||Physician Reference Materials:
Position Statement 35
Idiopathic environmental intolerances
AAAAI Board of Directors
IEI: Idiopathic environmental intolerances
MCS: Multiple chemical sensitivities
The condition now called idiopathic environmental intolerances (IEI)1-3 and
formerly known as multiple chemical sensitivities (MCS)4 or environmental
illness was addressed in the AAAI Position Statement on Clinical Ecology published in
1986.5 Since then, additional research and clinical studies have been reported.
This updated position by the AAAAI reflects the current status of this condition as
documented in the published scientific literature.
Definition and Terminology
The term environmental illness was used for many years to refer to a subjective illness in
certain persons who typically describe multiple symptoms, which they attribute to numerous
and varied environmental chemical exposures, in the absence of objective diagnostic
physical findings or laboratory test abnormalities that define an illness. Other terms,
such as universal allergy, 20th-century disease, chemical hypersensitivity syndrome, total
allergy syndrome, and cerebral allergy have also been used to describe the same condition.
Since the last AAAAI position statement on this subject, the name multiple chemical
sensitivities has largely supplanted these names. In February 1996, the invited experts
forming a workshop organized by the International Programme on Chemical Safety of the
World Health Organization and other organizations, recommended a new name-idiopathic
environmental intolerances-because the term MCS "makes an unsupported judgment on
causation" (ie, environmental chemicals), does not refer to "a clinically
defined disease," and is not based on "accepted theories of underlying
mechanisms nor validated clinical criteria for diagnosis."1,3 Furthermore,
the "relationship between exposures and symptoms is unproven."1,3
History of the IEI Phenomenon
The existence of IEI as a medical illness was first proposed by Randolph,6-10
who founded a movement known as clinical ecology. He published his theories and numerous
case reports in a series of books and articles beginning in the 1950s. He and others10-15
attributed the illness to a failure of human adaptation to virtually all modern-day (20th
century) synthetic chemicals. However, more than a century ago, Beard16
described the same clinical condition, which he in turn ascribed to certain items and
activities introduced into 19th-century living, specifically the telegraph, the sciences,
industry, the periodical press, and female education. Shorter17 has written an
excellent treatise with a unique historical and social perspective about related symptom
complexes from the late 18th century to the present.
Clinical Description of IEI
Because of the varied and subjective nature of the illness, no precise case definition or
diagnostic criteria exist. Nevertheless, reports of individual cases and series of cases
reveal that the diagnosis is made almost exclusively in adults and primarily in women.12,18-28
Although the "typical" patient has numerous symptoms that appear to involve many
organ systems,4 careful review of case material reveals that IEI has been
diagnosed sometimes in persons with few or no symptoms.26
The central focus of the diagnosis is the fact that the patient describes symptoms in
relation to environmental exposures. As mentioned earlier, there are no physical
examination abnormalities in IEI.
The list of environmental chemical exposures triggering symptoms is virtually
unlimited. They are usually, although not always, identified by odor. The more common ones
cited are 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. In many patients symptoms are triggered also by certain foods,
food additives, and drugs and in some cases by electromagnetic fields and mercury in
dental fillings. There have been no dose-response studies of this phenomenon, but patients
report that these materials provoke symptoms at concentrations at or below commonly
encountered ambient levels. Furthermore, symptoms bear no relationship to established
toxic effects of the specific chemical and occur at concentrations far below those
expected to elicit toxicity. The latent period for response varies considerably.26,27
Certain environmental irritants, including some of those mentioned above, are
recognized as triggers for patients with asthma and rhinitis. However, this phenomenon
differs from that of IEI in that objective changes of bronchial or nasal obstruction and
hypersecretion occur rather than subjective symptoms only.
The patient may not be able to identify the circumstances surrounding the onset of
illness. In those cases involving litigation for workers-compensation benefits or alleged
personal injury caused by the actions of a third party, however, the patient typically
attributes the disease to a specific initiating exposure event.23,26,28 IEI has
been claimed to arise from silicone breast implants and has been attributed to military
service in southwest Asia during the brief 1991 hostilities (Gulf War Syndrome).29,30
Over the past 40 years, a number of theories have been put forward to
address the cause of IEI and the mechanism by which diverse environmental exposures
produce symptoms. Immunologic, toxicologic, psychologic, and sociologic theories
predominate. Opinions about etiology and pathogenesis are sharply divided.31
Immunologic and toxicologic explanations of IEI are favored by clinical ecologists. These
physicians place emphasis on the disease being a previously unrecognized form of allergy
or immunologic hypersensitivity.7,32-34 This concept was gradually replaced by
various immunotoxic theories in which environmental chemicals are believed to cause
autoimmunity or immunodeficiency.35-37 More recently, a neurotoxic theory of
IEI has been introduced.38-40 According to this theory, symptoms arise from
stimulation of the olfactory-limbic system of the brain and the hypothalamus. The
condition has also been ascribed to the effects of oxidative damage to unspecified
tissues.41-43 IEI has been interpreted by some as an overly sensitive state of
the respiratory44 or nasal mucosa.45-47
Many physicians have proposed that IEI is a manifestation of a psychiatric disease or
personality disorder.21,48,49 A comparison with somatoform illness has been
noted by some21,33,50,51 and with panic disorder52-54 or mass
hysteria by others.55,56 Additional psychologic interpretations include
atypical posttraumatic stress disorder,57,58 behavioral conditioning,59,60
and adult manifestation of childhood abuse.24 Several investigators have
observed a high prevalence of several different psychiatric diagnoses among patient with
IEI.18,27,61,62 Clinical ecologists often interpret the presence of
psychopathology in patients with IEI to be the result and not the cause of the illness.7,63
The diagnosis of IEI is typically made on the basis of the patient's
history, without any defining criteria. There are no diagnostic symptoms, and there are no
diagnostic objective physical signs. Many different tests and procedures have been
proposed, but no single test or combination of tests has been validated as diagnostic. The
tests most frequently used by practitioners who diagnose IEI are
provocation-neutralization11,64-68 and a panel of immunologic tests. The latter
encompasses measurements of serum immunoglobulins, complement levels, blood lymphocyte
subset counts, autoantibodies, and serum antibodies to chemicals.20,23,26,68-81
Some practitioners obtain blood, urine, or fat levels of environmental chemicals, as well
as brain imaging studies, neuropsychologic testing,24,49,76-78 and
psychologic/psychiatric interviews.28,50,52,82-84 Studies to date have failed
to confirm that any immunologic tests are diagnostic for chemically induced
symptomatology.76,79 The diagnostic validity of the other procedures has yet to
Several medical societies and organizations have issued position
statements pointing out the shortcomings of the IEI diagnosis, the unreliability and
misuse of certain diagnostic procedures, and the lack of scientific support for and
clinical evidence of the alleged toxic effects from environmental chemicals in these
particular patients. In 1986, the AAAI was the first to do so.5 The American
College of Physicians published a position paper in 1989,84 which was later
adopted by the American College of Occupational and Environmental Medicine. The Council on
Scientific Affairs of the American Medical Association published a critical review in
1992.85 The Ministry of Health of the Province of Ontario86 and the
California Medical Association65 have published results of their investigations
of the IEI phenomenon. The US National Academy of Sciences,87 the World Health
Organization,1 and the International Society of Regulatory Toxicology and
Pharmacology88 have held symposia on the subject. The American Council on
Science and Health89 and the Royal College of Physicians and Royal College of
Pathologists in Great Britain90 have also published reports detailing the
unscientific basis for IEI.
Treatment Recommendations for Patients with the Diagnosis of
Those physicians who view the symptoms of IEI as arising from the toxic effect of
environmental chemicals (and foods) stress an avoidance program that is sometimes extreme.
This is usually supplemented with vitamins and minerals, occasionally with intravenous
gamma globulin, and often with "neutralizing" administration of chemical and
food extracts by injection or sublingual drops. To date, no controlled clinical trial has
been carried out to evaluate this approach. There is evidence that such a program may make
the patient worse.26 Others advocate an undocumented form of
"detoxification" through induced sweating and the administration of oral
minerals and oils.91
A psychotherapeutic approach is recommended by those who find evidence for current
psychopathology in the patient's history. One study found short-term benefit from a brief
course of inpatient psychotherapy,92 but no long-term studies have yet been
Comparison with Other Illness
Some observers have interpreted IEI as part of a spectrum of nonphysical illnesses
characterized by multiple somatic complaints. Others see it as a distinct entity. The
so-called Candida hypersensitivity syndrome has been claimed to be a similar illness,93
but there is no scientific proof that Candida albicans causes such a condition.94
Some psychiatrists have pointed out the similarity of IEI to the somatoform/conversion
disorders,19,28,50,51,83 which in the past were called neurasthenia. Myalgic
encephalomyelitis and the chronic fatigue syndrome95 share features in common
with IEI, but these patients do not attribute their symptoms to environmental exposures.
The influence of social and cultural factors in shaping the interpretation of unexplained
somatic symptoms has been discussed84,96 and could be relevant to IEI because
of the current widespread concern about environmental pollution.
IEI is distinct from true environmentally caused diseases. Infectious microorganisms,
allergens, toxins, and irritants are responsible for diseases that are clinically well
characterized and for which specific diagnostic procedures are available. In a few
situations these pathogens have been proven to cause certain building-related illnesses,
such as Legionnaire's disease97 and hypersensitivity pneumonitis.98
The term sick building syndrome has been applied to a condition of mucous membrane
irritation caused by inadequate air-handling systems in new, energy-efficient office
buildings.99 Unlike IEI, however, these patients experience a limited range of
symptoms, and they occur in the affected building only. Reactive airways dysfunction
syndrome is a persisting asthma-like illness that arises in some persons with no
preexisting asthma after an acute exposure to a toxic substance sufficient to induce a
IEI-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 cannot be based on the results
of currently published scientific studies.
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