Posted on: Saturday, 14 June 2008, 03:00 CDT
By Spencer, Taylor R Schur, Paul M
www.redorbit.com

Abstract Environmental health professionals frequently come across a health-related problem with no clear cause-and-effect relationship. A typical case occurs when a person complains of experiencing symptoms, often in an indoor setting, that may vary from vague to severe. Multiple Chemical Sensitivity (MCS) may be a factor at play in some of these situations. The condition is characterized by persistent symptoms that follow exposure to chemically unrelated compounds at doses well below those that have been established individually to cause harmful effects. An understanding of MCS among environmental health and medical professionals is encouraged. The following article provides a review of the current literature about MCS and discusses the difficulties, from various sources, in resolving health complaints that may be caused by exposure to low doses of multiple chemicals

Introduction

In the 1950s, under the banner of his "clinical ecology" movement, Chicago allergist Theron Randolph proposed what has come to be known as "multiple chemical sensitivity" or MCS (AAAAI Board of Directors, 1999; Whited, 2004). This condition is "an acquired disorder characterized by recurrent symptoms, referable to multiple organ systems, occurring in response to demonstrable exposure to many chemically unrelated compounds at doses far below those established in the general population to cause harmful effects (Cullen, 1987)." Pesticides, cigarette smoke, paint fumes, wood preservatives, office photocopier fumes, perfumes, and epoxy are among the chemically unrelated compounds that commonly trigger MCS (Multiplechemicalsensitivity. org). These in turn produce vague and multisystemic responses which might include any collection of symptoms, such as rapid heart rate, shortness of breath, fatigue, flushing, dizziness, nausea, coughing, or difficulty concentrating (Beers, 2003). As the diversity of causes and manifestations might indicate, MCS is probably best considered not as a single disease but as a class of disorders parallel to infectious or immunologic conditions (Miller, 1997).

MCS has significant psychosocial and economic costs. According to one study, chemical hypersensitivity results in job loss in 13.5% of cases, representing 1.8% of the general population (Caress & Steinemann, 2003). Limited specific information is available on the economic costs of MCS, and it is difficult to quantify objectively and compare the morbidity of many of the symptoms.headaches versus dizziness, for example (The Interagency Workgroup on Multiple Chemical Sensitivity, 1998; Steinemann, 2000). It is difficult, furthermore, to quantify the magnitude of the psychological sequelae that develop (in possibly a third of affected individuals)after onset of physical symptoms (Caress & Steinemann, 2003). The abundant.and at least superficially diverse.effects attributed to chemical sensitivity incorporate significant morbidity and mortality, and economic, healthcare, and social burdens (Gibson, 2005).

a Vague Entity

The study of MCS has shown some evolution over time towards a cohesive and consistent (at least internally) understanding of the disorder. As a social phenomenon, independent of any physiological basis, MCS may be understood in part through the lens of the reactionary response to modern chemicals and hazards (Whited, 2004). Significant difficulty persists, however, in resolving the diverse manifestations and associations into a unifying, underlying disease process. Intensive efforts are ongoing to resolve the inconsistencies of MCS as a class of disorders with the current understanding of disease pathogenesis, encompassing "a profound but little- recognized scientific debate concerning the origins of disease (Miller, 1997)." The history of MCS consists of attempts to address this inconsistency. The resulting conflict, between those who argue that the disease process has an illusive organic basis and those who claim it is entirely psychological or fictitious, remains unresolved.

Given the diverse manifestations and unknown pathogenesis of MCS, no accepted diagnostic physiologic test has been developed, such as complete blood count or antibody levels, which correlates with symptoms (AAAAI Board of Directors, 1999; Beers, 2003). Diagnosis is primarily based on a patient's subjective reports, leading to wide variation in clinicians' assessments (AAAAI Board of Directors, 1999). Diagnosis is further complicated by "masking".the background of routine exposures which obscures effects of specific chemicals. Even when an MCS-like response is recognized, a specific initiating trigger may not be identified and linked to the patient's ensuing sensitivities. Theoretically, precise diagnosis might require an intensive process in an "environmental medical unit": a controlled setting devoid of triggers, even drinking water. After days in this setting, allowing "unmasking" to eliminate the routine chemical exposures, the specific effects of individual acute exposures would be diagnosed (Miller, 1997). Presently, however, MCS at best may be substantiated empirically by symptomatic responses to a variety of unrelated substances, by recurrence of symptoms after repeated exposure at a low, normally tolerated threshold, and by resolution with a change of environment (Beers, 2003).

Perhaps an understanding of the underlying pathogenesis of MCS might facilitate diagnosis. No clear etiology, however, is universally accepted. The theory of "toxicantinduced loss of tolerance" (TILT) is one of the proposed theories that has gained favor in some circles. TILT describes a two-step process, in which the first stage, an initial acute or chronic toxicant exposure, precipitates the second stage, a subsequent hypersensitivity to extremely low concentrations of previously tolerated triggers (Miller, 1997).

Even this description, however, leaves the question of the exact mechanism open for debate. One proposed mechanism is pollutant injury of the lungs or liver which might generate free radical- mediated injury through enzyme detoxification systems. This, in turn, would trigger a myriad of end organ responses. Other proposed mechanisms include incorporated immunologic disruption and allergy, changes in the nervous system (such as limbic kindling or olfactory threshold sensitivity), altered biochemical or biotransformative capacity (including biochemical energy production pathways or neurochemical pathways), or changes in psychological or neurobehavioral function (such as panic disorder, psychosomatic condition, or malingering) (Winder, 2002). At present, although abundant, these ideas still represent little more than unproven theory.

Should a molecular pathway become elucidated, therapy could intervene at this level. With little acceptance of a mechanism, treatment at the present time primarily consists of avoidance (Gibson, Elms, & Ruding, 2003). Other proposed treatments are abundant and include antifungal therapies, strict diets which rotate content to avoid triggers, and the "radical separatist avoidance approach," which avoids human-made chemicals entirely. All, however, are unproven (Magill & Suruda, 1998).

Efforts to describe the epidemiology of MCS are similarly hindered by a vague understanding and lack of consensus for a case definition (The Interagency Workgroup on Multiple Chemical Sensitivity, 1998). Although some have presumed a 2%-10% prevalence of diagnosed MCS that forces alterations in daily lives (Mooser, 1987), others regard these estimates as much too high (Cullen, 1994). State health department surveys in New Mexico and California indicate that 2%-6% of respondents had been diagnosed with MCS (Kreutzer, Neutra, & Lashuay, 1999; Voorhees, R.E., personal communication, March 13, 1998), while other research finds a prevalence of 2.5% (Caress & Steinemann, 2004). Perhaps anywhere from 75% to 90% diagnosed cases are women. Most are at least thirty at the onset of symptoms (Cullen, Pace, & Redlich, 1992; Neutra, 1994).

Self-reporting would indicate that the rate of diagnosis significantly understates true prevalence. An 11.2% (Cullen, Pace, & Redlich, 1992) or 12.6% (Caress & Steinemann, 2003) prevalence of self-reported hypersensitivity has been reported. In California and New Mexico, 16% of randomly selected adults claim an "unusual sensitivity" to common everyday chemicals (Kreutzer, Neutra, & Lashuay, 1999; Voorhees, R.E., personal communication, March 13, 1998). Other research finds that 33% of adults from a rural setting report sensitivity to between three and five chemicals, particularly pesticides and solvents (Meggs, Dunn, Bloch, Goodman, & Davidoff, 1996).

Opposition

Currently, a productive approach to multiple chemical sensitivity is marred by conflict between the argument that the illness has an organic basis and considerable doubt from the scientific community, political leadership, and many in the general public who claim that it is psychological. Some research supports the latter argument (Hausteiner, Mergeay, Bornschein, Zilker, & Forstl, 2006; Papo et al., 2006). Although not extensive enough to wholly refute MCS, research that undermines the Olfactory Threshold Sensitivity Theory, for example, has been done (Hausteiner, Mergeay, Bornschein, Zilker, & Forstl, 2006). Long-standing doubters include many organizations and institutions (Magill & Suruda, 1998) including the American College of Physicians, which found in 1989 that "review of the clinical ecology literature provides inadequate support for the beliefs and practices" relating to MCS (American College of Physicians, 1989). The American Medical Association opposed MCS in 1992 but was somewhat less dismissive in 1994 (American Medical Association Council on Scientific Affairs, 1992; U.S. Environmental Protection Agency, American Lung Association, Consumer Product Safety Commission, & American Medical Association, 1994). The Centers for Disease Control and Prevention (CDC) do not recognize MCS, while the U.S. Environmental Protection Agency (U.S. EPA) finds "at present no medical consensus concerning the definition or nature of this disorder (U.S. Environmental Protection Agency, 1996)," although it did receive a proposal from the National Environmental Justice Advisory Council (NEJAC) that advocates an agenda for MCS (Barrett, 2000). Frequent ambivalence or downright opposition within key federal agencies hinders raising the political will to address, or even to explore more fully, the possibilities and implications of MCS. Even advocates of MCS often concede that the lack of clear biomarkers, the tenuous (at best) causal relationship, and the time lag between exposure and disease, make it "technically, and increasingly politically, difficult to develop the extensive body of evidence needed to regulate many chemicals and industrial processes or to compensate the chemically injured (Ashford & Miller, n.d.)." Chemical industry lobby groups and organizations such as Responsible Industry for a Sound Environment (RISE) or Environmental Sensitivities Research Institute (ESRI) further deny that MCS exists or merits further research. Given this resistance and paucity of objective evidence, class-action lawsuits (like those against the tobacco companies) or compensation funds (as in mesothelioma- causing asbestos) are not politically viable options (McCampbell, 2001). The barriers to scientific and political legitimacy shape perceptions and approaches to MCS.

What Would It mean?

The inescapable challenge of MCS is that it is not consistent with current ideas in toxicology. If the chemical sensitivity of MCS is in fact a pathogenic disease process, as its proponents argue, this would mandate a profound restructuring of our research efforts, and our therapeutic and public health responses.

Rather than the "gold standard" of randomized controlled trials, a single-subject longitudinal design may be warranted, with strict control of exposures using the "environmental unit." Explicit time series analyses are needed because "the syndrome is not cohesive enough to warrant group designs" in which averages would obscure individually significant results. Subsequent research would then be predicated on first verifying the MCS process on an individual basis (Weiss, 1997).

However, the amount of ongoing federally supported MCS-specific research still consists of only a limited ancillary effort. No federal effort formulates and oversees a collaborative MCS research plan or its relevance to occupational and environmental health (The Interagency Workgroup on Multiple Chemical Sensitivity, 1998). Agencies such as CDC and U.S. EPA, although historically less responsive to MCS, should be key participants in any federal response. Government funding and support impacts the legitimization of the experiences of millions of ill Americans, independent of whatever the etiology may be.

In the absence of a convincing body of research, best practices and an appropriate response to MCS diagnoses also have yet to be determined while the political implications and public impact are largely speculative. The theory, if valid, would have significant ramifications for health departments. The acceptance of MCS would mandate a significant reconceptualization of risk assessment and regulation of pollutants and other chemicals. If MCS is valid, the precautionary principle ought to be adopted with regulation of potentially harmful chemicals when scientific evidence, although imperfect, is compelling (Ashford & Miller, 1998). The effects of these chemicals could be profound if, even at low levels, they sensitize individuals to MCS. In extreme cases, policy makers may fail to regulate a chemical that is later discovered to be harmful or else may overly regulate a chemical later determined to be safe, at cost to industry and consumers. If MCS is valid, adopting a "systems-focused approach" would facilitate navigation through politically tenuous terrain and associated economic concerns posed by this uncertainty. The validity of MCS would obligate major stakeholders to partner for informed and coordinated responses. The onus would be on industry, which would be expected to foster a new corporate stewardship and a fiduciary duty. The general public would be engaged so as to harmonize their needs as customers with their expectations of protection. The media, public interest groups, and nongovernmental organizations would function to strengthen links and disseminate information for protections (Ashford & Miller, 1998). These relationships would benefit public health as a whole by redefining and energizing roles.

MCS, as with other illnesses caused by environmental triggers from air pollution to toxic waste, arguably falls within the realm of government regulation. The federal government would have an expanded obligation to protect the citizenry if a significant acquired disorder does in fact occur in response to exposure to many chemically unrelated compounds at very low doses. In 1988, the Social Security Administration included a section specific to MCS, and by 1990, the Department of Housing and Urban Development established disability status for the disorder (Whited, 2004). But it was the Agency for Toxic Substances and Disease Registry (ATSDR), empowered by the Comprehensive Environmental Response, Compensation, and Liability Act of 1980, that called for itself to "take a leadership role in the investigation of MCS" in a unanimously adopted recommendation from the Board of Scientific Counselors (Donnay, 1998; The Interagency Workgroup on Multiple Chemical Sensitivity, 1998). ATSDR participated in a working group on MCS with a number of other governmental agencies. The group's predecision draft stated that a strategic plan for MCS was warranted (The Interagency Workgroup on Multiple Chemical Sensitivity, 1998). A NEJAC resolution in 2000 urged standard-setting and regulatory action by U.S. EPA, including examining environmental laws to revise or add standards as appropriate. It further suggests establishing disease registries with MCS as a "reportable condition," increasing funds and programs, and minimizing use of toxic chemicals in its activities (Barrett, 2000). Ultimately, the implication of these efforts would be a reinforcement of government's power to protect its citizens' health and, hopefully, government's will to assume "its role as a trustee of the environment, public health, and sustainability, and direct its interventions and research support to all phases of multistage diseases (Ashford & Miller, 1998)."

What remains to be Done

The current status of MCS is mired in an impasse between skeptics and proponents. With its fundamental nature in question, it is not surprising that the current status has not progressed in policy or practice. A review of literature shows a paucity of objective, welldesigned, and well-funded research (Ashford & Miller, 1998; The Interagency Workgroup on Multiple Chemical Sensitivity, 1998; Weiss, 1997).

The question of whether MCS is a legitimate physiologic disease process is, to some degree, only incidental. At present, MCS is illustrative of the dichotomy between illness (a feeling of not being well, with obvious manifestations), and disease (a pathophysiological process, which in the case of MCS has not yet been clarified). As much as MCS is accepted in the popular consciousness, it exists as an illness.a socially influenced presentation.and as an important public health issue. Even if MCS does not prove to be the disease its proponents claim, this does not negate the need for appropriate treatment for the illness. The health care system and public health as a whole should respond appropriately.

Regardless of whether MCS is a legitimate physiologic disease process or not, giving it due consideration is a useful exercise for the public health community. If proven scientifically valid, MCS would significantly impact public health in general and environmental health specifically. MCS could fundamentally alter our understanding of pathophysiology, affecting disease research design and disease prevention measures. On a much broader level, the government, private sector, consumers, and general population would be engaged in a partnership that would benefit all of public health. A nimble, adaptable public health infrastructure benefits from at least considering MCS and the state of environmental health. It is an important exercise to consider these implications and the ability of public health to respond. A public health community that is unable or unwilling at a minimum to contemplate paradigm-altering possibilities neglects its duty. With such significant implications, neglect would be insensitive.




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