PART ICCASE STUDIES

Since the overexposure Mrs. B is unable to tolerate common chemicals found in the ordinary living situation. Examples are as follows:

Under environmental control the patient=s speech gradually improved over a three-week period and was quite understandable before discharge. Five foods produced such symptoms as mild nausea and anxiety. Fifteen-minute ambient concentration exposures to natural gas, alcohol, cigarette smoke, formaldehyde, chlorine, and an insecticide produced no reaction. When challenged with a single inhalation of acrylic enamel spray paint, Mr. C immediately developed headache, nausea, chest pains, nervousness, heartburn, drawing sensation of his face, and severe impairment of his speech which lasted for 48 hours.

The testing in a Chicago unit similar to ours showed the patient to have widespread food and chemical susceptibility. After leaving the Chicago environmental unit, the patient was unable to tolerate the polluted city air. She became paralyzed from the waist down and developed severe tachycardia, uncontrollable with drugs. She was sent to the Dallas environmental unit, where most symptoms gradually cleared. She had severe reactions to numerous test foods. A challenge ingestion of one drop of kerosene diluted 5^-15 in saline produced spontaneous bruising and hemoptysis. One drop of sublingual phenol (0.4% concentrate diluted by factor of 5^-15) produced hemoptysis and spontaneous bruising. The patient was put on a rotary diet of chemically less contaminated food and sent to live with a local patient in an environmentally controlled home that was electrically heated and free of petrochemicals, including plastics. Though her sensitivities have diminished over the last year, she still must live in a relatively natural environment and cannot tolerate exposure to any of the chemicals which produced symptoms during testing.

After an acceptable water which did not produce symptoms was determined, individual challenges with various (no more than four per day) chemically less contaminated source foods (source foods=distinct biological entities such as wheat, oats, rice, beef, pork, lettuce, and carrots) were made. Once acceptable foods were determined, oral challenge was repeated with the same foods but in a form grown, processed and stored according to conventional marketing methods. Finally, double-blind challenges with ambient concentrations of common types of inhaled chemicals were performed. Attempts were made to include the chemical which apparently had precipitated the patient=s problem.

The following laboratory tests were done to investigate possible mechanisms: complete blood count by the Coulter Model S Method; sodium, potassium, chloride, carbon dioxide, blood urea nitrogen, serum glutamic oxalo-acetic aminase, lactic dehydrogenase, and serum calcium by the SMA Method; protein electrophoresis by the Helena Cellulose Acetate Method; immunoglobulins (IgE, IgG, IgA, IgM) C₃ and C₄, alpha 1 antitrypsin and C-reactive protein by the Behring Radial Immuno Diffusion Method; total hemolytic serum complements CH₁₀₀ and serum complement components by the Hemolysis Sheep Cells Method; prothrombin time, partial thromboplastin time, platelets, and Lee White clotting time by the Dade Reagents Method; phosphorus by the Hycel Metho, fibrinogen, and fibrinolysins, clot lysis by the Biuret Quantitative Method; fibrin split products by the Burroughs-Wellcome Method; C₁ esterase inhibitor by the Behring IEP Method; B lymphocytes and T lymphocytes by the Sheep Cell Rosetting Method. All tests were performed when the patient entered the test room and at the beginning and end of the challenge period. C₃ and C₄ were measured daily during the period of fasting.

The findings in this series of patients confirm Randolph=s observations and re-emphasize the seriousness of exposures to levels of some chemicals in our environment which were previously considered safe. Since safety has only been determined in studies of acute exposure to uniform genetic animals, a high level of error exists as to what amount of chemicals are safe in the environment. Susceptible humans acting as monitors might help us to better determine safe levels of chemicals in our environment.

It is notable that those patients who developed food intolerance did not have it before they had massive chemical exposures. Most could eat any foods as much as often as desired. After the exposure, it was apparent to most of these patients that the ingestion of foods in general seemed to bother them. Until the unmasking process occurred in the environmental unit, it was not clear which specific foods were involved in triggering their symptoms. Many found that by using meticulous selection they could have a symptom-free meal for the first time in months. In order to remain symptom free, it was clear that these patients had to continue avoiding their symptom-producing foods for a period of at least six to twelve months. As their daily chemical exposure decreased their tolerance increased and they were then able to eat the foods previously not tolerated. In fact, many of the foods could be returned to the diet in rotation after a long period of avoidance. Furthermore, during visits to areas of significantly less air pollution, they could suddenly tolerate foods to which they were usually susceptible.

A working hypothesis that has evolved from the study of these patients with chemical overexposure is that of total body load. One might make the analogy of a person being a barrel. When the barrel fills and subsequently overflows, symptoms are produced. Once the overflow load is reached minute levels of inhaled or ingested chemicals cause symptoms. Each person in this series apparently reached and exceeded his total body chemical load, with the result of extreme sensitivity and chemical intolerance. Presumably at the total tolerated load, enzyme systems or mediators have been maximally interfered with so that any further interference leads to chemically expressed symptoms.

This body load is created by many factors. In addition to the daily exogenous load from the foods per se, the body=s adaptive mechanism must cope with the large amount of synthetic chemicals in food. It is estimated that the average individual ingests at least one gallon of synthetic additives, coloring agents, pesticides and preservatives in a year=s time. For all patients in this series it was necessary to acquire specially grown, chemically less contaminated foods.

Daily use of chemically contaminated water is still another major component of the total environmental load. In a recent analysis in which local city water was compared to various spring waters, city water was shown to have 1,000 to 10,000 times more synthetic compounds.¹² Water intolerance was a problem in these patients and necessitated the use of spring water.

The additive effect continues with the air that is breathed. Outdoor air pollution is increasing in many areas. Studies by Whitby¹³ have shown that city air may be three to four thousand times more polluted than sea air. If one then adds an increase in indoor air pollution at the place of employment to his already burgeoning load, one can see how environmentally triggered disease could occur. For example, one place of work which was analyzed had 400 times greater concentrations of chemicals in the air when compared with outside air. Of course, each threshold limit was below the theoretically safe level for individual exposure to that particular chemical. However, in this instance, combined and accumulated effects of multiple chemicals had never been evaluated, and the patient became ill from the overexposure.

Together with the high ambient levels of chemicals in city and industrial air, the environment of the average home has been shown to be highly polluted.^15,16 Fumes from gas heating and cooling appliances, from the outgassing of the soft plastics such as Nylon, polyester, polyurethane, and polyethylene and from routinely using pesticides all contribute to this domiciliary air contamination. Acute chemical exposures can add insults that persist after cessation of the exposure. Stewart,¹⁷ for instance, showed that people using furniture paint stripper would continue to have an adverse change in their carboxyhemoglobin for several hours after leaving the exposure. Isolated exposures of this nature might still be tolerated if a person had a chronic total load and was able to obtain fresh air at home. Our study suggests that patients become symptomatic on exposure to minute amounts of several chemicals as a result of cumulative acute and chronic exposures.

The total load concept is related to Selye=s¹⁸ model of general adaptation. He observed that a general environmental stimulus causes an initial alarm reaction. If the stimulus continues, a stage of adaptation follows and lasts from minutes to years. Finally, adaptation fails and the stage of exhaustion develops, in which the organism enters a disease state and eventually expires. Adolph¹⁹ further expanded these ideas to include individual differences in response to specific stressors. Randolph²⁰ later showed that individual susceptibility interacted with long-term and /or massive chemical exposure to produce clinical maladaptation or rapid exhaustion.

The bipolar nature of the chemically maladapted state has been described by Randolph.^.21 Frequently patients in the present series who developed chemical susceptibility reported stimulatory responses of central nervous system activation with such symptoms as increased motor activity, anxiety, insomnia, etc., when they initially came in contact with the chemical to which they eventually became susceptible. Some even experienced an unusually euphoric feeling of being in an intoxicated-like high. Of course, once their bodies reached the stage of exhaustion, they then perceived only the maladaptive withdrawal response with physical symptoms and central nervous system depression. Such bipolar responses are well-known in addictions to drugs such as opiates and alcohol and to other items such as cigarettes, coffee, candy, and soft drinks and suggest a common mechanism of homeostatic disruption. In food and chemical maladaptation, both the stimulatory and withdrawal phases can last from minutes to hours to years.

It was Rinkel²² who utilized the adaptation principle to evaluate food intolerance. He showed that temporary avoidance (4-5 days) of foods to which an individual was maladapted would unmask or return the patient to the stage of alarm reaction. Therefore, acute challenge with an offending food that has been unmasked would cause a definitive reaction. Similar tests with foods to which the individual was not susceptible would cause no reaction. Both unintentional and deliberate test exposures by Rinkel=s approach in the current series have confirmed the usefulness of his diagnostic technique.

The nature of the specific derangement(s) of the internal homeostatic mechanism is currently ambiguous but the altered laboratory tests suggest that different elements of the system were involved in individual patients. Unfortunately, laboratory work thus far has not defined the initial steps which trigger the subsequent ecologic and/or cellular abnormalities during adverse reactions to incitants. Involvement of the immune system, although not readily apparent, is possible. The chemicals may have acted as haptens. Reaginic IgG may have been active since IgE levels were not significantly elevated in most of the patients studied. Furthermore, IgG was changed on challenge by individual incitants in some patients in this series. This type of change has been reported with food challenge.²³ Certainly activation of the complement system was present in some patients. When all nine components were measured in some select patients, C 1, 4, and 2 were near control values when C₃ was depressed, suggesting alternate pathway involvement. Since total hemolytic complement depression occurred during challenge in some instances with resulting bruising or purpura, immune complexes may have been involved. Perhaps these were bound to cutaneous blood vessels, causing leaking of erythrocytes. Possibly this is similar to the C₁ and IgG deposition reported by Papish²⁴ in animals and Theorell²⁵ in humans. Unfortunately, fluorescence studies were not available on the biopsies of our patients. However, light microscope section in patients who bruised showed a monocellular infiltrate in the precapillary arterioles. While no evidence of involvement of the fibrinolytic or clotting systems was seen, local levels could have been changed without being reflected in the patient=s peripheral blood. Also, clotting studies were not done during challenge reactions. Direct kinin activation also could have been involved but was not measured in this series. Since T-cell depression occurs in some patients and returns to higher levels when being away from the chemicals, it would appear that this system is significantly involved. Thus, derangements of different potential mediating mechanisms were apparent. Presumably they were secondary to some as yet unknown primary change in body physiology.
 
 

Double-blind rechallenge with ambient dose levels of synthetic chemicals reproduced most of the symptomatology. Laboratory findings included abnormalities in complement, T-lymphocytes, eosinophils, and IgG.