Multiple chemical sensitivities was first proposed as a new disease in the 1950s, at which time it was called "environmental illness" [2]. For many years, proponents of the existence of environmental illness, or multiple chemical sensitivities, have theorized that the disease results from an immunologic dysfunction caused by inhalation of fumes from various chemicals. The chemically induced toxic damage to the immune system is postulated to then lead to "sensitivities" to other chemicals [3]. Recently, a neurologic dysfunction theory has emerged as an alternative explanation of multiple chemical sensitivities [4]. This theory proposes that inhaled chemical molecules travel along the olfactory nerve to the forebrain, the hypothalamus, and other parts of the limbic system. The many symptoms and alterations in mood and thought processes that these patients experience are thought to be of neurotoxic origin, and reactions to other chemicals are explained on the basis of "kindling".

The phenomenon of multiple chemical sensitivities as a disease has generated widespread skepticism among clinicians who encounter patients with this diagnosis [5]. Seasoned internists, other primary care physicians, and specialists recognize in these patients an all-too-familiar pattern of over-utilization of medical diagnostic facilities because of many longstanding unexplained symptoms. The only thing that distinguishes environmental illness or multiple chemical sensitivities from this pattern is the attribution of symptoms to environmental exposures.

A series of clinical investigations of patients with multiple chemical sensitivities, including the one by Simon and colleagues [6] in this issue of Annals, now provides a reasonably coherent medical picture of the multiple chemical sensitivities phenomenon. Immunologically, these patients are functionally intact [7]. As a group they display no deficiency or excess in their ability to mount appropriate immune responses, nor do they suffer an excess prevalence of unusual or opportunistic infections, allergic reactions, autoimmune disease, or cancer [8].

Because of the absence of consistent physical, biochemical, or immunologic abnormalities, most studies have focused attention on a possible psychiatric cause. Although selection bias and small numbers of patients suggest the need for some caution in interpreting these studies, it is clear that diagnosable psychiatric illness is common in patients with this disorder [9-12]. Early studies suggested that the multiple chemical sensitivities entity was merely undiagnosed somatoform illness [9, 13]. Later reports, however, documented that anxiety, depression, panic disorder, schizophrenia, and affective disorders, with or without somatization, could be diagnosed in most patients [10-12]. Does this mean that common everyday environmental chemicals cause a group of disparate mental illnesses? Probably not; psychological testing of patients with multiple chemical sensitivities, as reported by Simon and colleagues and others, reveals a substantial number with preexisting diagnosable psychiatric illness. Other investigations that analyzed the previous medical records of these patients point strongly to a much higher prevalence of preexisting psychiatric illness compared with that uncovered by current psychological tests [14].

The temporal association of symptoms with chemical exposure rests solely on patient reports. In most cases, awareness of an odor is the triggering factor. An odorant-induced learned response has been proposed to account for an expanding range of chemical "sensitivities" [15]. Thus, a pattern of increasing intolerance to common, familiar, and formerly innocuous environmental exposures, coupled with the iatrogenic suggestion of a serious underlying lack of immunologic protection, readily explains the anxiety, depression, fear, and frank panic experienced by patients with a diagnosis of multiple chemical sensitivities.

The immunotoxic concept, however, can be acceptable to individuals with either a susceptible personality type or a preexisting psychiatric illness who then perceive their environment as physically harmful to them. The perception is reinforced by frequent media reporting of pollution incidents and environmental disasters and by inappropriate avoidance therapy prescribed by certain "environmental" physicians. These physicians typically recommend a variety of therapies of unproven worth [16, 17]. Central to their goal of preventing multiple environmental sensitivities are chemical avoidance strategies, often reaching extremes of social isolation and restrictive diets [18]. Detoxification franchises are appearing that offer a program of niacin-induced flushing followed by exercise and sauna combined with high-dose vitamin and fatty acid ingestion promoted as a means of ridding the body of foreign chemicals [19]. Vitamins, minerals, diets, intravenous globulin, and other medications are prescribed allegedly to enhance immunologic function. No clinical trials assessing safety or efficacy exist to support these measures. In fact, some evidence exists that patients worsen with such a treatment regimen [8]. Avoidance therapy, rotation diets, sauna detoxification, and various maneuvers to "boost" the immune system serve merely to reinforce a counterproductive behavior pattern.

Investigation of multiple chemical sensitivities by proven methods of clinical science is a daunting endeavor. Clearly, more work needs to be done, but the existing data provide clinicians with a reasonable framework for dealing with these challenging patients who are disabled by factors that cause them no physical illness or physiologic impairment. The task is made all the more difficult by their mistrust of and hostility toward the medical profession in general. It is not necessary to offer advice to treat patients with multiple chemical sensitivities with sympathy and understanding, because compassion and respect should not be withheld from any class of patients. Scheduling regular visits, making extra time available for these visits, and establishing short-term, modest, workable goals aimed at reducing disability rather than focusing on specific symptoms is helpful. The temptation to order still another test when the "going is rough" should be resisted. Antidepressant medication and psychotherapy are rational approaches to current depression and anxiety, although these patients usually reject psychiatric intervention, which they often express in symptomatic intolerance to even low doses of antidepressant medications. Beyond these general suggestions, firm recommendations for specific treatment modalities must await results of definitive clinical trials. Based on the current knowledge of multiple chemical sensitivities, behavior modification therapy seems to be a good place to start.