Diagnosis and Management of Idiopathic Environmental Intolerance (i.e., Multiple Chemical Sensitivities)
|Original Policy Date
|Last Review Status/Date
Reviewed with literature search/5:2013
|Return to Medical Policy Index|
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Idiopathic environmental intolerance is typically characterized by recurrent, nonspecific symptoms that the patient or clinician believes 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 treatment, e.g., immunoglobulin therapy (IVIg), have been proposed.
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 More recently, MCS has been replaced by idiopathic environmental intolerance, a term that reflects the uncertain nature of the condition and its relationship to chemical exposure.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 in 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 exposure, either or both in the environment or in the diet. 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 levels of trace minerals in the blood, urine, or intracellular levels. 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 psychological/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.
No specific U.S. Food and Drug Administration (FDA) approval or clearance of a test for idiopathic environmental intolerance was found.
Laboratory tests designed to affirm the diagnosis of idiopathic environmental intolerance are considered investigational. (See Policy Guidelines.)
Treatment of idiopathic environmental intolerance with IVIg, neutralizing therapy of chemical and food extracts, avoidance therapy, elimination diets, and oral nystatin (to treat Candida) is considered investigational.
Laboratory tests for the diagnosis of idiopathic environmental intolerance may be broadly subdivided into those intended to rule out specific diseases with well-defined presentations and diagnostic criteria and those tests designed to affirm the diagnosis of idiopathic environmental intolerance. 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 nonspecific 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. A variety of psychiatric or psychologic assessments may be performed to assess underlying conditions. However, at the present time, no specific tests can confirm the diagnosis of idiopathic environmental intolerance, 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, deregulation of the 2,5A RNase L antiviral pathway), 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), positron emission tomography (PET) scans, or neuropsychologic testing and elaborate nutritional assessment, including intracellular micronutrient assays.
In addition, such treatments as immunoglobulin (IVIg) therapy, provocation therapy, or counseling regarding specific avoidance environments or elimination diets would be considered investigational in the absence of specific symptoms.
BlueCard/National Account Issues
Diagnosis and treatment of idiopathic environmental illness 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, California and Redlabs USA, in Reno, Nevada.
This policy was originally created in 1995 and was updated regularly with searches of the MEDLINE database. The most recent literature search was performed for the period March 2012 through March 20, 2013. 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)
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 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 individuals with multiple chemical sensitivity (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, individuals 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, individuals with MCS are unable to reliably identify active stimuli. The authors further commented that there may be psychological or behavioral factors leading individuals to have physiologic responses to stimuli when they are aware of the exposure. In reports from Europe, researchers have found that findings of psychological distress, the 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 and colleagues published the findings of a double-blind, placebo-controlled provocation study, conducted in Germany that included 20 patients with MCS and 17 healthy controls matched for age and gender. (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 one participant failed to complete the provocation sessions. A positive reaction to exposure was defined as 1) the individual believed he or she had been exposed to an active agent; 2) there was an 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% versus 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 and colleagues identified 29 studies which 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 of 20 (10%) 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 measuring blood chemistry or 3 studies measuring brain physiology found a significant effect of EMF levels on outcomes. Seven studies tested cognitive function; 2 of 7 (29%) had at least one positive finding. The authors concluded that there is insufficient evidence suggesting that individuals with idiopathic environmental intolerance attributed to EMF experience their physiological reactions as a result of exposure to EMF.
In 2012, Baliatsas and colleagues reviewed 63 studies that included definitions or criteria for identifying individuals with idiopathic environmental intolerance related to EMF exposure. (14) The major criteria used in the studies were: 1) attribution of non-specific 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.
In 2012, Skovbjerg and colleagues in Denmark published a randomized non-blinded pilot study to evaluate mindfulness-based cognitive therapy to treat multiple chemical sensitivities. (15) Thirty-seven individuals 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 (Brief IPQ). 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 and 0.79 in the control group (p=0.59)
There is a lack of clear diagnostic criteria for idiopathic environmental intolerance (also known as multiple chemical sensitivities) 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 individuals 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.
PracticeGuidelines 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 (ACOEM) published a position statement (17) that concluded, in part:
Although specific diagnostic test and treatment 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 [multiple chemical sensitivity].
Medicare National Coverage
No national coverage determination for idiopathic environmental intolerance or multiple chemical sensitivities.
- Aaron LA, Buchwald D. A review of the evidence for overlap among unexplained clinical conditions. Ann Intern Med 2001; 134(9 pt 2):868-81.
- Barsky AJ, Borus JF. Functional somatic syndromes. Ann Intern Med 1999; 130(11):910-21.
- Graveling RA, Pilkington A, George JP et al. A review of multiple chemical sensitivity. Occup Environ Med 1999; 56(2):73-85.
- 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):257-68.
- Winder C. Mechanisms of multiple chemical sensitivity. Toxicol Lett 2002; 128(3-Jan):85-97.
- Das-Munshi J, Rubin GJ, Wessely S. Multiple chemical sensitivities: a systematic review of provocation studies. J Allergy Clin Immunol 2006; 118(6):1257-64.
- 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):766-75.
- 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.
- 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):141-50.
- 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.
- 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.
- 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):443-9.
- 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.
- 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.
- Skovbjerg S, Hauge CR, Rasmussen A et al. Mindfulness-based cognitive therapy to treat multiple chemical sensitivities: a randomized pilot trial. Scand J Psychol 2012; 53(3):233-8.
- American Academy of Allergy Asthma and Immunology Position Statement on Idiopathic Environmental Intolerances. 1999. Available online at: http://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20and%20Parameters/Idiopathic-environmental-intolerances-1999.pdf. Last accessed March, 2013.
- American College of Occupational Environmental Medicine Position Statement. Multiple chemical sensitivities: idiopathic environmental intolerance. J Occup Environ Med 1999; 41(11):940-2.
|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|
|The following ICD-9 codes are listed in the section on “Toxic Effects of Substances Chiefly Nonmedicinal as to Source”|
|980.0–989.9||Code range; toxic effects of substances chiefly nonmedicinal as to source. The use of the fourth digit “9,” i.e., xxx.9 indicated unspecified agent|
|ICD-9-CM Procedure||No Code|
|ICD-10-CM (effective 10/1/14)||Investigational for all relevant diagnoses|
|R00.0-R09.89||Symptoms and signs involving the circulatory and respiratory systems, code range|
|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 10/1/14)||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
Allergy, Clinical Ecology
Diagnosis and Management of Idiopathic Environmental Intolerance
Idiopathic Environmental Intolerance
Multiple Chemical Sensitivities
|12/15/95||Add to Medicine section||New policy|
|10/08/02||Replace policy||Policy updated with literature review; policy retitled to reflect evolving terminology, expanded discussion, rationale, more specific policy statement, and policy guidelines, but underlying policy statement essentially unchanged|
|07/17/03||Replace policy||Policy cross-referenced to policy on idiopathic environmental intolerance; no change in policy statement|
|02/25/04||Replace policy||Information included on micronutrient analysis; no change in policy statement|
|03/15/05||Replace policy||Policy updated with literature review; no change in policy statement|
|12/14/05||Replace policy||Policy updated with literature review; no change in policy statement|
|04/25/06||Replace policy||Policy updated with literature review through March 2006; information on RNase L added. No change in policy statement|
|01/10/08||Replace policy||Policy updated with literature search; no change in policy statements. Reference numbers 16 and 17 added. Policy reference in description section corrected.|
|01/08/09||Replace policy||Policy updated with literature search; reference numbers 18 – 20 added. No change in policy statements|
|05/13/10||Replace policy||Policy updated with literature search through March 2010. Rationale rewritten; reference numbers 11 and 13 added; other references re-numbered/removed. For clarification and consistency, in policy statements, idiopathic environmental illness changed to idiopathic environmental intolerance.|
|5/12/11||Replace policy||Policy updated with literature search through March 2011. Reference numbers 12 and 13 added; other references renumbered. No change to policy statements.|
|05/10/12||Replace policy||Policy updated with literature search through March 2012. Reference 17 added; other references renumbered/removed. The term “clinical ecology” in title removed and replaced with “multiple chemical sensitivities”. Policy statement on nutritional assessments, including intracellular analysis of micronutrients removed and 2.04.73 Intracellular Micronutrient Analysis added as related policy.|
|05/09/13||Replace policy||Policy updated with literature search through March 20, 2013. Wording in statement on treatment modified for clarification. References 14 and 15 added; other references renumbered/removed.|