of methane-producing organisms (IMO) in symptomatic patients with constipation (conditional (weak) recommendation, very low level of evidence).”

The ACG also notes that although “Small bowel aspirate and culture is often considered the gold standard for the diagnosis of SIBO,” there have been some preliminary studies focusing on use of nucleic acid testing to diagnose SIBO. However, the ACG remarks that “Large-scale studies are currently underway to evaluate this further” (Pimentel et al., 2020).

Table of Terminology

References: 

1. AAAAI. (1986). Clinical ecology. Executive Committee of the American Academy of Allergy and Immunology. J Allergy Clin Immunol, 78(2), 269-271. 
2. AAAAI. (1999). Idiopathic environmental intolerances. American Academy of Allergy, Asthma and Immunology (AAAAI) Board of Directors. J Allergy Clin Immunol, 103(1 Pt 1), 36-40. 
3. ACOEM. (1999). ACOEM position statement. Multiple chemical sensitivities: idiopathic environmental intolerance. College of Occupational and Environmental Medicine. J Occup Environ Med, 41(11), 940-942. 
4. ACP. (1989). Clinical ecology. American College of Physicians. Ann Intern Med, 111(2), 168-178. 
5. AMA. (1992). Clinical ecology. Council on Scientific Affairs, American Medical Association. Jama, 268(24), 3465-3467. 
6. AND. (2017). Should Albumin and Prealbumin Be Used as Indicators for Malnutrition? https://jandonline.org/article/S2212-2672(17)30444-6/pdf
7. ANSES. (2018). OPINION of the French Agency for Food, Environmental and Occupational Health & Safety regarding the expert appraisal on “electromagnetic hypersensitivity (EHS) or idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF)”. https://www.anses.fr/en/system/files/AP2011SA0150EN.pdf
8. Baker, J. R., Chey, W. D., Watts, L., Armstrong, M., Collins, K., Lee, A. A., Dupati, A., Menees, S., Saad, R. J., Harer, K., & Hasler, W. L. (2021). How the North American Consensus Protocol Affects the Performance of Glucose Breath Testing for Bacterial Overgrowth Versus a Traditional Method. Am J Gastroenterol, 116(4), 780-787. https://doi.org/10.14309/ajg.0000000000001110 
9. Barsky, A. J., & Borus, J. F. (1999). Functional somatic syndromes. Ann Intern Med, 130(11), 910-921. 
10. Bharadwaj, S., Ginoya, S., Tandon, P., Gohel, T. D., Guirguis, J., Vallabh, H., Jevenn, A., & Hanouneh, I. (2016). Malnutrition: laboratory markers vs nutritional assessment. Gastroenterol Rep (Oxf), 4(4), 272-280. https://doi.org/10.1093/gastro/gow013 
11. Black, D., & Temple, S. (2021, May 29). Idiopathic environmental intolerance (multiple chemical sensitivity). UptoDate. https://www.uptodate.com/contents/idiopathic-environmental-intolerance-multiple-chemical-sensitivity
12. Black, D. W., Carver, R. J., & Carver, L. A. (2020, July). Idiopathic Environmental Intolerance (Multiple Chemical Sensitivity; Environmental Illness). Merck Sharp & Dohme Corp. https://www.merckmanuals.com/professional/special-subjects/idiopathic-environmental-intolerance/idiopathic-environmental-intolerance
13. Bratten, J. R., Spanier, J., & Jones, M. P. (2008). Lactulose breath testing does not discriminate patients with irritable bowel syndrome from healthy controls. Am J Gastroenterol, 103(4), 958-963. https://doi.org/10.1111/j.1572-0241.2008.01785.x 
14. Bush, R. K., Portnoy, J. M., Saxon, A., Terr, A. I., & Wood, R. A. (2006). The medical effects of mold exposure. J Allergy Clin Immunol, 117(2), 326-333. https://doi.org/10.1016/j.jaci.2005.12.001 
15. Bushyhead, D., & Quigley, E. M. M. (2022). Small Intestinal Bacterial Overgrowth-Pathophysiology and Its Implications for Definition and Management. Gastroenterology, 163(3), 593-607. https://doi.org/10.1053/j.gastro.2022.04.002 
16. Eltiti, S., Wallace, D., Russo, R., & Fox, E. (2018). Symptom Presentation in Idiopathic Environmental Intolerance With Attribution to Electromagnetic Fields: Evidence for a Nocebo Effect Based on Data Re-Analyzed From Two Previous Provocation Studies. Front Psychol, 9, 1563. https://doi.org/10.3389/fpsyg.2018.01563 
17. Genova. (2020). Testing Services Overview. https://www.gdx.net/files/clinicians/how-to-order/Genova-Diagnostics-Testing-Services-Overview.pdf
18. Genova. (2021a). NutrEval® FMV. Retrieved 1/5/21 from https://www.gdx.net/product/nutreval-fmv-nutritional-test-blood-urine
19. Genova. (2021b). ONE (Optimal Nutritional Evaluation) FMV™. Retrieved 1/5/21 from https://www.gdx.net/product/one-fmv-nutritional-test-urine
20. Genova. (2021c). Organix® Comprehensive Profile - Urine. Retrieved 1/5/21 from https://www.gdx.net/product/organix-comprehensive-profile-metabolic-function-test-urine
21. Genova. (2021d). TRIAD® Bloodspot Profile. Retrieved 1/5/21 from https://www.gdx.net/product/triad-bloodspot-profile-metabolic-nutritional-test-blood-spot
22. Ghoshal, U. C., Srivastava, D., Ghoshal, U., & Misra, A. (2014). Breath tests in the diagnosis of small intestinal bacterial overgrowth in patients with irritable bowel syndrome in comparison with quantitative upper gut aspirate culture. Eur J Gastroenterol Hepatol, 26(7), 753-760. https://doi.org/10.1097/meg.0000000000000122 
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Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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