Perspectives in Biology and Medicine

AN ENCOUNTER WITH THE SYNDROME OF MULTIPLE CHEMICAL SENSITIVITIES: REFLECTIONS OF A PHARMACOLOGIST PHILIP KLUBES* Prologue Little more than a few months after the occupational medical clinic began at Yale, in 1979, the staff was confronted with a problem none of us had ever seen before nor heard about. A middle-aged man was referred because of a delayed recovery from an episode of pneumonia that had resulted from a chemical spill on the job. As his x-ray cleared, he had become not better, but worse. Particularly striking was the history that exposure to chemical odors would markedly exacerbate baseline dyspnea and chest pain. Upon return to work he "passed out" on several occasions after a whiff of fume. Disability leave, however, did not resolve the situation. Increasingly, even common household products and environmental contaminants induced debilitating respiratory and constitutional symptoms, reducing his formerly vigorous life to a pitiful existence at home. In response we exhaustively investigated his list of chemical précipitants in search for some way to tie these toxicologically with his prior pneumonia, but without success. Equally unrevealing were results of extensive clinical tests undertaken to define his "lesion" pathophysiologically. Therapeutically, it would be generous to say that we accomplished very little. There were other cases too. One day, a strident former machine operator came to the clinic wearing, much to everyone's amazement, a respirator. Suddenly, the image of the "gas mask" precipitated recognition of an identifiable clinical constellation, characterized by severe, recurrent and toxicologically inexplicable symptomatic reactions to quite low levels of common airborne substances. We discovered shortly that we were not alone. Many of our colleagues practicing occupational medicine around the country began reporting similar cases; they too were stymied by them. Thus we became aware ofhow widespread the problem is and how incredibly expensive the costs are for medical care and disability in each case. Unfortunately, recognition of this "syndrome" did not lead readily to improved understanding nor to drastically enhanced theapeutic efficacy. ... In addition, we learned to avoid certain predictable pitfalls, such as extensive use of medications (which generally made patients worse) and projection of unrealistic *Professor of pharmacology, George Washington University Medical Center, 2300 Eye Street, N.W., Washington, D.C. 20037.© 1991 by The University of Chicago. All rights reserved. 003 1-5982/9 1/3403-0725$0 1 .00 Perspectives in Biology and Medicine, 34, 3 ¦ Spring 1991 | 355 expectations for rapid recovery after the almost invariably necessary step of removing the patient from his/her work environment. . . . But on the whole, though we were referred as many as one new patient monthly, neither our understanding nor our approach substantially improved. [1] On the basis of their subsequent experience with additional patients, in 1987 the group at Yale developed a diagnostic definition for this uncommon and unusual syndrome in which patients manifested atypical reactions to very low levels of a variety of volatile chemicals. They termed the syndrome multiple chemical sensitivities (MCS), and they defined it as follows: MCS 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 found to cause harmful effects in the general population. No single widely accepted test of physiologic function can be shown to correlate with symptoms. Using this case definition, one can distinguish seven major diagnostic features. (1) The disorder is acquired in relation to some documentable environmental exposure(s), insult(s) or illness(es). (2) Symptoms involve more than one organ system . (3) Symptoms recur and abate in response to predictable stimuli. (4) Symptoms are elicited by exposures to chemicals ofdiverse structural classes and toxicologic modes of action. (5) Symptoms are elicited by exposures that are demonstrable (albeit of low level). (6) Exposures that elicit symptoms must be very low, that is, many standard deviations below "average" exposures known to cause adverse human responses. (7) No single widely available test of organ system function can explain symptoms [I]. Despite the work of various investigators, MCS still remains a littleknown , poorly understood syndrome. In addition, there are valid, serious doubts and considerable questions about both the etiology and appropriate treatment for the...