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Chemical sensitivity in symptomatic Cambodia veterans.

Following their participation in a United Nations peacekeeping operation in Cambodia (1992-1993), Dutch veterans complained of symptoms similar to those reported by Gulf War veterans. The authors conducted a matched case-control study to evaluate 76 symptomatic and 32 matched asymptomatic Cambodia veterans on the basis of data collected by postal questionnaire. The number of symptomatic veterans who reported having used insect repellants that contained N,N,-diethyl-meta-toluamide (DEET) during the mission in Cambodia was significantly higher, compared with asymptomatic veterans. The percentage of veterans who reported feeling ill following brief exposures to chemicals such as paint or pesticides was equal in both groups, but the percentage was low compared with the results of other studies of Multiple Chemical Sensitivity Syndrome. The current study was limited by self-report and time delay (potential recall bias) between deployment to Cambodia and the time of survey. Nevertheless, the study results did not support the hypothesis that symptoms in the total group of Cambodia veterans could be related to Multiple Chemical Sensitivity Syndrome.

Adult↗

Multiple sensitivity to chemical stimuli in single human taste papillae.

The sensitivities of 15 human fungiform papillae were tested using a 5-alternative forced-choice procedure. Subjects were aked to recognize which of the following stimuli was presented to a papilla on each of 250 trials: 5.0 M NaCl, 0.5 N citric acid, 1.0 M quinine hydrochloride, and distilled H2O. Solution droplets were delivered to individual papillae from 0.5 mm diameter platinum wire loops. Based on each subject's responses to distilled H2O, corrections were made for individual response biases. Of the papillae tested, 33 percent responded to all four compounds, 33 percent to three, none to only two, 20 percent to only one, and 13 percent to none of the chemical stimuli. These results are contradictory to earlier work, in which it was suggested that taste quality is encoded by chemically specific papillae, but are consistent with the electrophysiological data suggesting multiple sensitivity of mammalian gustatory receptor cells and first-order neurons. The data suggested that the narrow range of sensitivity reported by von Békésy [2] was determined by the reciprocal relationship between the size of the stimulated area and the concentration necessary to elicit a threshold sensation.

Adolescent↗

Chemical sensitivity and the work place environment: research needs.

Large numbers of studies of multiple chemical sensitivity (MCS) have been performed, particularly in clinical settings. Epidemiological studies in the area are scarce, and this is also the case for cacosmia. Very few have studied the work place conditions for the MCS patient at the onset of symptoms, neither the chemical exposure nor psychosocial conditions. This type of research is of interest to understand the development of the syndrome and to suggest preventive actions in the work places.

Environment↗

Study of self-reported hypersensitivity to electromagnetic fields in California.

Cases of alleged hypersensitivity to electromagnetic fields (EMFs) have been reported for more than 20 years, and some authors have suggested some connection with the "multiple chemical sensitivity" illness. We report the results of a telephone survey among a sample of 2,072 Californians. Being "allergic or very sensitive" to being near electrical devices was reported by 68 subjects, resulting in an adjusted prevalence of 3.2% (95% confidence interval = 2.8, 3.7). Twenty-seven subjects (1.3%) reported sensitivity to electrical devices but no sensitivity to chemicals. Characteristics of the people reporting hypersensitivity to EMFs were generally different from those of people reporting being allergic to everyday chemicals. Alleging environmental illness or multiple chemical sensitivity diagnosed by a doctor was the strongest predictor of reporting being hypersensitive to EMFs in this population. Other predictive factors apart from self-reporting chemical sensitivity were race/ethnicity other than White, Black, or Hispanic; having low income; and being unable to work. The perception of risk of exposure to EMFs through the use of hair dryers (vs. exposure to power and distribution lines) was the factor the most associated with self-reporting about hypersensitivity to EMFs. However, risk perception was not sufficient to explain the characteristics of people reporting this disorder.

Adolescent↗

Profile of patients with chemical injury and sensitivity.

Patients reporting sensitivity to multiple chemicals at levels usually tolerated by the healthy population were administered standardized questionnaires to evaluate their symptoms and the exposures that aggravated these symptoms. Many patients were referred for medical tests. It is thought that patients with chemical sensitivity have organ abnormalities involving the liver, nervous system (brain, including limbic, peripheral, autonomic), immune system, and porphyrin metabolism, probably reflecting chemical injury to these systems. Laboratory results are not consistent with a psychologic origin of chemical sensitivity. Substantial overlap between chemical sensitivity, fibromyalgia, and chronic fatigue syndrome exists: the latter two conditions often involve chemical sensitivity and may even be the same disorder. Other disorders commonly seen in chemical sensitivity patients include headache (often migraine), chronic fatigue, musculoskeletal aching, chronic respiratory inflammation (rhinitis, sinusitis, laryngitis, asthma), attention deficit, and hyperactivity (affected younger children). Less common disorders include tremor, seizures, and mitral valve prolapse. Patients with these overlapping disorders should be evaluated for chemical sensitivity and excluded from control groups in future research. Agents whose exposures are associated with symptoms and suspected of causing onset of chemical sensitivity with chronic illness include gasoline, kerosene, natural gas, pesticides (especially chlordane and chlorpyrifos), solvents, new carpet and other renovation materials, adhesives/glues, fiberglass, carbonless copy paper, fabric softener, formaldehyde and glutaraldehyde, carpet shampoos (lauryl sulfate) and other cleaning agents, isocyanates, combustion products (poorly vented gas heaters, overheated batteries), and medications (dinitrochlorobenzene for warts, intranasally packed neosynephrine, prolonged antibiotics, and general anesthesia with petrochemicals). Multiple mechanisms of chemical injury that magnify response to exposures in chemically sensitive patients can include neurogenic inflammation (respiratory, gastrointestinal, genitourinary), kindling and time-dependent sensitization (neurologic), impaired porphyrin metabolism (multiple organs), and immune activation.

Environmental Health↗

The Iowa follow-up of chemically sensitive persons.

Clinical symptoms and self-reported health status in persons reporting multiple chemical sensitivities (MCS) are presented from a 9-year follow-up study. Eighteen (69%) subjects from a sample of 26 persons originally interviewed in 1988 were followed up in 1997 and given structured interviews and self-report questionnaires. In terms of psychiatric diagnosis, 15 (83%) met DSM-IV criteria for a lifetime mood disorder, 10 (56%) for a lifetime anxiety disorder, and 10 (56%) for a lifetime somatoform disorder. Seven (39%) of subjects met criteria for a personality disorder using the Personality Diagnostic Questionnaire-IV. Self-report data from the Illness Behavior Questionnaire and Symptom Checklist-90-Revised show little change from 1988. The 10 most frequent complaints attributed to MCS were headache, memory loss, forgetfulness, sore throat, joint aches, trouble thinking, shortness of breath, back pain, muscle aches, and nausea. Global assessment showed that 2 (11%) had "remitted", 8 (45%) were "much" or "very much" improved, 6 (33%) were "improved", and 2 (11%) were "unchanged/worse". Mean scores on the SF-36 health survey showed that, compared to U.S. population means, subjects reported worse physical functioning, more bodily pain, worse general health, worse social functioning, and more emotional-role impairment; self-reported mental health was better than the U.S. population mean. All subjects maintained a belief that they had MCS; 16 (89%) acknowledged that the diagnosis was controversial. It is concluded that the subjects remain strongly committed to their diagnosis of MCS. Most have improved since their original interview, but many remain symptomatic and continue to report ongoing lifestyle changes.

Aged↗

Efficacy of distant healing--a proposal for a four-armed randomized study (EUHEALS).

BACKGROUND: Distant healing as a treatment modality is frequently used by patients and healers. Some preliminary evidence suggests possible effects. Since patients suffering from multiple chemical sensitivity and chronic fatigue syndrome have only few effective treatment options, distant healing will be offered as a treatment within a formal trial of distant healing. DESIGN AND METHOD: A four-armed randomized trial will include 400 patients with self-attributed, environmental problems who fulfil the diagnostic criteria of severe idiopathic chronic fatigue, chronic fatigue syndrome or multiple chemical sensitivity. Patients will be recruited by specialized general practitioners and environmental clinics. They will be treated by healers distributed all over Europe, coming from various healing traditions and nationalities. Each patient will be treated by 3 healers. Healers will have no contact with the patients and will only be provided with the patient's Christian name and a photograph. The patients will be randomized to one of 4 groups in a 2 x 2 factorial design. They will either receive (distant) healing or not, and either know or not know this decision. Thereby the effects of expectation and of time can be disentangled from the specific effects of healing. OUTCOME MEASURE: Primary outcome measure will be the mental health summary scale of the MOS SF-36. The measure will be taken at the beginning and at the end of a 6- month treating or waiting period, respectively. A variety of moderator variables will be considered to evaluate which of these may be predictive of outcome.

Fatigue Syndrome, Chronic↗

Comorbid clinical conditions in chronic fatigue: a co-twin control study.

OBJECTIVES: Chronically fatiguing illness, defined as fatigue for at least 6 months, has been associated with various physical health conditions. Our objective was to determine whether there is a significant relationship between chronically fatiguing illness and 10 clinical conditions that frequently appear to be associated with fatigue, adjusting for the potentially confounding effects of psychiatric illness. DESIGN: A co-twin control study controlling for genetic and many environmental factors by comparing chronically fatigued twins with their nonfatigued co-twins. SETTING: A nationally distributed volunteer twin registry. PARTICIPANTS: The study included 127 twin pairs in which one member of the pair experienced fatigue of at least 6 months' duration and the co-twin was healthy and denied chronic fatigue. Fatigued twins were classified into 3 levels using increasingly stringent diagnostic criteria. MEASUREMENTS AND MAIN RESULTS: Twins reported on a history of fibromyalgia, irritable bowel syndrome, multiple chemical sensitivities, temporomandibular disorder, interstitial cystitis, postconcussion syndrome, tension headache, chronic low back pain, chronic pelvic pain (women), and chronic nonbacterial prostatitis (men). The prevalence of these comorbid clinical conditions was significantly higher in the fatigued twins compared to their nonfatigued co-twins. Most notably, compared to their nonfatigued co-twins, the chronically fatigued twins had higher rates of fibromyalgia (> 70% vs < 10%) and irritable bowel syndrome (> 50% vs < 5%). The strongest associations were observed between chronic fatigue and fibromyalgia (odds ratios > 20), irritable bowel syndrome, chronic pelvic pain, multiple chemical sensitivities, and temporomandibular disorder (all with odds ratios > or = 4). Regression analysis suggested that the number of comorbid clinical conditions associated with chronic fatigue could not be attributed solely to psychiatric illness. CONCLUSIONS: Chronically fatiguing illnesses were associated with high rates of many other clinical conditions. Thus, patients with chronic fatigue may present a complex clinical picture that poses diagnostic and management challenges. Nonetheless, clinicians should assess such patients for the presence of comorbid clinical conditions. Future research should provide a better understanding of the temporal relationship of the onset of fatigue and these conditions, and develop strategies for early intervention.

Adult↗

Behavioral sensitization after repeated formaldehyde exposure in rats.

Multiple chemical sensitivity (MCS) is a phenomenon whereby individuals report increased sensitivity to chemicals in the environment, and attribute their sensitivities to prior exposure to the same or often structurally unrelated chemicals. A leading hypothesis suggests that MCS is akin to behavioral sensitization observed in rodents after repeated exposure to drugs of abuse or environmental stressors. Sensitization occurring within limbic circuitry of the central nervous system (CNS) may explain the multisymptom complaints in individuals with MCS. The present studies represent the continuing development of an animal model for MCS, the basis of which is the CNS sensitization hypothesis. Three behaviors were assessed in rats repeatedly exposed to formaldehyde (Form) inhalation. In the first series of experiments, rats were given high-dose Form exposure (11 parts per million [ppm]; 1 h/day x 7 days) or low-dose Form exposure (1 ppm; either 1 h/day x 7 days or 1 h/day x 5 days/week x 4 weeks). Within a few days after discontinuing daily Form, cocaine-induced locomotor activity was elevated after high-dose Form or 20 days of low-dose Form inhalation. Approximately 1 month later, cocaine-induced locomotor activity remained significantly elevated in the 20-day Form-exposed rats. The second experiment assessed whether prior exposure to Form (20 days, as above) would alter the ability to condition to an odor (orange oil) paired with footshock. The results suggested a tendency to increase the conditioned fear response to the odor but not the context of the footshock box, and a decreased tendency to extinguish the conditioned fear response to odor. The third experiment examined whether CNS sensitization to daily cocaine or stress would alter subsequent avoidance responding to odor (Form). Daily cocaine significantly elevated approach responses to Form, while daily stress pretreatment produced a trend in the opposite direction, producing greater avoidance of Form. Preliminary studies indicated that repeated daily Form inhalation (20 days, as above) produced a greater avoidance to subsequent Form presentation, suggesting that daily Form inhalation may serve as a stressor. The results support the hypothesis that repeated chemical exposure in rats may produce CNS plasticity manifest as greater sensitivity to dopaminergic drugs, enhanced fear conditioning to odor paired with an aversive event, and greater avoidance of odors. Some of these behavioral changes observed in rats may provide a link with symptoms in a subset of individuals with MCS.

Administration, Inhalation↗

RADS and RUDS--the toxic induction of asthma and rhinitis.

Inhalation exposures can produce asthma and rhinitis by several mechanisms. Sensitization with the production of IgE specific for a substance can lead to symptoms on reexposure via mast cell degranulation and the release of inflammatory mediators. Some substances, known as environmental adjuvants, enhance the immune response to concomitant exposures with the environmental adjuvant. Respiratory irritants can lead to asthma and rhinitis through interaction with chemical irritant receptors in the airway, leading to release of substance P from sensory nerves and neurogenic inflammation. The reactive airways dysfunction syndrome is a chronic asthma-like syndrome resulting from a single acute exposure to a respiratory irritant, while the reactive upper-airways dysfunction syndrome is chronic rhinitis stemming from an irritant exposure. The dysregulation of neurogenic inflammation by chemical exposures may be an important mechanism in the toxic induction of reactive airways dysfunction syndrome and reactive upper-airways dysfunction syndrome and may play a role in understanding the sick building syndrome and the multiple chemical sensitivity syndrome.

Asthma↗

Medical evaluation of Persian Gulf veterans with fatigue and/or chemical sensitivity.

The purpose of this study was to determine if Gulf War veterans with complaints of severe fatigue and/or chemical sensitivity (n = 72) fulfill case definitions for chronic fatigue syndrome (CFS) and/or multiple chemical sensitivity (MCS) and to compare the characteristics of those veterans who received a diagnosis of CFS (n = 24) to a group of non-veterans diagnosed with CFS (n = 95). Thirty-three veterans received a diagnosis of CFS with 14 having MCS concurrently; an additional six had MCS but did not fulfill a case definition for CFS. The group of fatigued veterans receiving a diagnosis of CFS was comprised of significantly fewer women and fewer Caucasians than the civilian group, and significantly fewer veterans reported a sudden onset to their illness. Veterans with CFS had a milder form of the illness than their civilian counterparts based on medical examiner assessment of the severity of the symptoms, reported days of reduced activity, and ability to work. Since CFS in veterans seems less severe than that seen in civilians, the prognosis for recovery of veterans with this disorder may be better.

Environmental Exposure↗

Social support in persons with self-reported sensitivity to chemicals.

Social support was examined in 305 persons with multiple chemical sensitivity using the Personal Resource Questionnaire 85 (PRQ85; Weinert, 1987) and qualitative descriptions of respondents' social interactions. PRQ85 scores were lower than those of healthy populations, but similar to samples with chronic illness. Participants needed but were prevented from receiving support for personal difficulties due to their limited public access, their need for chemical avoidance including fragrances, and others' lack of information and negative attitudes regarding chemical sensitivities. Respondents drew some support and validation from support groups and from romantic relationships. Fatigue level, being in a romantic relationship, contact with a support group on a monthly or more frequent basis, chemical avoidance in the home, gender, and an improved course of illness predicted 19% of the variance for perceived social support. Qualitative data are used to illustrate particular problems of persons in this sample, and suggestions are made for practitioners who encounter this population.

Adaptation, Psychological↗

Clinical consequences of the EI/MCS "diagnosis": two paths.

There are two distinct paths down which patients "diagnosed" with environmental illness/multiple chemical sensitivities (EI/MCS) can travel. Along the first path, beliefs about low-level, multiple chemical sensitivities as the cause of physical and psychological symptoms are instilled and reinforced by a host of factors including toxicogenic speculation, iatrogenic influence mediated by unsubstantiated diagnostic and treatment practices, patient support/advocacy networks, and social contagion. Intrapsychic factors also reinforce this path through the motivational mechanism of factitious malingering, or unconscious primary and secondary gain, mediated through psychological defenses, particularly projection of cause of illness onto the physical environment. The second path involves restructuring distorted beliefs about chemical sensitivities. Explanations of the placebo effect, the physiology of the stress response, and the symptoms of anxiety and panic facilitate the direction of EI/MCS patients onto this path. A decision model is presented to discriminate among toxicogenic and psychogenic explanations of the EI/MCS phenomenon, based on appraisal of reaction and physiologic and cognitive responses during provocation chamber challenges under double-blind, placebo-controlled conditions. These studies have been helpful therapeutically for some patients in selecting the path that leads to wellness. This paper suggests how various therapeutic techniques can be employed with difficult patients. Often, supportive psychotherapy establishes a therapeutic alliance which facilitates cognitive therapy to restructure distorted beliefs. In the process of finding alternative explanations to chemical sensitivities, the etiology of symptoms is related to stressful life events, including childhood experiences which may have disrupted normal personality development and coping capacity. Furthermore, biological and physiological sequelae stemming from early, chronic trauma have been identified which could explain many of the multisystem complaints. The incidence of childhood abuse reported by EI/MCS patients is strikingly high, and it is recollection of trauma that many EI/MCS patients avoid by displacing the psychologic and physiologic adults sequelae onto the physical environment. The reenactment of these experiences may be necessary in the therapy of some affected individuals. Despite the significant therapeutic effort expanded, some patients who are imprisoned by a closed belief system about the harmful effects of chemical sensitivities are resigned to travel down the path which ultimately leads to despair and depression, social isolation, and even death.

Child↗

The Environmental Exposure and Sensitivity Inventory (EESI): a standardized approach for measuring chemical intolerances for research and clinical applications.

The lack of a generally accepted case definition for multiple chemical sensitivity (MCS) and the absence of a standardized approach for measuring salient aspects of chemical sensitivity that would permit cross-comparison of findings by different investigators have hindered progress in this area. Based upon findings from an earlier study of 112 persons with self-reported chemical sensitivity who attributed their chemical sensitivity to a well-defined exposure event, we developed an instrument with self-rating scales to assess Symptom Severity, Chemical (Inhalant) Intolerances, Other Intolerances (e.g., foods, medications, alcohol), Life Impact, and Masking (a measure of ongoing chemical exposures). When administered to four patient groups and controls, the scales showed good reliability and validity overall (n = 421) and in each group. Used together, the scales provided sensitivity of 92% and specificity of 95% in differentiating chemically sensitive persons from controls. Our results support use of these scales individually or collectively for a variety of applications including the selection of chemically sensitive subjects and controls for research, assessment of chemical sensitivity in various study populations, cross-comparison of groups studied by different investigators, pre- and post-assessment of therapeutic interventions, clinical evaluation of complex patients who report intolerances, and teaching medical residents and students how to evaluate patients for chemical sensitivity and MCS.

Environmental Exposure↗

Systematic review of multi-symptom conditions in Gulf War veterans.

BACKGROUND: Gulf War veterans have a number of health complaints. We therefore decided to carry out a systematic review to identify and summarize the findings from studies that have assessed multi-symptom conditions in Gulf War veterans and in an unexposed comparison group. METHOD: Studies published between January 1990 and May 2004 were identified by searching a large number of electronic databases. Reference lists and websites were also searched and key researchers were contacted. Studies were included if they compared the prevalence of chronic fatigue syndrome, multiple chemical sensitivity, CDC-defined chronic multi-symptom illness, fibromyalgia, or symptoms of either fatigue or numbness and tingling in Gulf War veterans and non-Gulf veterans. A total of 2401 abstracts were independently reviewed by two authors. RESULTS: Twenty-three publications fulfilled the inclusion criteria. Gulf deployment was most strongly associated with chronic fatigue syndrome (OR 3.8, 95% CI 2.2-6.7). Gulf War veterans were also approximately three and a half times more likely than non-Gulf veterans to report multiple chemical sensitivity or chronic multi-symptom illness as defined by CDC. The methodological quality of the studies varied but the later and larger studies were of a high methodological standard with robust sampling strategies, adequate response rates and good adjustment for confounders. CONCLUSIONS: The results support the hypothesis that deployment to the Gulf War is associated with greater reporting of multi-symptom conditions.

Anxiety Disorders↗

Gulf War illnesses: causation and treatment.

Soldiers returning from the Gulf War in 1991 described a range of symptoms, including some consistent with the chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivity. Well-defined adverse health events attributable to service in the Gulf occurred. However, controlled epidemiological studies in Gulf War veterans and controls describe significant excesses of symptoms that were not clearly associated with pathologic disease. At least 12% of veterans currently receive some form of disability from the Department of Veterans Affairs. A number of reports outline theories proposed to explain the excess, but few are scientifically supported. Management guidelines for this spectrum of disorders resembles that of many of "emerging overlap syndromes," including multiple chemical sensitivity, chronic fatigue syndrome, and fibromyalgia. They include the establishment of a trusting doctor-patient relationship, negotiations around a common ground of scientific and etiologic beliefs, non-labeling of the disorder, and work toward recovery in the absence of clear etiologic answers.

Adult↗

Testing the neural sensitization and kindling hypothesis for illness from low levels of environmental chemicals.

Sensitization in the neuroscience and pharmacology literatures is defined as progressive increase in the size of a response over repeated presentations of a stimulus. Types of sensitization include stimulant drug-induced time-dependent sensitization (TDS), an animal model related to substance abuse, and limbic kindling, an animal model for temporal lobe epilepsy. Neural sensitization (primarily nonconvulsive or subconvulsive) to the adverse properties of substances has been hypothesized to underlie the initiation and subsequent elicitation of heightened sensitivity to low levels of environmental chemicals. A corollary of the sensitization model is that individuals with illness from low-level chemicals are among the more sensitizable members of the population. The Working Group on Sensitization and Kindling identified two primary goals for a research approach to this problem: to perform controlled experiments to determine whether or not sensitization to low-level chemical exposures occurs in multiple chemical sensitivity (MCS) patients; and to use animal preparations for kindling and TDS as nonhomologous models for the initiation and elicitation of MCS.

Animals↗

Individual differences in neural sensitization and the role of context in illness from low-level environmental chemical exposures.

This paper summarizes the clinical phenomenology of multiple chemical sensitivity (MCS), outlines the concepts and evidence for the olfactory-limbic, neural sensitization model for MCS, and discusses experimental design implications of the model for exposure-related research. Neural sensitization is the progressive amplification of responsivity by the passage of time between repeated, intermittent exposures. Initiation of sensitization may require single toxic or multiple subtoxic exposures, but subsequent elicitation of sensitized responses can involve low or nontoxic levels. Thus, neural sensitization could account for the ability of low levels of environmental chemicals to elicit clinically severe, adverse reactions in MCS. Different forms of sensitization include limbic kindling of seizures (compare temporal lobe epilepsy and simple partial seizures) and time-dependent sensitization of behavioral, neurochemical, immunological, and endocrinological variables. Sensitized dysfunction of the limbic and mesolimbic systems could account in part for many of the cognitive, affective, and somatic symptoms in MCS. Derealization (an alteration in perception making familiar objects or people seem unfamiliar or unreal) is a common MCS symptom and has been linked with limbic dysfunction in clinical neuroscience research. Sensitization is distinct from, but interactive with, other neurobiological learning and memory processes such as conditioning and habituation (compare adaptation or tolerance). In previous studies, hypotheses for MCS involving sensitization, conditioning, and habituation (adaptation) have often been considered in isolation from one another. To design more appropriate chemical exposure studies, it may be important to integrate the various theoretical models and empirical approaches to MCS with the larger scientific literature on individual differences in these potentially interactive phenomena.

Adaptation, Physiological↗