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Clinical characteristics of chemical sensitivity: an illustrative case history of asthma and MCS.

A case history of the induction of asthma and chemical sensitivity in a 42-year-old registered nurse illustrates several of the characteristic features of multiple chemical sensitivity (MCS). This patient's problems started shortly after moving into a new home under construction, with associated chemical exposures. Other MCS patients report the onset of the condition with other chemical exposures such as those encountered at their places of work or use of pesticides at their residences. Patients often describe a spreading phenomenon of increasing intolerance to commonly encountered chemicals at concentrations well tolerated by other people. Symptoms usually wax and wane with exposures, and are more likely to occur in patients or families with preexisting histories of migraine or with classical allergies. Idiosyncratic medication reactions (especially to preservative chemicals) are common in MCS patients, as are dysautonomia symptoms (such as vascular instability) and poor temperature regulation. Myalgia and joint pains and food intolerance are common features as well. Contamination with xenobiotic chemicals is frequently found in these patients when they are tested. Reactive airways dysfunction syndrome is a recently identified condition that exhibits features of both asthma and chemical sensitivity. MCS patients frequently have patterns of neurotoxic brain metabolism that can be confirmed on single photo emission computed tomography imaging.

Adult↗

Chemical sensitivities and the Gulf War: Department of Veterans Affairs Research Center in basic and clinical science studies of environmental hazards.

The purpose of the New Jersey Center for Environmental Hazards Research is to define the illness referred to as Persian Gulf Syndrome (PGS). Our preliminary data indicated that more than half of the Persian Gulf Registry (PGR) veterans reported illness characterized by severe fatigue and symptoms consistent with chemical sensitivities. Therefore, our research approach focuses on investigations of veterans with chronic fatigue syndrome (CFS) and multiple chemical sensitivities (MCS). Project 1 is an epidemiological study of 2800 PGR veterans. Symptoms, indices of Chronic Fatigue (CF) and Chemical Sensitivity (CS), and risk factors will be surveyed with mailed questionnaires. Risk factors include demographics, past medical history, psychosocial variables, Gulf War experiences such as prophylactic medication use, occupational and environmental exposures, and pesticide exposures. Symptoms will be clustered to define Gulf War Syndromes. Significant associations between risk factors and these symptom clusters will also be investigated Subjects identified as CF, CS, or both will be recruited into Projects 2 and 3. In Project 2, healthy veterans will be compared to veterans with CF, CS, and CF concurrent with CS. Veterans will undergo four studies: (1) viral-immunological, (2) psychiatric, psychological, behavioral, and neuropsychological, (3) autonomic dysregulation, and (4) marker of P4501A2 induction resulting from exposure to combusting material. The purpose of Project 3 is to test the autonomic, immunologic, neuropsychologic, and psychologic responses of veterans with CS or CF to two stressors: controlled chemical exposure and exercise. CS subjects will undergo chemical exposures in our Controlled Environment Facility (CEF) to assess their biologic and psychologic response to low-level exposure. CF subjects will undergo a maximal treadmill exercise test. Circadian patterns of catecholamines and axillary temperature, viral burden, and cardiovascular and endocrine reactivity will be measured in response to this physical stressor. Project 4 is an animal study evaluating the interaction between stress and pathology/physiology when rats are predisposed to disease by exposure to Soman or to Dioxin. Two strains of rats that differ in stress reactivity will be used to determine the interaction of hereditary factors and chemical exposure.

Comorbidity↗

Hypothesis for induction and propagation of chemical sensitivity based on biopsy studies.

The reactive airways dysfunction syndrome (RADS), the reactive upper airways dysfunction syndrome (RUDS), the sick building syndrome (SBS), and the multiple chemical sensitivity syndrome (MCS) are overlapping disorders in which there is an intolerance to environmental chemicals. The onset of these illnesses is often associated with an initial acute chemical exposure. To understand the pathophysiology of these conditions, a study of the nasal pathology of individuals experiencing these syndromes was undertaken. Preliminary data indicate that the nasal pathology of these disorders is characterized by defects in tight junctions between cells, desquamation of the respiratory epithelium, glandular hyperplasia, lymphocytic infiltrates, and peripheral nerve fiber proliferation. These findings suggest a model for a relationship between the chronic inflammation seen in these conditions and an individual's sensitivity to chemicals. A positive feedback loop is set up: the inflammatory response to low levels of chemical irritants is enhanced due to the observed changes in the epithelium, and the epithelial changes are propagated by the inflammatory response to the chemicals. This model, combined with the concept of neurogenic switching, has the potential to explain many aspects of RADS, RUDS, SBS, and MCS in a unified way.

Biopsy↗

Increased limbic system symptomatology and sensitizability of young adults with chemical and noise sensitivities.

We previously hypothesized that individual differences in (a) limbic system reactivity and (b) central nervous system sensitizability underlie vulnerability to environmental stimuli, not only in the controversial clinical condition multiple chemical sensitivity (MCS), but also in the general population. Earlier research has shown overlaps in the characteristics of persons who report noise and air pollutant sensitivities. This study assessed questionnaire responses of 897 young adult college students who reported high versus low frequency of illness from several environmental chemical odors and concomitantly high versus low sensitivity to environmental noise. Subjects who reported increased rates of illness from chemical odors with or without noise sensitivity scored significantly higher (P < 0.0001) on a measure of limbic system symptomatology derived from ictal sensory, somatic, mnemonic, and behavioral manifestations of temporal lobe epilepsy. The group rating high both for illness from chemicals and for noise sensitivity had characteristics predictive of heightened sensitizability from the animal research on time-dependent sensitization (progressive response amplification to repeated, intermittent stimuli over time): i.e., higher female to male ratio (gender risk factor), increased rates of drug abuse problems in blood relatives (genetic risk factor), trait shyness (hyperreactivity to novelty), and increased carbohydrate craving. Despite the increased family histories of drug abuse and levels of personal anxiety and depression, the chemical- and noise-sensitive group reported the lowest rates of current smoking or personal drug abuse problems and the highest frequency of illness from drinking a small amount of alcohol. Taken together, the findings suggest that limbic system dysfunction associates more with chemical than with noise sensitivity; that individuals with both chemical and noise sensitivity may be the most sensitizable subset of the population for prospective studies, and that, in their substance use patterns, young adults with both chemical and noise sensitivity are more similar to MCS patients than are their peers with chemical or noise sensitivity alone.

Adolescent↗

History and clinical presentation of the chemically sensitive patient.

Although no one has all the answers to the mystery of chemical sensitivity, the reality of this condition, most recently called multiple chemical sensitivities, is not in doubt. Evidence is increasing of its possible physiologic mechanisms, which will be discussed later in this volume. From the evidence and from personal and professional experience, the author believes that chemical sensitivity is not a diagnosis of exclusion, and that fixed-name diseases may have environmental triggers or complicating factors (Rea, 1990b). With appropriate preparation and environmental controls, MCS can be investigated and diagnosed in a scientific and reproducible manner.

Adolescent↗

Evaluation of chemically sensitive patients.

An increasing number of patients have been presenting with multiple symptoms they attribute to low-level chemical exposures, ie, multiple chemical sensitivities (MCS). Although some studies have evaluated such patients, the selection criteria has not been rigorously defined. The present study is the first to use a relatively rigorous definition of MCS to select patients for study. Comprehensive evaluation of medical, psychiatric, neuropsychological, and immunological status of a series of MCS patients is presented. In contrast to previous studies, patients in this study did not have a history of psychiatric disorder. However, some patients were currently depressed. Neuropsychological assessment did not reveal any abnormalities with the exception of one test of verbal memory for which performance was consistently poor relative to the normative sample. No significant immunological abnormalities were noted.

Adult↗

Sensitization, subjective health complaints, and sustained arousal.

The purpose of this presentation is to discuss the possibility that sensitization is a psychobiological mechanism underlying not only multiple chemical sensitivity (MCS), but a much more general cluster of illness, referred to as "subjective health complaints". Sustained arousal, or sustained "stress" responses, may be an important factor for the development of these conditions. Patients with subjective complaints without objective changes are sometimes referred to as having "fashionable diagnoses" or "unexplained symptoms". They may be given diagnoses like MCS, epidemic fatigue, chronic fatigue syndrome, burnout, stress, a variety of intoxications, environmental illness, radiation, multiple chemical hypersensitivity, food intolerance, functional dyspepsia, irritable bowel, myalgic encephalitis, postviral syndrome, yuppie flu, fibromyalgia, or vital exhaustion. One issue is whether this is one general condition or separate entities. Another issue is whether sensitization may be the psychobiological mechanism for most or all of these conditions. Finally, is it likely that sustained arousal may facilitate the development of sensitization in some or many neural circuits? In this review, the main emphasis will be on musculoskeletal pain. This is the most frequent and most expensive condition for sickness compensation and disability. The comorbidity of other complaints, however, will also be taken into account.

Adaptation, Physiological↗

Drug sensitization, substance abuse, and chemical sensitivity.

Substance abuse, involving drugs such as cocaine, heroin, alcohol, marijuana, nicotine, barbiturates, etc., is by far by the most prevalent psychiatric disorder. Much has been learned about the abuse of these substances that may be useful to consider in designing and analyzing research concerning multiple chemical sensitivities (MCS). We review the central role of sensitization in this literature, including its definition, measurement, and expression in animals and human volunteers. Common factors among abused drugs, including sensitization, are discussed. Finally, empirical studies are delineated or proposed to test some of the notions presented in this paper.

Adaptation, Physiological↗

Patient statement: a canary's tale.

I am Jacob B. Berkson, a 68-year-old resident of Hagerstown, Maryland. I was a trial lawyer for some 40 years. I am now retired and writing a book on Environmental Pollution and Environmental Illness, titled A Canary's Tale. I was invited to speak to you as a patient--one who was poisoned by an organophosphate pesticide and who subsequently developed Multiple Chemical Sensitivity (MCS, or sometimes referred to as Environmental Illness, EI).

Aged↗

Neurobehavioral properties of chemical sensitivity syndromes.

Chemical sensitivity Syndromes refers to aggregations of symptoms marked by largely subjective neurobehavioral complaints and hypothesized links to immune system dysfunction. The entities reviewed here consist of the Multiple Chemical Sensitivity Syndrome, the Sick Building Syndrome, the Chronic Fatigue Syndrome, and the Gulf War Syndrome. Except for the Chronic Fatigue Syndrome, toxic chemical exposures are accorded a significant role in their etiology. The connections are ambiguous because of the variety of chemical agents cited and, for the most part, the relatively low levels at which exposures occur. Conventional clinical signs are also typically lacking. Explanatory mechanisms include psychiatric diagnoses such as somatization, behavioral mechanisms such as conditioning and generalization, neuropharmacological mechanisms such as sensitization, and psychoneuroimmunological mechanisms such as those involving the hypothalamic-pituitary-adrenal axis. Laboratory animal experimentation and controlled clinical trials, especially with inhaled material, provide the means for exploring the proffered explanations.

Fatigue Syndrome, Chronic↗

Prevalence of people reporting sensitivities to chemicals in a population-based survey.

To describe the prevalence and correlates of reports about sensitivities to chemicals, questions about chemical sensitivities were added to the 1995 California Behavior Risk Factor Survey (BRFS). The survey was administered by telephone to 4,046 subjects. Of all respondents, 253 (6.3%) reported doctor-diagnosed "environmental illness" or "multiple chemical sensitivity" (MCS) and 643 (15.9%) reported being "allergic or unusually sensitive to everyday chemicals." Sensitivity to more than one type of chemical was described by 11.9% of the total sample population. Logistic regression models were constructed. Hispanic ethnicity was associated with physician-diagnosed MCS (adjusted odds ratio (OR) = 1.82, 95% confidence interval (CI) 1.21-2.73). Female gender was associated with individual self-reports of sensitivity (adjusted OR = 1.63, 95% CI 1.23-2.17). Marital status, employment, education, geographic location, and income were not predictive of reported chemical sensitivities or reported doctor diagnosis. Surprising numbers of people believed they were sensitive to chemicals and made sick by common chemical exposures. The homogeneity of responses across race-ethnicity, geography, education, and marital status is compatible with a physiologic response or with widespread societal apprehensions in regard to chemical exposure.

Adolescent↗

Neuroanatomy and neurochemical mechanisms of time-dependent sensitization.

Time-dependent sensitization (TDS) is a phenomenon described in rodents as an enhancement in the behavioral and neurochemical responses to intermittent exposure to psychostimulant drugs. Time-dependent sensitization also occurs after repeated encounters with environmental stress. Several features of TDS parallel those of multiple chemical sensitivity (MCS) in humans, and these similarities have led to the hypothesis that MCS may be explained in part by a similar sensitization process that occurs in rodents. In the studies presented here, we discuss some of the critical features of TDS following repeated exposure to cocaine and environmental stress, including the anatomical and neurochemical pathways utilized in expressing TDS. In addition, we discuss the possible neurochemical basis for individual differences in responsiveness to stimuli, including novelty and cocaine. The striking similarities between TDS and MCS suggest it may be possible to develop an animal model of MCS, using TDS in rodents as its basis.

Adrenal Cortex Hormones↗

Chamber challenges: the necessity of objective observation.

the specialty of Allergy-Immunology has used human challenge testing procedures to test theories of causal relationships for decades. This includes highly characterized airborne allergens and chemicals with allergic sensitization potential. The utility of such testing to establish allergic sensitivity is well accepted. The causal relationship of chemical exposure and myriad clinical syndromes is a very contentious issue. The completion of the challenge chamber facility at EPA's Human Exposure Research Facility presents a grand opportunity for government investigators to work harmoniously with other government investigators in an effort to bring the redeeming spotlight of scientific discipline to the testy considerations of multiple chemical sensitivity, chronic fatigue, and Gulf War illness phenomena.

Air Pollutants↗

Sex differences in task performance associated with attention to ambient odor.

The effects of ambient odor (pleasant, unpleasant, none); odor suggestion (present, absent); and sex of subject on mood and performance measures were explored in a 3 x 2 x 2 experimental design. A total of 40 men and 40 women performed a clerical task and a speed and accuracy task (digit deletion), filled out self-evaluations of mood, predicted performance, and rated the odor quality of the test room. Ambient odor conditions significantly affected room smell ratings, but they had no effect on performance or mood. Odor suggestion produced a significant sex-related interaction effect on the digit deletion task, irrespective of actual ambient odor. The results are discussed with respect to sex differences observed in laboratory studies and in epidemiological investigations of multiple chemical sensitivity and sick building syndrome.

Adult↗

Self-reported chemical sensitivity in Germany: a population-based survey.

OBJECTIVES: Environmental clinics are frequented by patients with fears and complaints related to environmental triggers. A dose-independent overreaction to small doses of widely used and generally non-toxic chemicals is referred to as multiple chemical sensitivity (MCS), but no clearly defined clinical syndrome with objective physical findings has been delineated so far. We aimed to obtain information about symptoms, supposed environmental triggers, the frequency of self-reported chemical sensitivity, and of the diagnosis MCS in Germany. METHODS: We conducted a representative survey among 2032 adult Germans. RESULTS: We found self-reported chemical sensitivity in 9% and physician-diagnosed MCS in 0.5% of our representative sample. Physical complaints were common in the whole study population and in chemically sensitive individuals, but there was no clear-cut symptom constellation among the latter. The most common complaints were headache, fatigue, sleep disturbances, joint pain, mood changes and nervousness. A subjective connection between complaints and environmental triggers was denied by 67% of the whole group and by 35% of the self-reported chemically sensitive. Factor analysis of environmental triggers suggested that a specific exposure situation rather than chemical similarity is the basis for individual trigger combinations. CONCLUSIONS: The prevalence of subjective sensitivity towards chemicals is similar to such rates reported from other countries. There is a relatively low awareness of the MCS-concept, and it appears to be diagnosed less frequently than, e.g., in the USA. Since symptoms and triggers in chemically sensitive individuals did not differ from the general population, our data do not suggest the existence of a widespread new syndrome related to chemical sensitivities in Germany. We outline the limitations of self-reported chemical sensitivity as the major criterion for such a contentious diagnosis as MCS.

Adolescent↗

Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways.

Proper bodily response to environmental toxicants presumably requires proper function of the xenobiotic (foreign chemical) detoxification pathways. Links between phenotypic variations in xenobiotic metabolism and adverse environmental response have long been sought. Metabolism of the drug S-carboxymethyl-L-cysteine (SCMC) is polymorphous in the population, having a bimodal distribution of metabolites, 2.5% of the general population are thought to be nonmetabolizers. The researchers developing this data feel this implies a polymorphism in sulfoxidation of the amino acid cysteine to sulfate. While this interpretation is somewhat controversial, these metabolic differences reflected may have significant effects. Additionally, a significant number of individuals with environmental intolerance or chronic disease have impaired sulfation of phenolic xenobiotics. This impairment is demonstrated with the probe drug acetaminophen and is presumably due to starvation of the sulfotransferases for sulfate substrate. Reduced metabolism of SCMC has been found with increased frequency in individuals with several degenerative neurological and immunological conditions and drug intolerances, including Alzheimer's disease, Parkinson's disease, motor neuron disease, rheumatoid arthritis, and delayed food sensitivity. Impaired sulfation has been found in many of these conditions, and preliminary data suggests that it may be important in multiple chemical sensitivities and diet responsive autism. In addition, impaired sulfation may be relevant to intolerance of phenol, tyramine, and phenylic food constituents, and it may be a factor in the success of the Feingold diet. These studies indicate the need for the development of genetic and functional tests of xenobiotic metabolism as tools for further research in epidemiology and risk assessment.

Carbocysteine↗

Health symptoms caused by molds in a courthouse.

A majority of occupants of a newly renovated historic courthouse in Calgary, Alberta, Canada, reported multiple (3 or more) health-related symptoms, and several reported more than 10 persistent symptoms. Most required at least 1 day outside of the building to recover from their symptoms. Molds that produce mycotoxins, such as Stachybotrys chartarum and Emericella nidulans, were identified in the building, along with fungal organisms of the genera Aspergillus, Penicillium, Streptomyces, Cladosporium, Chaetomium, Rhizopus/Mucor, Alternaria, Ulocladium, and Basidiomycetes. Renovations to this historic had building failed to provide adequate thermal and vapor barriers, thus allowing moist indoor air to migrate into the building enclosure, causing condensation to develop. Mold grew on the condensation and was dispersed throughout the courthouse, including on furniture and files. The courthouse was closed and a new facility was modified with low-offgassing materials, better ventilation and air filtration, and strict building maintenance to accommodate those occupants of the older building who had developed multiple chemical sensitivities.

Air Pollutants↗

Neurogenic switching: a hypothesis for a mechanism for shifting the site of inflammation in allergy and chemical sensitivity.

Neurogenic switching is proposed as a hypothesis for a mechanism by which a stimulus at one site can lead to inflammation at a distant site. Neurogenic inflammation occurs when substance P and other neuropeptides released from sensory neurons produce an inflammatory response, whereas immunogenic inflammation results from the binding of antigen to antibody or leukocyte receptors. There is a crossover mechanism between these two forms of inflammation. Neurogenic switching is proposed to result when a sensory impulse from a site of activation is rerouted via the central nervous system to a distant location to produce neurogenic inflammation at the second location. Neurogenic switching is a possible explanation for systemic anaphylaxis, in which inoculation of the skin or gut with antigen produces systemic symptoms involving the respiratory and circulatory systems, and an experimental model of anaphylaxis is consistent with this hypothesis. Food-allergy-iducing asthma, urticaria, arthritis, and fibromyalgia are other possible examples of neurogenic switching. Neurogenic switching provides a mechanism to explain how allergens, infectious agents, irritants, and possibly emotional stress can exacerbate conditions such as migraine, asthma, and arthritis. Because neurogenic inflammation is known to be triggered by chemical exposures, it may play a role in the sick building syndrome and the multiple chemical sensitivity syndrome. Thus neurogenic switching would explain how the respiratory irritants lead to symptoms at other sites in these disorders.

Environmental Exposure↗