Environmentally Triggered Disorders

Dr. William J. Rea
Environmental Health Center - Dallas

Originally published in Sandorama Vol. IV, 1982, pp. 27-31

Abstract

Since the development of the germ theory, medical science has evinced an accelerating interest in the treatment and prevention of environmentally triggered diseases. The technology of infection control, made possible by the development of antibiotics and aseptic practices, has facilitated exploration of such phenomena as the absence of resistance and the susceptibility to recurrent infection in a large proportion of the patient population. It would appear that the interaction of the individual's total environment with his bodily homeostatic mechanisms is the pivotal factor in the breakdown of resistance mechanisms. The intention of this review is to provide an understanding of the numerous ways in which environmental overload may trigger disease processes, and to provide some indication of measures that can be taken to ensure optimum health.

Objectives

In its attempt to elucidate the complex interactions between environment and bodily homeostatic mechanisms, the following review outlines the principles operative in environmentally triggered disease, as well as the organ systems most likely to be affected. The mechanisms of disease development and various laboratory measurements which define change in homeostasis are treated in some detail.

Diagnostic and treatment issues are considered from the perspective of clinical ecology. Finally, some case histories are presented that illustrate diagnostic and treatment procedures.

Principles

Any analysis of environmentally triggered disease and preventive health measures demands a comprehension of the following principles, which are crucial to the processes of diagnosis and treatment of these disorders.

The first principle is the fact that medical environmental technology lags far behind the development of technologies employed in the environment. Ignorance on the part of the public and medical profession regarding potential triggering agents in the environment often hides otherwise apparent cause-effect relationships and may well negate the effects of conventional treatment.

The second prinicple deals with the concept of total body load, the sum of all incitants, including pollutants, which the body has to handle in order to function. The importance of body load as so conceived lies in its ability to distort many bodily homeostatic mechanisms. The vast amount of environmental pollution, in the form of water systems overloaded with synthetic chemicals, contamination with pesticides and via food additives, and home environments corrupted with outgassing synthetics, has resulted in a tremendous increase in body load and a consequent distortion of the homeostatic mechanisms.

The third principle is that of masking, which occurs when an individual is repeatedly exposed to a substance to which he is susceptible. The repeated exposures cover up the cause-effect reactions, resulting in nonrecognition of the relationship. Following a period of avoidance, an unmasking effect occurs, whereby reaction to challenge, and hence a cause-effect relationship, may be clearly established. A comparable phenomenon is seen in drug addiction.

Finally, the concept of bipolarity suggests that an individual may have an immediate stimulatory reaction to a substance, which is followed, after a variable interval, by noxious withdrawal symptoms which appear to be a function of the breakdown of the body's defense system. Examples of such phenomena are seen in narcotic, tobacco, and alcohol addiction.

Organ Involvement

While any smooth muscle represents a potential target organ of environmentally triggered disease, the principal categories into which such target systems may be divided comprise the respiratory tree, the gastrointestinal tract, the genitourinary system, the cardiovascular system, and the skin. Within the respiratory system, ear, nose, and throat involvements often appear as early warning signs of environmentally triggered disease. Rhinitis, recurrent sinusitis, severe otitis, vertigo, and laryngeal edema are frequent manifestations of such tissue involvement. Inflammatory diseases present in the gastrointestinal system may take the form of pharyngitis, esophagastritis, enteritis, or colitis. Involvement in the genitourinary system is often demonstrated by the presence of of urinary frequency and urgency, cystitis, and uterine bleeding. Certainly, a plethora of symptoms may accompany cardiovascular inveolvement. These include phlebitis, nonarteriosclerotic arrhythmias, vasculitis, and Raynaud's disease and phenomena. In addition, arthritis, mysitis, and fibrositis are frequently present. A symptom complex which often occurs with vascular response includes acneiform lesion, petechiae, spontaneous cyanosis, and edema. Skin diseases which may also be manifestations of food and chemical sensitivity include chronic itching, eczema, and dermatitis rashes.

It appears that triggering of such inflammatory diseases may occur through the homeostatic mechanism, via both the immune and nonimmune systems, through immunoglobulins or by the amplification systems directly; for example, activation of the alternate pathway of complement or other mediators such as kinin or prostaglandin. The result is membrane irritability with increased permeability, the consequence of which is edema, the initial symptom observed in many environmentally sensitive individuals. Edema may be generalized or localized, and rupturing of vessels may result in bruising, purpura, and petechiae. Biopsy of such lesions shows the leukocytoclastic type with polymorhonuclear invasaion, the lymphocytic infiltrative, or the perivascular type. With continued pathologic involvement, disease processes become mixed and are recognized as clinical entities such as angiitis, arteritis, vasculitis, collagen disease, etc.

Protocol for Isolation of Environmental Incitants

From the techniques of Rowe, Cocoa, Randolph and Rinkel, a method was developed whereby discrimination of incitants could be made. This is now possible in a more highly refined manner which takes into consideration all of the following parameters operative in environmentally triggered disease: contaminants in air, food and water, which constitute the major factors with which diagnosis and treatment should be concerned.

The rationale for the creation of the Brookhaven Environmental Unit in Dallas was the need to have an ambience in which these parameters might be more clearly defined, by reducing the patient's total body load and by isolating environmental incitants. It should be noted that failure on the part of the physician investigating environmentally triggered disease to control the ambient air of his office may result in misdiagnosis and inappropriate treatment.

The Brookhaven Unit comprises a wing of the hospital, complete with firewall and double doors to exclude potenyial pollutants. Air conditioning was managed by the use of all-metal window coolers, but heating represented a more difficult problem, since many chemically sensitive individuals are also sensitive to many types and sources of heat. Since the vast majority of these patients are highly sensitive to the fumes of natural gas or different electric heating elements, radiators of steel, cast iron, or ceramic were frequently used, with varying degrees of tolerance.

Certainly, air is the most difficult parameter to assess, given the small amount of technology devoted to analysis of indoor pollution. Air depollution devices include charcoal, aluminum oxide impregnated with potassium permanganate, steel mesh, and paper filters. All of them have their own set of problems for the environmentally sensitive individual. Nevertheless, attempts were made to control ambient air by prohibiting outgassing from rapidly disintegrating synthetic fabrics, and by installing depollution devices constructed of relatively inert materials. Rooms in the Unit were also constructed of such relative inert materials; the most readily available for this purpose include plasterboard, aluminum wallpaper, plaster, ceramic tile, and porcelain steel. Besides symptom clearance and laboratory test results, an additional means by which air content was assessed at the Unit was direct analysis by gas chromatography and mass spectometry.

In order to study food as a principal parameter, it was necessary to utilize chemically less contaminated foods, given the high levels of additives and pesticides contained in commercially available food products. To this end, a food cooperative was established which contracted with farmers for the production of food grown without herbicides, pesticides, or other contaminants; the food was then stored in containers of uncoated cellophane or glass in order to prevent contamination. Furthermore, all food used for testing was prepared in iron, steel, or glass cookware in order to prevent contamination at a later stage.

Recent studies indicate significant contamination of our urban water supplies, and it would appear that both lay and the medical community are largely ignorant of the potentially harmful effects of such water pollution. After approximately two days in the Unit, a cause-effect relationship may be established between water contaminants and patient reaction. Double-blind studies reveal that approximately 90% of chemically sensitive patients are intolerant of tap water. Clinical experience reveals that certain spring waters are optimal water for use in the study of environmentally triggered diseases.

Laboratory Tests

The following parameters have proved to be useful, if not always specific, indices of changes in those of the body's homeostatic mechanisms which are a function of incitant exposure.

Eosinophils. Total body eosinophil count is typically found to be in a depressed state in individuals with environmentally triggered disease. Of 300 patients in the Unit who entered with food and chemical sensitivities, 90% had eosinophil counts depressed below 35mm3 or completely absent, while 10% had elevated counts. If the eosinophil count was depressed on admission, challenege produced a further depression. If it was elevated on admission, challenge evoked an elevation.

IgG. Peripheral IgG was depressed on admission in some 5% of the patients studied. The depression that occurs on challenege remains unexplained at present.

Complement. Total hemolytic serum complement Ch50 and CH100 as well as the C3 and C4 componhents have been measured in some 300 patients. In 25% of the patients seven complements were abnormal. Incitant challenge appears to depress the total complement in 75% of the abnormalities and elevate it in the other 75%. Complements returned to control levels following an avoidance program.

T and B lymphocytes. B lymphocytes were depressed in less than 5% of the same patients and elevated in another 5%. The majority of patients had an absolute T lymphocyte count below 1000/mm3 (E rosettes). It would appear that this parameter is a sensitive indicator in many patients, since T lymphocytes and their factors are frequently depressed upon challenge.

Blastogenesis. Lymphocyte transformation due to incitant stimulation has been found, in certain concentrations, to be important in the assessment of sensitivity. Twenty-five percent of the patients have T lymphocyte blastogenesis problems.

IgE. Immunoglobulin E would appear to be of much less significance in the assessment of environmentally triggered disease than has traditionally been thought. Only 20% of our patients have high IgE levels. It should be emphasized that low IgE levels and negative RAST results do not necessarily indicate a lack of sensitivity. Patients with low IgE levels may well be skin-test positive on intradermal testing and be sensitive to inhalant antigens. This abnormaility may occur in the IgG system or through a disorder in another, as yet undefined, mechanism.

While tests of leukocyte inhibitory factor and cytotoxic food tests have demonstrated mixed results, the challenge test under controlled conditions remains the most reliable and reproducible index.

Methods of Diagnosis

Intradermal skin tests and RAST assays continue to be helpful diagnostic indices for the analysis of pollen, dust, and mold sensitivities. Caution, however, should be exercised regarding those patients who, although extremely sensitive, evidence no skin whealing.

Withdrawal and challenge remain the optimal tool for the diagnosis of food sensitivity. Intradermal skin whealing appears to correlate very highly (70%-80%) with food challenge in the Unit. Both the rotary diet and the process of intradermal neutralization, following the serial dilution technique, serve diagnostic as well as treatment functions.

Perhaps the greatest problem in diagnosing and treating environmentally triggered diseases is represented by the growing number of synthetic and natural chemical incitants. While skin testing has proven unrewarding with this group of incitants, controlled testing, using a stainless steal booth in which inhalation challenge is carried out, represents a critical diagnostic tool which is amenable to a double-blind procedure.

Treatment

It has become apparent that a treatment approach which considers in a long-range perspective the whole patient and the environment in which he lives can culminate in a preventive medicine which arrests early-stage envrionmentally triggered diseases before their development into end-stage inflammatory diseases. Traditional injection therapy clearly fails to the extent to which it neglects the reduction of the total body load which may be operative in the disease process.

An optimal treatment of pollen, dust, and mold sensitivities combines avoidance and injection therapy for hyposensitization with careful attention to the home environment, which must be purged of contaminants.

In cases of food susceptibility, the rotary diet in conjunction with food neutralization injection therapy appears to be of significant value in treatment. Nevertheless, chemical overload in food-sensitive patients may clearly attenuate the efficacy of injection therapy; thus, attention is directed to the need to decrease total chemical load in many food-sensitive patients.

Neutralization injection therapy for chemical sensitivity appears to be merely a stopgap measure;avoidance is clearly the treatment of choice, and for this reason treatment of such sensitivities is complex. Patients are advised to consume optimally tolerable water (usually spring water) filtered or distilled, and chemically less-contaminated foods. The need for environmentally safe home conditions is paramount and, to this end, patients are urged to remove gas appliances as well as plastic and synthetic objects and other outgassing substances.

Case Studies

The following cases offer illustrations of diagnosis and treatment of environmentally triggered diseases of various types. In each case the control values for each immunological parameter assessed are given in parenthesis following the value obtained from the patient.

Case 1: A 46-year-old white male surgeon entered the Unit with chief complaints of loss of fine function of the right hand, weakness of the right leg, numbness of the right hand, arthralgia, and poor function of the right foot. Pulmonary symptoms had accompanied his exposure to defoliating agents in Vietnam some years ago, but his present symptoms began one year prior to admission. He was unable to move the right arm, except for gross movements. Rotation of the right hand was impossible. The fingers were swollen and blue on this hand. A pinch motion of the right thumb and index finger was impossible. The right leg dragged in a manner similar to that resulting from past cerebral vascular accident. Physical examination revealed 2+ left superficial temporal pulse; left carotid pulse 2+ and tender, without bruit; butterfly rash on face, with petechiae. Arteriogram showed spasm of the left carotid system. Four days of fasting in a tile and aluminum unit brought symptom relief. Challenge with both foods and and chemicals, including chlorine, formaldehyde, phenol, and natural gas reproduced his symptoms. This acute exacerbation of vasculitis and immune deficiency was treated with a rotation diet of chemically less contaminated food and a chemical detoxification of the home environment. All standard laboratory tests were negative. Immunological parameters were assessed, revealing T lymphocytes upon entering the Unit at 783 (1600-2000) and after fasting 1287; B lymphocytes 501 (400-800); total complement 150 (70-120%); total eosinophils 158 (40-200/mm³); IgE 51 (41); CRP negative; and IgG 1120 (800-1800 mg/dl).

Case 2: This 12-year-old white female presented with chief complaints of burning sensation during urination, bladder pain with enuresis, nausea, and stomach cramping. The physical examination was unremarkable. Cytoscopy revealed nonspecific inflammation of the bladder. After five days of fasting in a plaster room at the Environmental Control Unit, the patient experienced clearing of symptoms. It was found that several foods and chemicals, including natural gas, chlorine, and phenol, reproduced the initial symptoms, incuding enuresis. The dysuria secondary to food and chemical sensitivities was treated by both injection and avoidance, using food, chemical, and inhalant antigens, in conjunction with a rotation diet of chemically less-contaminated foods. Standard laboratory tests were negative. Immunological data showed T lymphocytes 624 (1600-2000); B lymphocytes 528 (400-800); total complement 103 (70-120%); total eosiniphils 53 (50-200/mm³); IgE 18 (41); CRP negative; and IgG 1160 (800-1600 mg/dl).

Case 3: A 38-year-old female presented with complaints of joint stiffness, red splotches on chest and arms, and soreness and edema of the left side of the body. Initial investigation suggested evidence of angioedema and vasculitis. Biopsy of spontaneous bruising revealed lymphocytic perivasculitis. Subsequent investigation led to the discovery of a developmental abnormality of the pancreas, in the form of a pancreatic divisum. During her hospitalization at the Unit, several food and chemical sensitivities were discovered, and following pancreatic surgery these sensitivities showed considerable improvement. It would appear that the patient's congenital abnormality aggravated the condition by preventing proper digestion of her food, thus exposing her to intolerable food and chemical incitants. All standard laboratory tests were negative except for serum amylase 330. Immunological parameters were assessed as follows: T lymphocytes 1300 (1600-2000); B lymphocytes 1040 (400-800); total complement 87 (70-120%); total eosinophils 35 (50-200/mm³); CRP negative; and IgG 1040 (800-1800mg/dl). T lymphocytes returned to the 1040 to 1400 range one week after surgery. During the previous six months they had been depressed.

Case 4: A 65-year-old white male presented with chief complaints of upset stomach, sleeping spells and fainting spells. The onset of symptoms was six months prior to admission when the patient experienced irregular heartbeats, shaking spells, and fainting spells. He had been diagnosed as having cardiac arrest and had been worked up with a variety of cardiac modalities, including ECG, stress tests and coronary angiograms, all of which were negative. Clinical observation led to the discovery that the patient's movement from areas of high temperature to areas of low temperature or the reverse (i.e., entering or leaving air-conditioned building during the summer months) triggered fainting spells. He also had a severe sensitivity to perfume that would partially reproduce some of his symptoms. Sensitivities to pollen, dust, and molds were found but desensitization was ineffective. It was felt that the patient had a hyperactive carotid sinus reflex secondary to environmental sensitivities. A pacemaker was placed and symptom relief followed. His symptoms of cardiovascular and gastrointestinal distress were found to be reproduced following challenge with a variety of foods and chemicals. Weakness and passing out followed exposure to phenol and perfume, and this phenomenon was eliminated after pacemaker insertion. Treatment consisted of a combination of avoidance and injection therapy. The patient has remained asymptomatic for one year. Immunological testing showed T lymphocytes at 811 (1600-2000); B lymphocytes at 70 (400-800); total complement 168 (70-120%); total eosinophils 194 (50-200/mm³); IgE 1?(41); CRP negative; and IgG 1375 (800-1800 mg/dl).

Bibliography

1. Rea WJ. JCEORL and Allergy, The environmental aspects of ear, nose and throat disease, Part I, 41(7), 1979, pp. 41-56.

2. Rea WJ. JCEORL and Allergy, The environmental aspects of ear, nose and throat disease, Part II, 41(8/9), 1979, pp. 41-54.