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

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

Description

Idiopathic environmental illness has been labeled in a variety of ways over time. The original term, clinical ecology was replaced by the term multiple chemical sensitivity (MCS), and most recently has been replaced by idiopathic environmental illness, a term which reflects the uncertain nature of the condition and its relationship to chemical exposure. The central focus of the condition is the fact that the patient describes recurrent, nonspecific symptoms referable to multiple organ systems that the sufferers believe are provoked by exposure to low levels of chemical, biological 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 symptoms 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. In addition to multiple chemical sensitivity, other terms used to describe idiopathic environmental intolerance include universal allergy, 20th century disease or cerebral allergy. 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. Intestinal dysbiosis is a diagnosis that could be considered within the category of idiopathic environmental intolerance. Intestinal dysbiosis is considered separately in policy Laboratory No. 35.

The variable nature of the reported symptoms and the lack of recognized pathologic abnormalities makes it extremely difficult to establish objective diagnostic criteria for the condition, which further hinders research into both the causes and appropriate treatment. One of the commonly quoted conceptual definitions, proposed by Cullen in 1987 (2), includes the following elements:

• The syndrome is acquired after a documentable environmental exposure that may have caused objective evidence of health effects
• Symptoms are referable to multiple organ systems and vary predictably in response to environmental stimuli
• The symptoms occur in relation to measurable levels of chemicals, but the levels are below those known to harm health
• No objective evidence of organ damage can be found.

Various causes for idiopathic environmental intolerances have been proposed, which have prompted different diagnostic and treatment approaches. An unrecognized form of allergy or immunologic hypersensitivity is a commonly proposed cause. Advocates of this cause may recommend a large series of tests, including a variety of provocation-neutralization tests and a panel of immunologic tests, including immune function tests, and levels of lymphocyte subsets (e.g., natural killer cells, CD8 cells) Proposed therapies have included avoidance of exposure, either in the environment or in the diet. IVIG 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) micronutrients, such as vitamins, minerals, and antioxidants in lymphocytes.

It has also been proposed that idiopathic environmental illness is a manifestation of a psychiatric disease or personality disorder. Studies supporting this etiology may include brain imaging studies (including PET scans) or psychological or psychiatric interviews. In some instances, symptoms may appear to coincide after exposure to a viral illness (particularly common with chronic fatigue syndrome); supporters of this theory may recommend a wide variety of tests to detect antibodies or antigens of various viruses. Finally, some have 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.

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 they occur in the affected building only.

Note: Policy Laboratory 35 addresses fecal analysis in the diagnosis of intestinal dysbiosis. The diagnosis of intestinal dysbiosis may overlap with idiopathic environmental intolerance.

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 which are designed to affirm the diagnosis of idiopathic environmental illness. For example, a basic diagnostic work up including a standard panel of chemistry tests and blood work up 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, there are no specific tests that 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 medical necessity. For example, the following should be reviewed closely, particularly when ordered simultaneously:

• Laboratory tests of immune function (e.g., lymphocyte transformation)
• Lymphocyte subsets (e.g., natural killer cells, CD4, CD8),
• Immunoglobulin levels (e.g., IgG, IgE, etc.),
• Levels of trace minerals in the serum or urine (e.g., selenium, manganese, mercury among others)
• Antibodies for a variety of infectious agents simultaneously
• Allergy services (including provocation testing)
• PET scans
• Neuropsychologic testing

Policy/Criteria

1. Laboratory tests designed to affirm the diagnosis of idiopathic environmental illness are considered investigational.
2. Nutritional assessments, including intracellular analysis of micronutrients is considered investigational in both asymptomatic patients and patients with symptoms suggestive of idiopathic environmental illness.
3. Treatment of idiopathic environmental illness with IVIG, neutralizing therapy of chemical and food extracts, avoidance therapy, elimination diets, provocation therapy, and oral nystatin (to treat Candida) is considered investigational.

Scientific Background

The clinical entity of idiopathic environmental illness has been controversial for decades, in part due to 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. A variety of organizations have presented position papers on idiopathic environmental illness, previously referred to as multiple chemical sensitivity or clinical ecology. Most recently, in 1999 the American Academy of Allergy, Asthma and Immunology updated their original 1986 position statement on clinical ecology (3) This statement offered the following summary:

"IEI [idiopathic environmental illness] - 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. The patient experiences wide-ranging symptoms, but evidence of pathology or physiologic dysfunction in such patients has been lacking in studies to date. Because of the subjective nature of the illness, an objective case definition is not possible. Allergic, immunotoxic, neurotoxic, cytotoxic, psychologic, sociologic, and iatrogenic theories have been postulated for both etiology and production of symptoms, but 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 conclusions cannot be made based on the results of currently published scientific studies."

In 1999, the American College of Occupational and Environmental Medicine also published a position statement (4) 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, unproved diagnostic tests or remedies that may increase a patient's distress or disease
4. Treating all diagnosable medical and psychologic problems
5. Individualizing medical and behavioral coping strategies useful in managing symptoms
6. Educating the patients about the current state of knowledge about MCS [multiple chemical sensitivity]

In 1989, The American College of Physicians published a position paper on clinical ecology (5) that recommended the following:

"The controversial nature of clinical ecology within the medical profession today requires that acceptance or rejection of its theories and practice be based on standards of evidence as rigorous as those currently being applied in other areas of medicine. Clinical ecologists who wish to carry out definitive study of provocation-neutralization testing and neutralizing therapy should establish a precise definition of the condition to be diagnosed and treated, and they should document that study subjects fulfill these criteria. Each study should include control subjects whose symptoms and vital statistics match those of the patients as closely as possible."

The published literature suggests ongoing controversy regarding the etiology of the condition, appropriate diagnostic criteria and treatment strategies. (6-12) Smith and Sullivan conducted a randomized, double-blind placebo-controlled clinical trial to assess the relationship between neuropsychological functioning and exposure to chemical trigger substances and to explore the relationship between neuropsychological performance and perceptions about exposure substances in patients with chronic fatigue syndrome. (12) Contrary to expectations, the study failed to show a significant decrease in performance following substance exposure on any of the tests of attention, concentration, and visuospatial ability, processing speed or auditory-verbal memory. This study disproves the theory that there is a relationship between neuropsychological functioning and exposure to chemical trigger substances in patients with chronic fatigue syndrome.

An updated literature search through January 16, 2008 returned several published studies which further attempt to characterize the psychiatric morbidity associated with idiopathic environmental intolerance. (13-19) Each study found that psychosocial factors, were significantly more prevalent in patients diagnosed with IEI than physical factors.  For example, Marmot and colleagues in a study of 4,052 participants working in 44 buildings noted that isolating the particular environmental features responsible for the group of symptoms associated with sick building syndrome (SBS) has proven difficult. (13) The authors explored the role and significance of the physical and psychosocial work environment in explaining SBS.  The cross sectional study found no significant relation between most aspects of the physical work environment and symptom prevalence, adjusted age, sex, and employment grade.  Greater effects were found with features of the psychosocial work environment including high job demands and low support.  Only psychosocial work characteristics and control over the physical environment were independently associated with symptoms in the final analysis.  Other recent studies reached similar conclusions regarding the etiology of symptoms associated with IEI. (14-21) The body of evidence substantially supports the policy/criteria as written.

References

1. BlueCross and BlueShield Association Medical Policy Reference Manual, Policy No. 2.01.01
2. Cullen MR. The worker with multiple chemical sensitivities: an overview. Occup Med 1987;2(4):655-61
3. American Academy of Allergy, Asthma, and Immunology (AAAAI) Board of Directors. Position statement: Idiopathic environmental intolerances. J Allergy Clin Immunol 1999;103:(1 Pt. 1)36-40
4. American College of Occupational and Environmental Medicine. (ACOEM) Position Statement. Multiple chemical sensitivities: Idiopathic environmental intolerance. J Occup Environ Med 1999;41:940-41
5. American College of Physicians. Clinical Ecology. Ann Intern Med 1989;111:168-78.
6. Bolt HM, Kiesswetter E. Is multiple chemical sensitivity a clinical defined entity? Toxicol Lett 2002;128:99-106
7. Winder C. Mechanisms of multiple chemical sensitivity. Toxicol Letter 2002;128:85-97
8. Aaron LA, Buchwald D. A review of the evidence for overlap among unexplained clinical conditions. Ann Int Med 2001;134:868-81
9. Graveling RA, Pilkington A, George JP et al. A review of multiple chemical sensitivity. Occup Environ Med 1999;56:73-85
10. Barsky AJ, Borus JF. Functional somatic syndromes. Ann Intern Med 1999; 130:910-21
11. Lacour M, Zunder T, Huber R et al. The pathogenetic significance of intestinal Candida colonization-asystematic review from an interdisciplinary and environmental medical point of view. Int J Hyg Environ Health 2002 May;205(4):257-68
12. Smith S, Sullivan K. Examining the influence of biological and psychological factors on cognitive performance in chronic fatigue syndrome: A randomized, double blind, placebo-controlled, crossover study. Int J Behavioral Med 2003;10(2):162-173
13. Marmot AF, Eley J, Stafford T. Building health: an epidemiological study of "sick building syndrome" in the Whitehall II study. Occup Environ Med. 2006 Apr;63(4):283-9
14. Binder LM, Storzbach D, Salinsky MC. MMPI-2 profiles of persons with multiple chemical sensitivity. Clin Neuropsychol. 2006 Dec;20(4):848-57
15. Witthoft M, Gerlach AL, Bailer J. Selective attention, memory bias, and symptom perception in idiopathic environmental intolerance and somatoform disorders. Abnorm Psychol. 2006 Aug;115(3):397-407J
16. Bailer J, Witthoft M, Rist J. The Chemical Odor Sensitivity Scale: reliability and validity of a screening instrument for idiopathic environmental intolerance. Psychosom Res. 2006 Jul;61(1):71-9F
17. Papo D, Eberlein-Konig B J. Chemosensory function and psychological profile in patients with multiple chemical sensitivity: comparison with odor-sensitive and asymptomatic controls. Psychosom Res 2006;60(2):199-209
18. Hausteiner C, Mergeay A, Bornschein S. New aspects of psychiatric morbidity in idiopathic environmental intolerances. J Occup Environ Med. 2006 Jan;48(1):76-82
19. Bornehag CG, Sundell J, Sigsgaard. Potential self-selection bias in a nested case-control study on indoor environmental factors and their association with asthma and allergic symptoms among pre-school children. Scand J Public Health. 2006;34(5):534-43
20. 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.
21. Das-Munshi J, Rubin GJ, Wessely S. Multiple chemical sensitivities: review. Curr Opin Otolaryngol Head Neck Surg 2007;15(4):274-80.

Cross References

Fecal Analysis in the Diagnosis of Intestinal Dysbiosis, Regence Medical Policy Manual, Laboratory, Policy No. 35

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