CAM 20101

Diagnosis and Management of Idiopathic Environmental Intolerance (i.e., Clinical Ecology)

Category:Medicine   Last Reviewed:April 2019
Department(s):Medical Affairs   Next Review:April 2020
Original Date:December 1995    

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, 2018).

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

  1. Laboratory tests designed to affirm the diagnosis of idiopathic environmental illness are considered  INVESTIGATIONAL.
  2. Screening blood, saliva, serum, plasma, urine, and/or stool samples for volatile solvents, organic acids, and organophosphates are considered INVESTIGATIONAL in all circumstances including but not limited to the following compounds:
    • 2-methylhippurate
    • 2-methylpentane
    • 3-methylpentane
    • 3,4-dihydroxyphenylpropionate
    • 4-nonylphenol
    • alpha-keto-beta-methylvalerate
    • alpha-ketoisovalerate
    • arabinitol
    • atrazine or atrazine mercapturate
    • benzene
    • benzoate
    • bisphenol A (BPA)
    • diethydithiophosphate (DEDTP), diethylthiophosphate (DETP), dimethyldithiophosphate (DMDTP), dimethylthiophosphate (DMTP)
    • ethylbenzene
    • hexane
    • Hippurate
    • Indican
    • Picolinate
    • Polychlorinated biphenyls (PCBs)
    • Quinolinate
    • Styrene
    • Taurine
    • Toluene
    • Triclosan
    •  Xylene
  3. Phthalates and parabens profiling using a blood, serum, plasma, saliva, urine, and/or stool sample is considered INVESTIGATIONAL.
  4. Chlorinated pesticides, including DDE and DDT, profiling in asymptomatic patients using a blood, serum, plasma, saliva, urine, and/or stool sample is considered INVESTIGATIONAL.
  5. Testing 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 are considered INVESTIGATIONAL in asymptomatic individuals and/or during general encounters.  These tests include, but are not limited to, the following:
    • Amino acid testing except for newborn screening and for documented metabolic disorders
    • Carotene/beta-carotene
    • Citrate
    • Vanillylmandelic acid (VMA) testing except for use in diagnosis of neuroblastoma or neuroendocrine tumors or for monitoring effectiveness of treatment of cancer
    • Homovanillic acid (HVA) testing except for use in diagnosis and evaluating neuroblastomas
    • 5-hydroxyindolacetic acid (5-HIAA) testing except for use in diagnosis and evaluating carcinoid syndrome or for staging, treatment, and surveillance of suspected neuroendocrine tumors
    • Elastase except for pancreatic insufficiency
    • Fat differentiation testing, qualitative and quantitative
    • CoQ10
  6. Testing blood, serum, plasma, saliva, urine, and/or stool samples for vitamin sufficiency, mineral sufficiency, and/or nutritional analysis is considered INVESTIGATIONAL in asymptomatic individuals and/or during general encounters without abnormal findings.  These tests include, but are not limited to, the following:
    • Amino acid testing except for newborn screenings or for documented metabolic disorders
    • Allergen-specific IgG testing for screening food sensitivities, vitamin sufficiency, or mineral sufficiency
    • Carotene/beta-carotene
    • Citrate
    • Vanillylmandelic acid (VMA) testing except for use in diagnosis of neuroblastoma or neuroendocrine tumors or for monitoring effectiveness of treatment of cancer
    • Homovanillic acid (HVA) testing except for us in diagnosis and evaluating neuroblastomas
    • 5-hydroxyindolacetic acid (5-HIAA) testing except for use in diagnosis and evaluating carcinoid syndrome or for staging, treatment, and surveillance of suspected neuroendocrine tumors
    • Lipid peroxides
    • Behenic acid
    • Lignoceric acid
    • Fat differentiation testing, qualitative and quantitative
  7. Testing blood, serum, urine, cerebrospinal fluid, fingernails, hair, and/or stool sample for metals, including but not limited to, aluminum, arsenic, cadmium, chromium, copper, lead, magnesium, manganese, mercury, molybdenum, nickel, zinc, and heavy metals not otherwise specified is considered INVESTIGATIONAL in asymptomatic individuals and/or general encounters without abnormal findings.

Policy Guidelines:

  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 (Hydroxy indoleacetic 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 and Medicaid (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 IEI typically report sensitivity to multiple, chemically unrelated substances and becoming ill with 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, 2018). 

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. The classification of IEI as a distinct medical disorder is also in question, as 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 it (Black & Temple, 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. However, these tests 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, 2018). Due to the vast amount 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, 2018).

Due to the amount 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 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, 2019d). 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, 2019b), the NutrEval FMV (which tests 118 analytes for symptoms such as fatigue, weight issues, and sports fitness optimization), (Genova, 2019a), the Allergix IgG4 Food Antibodies (tests 90 foods for sensitivity) and the Toxic Effects Core (tests 45 environmental analytes) (Genova, 2019c). 

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, 2018). 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, 2018; Gilbody, Richards, Brealey, & Hewitt, 2007)

Due to the dubious nature of this condition, several prominent medical studies have regarded this condition with suspicion. In 1992, the American Medical Association 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, 2006) 
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, Portnoy, Saxon, Terr, & Wood, 2006). 

American College of Occupational and Environmental Medicine (ACOEM, 1999) 
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). 

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 19999 Consensus Document is the most widely used criteria for recognition of MCS (Martini, Iavicoli, & Corso, 2013).

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. Barsky, A. J., & Borus, J. F. (1999). Functional somatic syndromes. Ann Intern Med, 130(11), 910-921.
  7. Black, D., & Temple, S. (2018). Overview of idiopathic environmental intolerance (multiple chemical sensitivity) - UpToDate. In D. Solomon (Ed.), UpToDate. Waltham. MA. Retrieved from https://www.uptodate.com/contents/overview-of-idiopathic-environmental-intolerance-multiple-chemical-sensitivity?source=search_result&search=idiopathic%20enviornmental%20intolerance&selectedTitle=1~150#H20.
  8. 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.
  9. Genova. (2019a). NutrEval® FMV. Retrieved from https://www.gdx.net/product/nutreval-fmv-nutritional-test-blood-urine
  10. Genova. (2019b). Organix® Comprehensive Profile - Urine. Retrieved from https://www.gdx.net/product/organix-comprehensive-profile-metabolic-function-test-urine
  11. Genova. (2019c). Toxic Effects CORE. Retrieved from https://www.gdx.net/product/toxic-effects-core-test-urine-blood
  12. Genova. (2019d). TRIAD® Bloodspot Profile. Retrieved from https://www.gdx.net/product/triad-bloodspot-profile-metabolic-nutritional-test-blood-spot
  13. Gilbody, S., Richards, D., Brealey, S., & Hewitt, C. (2007). Screening for depression in medical settings with the Patient Health Questionnaire (PHQ): a diagnostic meta-analysis. J Gen Intern Med, 22(11), 1596-1602. doi:10.1007/s11606-007-0333-y
  14. Martini, A., Iavicoli, S., & Corso, L. (2013). Multiple chemical sensitivity and the workplace: current position and need for an occupational health surveillance protocol. Oxid Med Cell Longev, 2013, 351457. doi:10.1155/2013/351457
  15. Multiple chemical sensitivity: a 1999 consensus. (1999). Arch Environ Health, 54(3), 147-149. doi:10.1080/00039899909602251
  16. Rossi, S., & Pitidis, A. (2018). Multiple Chemical Sensitivity: Review of the State of the Art in Epidemiology, Diagnosis, and Future Perspectives. J Occup Environ Med, 60(2), 138-146. doi:10.1097/jom.0000000000001215 

Coding Section

Code 

Number

 Description

CPT 

82127

Amino acids; single, qualitative, each specimen 

 

82136

Amino acids, 2 to 5 amino acids, quantitative, each specimen

 

82139

Amino acids, 6 or more amino acids, quantitative, each specimen

 

82379

Carnitine (total and free), quantitative, each specimen

 

82380

Carotene

 

82441

Chlorinated hydrocarbons, screen

 

82495

Chromium

 

82507

Citrate

 

82525

Copper

 

82542

Column chromatography includes mass spectrometry, if performed (eg, HPLC, LC, LC/MS, LC/MS-MS, GC, GC/MS-MS, GC/MS, HPLC/MS), non-drug analyte(s) not elsewhere specified, qualitative or quantitative, each specimen 

 

82656

Elastase, pancreatic (EL-1), fecal, qualitative or semi-quantitative

 

82715

Fat differential, feces, quantitative

 

82978

Glutathione

 

83150

Homovanillic acid (HVA) 

 

83497

Hydroxyindolacetic acid, 5-(HIAA) 

 

83918

Organic acids; total, quantitative, each specimen

 

83919

Organic acids; qualitative, each specimen

 

83921

Organic acid, single, quantitative

 

84255

Selenium

 

84585

Vanillylmandelic acid (VMA), urine

 

84600

Volatiles (eg, acetic anhydride, diethylether) 

 

84630

Zinc

 

84999

Unlisted chemistry procedure

 

86001

Allergen specific IgG quantitative or semiquantitative, each allergen 

 

86353

Lymphocyte transformation, mitogen (phytomitogen) or antigen induced blastogenesis

 

88348

Electron microscopy, diagnostic

 

83015

Heavy metal (eg, arsenic, barium, beryllium, bismuth, antimony, mercury); qualitative, any number of analytes

 

83018

Heavy metal (eg, arsenic, barium, beryllium, bismuth, antimony, mercury); quantitative, each, not elsewhere specified 

 

82108

Aluminum

 

82300

Cadmium

 

83735

Magnesium

 

83885

Nickel

 

83785

Manganese

 

82726

Very long chain fatty acids

 

89125

Fat stain, feces, urine, or respiratory secretions

 

82710

Fat or lipids, feces; quantitative

 

84590

Vitamin A

 

84446

Tocopherol alpha (Vitamin E)

 

83655

Lead

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 and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

"Current Procedural Terminology © American Medical Association.  All Rights Reserved" 

History From 2014 Forward     

04/04/2019 

Annual review with major rewrite of policy for clarity and specificity of testing. Also updating description, rationale, references and coding. 

04/17/2018 

Annual review date updated, no change to policy with interim review. 

10/19/2017 

Annual review, no change to policy intent. 

09/28/2017 

Updated policy with 2018 coding. No other changes made. 

05/16/2017 

Annual review, no change to policy intent.

05/03/2016 

Annual review, no change to policy intent. Updating background, description, rationale and references. 

06/01/2015 

Annual review, no change to policy intent. Updated rationale and references. Added coding. 

05/26/2014

Annual review. Updated background, rationale and references. Added related policies. No chang to policy intent.


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