CAM 20101

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

Category:Medicine   Last Reviewed:April 2018
Department(s):Medical Affairs   Next Review:April 2019
Original Date:December 1995    

Description: 
Idiopathic environmental intolerance (also known as multiple chemical sensitivities) is typically characterized by recurrent, nonspecific symptoms that the patient or clinician believe are provoked by low levels of exposure to chemical, biologic or physical agents. Reported symptoms are wide-ranging, and there are not clearly established diagnostic criteria. Various tests (e.g., nutritional assessment) and treatments (e.g., immunoglobulin therapy [IVIg]) have been proposed.

There is a lack of clear diagnostic criteria for idiopathic environmental intolerance and a lack of evidence on the diagnostic accuracy of laboratory or other tests for this condition. Overall, studies using existing criteria have not found that subjects diagnosed with the condition can reliably distinguish between chemical exposure and placebo. Moreover, studies have not consistently found that low-level electromagnetic field exposure affects objective outcomes (e.g., heart rate or cognitive function). In addition, there is a lack of controlled studies to evaluate treatments for idiopathic environmental intolerance. Thus, all tests and treatments for this condition are considered investigational.

Background 
Idiopathic environmental intolerance has been labeled in a variety of ways over time. The original term, clinical ecology, was replaced by the term multiple chemical sensitivity (MCS). More recently, MCS has been replaced by idiopathic environmental intolerance, a term that reflects the uncertain nature of the condition and its relationship to chemical exposure. The central focus of the condition is patient reporting of recurrent, nonspecific symptoms referable to multiple organ systems that the patient believes are provoked by exposure to low levels of chemical, biologic or physical agents. The most common environmental exposures include perfumes and scented products, pesticides, domestic and industrial solvents, new carpets, car exhaust, gasoline and diesel fumes, urban air pollution, cigarette smoke, plastics and formaldehyde. Certain foods, food additives, drugs, electromagnetic fields and mercury in dental fillings have also been reported as triggering events. However, symptoms do not bear any relationship to established toxic effects of the specific chemical and occur at concentrations far below those expected to elicit toxicity.

Reported symptoms are markedly variable but generally involve the central nervous system, respiratory and mucosal irritation or gastrointestinal symptoms. Symptoms may include fatigue, difficulty concentrating, depressed mood, memory loss, weakness, dizziness, headaches, heat intolerance and arthralgia. In contrast to the frequently debilitating symptomatology, no specific and consistent abnormalities are noted on laboratory or other diagnostic testing Other primarily subjectively defined disorders have symptoms that overlap with idiopathic environmental intolerance, including chronic fatigue syndrome, sick building syndrome, fibromyalgia, irritable bowel syndrome and Gulf War syndrome. A diagnosis of intestinal dysbiosis could be considered within the category of idiopathic environmental intolerance. (Intestinal dysbiosis is addressed separately in Policy No. 2.04.26.)

The variable nature of the reported symptoms and the lack of recognized pathologic abnormalities make it extremely difficult to establish objective diagnostic criteria for the condition, which further hinders research into both the causes and appropriate treatment. Various causes for idiopathic environmental intolerances have been proposed; these have prompted different diagnostic and treatment approaches. Some believe that the condition is an unrecognized form of allergy or immunologic hypersensitivity. Advocates of this etiology may recommend a large series of immunologic tests, including a variety of provocation-neutralization tests and a panel of immunologic tests, including immune function tests (e.g., deregulation of the 2,5A RNase L antiviral pathway in peripheral mononuclear blood cells) and levels of lymphocyte subsets (i.e., natural killer cells, CD8 cells). Proposed therapies have included avoidance of environmental and/or dietary exposures. Immune globulin may be recommended for injection or sublingual drops of "neutralizing" chemical and food extracts. Others have proposed that exposure to toxic substances may have prompted the immunologic abnormality and, based on this theory, testing of levels of environmental chemicals in the blood, urine or fat may be suggested. Detailed nutritional analyses have also been performed, including blood, urine and intracellular levels of trace minerals. Such elaborate nutritional assessments may also be performed in asymptomatic subjects. For example, Functional Intracellular Analysis (FIA) is a series of laboratory tests offered by SpectraCell Labs that measure the intracellular levels of micronutrients, such as vitamins, minerals and antioxidants in lymphocytes.

In some instances, symptoms may appear to coincide after exposure to a viral illness (particularly common in the related condition of chronic fatigue syndrome); supporters of this theory may recommend a wide variety of tests to detect antibodies or antigens of various viruses. Some have also suggested that hypersensitivity to Candida may present with a similar array of subjective complaints and thus recommend testing for Candida in the stool or urine. Finally, it has also been proposed that idiopathic environmental intolerance is a manifestation of a psychiatric disease or personality disorder based in part on results of psychologic/psychiatric interviews

It should be noted that some environmentally caused illnesses can be well-characterized by their clinical presentation and laboratory tests. For example, in certain instances, "sick building" syndrome can be traced back to exposure of microorganisms related to air-handling systems. However, in contrast to idiopathic environmental intolerances, these patients experience a limited range of symptoms, and those symptoms only occur in the affected building.

Regulatory Status
No specific U.S. Food and Drug Administration (FDA) approval or clearance of a test for idiopathic environmental intolerance was found.

Related Policies
20426 Fecal Analysis in the Diagnosis of Intestinal Dysbiosis
20473 Intracellular Micronutrient Analysis

Policy:
Laboratory tests designed to affirm the diagnosis of idiopathic environmental illness are considered INVESTIGATIONAL.

Treatment of idiopathic environmental illness with IVIg, neutralizing therapy of chemical and food extracts, avoidance therapy, elimination diets and oral nystatin (to treat Candida) is considered INVESTIGATIONAL.

Challenge ingestion food testing has not been proven to be effective in the diagnosis of rheumatoid arthritis, depression or respiratory disorders and is considered INVESTIGATIONAL for these issues.

Policy Guidelines:
Laboratory tests for the diagnosis of idiopathic environmental illness may be broadly subdivided into those intended to rule out specific diseases with well-defined presentations and diagnostic criteria, and those tests that are designed to affirm the diagnosis of idiopathic environmental illness. For example, a basic diagnostic workup, including a standard panel of chemistry tests and blood workup, would be considered appropriate as an initial diagnostic step, even in patients with non-specific symptoms, to rule out well-defined illnesses. Additional tests may be considered medically necessary in patients with more specific symptoms, suggestive, for example, of an autoimmune connective tissue disease, or infectious mononucleosis. However, at the present time, no specific tests can confirm the diagnosis of idiopathic environmental illness and, thus, a large battery of tests performed for a patient with non-specific symptoms must be reviewed carefully for medically necessity. For example, the following should be reviewed closely, particularly when ordered simultaneously: laboratory tests of immune function (i.e., lymphocyte transformation), lymphocyte subsets (e.g., natural killer cells, CD4, CD8), immunoglobulin levels (e.g., IgG, IgE), levels of trace minerals in the serum or urine (e.g., selenium, manganese, mercury), antibodies for a variety of infectious agents simultaneously, allergy services (including provocation testing), PET scans or neuropsychologic testing and elaborate nutritional assessment, including intracellular micronutrient assays.

In addition, claims for such treatments as IVIg therapy, provocation therapy or counseling regarding specific avoidance environments or elimination diets would be considered investigational in the absence of specific symptoms.

Benefit Application:
BlueCard®/National Account Issues
Diagnosis and treatment of idiopathic environmental intolerance may be offered by specialty clinics. Claims from these clinics must be reviewed carefully to determine which services would be considered medically necessary and which would be considered investigational. RNase-L testing sites are limited and include Immunosciences Lab in Beverly Hills, CA, and Redlabs USA, in Reno, NV
.

Rationale 
This policy was originally created in 1995 and was updated regularly with searches of the MEDLINE database. The most recent literature review was performed through April 24, 2015. Following is a summary of the key literature to date.

The clinical entity of idiopathic environmental intolerance has been controversial for decades, in part due to the lack of a set of reproducible diagnostic criteria. Absent a clear definition of the disorder, basic science research into the etiology of the disorder, appropriate laboratory tests and identifications of effective treatment are obviously problematic. Published reviews and opinion pieces suggest controversy regarding the etiology of the condition, appropriate diagnostic criteria and treatment strategies.1-5

Diagnosis
No well-designed studies were identified in the literature searches that evaluated the ability of laboratory tests, nutritional assessments or other diagnostic tests to accurately diagnose idiopathic environmental intolerance (or multiple chemical sensitivity (MCS)).

Studies to date have focused on developing reliable criteria for characterizing idiopathic environmental intolerance and defining an optimal approach to diagnosing the condition. In 2006, Das-Munshi et al. published a systematic review of provocation studies in subjects with MCS.6 The investigators identified 37 studies that included a total of 784 patients who had been diagnosed with MCS. Blinding was inadequate in most cases. In 8 of 11 studies that were described as double-blind but likely had discernible odors, subjects with MCS had positive responses to provocation. However, of the 7 studies that used chemicals at or below the threshold of detectable odors, 6 failed to show consistent responses in patients with MCS after active provocation. In the 3 studies that used olfactory-masking agents to conceal the identity of the stimulus, none found associations between provocation and response. The authors concluded that persons with MCS react to chemical challenges when they can discern differences between active and sham substances, but when stimuli are adequately masked, subjects with MCS are unable to reliably identify active stimuli. The authors further commented that there may be psychologic or behavioral factors leading subjects to have physiologic responses to stimuli when they are aware of the exposure. In reports from Europe, researchers have found that findings of psychologic distress, ability to express emotions, somatic attribution, amplification (susceptibility to sensation) and absorption (predisposition to become deeply immersed in sensory or mystical experiences) were related to the presence of idiopathic environmental intolerance.7-11  

In 2008, Bornschein et al. in Germany published the findings of a double-blind, placebo-controlled provocation study that included 20 patients with MCS and 17 healthy controls matched for age and sex.12 Patients with MCS met several sets of diagnostic criteria developed in the 1990s, including criteria for idiopathic environmental intolerances defined by the International Program for Chemical Safety. Specific eligibility criteria included reporting symptoms that usually arise and recede within a time span of 10 minutes after the beginning of exposure and MCS symptoms that can be provoked by organic solvents. Provocations took place in a "climate chamber" (room for climatologic and chemical provocations). Participants underwent 6 consecutive 15-minute sessions, each followed by a 15-minute break. Three sessions were exposures to solvents and the other 3 were exposure to placebo (clean air), in random order; patients and staff were blinded. The solvents were a mixture of 6 hydrocarbons found in common household solvents; to avoid the need for olfactory masking, room air concentrations were set below a detectable odor threshold. Only 1 participant failed to complete the provocation sessions. A positive reaction to exposure was defined as (1) subject believed he or she had been exposed to an active agent; (2) objective sign of a reaction (e.g., rash, increase in heart rate); or (3) symptom severity rose to 3 or 4 (on 4-point scale). Fifty percent of patients with MCS and 53% of matched controls showed a positive reaction in all 6 exposure sections. Eighty-two percent of controls and 50% of patients had 3 correct reactions. However, more patients than controls (30% vs. 12%, respectively) reacted correctly more than 3 times. Considering only the subjective perception of exposure, 40% of patients and 35% of controls voted correctly more than 3 times. Overall, study findings suggest that patients with MCS disorders cannot reliably distinguish between solvents and placebo.

Several systematic reviews of studies on the diagnosis of idiopathic environmental intolerance attributed to electromagnetic fields (EMF) have been published. A 2011 systematic review by Rubin et al. identified 29 studies that were single- or double-blind, exposed participants to EMF fields and measured objective outcomes.13 Twenty of the 29 studies used outcomes related to the autonomic nervous system (e.g., heart rate or blood pressure). Two (10%) of 20 studies found a significant impact of EMF on function, and the other 18 studies found no effect. The authors noted that findings of the 2 positive studies might have been influenced by the order of exposure (e.g., including a sham exposure that was always first or second in a series of 3 or 4 consecutive exposures). None of the 4 studies that measured blood chemistry or 3 studies that measured brain physiology found a significant effect of EMF levels on outcomes. Seven studies tested cognitive function; 2 (29%) of 7 had at least 1 positive finding. The authors concluded that there is insufficient evidence to suggest that subjects with idiopathic environmental intolerance attributed to EMF experience their physiologic reactions as a result of exposure to EMF.

In 2012, Baliatsas et al. in The Netherlands reviewed 63 studies that included definitions or criteria for identifying subjects with idiopathic environmental intolerance related to EMF exposure.14 Major criteria used in the studies were: (1) attribution of nonspecific physical symptoms to either various or specific sources of EMF (n=13 studies); (2) self-reported idiopathic environmental intolerance attributed to EMF exposure (or similar terms) (n=14 studies); (3) experience of symptoms during or within 24 hours after perceived or actual EMF exposure (n=10 studies); and (4) high score on a symptom scale (n=6). The review found considerable variation among studies in terms of definitions and criteria; uniform diagnostic criteria have not yet been developed.

Treatment
In 2012, Skovbjerg et al. in Denmark published a randomized nonblinded pilot study to evaluate mindfulness-based cognitive therapy to treat multiple chemical sensitivities.15 Thirty-seven participants with self-reported symptoms attributed to exposure to common airborne chemicals, or with physician-diagnosed MCS, were included. Participants were randomized to receive weekly group therapy for 8 weeks or usual care. At the 4-, 8- and 12-week follow-ups, no statistically significant differences were found between groups in the 2 main outcome measures, the Symptom Checklist‒92 (SCL-92) and the Brief Illness Perception Questionnaire. For example, 8 weeks after the beginning of the intervention, mean scores on the Somatization Scale of the SCL-92 were 0.78 in the therapy group versus 0.79 in the control group (p=0.59).  

Summary of Evidence
There is a lack of clear diagnostic criteria for idiopathic environmental intolerance and a lack of evidence on the diagnostic accuracy of laboratory or other tests for this condition. Overall, studies using existing criteria have not found that subjects diagnosed with the condition can reliably distinguish between chemical exposure and placebo. Moreover, studies have not consistently found that low-level electromagnetic field exposure affects objective outcomes (e.g., heart rate or cognitive function). In addition, there is a lack of controlled studies to evaluate treatments for idiopathic environmental intolerance. Thus, all tests and treatments for this condition are considered investigational. 

Practice Guidelines and Position Statements
A variety of organizations have presented position papers on idiopathic environmental intolerance, previously referred to as multiple chemical sensitivity or clinical ecology.

In 1999, the American Academy of Allergy, Asthma and Immunology (AAAAI) issued a position statement on idiopathic environmental intolerance. This statement is still posted on the AAAAI website, but it has been archived.16 The summary of the position states:

IEI (idiopathic environmental intolerances) -- also called environmental illness and multiple chemical sensitivities -- has been postulated to be a disease unique to modern industrial society in which certain persons are said to acquire exquisite sensitivity to numerous chemically unrelated environmental substances…. Because of the subjective nature of the illness, an objective case definition is not possible … there is an absence of scientific evidence to establish any of these mechanisms as definitive. Most studies to date, however, have found an excess of current and past psychopathology in patients with this diagnosis. The relationship of these findings to the patient's symptoms is also not apparent. Rigorously controlled studies to verify the patient's reported subjective sensitivity to specific environmental chemicals have yet to be done. Moreover, there is no evidence that these patients have any immunologic or neurologic abnormalities. In addition, no form of therapy has yet been shown to alter the patient's illness in a favorable way. A causal connection between environmental chemicals, foods and/or drugs and the patient's symptoms continues to be speculative and cannot be based on the results of currently published scientific studies. 

In 1999, the American College of Occupational and Environmental Medicine published a position statement17 that concluded, in part:

Although specific diagnostic tests and treatments have not yet been demonstrated to be helpful, a generalized clinical approach useful in the management of other nonspecific medical syndromes can be adopted pending further scientific findings. This approach emphasizes 1) establishing a therapeutic alliance with a goal toward functional restoration; 2) performing a medical evaluation appropriate to the presenting complaints and physical findings; 3) avoiding ineffective, costly and potentially hazardous, unproven diagnostic tests or remedies that may increase a patient’s distress or disease; 4) treating all diagnosable medical and psychological problems; 5) individualizing medical and behavioral coping strategies useful in managing symptoms; and 6) educating the patients about the current state of knowledge about MCS. 

U.S. Preventive Services Task Force Recommendations
Not applicable.

References: 

  1. Aaron LA, Buchwald D. A review of the evidence for overlap among unexplained clinical conditions. Ann Intern Med. 2001;134(9 pt 2):868-881.
  2. Barsky AJ, Borus JF. Functional somatic syndromes. Ann Intern Med. 1999;130(11):910-921. 
  3. Graveling RA, Pilkington A, George JP, et al. A review of multiple chemical sensitivity. Occup Environ Med. 1999;56(2):73-85.
  4. Lacour M, Zunder T, Huber R, et al. The pathogenetic significance of intestinal Candida colonization--a systematic review from an interdisciplinary and environmental medical point of view. Int J Hyg Environ Health. 2002;205(4):257-268.
  5. Winder C. Mechanisms of multiple chemical sensitivity. Toxicol Lett. 2002;128(3-Jan):85-97.
  6. Das-Munshi J, Rubin GJ, Wessely S. Multiple chemical sensitivities: a systematic review of provocation studies. J Allergy Clin Immunol. 2006;118(6):1257-1264.
  7. Bailer J, Witthoft M, Rist F. Psychological predictors of short- and medium term outcome in individuals with idiopathic environmental intolerance (IEI) and individuals with somatoform disorders. J Toxicol Environ Health A. 2008;71(11-12):766-775. PMID 18569575
  8. Witthoft M, Rist F, Bailer J. Evidence for a specific link between the personality trait of absorption and idiopathic environmental intolerance. J Toxicol Environ Health A. 2008;71(11-12):795-802. PMID 18569578
  9. Skovbjerg S, Zachariae R, Rasmussen A, et al. Attention to bodily sensations and symptom perception in individuals with idiopathic environmental intolerance. Environ Health Prev Med. 2010;15(3):141-150.
  10. Skovberg S, Zachariae R, Rasumussen R, et al. Regressive coping and alexithymia in idiopathic environmental intolerance. Environ Health Prev Med. 2010;15(5):299-310.
  11. Skovbjerg S, Rasmussen A, Zachariae R, et al. The association between idiopathic environmental intolerance and psychological distress, and the influence of social support and recent major life events. Environ Health Prev Med. 2012;17(1):2-9.
  12. Bornschein S, Hausteiner C, Rommelt H, et al. Double-blind placebo-controlled provocation study in patients with subjective Multiple Chemical Sensitivity (MCS) and matched control subjects. Clin Toxicology. 2008;46(5):443-449.
  13. Rubin GJ, Hillert L, Nieto-Hernandez R, et al. Do people with idiopathic environmental intolerance attributed to electromagnetic fields display physiological effects when exposed to electromagnetic fields A. systematic review of provocation studies Bioelectromagnetics 2011;32(8):593-609.
  14. Baliatsas C, Van Kamp I, Lebret E, et al. Idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF): a systematic review of identifying criteria. BMC Public Health. 2012;12:643. PMID 22883305
  15. Skovbjerg S, Hauge CR, Rasmussen A, et al. Mindfulness-based cognitive therapy to treat multiple chemical sensitivities: a randomized pilot trial. Scand J Psychol. Jun 2012;53(3):233-238. PMID 22530938
  16. American Academy of Allergy Asthma and Immunology Position Statement on Idiopathic Environmental Intolerances. 1999; http://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20and%20Parameters/Idiopathic-environmental-intolerances-1999.pdf. Accessed March, 2015.
  17. American College of Occupational Environmental Medicine Position Statement. Multiple chemical sensitivities: idiopathic environmental intolerance. J Occup Environ Med. 1999;41(11):940-942. 

Coding Section

Codes Number Description
CPT   A wide variety of laboratory and other diagnostic tests; see Policy Guidelines section
ICD-9-CM Diagnosis   Investigational for all relevant diagnoses
  The following ICD-9 codes are listed in the section on “Symptoms, Signs and Ill-Defined Conditions”:
  780.4 Dizziness and giddiness
  780.79 Other malaise and fatigue
  780..91-780.99 other general symptoms, code range
  781.1 Disturbance of sensation of smell and taste
  786.00-786.9 code range for symptoms involving respiratory system and other chest symptoms
  787.01-787.99 Code range for symptoms involving digestive system
  The following ICD-9 codes are listed in the section on “Poisoning by Drugs, Medicinal and Biological Substances”:
  960.0-979.9 Poisoning code range. Codes are arranged according to agent and target organ. The use of the fourth digit “9,” i.e., xxx.9 indicated unspecified agent
ICD-9-CM Procedure    No code 
HCPCS   No code 
ICD-10-CM (effective 10/01/15)    Investigational for all relevant diagnoses 
  R06.03 (effective 1/1/2018)  Acite respiratory distress 
  R00.0-R09.89  Symptoms and signs involving the circulatory and respiratory systems, code range 
  R06.03 (effective 1/1/2018)  Acute respiratory distress 
  R10.0-R19.8  Symptoms and signs involving the digestive system and abdomen, code range 
  R42  Dizziness and giddiness 
  R43.0-R43.9  Disturbances of smell and taste, code range 
  R50.2-R69  General symptoms and signs, code range 
  T36.0x1-T50.996  Poisoning by adverse effect of and underdosing of drugs, medicaments and biological substances, code range 
 

T51.0x1-T65.94

Toxic effects of substances chiefly nonmedicinal as to source, code range 
ICD-10-PCS (effective 10/01/15)    Not applicable. ICD-10-PCS codes are only used for inpatient services. There are no ICD procedure codes for laboratory tests. 
Type of Service  Medical   
Place of Service Outpatient/Physician's Office   

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     

04/17/2018 

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 change to policy intent.


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