Much media attention and professional controversy has focused on the approximately 6% of the population who have multiple chemical sensitivity (MCS) (Kreutzer et al., 1999), i.e., severe low-level chemical intolerance (CI), multisystem chronic symptomatology, extreme chemical avoidant behaviors and associated disability. Chemical intolerance involves negative symptoms such as headache, dizziness, difficulty concentrating and/or nausea in response to the odors of low levels of environmental chemicals that the majority of people tolerate with neutral or even positive hedonic effects (Bell et al., 1996a, 1995). The triggering chemicals include multiple substances such as pesticides, solvents, perfumes, new carpets, automotive exhaust and tobacco smoke. A large proportion of people with chemical sensitivities also report multiple intolerances to common foods. Rates of immunoglobulin-E-mediated allergies per se are not necessarily elevated in MCS, although some patients may have immunoglobulin-G-mediated adverse food reactions. Thus, despite popular references to "chemical allergies," evidence for immune system disturbances as the primary mediator of MCS has not been persuasive, beyond possibly secondary adverse effects of chronic psychological and physical stress on cellular and humoral immune function (Winder, 2002). Figure 1 illustrates the point that all MCS patients have CI, but only a subset of people with CI meet diagnostic criteria for MCS.
Sixty percent of solvent-exposed workers reported CI (Morrow et al., 1990). Up to half of patients with chronic fatigue syndrome (CFS) and fibromyalgia (FM) (Aaron et al., 2001; Buchwald and Garrity, 1994) (Figure 2) as well as a subset of Gulf War veterans (Bell et al., 1998e) present with CI. Numerous surveys show that mild CI is a symptom in 15% to 30% of the population (Bell et al., 1998b). The demographics of CI suggest that the majority with either MCS or subclinical presentations are women (80%) (Levy, 1997).
Comorbid psychiatric symptoms and disorders are primarily anxiety, especially panic disorder and depression (Fiedler et al., 1996). Psychosis is rare. People with CI report histories of physical, sexual and emotional abuse at increased rates (Bell et al., 1998a), but the psychophysiological electroencephalographic patterns of women with CI diverge from those of depressed or sexually abused women without CI (Bell et al., 1998b; Fernandez et al., 1999). Although some investigators have proposed that MCS is a variant of posttraumatic stress disorder (PTSD), systematic evaluations of patients with MCS have not found increased rates of PTSD. Unlike the general psychiatric patient population, patients with MCS report an inability to tolerate alcoholic beverages and many drugs (Miller and Prihoda, 1999). As a result, few patients with MCS have comorbid alcohol problems. Interestingly, however, the family histories reveal elevated rates of substance abuse, especially alcoholism (Bell et al., 1999a; Black et al., 1999).
Many physicians, finding normal clinical laboratory tests, conclude that such patients have a somatoform disorder with or without other Axis I or II psychopathology, and refer these patients to psychiatrists for ongoing care. However, the patients, who may acknowledge that psychological stress can worsen their condition, generally perceive their condition as a medical, rather than psychiatric, problem (Bell, 1994).
Differentiating MCS Subtypes
Interestingly, some observers have differentiated two general subclasses of MCS: those who can identify a specific peak chemical exposure, usually at higher levels, that initiated their chronic susceptibility to low doses of many other chemicals (approximately 60%) and those who cannot identify such an initiating chemical agent but nonetheless now have adverse reactions to various exposures (approximately 40%) (Fiedler et al., 1996). Of note, patients without an identified initiating chemical exposure have higher rates of lifetime psychopathology than do those with identified initiating chemicals (69% versus 43%). Other studies have found that at least 25% of MCS patients have no current psychiatric diagnosis (Simon et al., 1993).
Moreover, although standard batteries of neuropsychological tests for memory, naming and attention vary in outcomes with MCS (Bolla, 1996), Bell et al. (1999b, 1996b) have repeatedly demonstrated that people with CI exhibit deficits in performance of a visual divided-attention task, a finding similar to patients with CFS (Ross et al., 2001). In solvent-exposed workers, the presence of CI symptoms accounts for a significant portion of the variance in poorer performance on tests of learning and memory (Ryan et al., 1988). Taken together, the specific phenomenological and psychophysiological evidence in MCS indicates that affected individuals diverge from the clinical pictures of typical psychiatric patients, despite some overlaps.
The Misattribution Model
A number of skeptics of MCS as a discrete diagnosis have proposed that patients are somatizers with anxiety and depression who are misattributing their symptoms to chemical exposures (Staudenmayer, 2000). The evidence in support of the misattribution model is limited. Studies in which patients with MCS believe that they have been exposed to chemicals in the laboratory reveal increased symptoms of anxiety and panic. The designs of these studies are largely unsophisticated from the perspective of recruitment bias or cognitive set research.
Better-controlled studies have screened MCS patients for those with panic disorder symptomatology and have shown that, like other panic patients, the panic-prone MCS subgroup develops panic symptoms at increased rates during single-blind lactate infusions (Binkley and Kutcher, 1997) or carbon dioxide exposures (Poonai et al., 2000). Follow-up genetic investigations of the panic-prone MCS subset have shown a significantly increased prevalence of the panic disorder-associated cholecystokinin (CCK) receptor allele 7 compared with controls (41% versus 9%) (Binkley et al., 2001). Thus, genetic factors may play a role in vulnerability to MCS.
The findings of biological and genetic overlaps between MCS and panic disorder are especially striking from an interdisciplinary perspective. In industrial hygiene, carbon dioxide levels in indoor environments are one nonspecific marker of poor air quality. Studies on panic disorder demonstrated the ability to provoke panic attacks in the laboratory, even with levels of CO2 at 5% (Sanderson et al., 1989), similar to those in certain indoor air settings (Lee and Chang, 1999). Therefore, environmental factors such as carbon dioxide could play a clinically meaningful role in triggering symptoms in indoor environments where panic-prone people with CI spend time.
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