Jonathan M. Samet and Devra Lee Davis
The diagnostic label of multiple chemical sensitivity is being applied increasingly, although definition of the phenomenon is elusive and its pathogenesis as a distinct entity is not confirmed. Multiple chemical sensitivity has become more widely known and increasingly controversial as more patients have received the label
The emergence of multiple chemical sensitivity as a phenomenon that needs investigation coincides with recognition that myriad exposures to environmental agents are sustained in indoor and outdoor environments (National Research Council 1991; Samet, Marbury, and Spengler 1987, 1988). Regulatory activity has focused on outdoor air pollution, but children and adults in the United States and other developed countries spend most of their time indoors (National Research Council, 1991) and personal exposures to many air pollutants are thus determined largely by indoor pollutant concentrations. Monitoring studies conducted during the 1970s and 1980s showed that homes, public buildings, and nonindustrial workplaces can be contaminated by diverse gaseous and particulate pollutants that originate in unvented combustion, evaporation of volatile agents from various materials and solutions, grinding and abrasion, sod gas, and biologic sources (Samet, Marbury, and Spengler, 1987, 1988). Absorption of the pollutants can occur through the lungs, gastrointestinal tract and skin.
The concept that multiple chemical sensitivity is a distinct entity that is mused by responses to chemicals originated in the work of Randolph in the 1950s (American College of Physicians 1989, Ashford and Miller 1991). In the disease model proposed by Randolph, multiple chemical sensitivity consists of an inability to adapt to chemicals and the development of responsiveness to extremely low concentrations after sensitization (Randolph 1956); the model postulates multiple symptoms that reflect involvement of multiple organ systems. Randolph's pathogenic schema includes "adaptation." Symptoms can occur on exposure to chemicals or on withdrawal from exposure after an adaptive response has taken place. Randolph and others who apply this model of pathogenesis have used controlled exposures to establish the presence of multiple chemical sensitivity: patients are placed in environments judged to eliminate deleterious agents and then exposed to suspect chemicals.
Many of the physicians who apply that model are now referred to as clinical ecologists. Randolph and others founded the Society for Clinical Ecology in 1965 and it became the
American Academy of Environmental Medicine in 1984. This organization offers a definition of multiple chemical sensitivity which is also referred to as ecologic illness: "Ecologic illness is a poly-symptomatic, multi-system chronic disorder manifested by adverse reactions to environmental excitants, as they are modified by individual susceptibility in terms of specific adaptations. The excitants are present in air, water, drugs, and our habitats." Clinical ecology has been controversial, and committees of other specialty organizations have considered its diagnostic and therapeutic approaches to be inadequately supported by published studies (American Academy of Allergy and Immunology 1986; California Medical Association 1986; American College of Physicians 1989). Several recent reviews provide a more comprehensive background on multiple chemical sensitivity (Cullen 1987, Bascom 1989, Ashford and Miller 1991).
Although the literature addressing multiple chemical sensitivity is increasing, information on its frequency and natural history is lacking. Even defining multiple chemical sensitivity and developing criteria for diagnosis have proved difficult. Diverse pathogenic mechanisms have been postulated, but experimental models for testing them have not been established.
At the request of the Environmental Protection Agency, the National Research Council conducted a workshop to develop a research agenda to study the phenomenon of multiple chemical sensitivity. The workshop was convened with the overall objective of addressing the gaps in the scientific evidence on multiple chemical sensitivity. Workshop participants were multidisciplinary and included clinicians, immunologists, toxicologists, epidemiologists. psychiatrists, psychologists, and other involved in research or clinical activity relevant to the problem. The participants had an extensive range of experience and views on multiple chemical sensitivity. Three groups were formed to develop a research agenda. The subjects assigned were 1) case evaluation and criteria for diagnosis 2) mechanisms potentially underlying multiple chemical sensitivity and 3) epidemiologic approaches to investigating multiple chemical sensitivity.
This volume includes the papers prepared and presented by individual workshop participants; the papers have not undergone peer review. The papers offer a variety of views of the pathogenesis of multiple chemical sensitivity, its definition and diagnosis, and its management. They also illustrate the range of opinions as to the legitimacy of multiple chemical sensitivity as a unique clinical entity and the approaches used to treat it.
The paper by Lebowitz reviews key concepts of sensitization central to considering possible immunologic mechanisms of multiple chemical sensitivity. Lebowitz points to the distinction between sensitization (sensitized persons respond at lower doses than nonsensitized persons) and irritation. Burrell and Meggs also address the immune system and multiple chemical sensitivity; multiple chemical sensitivity is not seen as consistent with the specificity of immune responses, and authors point to immune mechanisms that might produce this phenomenon.
Bell emphasizes the need to use an integrated neuropsychiatric and biopsychosocial approach in considering multiple chemical sensitivity. Both she and Miller and Ashford suggest a possible role of the limbic system in triggering by odor. Experimental approaches to addressing mechanisms are described by Karol (an animal model) and by Meggs ( a clinical research protocol).
Miller and Ashford address the difficult problem of defining multiple chemical sensitivity, offering this operational definition: "The patient with multiple chemical sensitivity can be discovered by removal from the suspected offending agents and by rechallenge, after an appropriate interval, under strictly controlled environmental conditions.
Causality is inferred by the clearing of symptoms with removal from the offending environment and recurrence of symptoms with specific challenge." In a separate paper, Miller and Ashford address the distinction between allergy and multiple chemical sensitivity.
Several papers describe patients in whom multiple chemical sensitivity has been diagnosed. Heuser and collies report on 135 patients, providing the results of serologic testing for various antibodies. Rea and colleagues review 16 years of experience with over 20,000 patients studied at the Environmental Health Center in Dallas. Fiedler and Kipen provide the results of a detailed neurobehavioral and psychologic assessment of a small number of patients who met rigid case criteria.
Welch describes aspects of occupational asthma, an entity caused by specific chemicals or exposures. DeHart summarizes the positions of four professional societies that question many of the concepts concerning multiple chemical sensitivity and clinical ecology.
Three working groups were formed and provided an approach to research that needs to be done in this area. The first working group provided lists of case criteria, candidate populations for investigation, and approaches for evaluating patients with multiple chemical sensitivity. The group advocated the use of an environmental control unit to test the adaptation-deadaptation hypothesis. The workshop participants agreed that the recommendations of this working group should have the highest priority in any research agenda.
The second group also proposed the use of controlled exposures of subjects in whom multiple chemical sensitivity is diagnosed and of control subjects. This group advocated the formulation of animal models, the investigation of tissues, and the development of a data base of chemicals, foods, and drugs reported to be associated with multiple chemical sensitivity.
The third group was concerned with epidemiologic approaches. A multicenter clinical assessment of patients was advocated for early attention. The results of the multicenter study would be used to develop methods for determining the prevalence of multiple chemical sensitivity. This group also suggested follow-up of populations with discrete and sudden chemical exposures.
This volume is published as an addendum to Biologic Markers in Immunotoxicology (NRC 1992).
American Academy of Allergy and Immunology, Executive Committee. 1986. Clinical ecology. J. Allergy Clin. Immunol. 78:269-270.
American College of Physicians. 1989. Clinical ecology. Ann. Intern. Med. 111:168-178.
Ashford, N.A., and C.S. Miller. 1991. Chemical Exposures. Low Levels and High Stakes. New York: Van Nostrand Reinhold. 214 pp.
Bascom, R. 1989. Chemical Hypersensitivity Syndrome Study. Baltimore: Department of Environment of the State of Maryland.
California Medical Association Scientific Board Task Force on Clinical Ecology. 1986. Clinical ecology—A critical appraisal. West. J. Med. 144:239-245.
Cullen, M.R. 1987. The worker with multiple chemical sensitivities: An overview. Occup. Med. State Art Rev. 2:655-661.
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