William J. Rea, MD, FACS, Environmental Control Unit,
Brookhaven Medical Center, Dallas, TX, USA
Environmental triggering agents for cardiovascular responses, excluding infectious agents, have rarely been reported. However, Hare,1 in the early 1900s, described vasoactive phenomena in patients after food challenges and showed that there was an increase in heart rate in some. In 1925, Lichtwitz2 demonstrated what was probably the first causal relationship between food and a case of angina pectoris. In the next decade numerous case reports and small series showed a direct cause-and-effect relationship between the ingestion of food and arrhythmias.2 Harkavy3 demonstrated that in some patients angina could be triggered by cigarette smoke. Using a semi-controlled environment, T.G. Randolph (personal communication) has been able to demonstrate a whole spectrum of arrhythmias in patients challenged with synthetic chemicals.
Recently, much has been written about the ill effects produced by aerosols and fluorocarbons. This may have been stimulated by Taylor and Hern=s4 report of a cardiac death in a 16-year-old boy due to sniffing an aerosol. The harmful effects of fluorocarbons were brought home by Spizer and his colleagues,5 who reported an increase in arrhythmias with an increase in length of exposure to fluorocarbons.
Certainly Nour-Elden=s6 studies showing that the vascular tree has an increased affinity for phenol, coupled with Yevick=s7 demonstration of inflammatory and fibrotic changes in the cardiovascular system of sea animals exposed to oil spills, add weight to the possibility that excessive pollution has an adverse effect on the heart.
More recently, Finn8 has also shown that arrhythmias
can be caused by foods, and I have had experience of several cases in which
arrhythmias have apparently been triggered by environmental incitants.9
Degree of Air Pollution in Different Areas
|Sea air||0 (excluding salt particles)|
|Desert air||10 x|
|Towns (>2500 population)||35 x|
|Urban||150 x (good days)
1,000C4,000 x (average to bad days)
Masking or adaptation
The Masking or Adaptation Concept
|Stage I||Stage II||Stage III|
When the cardiovascular system is involved, symptoms can be widespread. Such entities as nontraumatic phlebitis,14 nonarteriosclerotic arrhythmias,15 and large or small vessel vasculitis16 can occur. Raynaud=s disease and phenomenon are often observed.17 Arthritis,18 arthralgia, myositis, fibrositis, and myalgia are frequently present. Perhaps myocardial infarctions and strokes are triggered.
A symptom complex is often seen which may give a lead
to the possibility of an environmental trigger. It consists of acneiform
lesions, petechiae, and/or spontaneous bruising and purpura, peripheral
coldness and cyanosis, and peripheral and periorbital edema. The acneiform
lesions usually occur on the face and shoulders and may number from one
to thousands. Localized edema or urticaria occasionally occurs, but the
more generalized peripheral and periorbital edema is much more common.
However, this is often subtle and may be overlooked. People almost accept
swelling of their fingers to the point that rings cannot be removed as
normal and expect edema to occur cyclically around the eyes and in the
feet. Should the blood vessels leak further, extravasation of red cells
leads to the appearance of bruising, purpura, and petechiae. Peripheral
spastic phenomena, in the absence of cold, occur when the body is challenged
with chemicals and foods. If the physician keeps in mind the possibility
that any or all of the major systems containing smooth muscle may be involved,
he will be better able to diagnose and treat environmentally triggered
Once blood vessels become inflamed, a myriad of symptoms becomes possible. If the inflammation is generalized, edema occurs. If it is localized, urticaria is seen. If the vessels leak further or even rupture, there is bruising, purpura, and petechiae. Biopsy of these lesions reveals either the leukocytoclastic type of vasculitis with invasion by polymorphonuclear leukocytes, the lymphocytic infiltrative type or the perivascular lymphocytic infiltrative type. Occasionally, the eosinophilic type is seen. As the pathological derangement progresses, clotting occurs and the disease process becomes much more fixed. When diseases become fixed and, therefore, usually irreversible, they are recognized as entities such as necrotizing or hypersensitivity angiitis, giant cell arteritis, Wegener=s granuloma, temporal arteritis or vasculitis, connective tissue disease such as systemic lupus erythematosus, or rheumatoid arthritis, and so on. Finally, should local necrosis not occur, healing takes place by the formation of granulomas of plaques.
Levi21 has proposed a mechanism for the triggering of vascular disease. This, theoretically, holds true even for the triggering of infarctions or strokes. Often environmental triggering involves only the heart and can be responsible for very severe symptoms. Frequently, these are suppressed by medication and can continue for years before death occurs. However, some patients are unable to tolerate even the medication and they become seriously incapacitated.
I have been able to stop and reproduce many arrhythmias,
including ventricular tachycardia, in 20 patients in the hospital under
environmental control. These patients were usually seen to have normal
large vessels on coronary angiography. Some, however, had coronary artery
spasm. A few had plaque formation and apparently suffered from arteriosclerosis
in addition to vasculitis.
Our original and baseline studies are done in a specially constructed wing of the hospital. Here, city air can be depolluted not only for particulates but also for gases. The wing is constructed of glass, steel, porcelain, and stone. Most inner materials are of natural fibers decontaminated for synthetic chemicals. Analytical measurements of the air are carried out using gas chromatography, mass spectrometry and portable counters, organoleptic monitors (usually emotionally stable sensitized human beings who respond to chemical contamination of the environment), and biological responses in environmentally sensitive individuals not receiving medication (when in the clean environment of the Unit their eosinophils, gamma globulin, complement, and T lymphocytes show a return to normal values). Inorganic pollutantsCsuch as carbon monoxide, nitrogen dioxide, sulphur dioxide, hydrogen cyanide, chlorine, and chlorine dioxideCare reduced by 70-100% in the Unit when compared to outside air and in other parts of the hospital. Organic pollutantsCsuch as formaldehyde, petroleum alcohol, pesticide (2,4 DNP), phenol, xylene, hexanes, and alkabenzenes are reduced by 90-100% in the Unit as compared to the rest of hospital and the home environment. Particulates are reduced five-fold compared to the rest of the hospital. Spring and distilled waters are used in place of piped city water.
Chemically less contaminated foods grown, stored, and prepared in the relative absence of petrochemicals are also used in order to have proper controls for reproducible studies in patients sensitive to foodstuffs.
Eosinophil cell count. This is usually depressed in patients with environmentally triggered disease. In a consecutive series of more than 300 patients presenting to our Unit with a food and chemical susceptibility, the eosinophil cell count was below 3.5 x 10?/? Cnormal range in our laboratory, 50-200/mm3) in 90%. The 10% of the patients who had an eosinophilia were usually those with asthma or dermatitisCand they were definitely in the minority of patients presenting with those conditions. Once the patient was in the basal state and his peripheral eosinophil cell count had returned to normal, he was challenged with incitants. Frequently, the count was found to be depressed in serial blood specimens drawn during the reaction. If the count was low on admission, it would be low on challenge. If it was elevated on admission, it would rise on challenge.
Peripheral IgG. This was depressed on admission in 15% of our patients. Usually, levels returned to control values without treatment other than avoidance. Often depression recurred upon challenge. The reason for this is unexplained since the body usually contains a large pool of IgG.
Complement. Total hemolytic serum complement CH50 and CH100 has been measured in more than 300 of our patients, as have the C3 and C4 components. Thirty-five percent of the patients appeared to have total complement levels outside the two standard deviation ranges of 80-120%, most being below 70% of control values. Incitant challenge depressed the total complement. The C3 level, when abnormal, may be depressed, whereas C4 was usually elevated. All nine complement components were assayed in 75 patients who presented with initial depression of their total complement levels and frequently C? was also found to be depleted. In 75% of cases, the depressed levels returned to control values by the time the patients had achieved an adequate and consistent program of avoidance.
Blastogenesis. Lymphocyte transformation as a result of stimulation with pokeweed mitogen and phytohemagglutinin has been measured in more than 200 patients. Different concentrations have been found to be important in assessing sensitivity, as stimulation may occur only at specific levels. Twenty percent of our patients showed low levels of transformation. These are the most difficult to work with and the slowest to respond to treatment. However, as treatment progresses, the response is reflected in a general increase in transformation.
C-Reactive protein. This was elevated in 10% of our patients but often returned to normal as the inflammation subsided.
IgE. Since IgE was isolated by Ishikawa and his colleagues,26 it has been regarded as the carrier immunoglobulin in allergy. IgE has been measured in more than 400 patients with a food and/or chemical problem: 10% had levels over 100 times the control. Although IgE levels are popularly thought to be elevated in individuals with pollen, dust, and mold allergies, they appear to be of much less significance in the total assessment of patients with environmentally triggered disease. Certainly, when IgE levels are elevated, skin tests will be positive and radioallergosorbent tests (RAST) will also show raised values; the patient will respond to injection therapy. These patients usually are easy to treat by hyposensitization, with the optimum dose best being worked out by skin tests employing serial dilution titration. However, caution is imperative when treating patients with low IgE levels and negative RAST results as they may well be extremely sensitive to inhalant antigens, probably through an abnormality in another as yet undefined mechanism.
IgA. Reports have indicated that low surface IgA levels may occur. However, fewer than 1% of our patients had low IgA levels. At present, therefore, we have been unable to correlate the apparent depletion of this immunoglobulin with clinical entities as have some other authors.
IgM and IgD. No correlation has been seen in more than 400 patients in whom these immunoglobulin levels have been determined.
Leukocyte inhibitory factor. Using the food to which the patient is sensitive on challenge, tests for this factor have been done on more than 400 patients with environmentally triggered disease. Food is placed in the patient=s fresh blood, and the number of leukocytes inhibited after incubation is counted. However, this test appears to be only about 60% accurate.
Cytotoxic food test. This test is not completely
reliable. In some individuals the correlation is almost 100%, but in others
there seems to be little correlation.
Hyposensitization. Usually pollen, dust, and mold hyposensitization is used, bearing in mind the precautions mentioned above. Sensitivity to phenol and glycerine appears to be an increasing problem. It has been my experience that many patients who have been intolerant to phenol or glycerine can be treated if these substances are omitted from the injections. Unfortunately, the extracts are then more hazardous as they have to be kept frozen except when in use.
Neutralization. Food neutralization injection therapy as advocated by Miller27 seems to be an excellent adjunct to the rotation diet. In our Unit, there is a high correlation between challenge testing and skin wealing in moderately sensitive patients. After neutralization, approximately 75% of the foods could be included in the rotation diet at least once every seven days. Some foods could be eaten without impunity but, more often, repetition led to loss of tolerance for that particular food.
Although this series was small and testing was not done in a double-blind manner, it was clear that repeated challenge consistently resulted in reactions to the food. When daily injections of the neutralizing dose of a food were given, the patient could eat the food on rechallenge. When the injections were withheld, sensitivity to the food rapidly returned. These tests were done under controlled conditions.
Physicians have been using neutralization techniques for food for long enough to realize that injection therapy may fail at any time. Although there is a multitude of reasons for this, chemical overload in food-sensitive patients appears to be the prime cause. As our environment steadily deteriorates, so the problem of chemical sensitivity increases.
The principles of chemical avoidance can be discussed only briefly here. Those who wish more details can consult Randolph,12 Dickey,19 or Golos.28 The book by Natalie Golos is of particular value to physician and patient alike.
Food with a low level of chemical contamination is most important for those with a chemical susceptibility. There is now a sufficient number of patients in all major cities in the USA to make the formation of cooperatives a worthwhile undertaking. We have found it necessary to ask farmers to grow chemically less contaminated foods in order to have a constant and safe supply. Reliance upon health food stores is difficult because many foods sold there are contaminated.
The home environment is the most important place to maintain free of pollution. There should be no gas appliances in the house. If coal or petroleum products are used, they should be kept away from the house and boilers used for heating; the hot water can then be pumped into the central system and the heat carried throughout the house. Lower temperature electric heating appears to be tolerated by many patients. The bedroom should be the main sanctuary. Bedding should be 100% cotton or linen, as previously described. Curtaining of the windows should be either 100% cotton or metal blinds. All clothing except that which the patient can tolerate must be removed from wardrobes, cupboards, and drawers. Articles remaining in the bedroom and/or en suite bathroom should be kept to a minimum; all plastics, cosmetics, and cleaning agents should be removed.
All clothing should be of washable cotton, linen, or silk. Since formaldehyde is often used in conditioning cotton materials, care should be taken to process new clothing before it is worn. A vinegar soak followed by laundering with sodium bicarbonate is the best method for removing substances used in the chemical treatment of cotton. This process may have to be repeated several times for the sensitive patient.
Finally, no pesticides, herbicides, fertilizers, or the
like should be used in or around the house.
1. Hare, F. (1905). The Food Factor in Disease. London: Longmans.
2. Lichtwitz, cited in Harkavy.
3. Harkavy, J. (1963). Vascular Allergy and Its Systemic Manifestations. Washington: Butterworths.
5. Spizer, F.E., Wegerman, D.H., and Ramiers, A. (1975). Palpitation rate associated with fluorocarbon exposure in a hospital setting. New England Journal of Medicine 292:624.
9. Rea, W.J. (1979). Environmentally triggered cardiac disease. Annals of Allergy 40:243.
10. Rea, W.J. (1979). Diagnosing food and chemical susceptibility. Continuing Education 16:47.
11. Rinkel, H., Randolph, T.G., & Zellner, M. (1946). Food Allergy. Springfield, IL: Thomas.
14. Rea, W.J. (1976). Environmentally triggered thrombophlebitis. Annals of Allergy 37:101.
15. Rea, W.J. (1978). Environmentally triggered cardiac disease. Annals of Allergy 40:243.
16. Rea, W.J. (1977). Environmentally triggered small vessel vasculitis. Annals of Allergy 38:245.
22. Rowe, A. H., and Rowe A, Jr. (1979). Food Allergy: Its Manifestations and Control and the Elimination Diets. A Compendium. Springfield, IL: Thomas.
25. Rinkel, H.J., Lee, C.H., Brown, D.W., Jr., Willoughby, J.W., & Williams, J.E. (1964). The diagnosis of food allergy. Archives of Otolaryngology 79:71.
26. Ishikawa, K., Ishikawa, T., & Hornbrook, M.M. (1966). Phys-co-chemical properties of human reaginic antibody IV. Presence of a unique immunoglobulin as a carrier of reaginic activity. Journal of Immunology 97:78.
28. Golos, N. (1975). The Management of Complex Allergies. Chicago: Human Action League.