Idiopathic Environmental Intolerance (IEI) 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 More recently, MCS has been replaced by idiopathic environmental intolerance, a term that reflects the uncertain nature of the condition and its relationship to chemical exposure.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 IEI, 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 medical policy MED207.118.)
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 IEI 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), lifestyle eating and performance (LEAP) testing, Mediator Released Testing (MRT) for food Testing, mucosal barrier testing, antigen leukocyte cellular antibody test (ALCAT), levels of lymphocyte subsets (i.e., natural killer cells, CD8 cells), serum allergy tests, multiple radioallergosorbent test (MAST), fluorescent allergosorbent test (FAST), enzyme-linked immunosorbent assay (IgG [ELISA]), serum immunoglobulins IgA and IgE (RAST), bronchial challenge testing, assays of B and T cells, complement levels and serial dilution end-point titration (SDET) or Rinkel/Rinkel method. 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.
Mucosal barrier testing is proposed as a new generation of laboratory testing. It purports to take into consideration an individual's immune system response to proteins and peptides that can challenge the immune system and produce antibodies when they enter the bloodstream. The proponents for this testing postulate that under healthy intestinal conditions this does not cause problems but may initiate onset of an autoimmune disorder in susceptible persons. Mucosal barrier testing is performed by BioHealth® Diagnostics.
The Mediator Release Test® (MRT®) involves the measurement of the aggregate release of inflammatory mediators from an individual's immunocytes after exposure to various food extracts and chemicals (e.g., food additives). A determination is made of the difference in volume of circulating immunocytes and plasma before and after an in vitro antigen challenge. For the Mediator Release Test®, a portion of an individual's blood sample is incubated with various food extracts and food additives (typically 150 different substances). The degree of reactivity is determined by the degree of mediator release from the cells. A response, change in cellular and plasma volume, is thought to indicate a hypersensitivity reaction and results are used as a basis for modifying an individual’s diet. The MRT® is one component of the Lifestyle Eating and Performance (LEAP®) Program of oligo antigenic dieting. This type of testing has been promoted for individuals with, among other conditions, irritable bowel syndrome, chronic fatigue syndrome, migraine headaches, and dermatologic conditions (e.g., eczema, dermatitis).
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 IEI 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 IEI, 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.