William J. Rea, M.D., F.A.C.S.

An exciting era is dawning in medicine. The merging of thought in the field of allergy, immunology, cardiovascular disease, and nutrition is opening up new vistas. It appears as if many of the inflammatory vascular diseases of unknown etiology may now have a potential of having their triggering agents defined. Capability of incitant definition not only would be a significant aid in treatment but would also allow us to advance further than ever before into the less costly areas of preventive medicine.

Many recent developments have allowed us to more clearly define incitant triggering. Detailed description by Randolph(1) of how to construct a totally controlled environmental unit has for the first time allowed us an exceptional tool to study inflammatory cardiovascular disease under environmentally controlled conditions. The development of the ability to measure numerous laboratory parameters such as immunoglobulins, total hemolytic complement and all its components, T and B lymphocytes, blastogenesis and numerous mediators such as kinin, serotonin, and histamine was critical. These developments have allowed us to track and plot challenge reactions induced under well-controlled conditions, thus giving us laboratory support of observed cause and effect phenomenon. Pathological studies developed by Zeek(2) and Parrish(3) and amplified by many other authors(4),(5), (6) allows us to even have biopsy verification in many cases.

Over the past two years, over 217 articles have been written on the subject of inflammatory vascular disease. Most of these are included in the bibliography. Since it is impossible to review all of the articles in the allotted pages in this section, a summary of concepts put forth in these articles will be given. To understand the scope and necessity of defining environmental triggering agents, it is important to understand the spectrum of inflammatory vascular disease (FIG. 1). This patho-physiology of blood vessel change is a spectrum of reversible to totally irreversible changes. Initially, after insult, localized edema or hives is well appreciated. However, the much more common but less well appreciated subtle generalized edema is often ignored. This usually occurs in the extremities and the periorbital areas. The poor understanding probably develops even though the triggering agents may be similar in both because of unawareness that generalized edema may develop into much more serious disease. The blood vessel wall develops greater leaks or even ruptures as the disease progresses, resulting in red blood cell extravasation with bruising, purpura, and petechiae.

Later, as the fibrinolytic system becomes depleted, clots occur and palpable purpura develop. Eventually, if the vessel is injured enough, ischemic necrosis can occur. If the area survives, granulomatous healing may occur. Atherosclerotic plaque formation can occur in other people after severe inflammation develops.

In inflammatory vascular disease, two different cell types occur. The lymphocytic type infiltrate will occur around the vessel wall. At first this appears as a mild form of vasculitis. However, this disease may smolder along for years and then suddenly accelerate into disabling or irreversible inflammatory

disease. The leukocytoclastic form appears to be more acute and perhaps more devastating initially. Here, the leukocytes occur around the vessels and then break up. The debris is incorporated into cells, thus the name leukocytoclastic.

Unfortunately, vasculitis in some circles has come to mean only the necrotizing variety. The bulk of the recent research has been done in this area. However, it is important to perceive that the non-necrotizing varieties exist and may well be more important than the necrotizing in that these may be a prodrome of more serious diseases and, thus, if diagnosed and treated early, are more easily preventable.

Internal disruption of the homeostatic mechanism that causes vessel damage may occur from any of several pathways (FIG. 2). Most of the past research has been devoted to delineating the first four mechanisms. It may be, however, that the bulk of vessel disruption is through the fifth or mediator systems. The research thrust in this area is just beginning to occur. Already Buisseret(7) has shown prostaglandin inhibition by preloading food-sensitive people with aspirin and indomethacin. Polish investigators have also shown kinin triggering in some patients after incitant challenge.(8)

For the last 70 years there have been isolated reports in the literature of environmental incitants causing vascular phenomena. The most noteworthy of these were by Hare(9), Schofield(10), Harkavy(11), Rowe(12) and Coca(13). Recently, renewed interest has occurred in defining noninfectious incitants and thus eliminating causes of diseases. This appears to be the direct result of several recent papers. Yevick,(14) at the Woods Hole Marine Biology Center, found the cardiovascular system of sea life exposed to oil spills to be severely affected. The vessels developed inflammation and resultant fibrosis. This appeared to occur more often with animals near the center of a spill. Taylor(15) then reported a fatal cardiac arrhythmia in a teenager after inhalation of a fluorocarbon spray. Later, increase in arrhythmias after prolonged use of the fixative for the frozen section machine were noted among a group of pathologists.(16) Stewart(17) also reported a fatal arrhythmia due to furniture removal substance. Boxer(18) and Klotz(19) both reported patients with arrhythmia due to environmental incitants. Rea(20) has shown a spectrum of arrhythmias that were induced while patients were under rigidly controlled conditions. These were done in a double-blind manner and appear convincing since they are reproducible.

The following case report is illustrative of what one might find by looking for environmental incitants.

This 42 year old female nurse had a 20-year history of recurrent sinusitis treated with antihistamines. No attempt was made to determine the etiology. She then developed severe lower extremity peripheral vascular spasm accompanied by tetany of the gastrocnemius muscle (FIG. 3). This was so severe that it required narcotics to control the pain. After 2 years of this, severe angina developed and coronary angiograms revealed spasm of the left anterior descending coronary artery (FIG. 4). Placement in the Environmental Unit revealed the following laboratory work:

PT Control
Hb gm 12.5
HCT % 35
WBC mm3 5, 100
THSC CH100 90 90-98%
T-Lymph E Rosette 41% 60%
B-Lymph EA Rosette 45% 20-40%
Absolute Lymph 650
C3 mg/dl 72 12-30
C4 mg/dl 74 20-40
IgE mg/dl 110 100
IgM mg/dl 184 70-280
IgG mg/dl 950 800-1800
IgA mg/dl 235 90-450
IgD mg/dl 21 0-40
Ca++ mg/dl 7.2

When studied in an environmental unit, one can observe sequential reactions such as was seen in this patient. The length of reactions would be from five to 110 hours. The sequence would be as follows: incitant challenge, immediate tickling in the throat with hoarseness, nausea and vomiting, shortness of breath, loss of peripheral pulse in 15 minutes, then spasm of gastrocnemius with severe tetany followed by a spontaneous bruise (FIG. 5) at five to twelve hours after challenge. C3 was changed during incitant reactions (FIG. 6 and 7). The patient was found to be sensitive to picomolar challenge of the pesticide methachlor. Her T-lymphocytes and serum Ca++ dropped on at least four separate ambient dose challenges. S-T depression occurred if reactions were severe enough (FIG 8). This patient had five foods out of 42 challenged and 12 synthetic chemicals out of 14 challenged that reproduced her symptoms.

One can see that, because of complexity of the disease and number of incitants involved, without a controlled environmental situation, this type patient would not have had her etiology defined. She would have been relegated to the insolvable category with more symptomatic treatment being given and observed as her health continued to deteriorate, as was seen over the previous several years.

Symptoms Reproduced

Hoarseness, Nausea and Vomiting, Shortness of Breath, Loss of Peripheral Pulse, Spasm of Gastrocnemius with Severe Tetany

FIG. 6: Formaldehyde Challenge (2 sniffs)

Symptoms Reproduced

Hoarseness, Nausea and Vomiting, Shortness of Breath, Loss of Peripheral Pulse, Spasm of Gastrocnemius with Severe Tetany

Fig. 7: Cod Fish Challenge

Finn(21) has confirmed cardiac environmental triggering by reporting a series of patients who were sensitive to foods and developed arrhythmias after double-blind challenge. Levy(22) recently reported histamine release in animals with coronary occlusions, and thinks that perhaps more cardiac arrhythmias and myocardial infarction should be ascribed to the hypersensitive mechanisms. In view of present knowledge, it certainly appears that the clinician will better be able to define triggering agents of cardiac disease if he will only look for them. If he understands the four basic principles he will have reproducible results. These principles are: (1) four-day avoidance before incitant challenge; (2) any trigger is possible including pollens, dusts, molds, terpenes, foods, or chemicals, and they are frequently multiple; (3) that responses can occur anywhere from five seconds to fourteen hours after a challenge; and (4) that the chemical environment must be well-controlled in a less polluted manner. He must also be cognizant that most of the reactions are not IgE mediated, though this does frequently occur. The most important perception that has evolved from this base of knowledge is that no matter what internal mechanism is disrupted, the search for triggering agents should be carried out before these secondary mechanisms become autonomous and cause irreversible changes in the tissue.

When considering the response of the cardiovascular system to incitants, one must perceive that any part of the system can be involved. Therefore, some patients may just exhibit heart involvement while others will show just venous involvement or small or large peripheral arterial involvement. Some patients can show a combination of any or all parts at the same or different times in the course of the inflammatory vascular disease. For example, a patient may have phlebitis at one time and spontaneous bruising at another, or they may occur together. Reynaud's phenomenon or hypertension may be present with cardiac arrhythmia or they may be isolated.


Large vessel involvement has been shown to occur with sensitivity to drugs such as Ergot22 and Coumadin(23). This author(24) has reported several patients with triggering agents due to foods and chemicals.

Grant(25) has now reported many patients with vascular headaches who were sensitive to multiple foods and chemicals. These substances were other than the commonly known monoamine oxidase inhibitors. She found that though the patients improved with elimination of cigarettes, Ergot, and birth control medication, they did not usually get totally well until food and chemical sensitivities were brought under control. The following are typical case reports of large vessel involvement.

Case 1: This 65-year old female presented with a five-year history of joint aches and calf cramps. She also noticed some "senile purpura" along with high blood pressure. After being in the Environmental Unit, off all medication, she cleared her symptoms. The blood pressure dropped from 210/120 to 130-80 and a return of dorsalis pedis and posterior tibial pulses from 0 to 4+occurred. She also lost her purpura after being in a basal state for several days. Challenge with corn gave the following sequence of events: immediate hoarseness; in five minutes, abdominal distension developed; within 1 hours, 20 diarrhea stools occurred; blood pressure went from 130/80 to 180/120. Peripheral pulses were lost at two hours (FIG. 9) illustrated by an angiogram showing spasm of the tibial arteries, and then purpura occurred at five hours. The whole sequence terminated 24 hours after it started with a return of all parameters to the baseline.

This patient was sensitive to 10 of 40 foods tested and three of eight synthetic chemicals tested (Table I). She also showed linear changes when plotting complement and eosinophils (FIG 10). The hypertension was reproducible with five foods as well as three positive chemical challenges on 30 separate occasions (FIG. 11). It has appeared over the three year follow-up that the hypertension is totally related to incitant sensitivity. Biopsy of the purpuric lesion showed a lymphatic infiltrate around the vessel wall with edema and extrusion of red blood cells. No necrosis was seen.

Table I


Reproducible 4 Times

Substance Reaction
Formaldehyde 4+
Phenol 4+
Ethanol 0
Chlorine 4+
Pesticide 0
Saline (Control) 0

Frequently, cerebral vascular involvement will also occur, and one sees isolated areas of the brain involved giving specific symptoms. The following is an example of this type involvement:

Case 2: This 42-year old surgeon was well until he developed asthma while in Vietnam. This was originally attributed to mold sensitivity but later it was perceived that he had been sprayed with 2,4,5, T (agent orange). Fat biopsies and inhalation challenge suggested the latter to be the primary cause. Carotid arteriogram during one of these spells revealed decrease in left carotid and left intracerebral flow (FIG. 12). The patient also developed spontaneous bruising, petechiae, and acneform lesions. After being placed in the Environmental Unit, off all medication, his symptoms subsided. He was able to rotate his arm and hand 40 times without the previously described clonic-like movements, a function he previously could not do. Double-blind challenge with certain foods and synthetic chemicals revealed the following sequence: Challenge with immediate right-sided peripheral cyanosis, then tenderness in left neck, decrease of superficial temporal pulse, then loss of use of right arm and hand followed by severe digital edema and very foggy thinking.

Symptoms Reproduced

Headache, Spontaneous Bruising, Depression, Hoarseness, Cough


___ Eosinophil

----- & Total Hemolytic Complement

Fig. 10: Trichlorethylene Challenge (15 Sec. Exposure)

PT Control
IgG mg/dl 930 800 - 1800
IgA mg/dl 187 90 - 450
IgM mg/dl 120 60 - 250
IgE mg/dl 51 100
Eos mm3 141 50 - 200
THSC CH100 93 90 - 98%
T-Lymph E Rosette 944 1800 + 200
Absolute Lymph 1656 2000-3000
50 mgm 17 14
10 mgm 6.2 14
PWM 12 31

The large vessel involvement may be more devastating since major organ supply is affected. It is possible for organ ischemia and/or necrosis to not only result in severe disability but also even in death The common incitants were always multiple with all three major categories of incitants involved (inhalants, foods, chemicals). Usually, there were distortions in the eosinophilic, complement and T-lymphocyte systems.


Parish(26) showed small vessel triggering due to various antigens in several animal studies. He further showed deposition of numerous substances such as IgG and C3 on vessel walls. Theorell(27) has now shown triggering of small vessel vasculitis due to birch tree pollen, foods, and chemicals in humans. These were leukocytoclastic types, one of the cellular types Parish has previously described in animals. The following is one of his case reports illustrating the multifactoral nature and need to clearly define all incitants.

Case 2. (E. J. born 1925) is a man who had diphtheria in 1946 and malaria in 1955, now healed. From August 1969 he has recurrent attacks of a cutaneous necrotizing leukocytoclastic angiitis with purpuric, nodular, ulcerating or angioedematous skin lesions (FIG. 13), myalgia, rhion-conjunctivitis, dry cough without ronchi and also hyperistalis. Total serum IgE level is elevated (660-2080 U/mi, N 500). Except for dental root infections since 1972, no other infections, no tumors, autoimmune diseases or drug intolerances are found. Chest x-rays show stationary emphysema in left inferior lung lobe. Nodular skin eruptions after tooth extractions and strong Arthus type skin test reactions to staphylococic toxoid, tuberculia and Candida antigens indicate significant allergy to microbes. ESR is 10-35 mm. During 1973 reduced C3 level (31%, N=60-140%) and hyperfibrinogenemia (maximum 660 mg%, N320 mg%) are seen. Levels of total serum IgG, IgA and IgM, alpha1 antitrypsin and alpha2 macroglobulin are normal.

During attack period in February 1973 euglobulin lysis time indicates normal fibrinolysis activation by venous stasis. Intradermal test with 4 U kallikrein gives a local necrotizing vasculitis after 24 hours.

The patient avoids eating pears and legumes since they give diarrhea. Several vasculitis attacks anamnestically follow-up visits to a flat with animal hair carpets and also appear within birch and grass pollen seasons. During autumn-winter seasons remissions of more than a week are seen when the patient stays in dust-free environment and keeps to goods he tolerates. Intradermal allergen tests in February 1974 show reactions of macroscopically purpuric type within 3-24 hours to horse and cow dander, sheep wool, house dust, aspergillus, brewer's yeast, vegetable mixture and grass pollens. Traces of reagins and elevated IgG-antibody tire against sheep wool are found in serum in June 1974. Dietary regimen, according to anamnesis and result of skin test, reduces skin eruptions from 40-200 new nodules per day (1973) to none during up to 10 days when observed in hospital stay in February 1974. During this month skin eruptions were observed after the patient has eaten corn products (4 times) and pears (2 times) and when he had shaken a sheep wool carpet."

Rea(28) has shown similar events to occur using extremely controlled double-blind conditions. A lymphocytic non-necrotizing vasculitis was also reproduced in some patients due to food and chemical incitants as well as to various pollens, dusts and molds.

It appears that it would be prudent to now examine most patients with small vessel inflammatory disease for multifactoral incitant triggering.


It is now generally accepted that there are several varieties of necrotizing vasculitis. Originally, those were all lumped under the title of periarteritis nodosa. However, with careful scrutiny, some patients have been divided out. Many classifications exist, however; Table II is an adequate working one. Though the bulk of research is centered here, unfortunately, no emphasis has been placed on the definition of triggering agents in these types of entities. The best appreciated cause and effect relationships existing in the necrotizing vasculitis are in systemic lupus erythematosus. Here, numerous drugs have been shown to trigger the autoantibody reactions or events appearing similar, with resultant vessel wall disruption.(29)

Our group has seen one patient with temporal arthritis and three with systemic lupus that were apparently triggered by certain inhalants, foods, and chemicals. In view of Theorell's reports, our unpublished cases and those drug-induced lupus', it would be logical for all the necrotizing vasculitis to be examined for triggering agents.







nodosa (PAN)

Immunologic Generalized classical PAN PAN with immunologic phenomena

PAN of methamphetamine sensitivity

Hepatitis B-antigen PAN (rare)

PAN associated with angioimmunoblastic


PAN-like syndrome of rheumatoid arthritis



PAN limited to:





Coronary arteries

(Infantile PAN)

Cutaneous PAN associated with Crobin's


Kawasaki's disease

Arteritis of pulmonary hypertension

Post-coarction repair syndrome




plex deposit

with self anti-


with foreign









Systemic lupus ery-


Rheumatoid arthritis

Mixed connective tissue disease

Serum sickness

Subacute bacterial


Rheumatic fever

Shunt nephritis

Lepromatous leprosy

Quartan malaria

Lupus vasculitis

Some rheumatoid vasculitis

Vasculitis of mixed connective tissue disease

Drug-induced immune complex


Hepatitis B-antigen vasculitis


Type I

Type II

Type III

Intermediate com-

plexes (non-cold


Cryoglobulinemic purpura

Hyperglobulinemic purpura

Hyperviscosity syndrome



Cellular hypersensitivity

Allergic angiitis

Eosinophilic granu-


Lymphocytic vasculitis

Allergides, nodulaires (Gougerot)

Arteriolitis cutis allergica

Vasculitis of chronic urticaria

Vasculitis of allergic drug reactions

Churg and Strauss syndrome

Loeffler's syndrome

Hypercosinophilic syndrome with


Vasculitis of intradermal tests

Erythema nodosum

Undetermined Dermatomyositis-


Progressive systemic sclerosis

Wegener's granu- lomatosis

Cogan's syndrome

Ocular vasculitis

Henoch-Schonicin purpura

Vasculitis of dermatomyositis - polymyositis

Childhood dermatomyositis polymyositis



Lethal midline granuloma

Pseudotumor of the orbit

Eales "disease"

Optic disc vasculitis

Giant cell


*Alcorn & Segovia

Unknown Cranial (temporal)


Takayasu's arteritis

Polymyalgia rheumatica

Pulseless disease

Other derived from various



Venous disease and environmental triggering has been sparsely reported in the literature. Earlier in the century, Conners(30) and Harkavy(31) reported cases of phlebitis due to foods. Many investigators including Zeek have recognized that some patients will have episodes of phlebitis during the course of their vasculitis if observed over a number of years, but they suggested no etiology.

Rea(32) has had an opportunity to observe several patients who presumably had intractable non-traumatic phlebitis. The majority of these patients were able to have their phlebitis cleared without medications while in a rigidly controlled environment. They also had their phlebitis reactivated with double-blind incitant challenge cleared within 48 hours without medication. This series of eight patients is contrasted to a parallel group of patients who were also sensitive to many incitants but who chose to ignore the avoidance of them and use medication for treatment. This group of eight patients had over 40 episodes of hospitalization plus countless periods of incapacity at home during a similar period of time. These were for recurrent phlebitis and pulmonary embolism. The two groups were about equal in severity at the onset of the study. In fact, the environmentally treated group appeared to be a bit more severe.



& Repro-












Before After





10 8 2 0 0 66 0
Control 8 8 30 20 10 58 40

It is quite clear that attention to defining triggering agents in non-traumatic phlebitis can decrease the cost of medicine as well as relief of the morbidity and, possibly, even mortality.

The following case is an example of environmentally induced phlebitis. This 33-year old female had a gradual onset of diarrhea, followed by sinusitis and spontaneous bruising. These occurred over a period of three years with only symptomatic treatment being given. As she deteriorated, she developed recurrent phlebitis and pulmonary embolism. She had been hospitalized six times in the previous year before she entered the Environmental Unit. She also was totally incapacitated at home between admissions. All anticoagulants had failed. After five days in the Environmental Unit, all symptoms and signs had cleared and the patient, who could not formerly walk, could now not only walk freely, but could now ride a bicycle for six miles without problems. Double-blind challenge with chemicals revealed the patient to be sensitive to phenol, pesticide, and natural gas. Also, numerous foods have been incriminated. This patient has been totally asymptomatic for the last 3 years and works every day. She has used no medication. It is now clear that any patient with indication of inflammatory vessel disease should have an intensive search made to define triggering agents. This should be done methodically and under as controlled conditions as possible before patients are doomed to a prolonged course of drug therapy which may last for years to a lifetime.

PT Control
HB gm 13.6
HCT % 41
WBC mm3 4,300
EOS mm3 88 50-200
THSC CH100 90% 90-98%
T-Lymph E Rosette 538 1800 200
Absolute Lymph 1656 2000-3000
IgG mg/dl 930 800-1800
IgA mg/dl 178 90-450
IgM mg/dl 183 70-280
IgE mg/dl 81 100
50 mgm 49 14
10 mgm 40 14
PWM 50 31

It should be emphasized that the IgE mechanism does not necessarily play a large part in determining incitants of cardiovascular diseases. Many other mechanisms are involved, and cause and effect incitant challenge, rather than the mechanism, should be the common denominator in describing the onset of disease.


When analyzing and considering whether environmentally triggered vascular disease is a factor in a given patient's illness, the clinician must perceive several principles.

First, he must realize that medical environmental technology is about 100 years behind environmental technology. Since our technology and overview is not well developed, it hampers us in diagnosing and treating disease caused by noninfectious processes. The environmentally contaminated situation present today would be similar to the time when people were rubbing manure into wounds, or physicians were doing pelvic exams after a postmortem, as was done 100 years ago before the germ theory became well understood. Also, the public, as well as the medical profession, is generally unaware of potential environmental triggering agents. These substances are readily found in homes, workplaces, and even in hospitals in such abundance at times as to negate all attempts at diagnosis and treatment with hope for recovery in many patients. Thus, an individual with environmentally triggered disease may be sensitive to natural gas but, when being exposed to it 24 hours per day because it heats his home, water, and food, may not perceive the acute cause and effect relationship. This may also be true in the individual sensitive to the chemicals in his water supply who is exposed so frequently because he uses it in his food, drinks it, and bathes in it.

The second principle that should be kept in mind is the concept of the total body load which tends to distort many of the body's homeostatic mechanisms (FIG. 14). This is the sum of all incitants that the body has to handle in order to function. This is the total of the pollutants in air, water, and food. The load principle seems simple until one perceives the amount and scope of pollution that has crept into our environment. The more important components comprising the total load are discussed in the following paragraphs.

pollen, dust, mold

Fig. 14: Total Body Load

Most public water systems are now overloaded with synthetic chemicals which will increase the body load to synthetics from 1,000 to 10,000 times (Table III). Unfortunately, public water supplies are rated only to bacterial contamination, with chemical content being ignored. Recent E.P.A. studies(33) of the 83 largest cities show all of the water supplies to be severely chemically contaminated. Apparently, our waters are now as badly polluted with chemicals as they were with bacteria years before the advent of chlorination.











Spring 26 3 1 10
Well 5 0 0 7
City 29,400 100 12,600 5,700

Ninety-four percent of the commercial food has pesticide in it.(34) It is also estimated that the average individual ingests one gallon of food additives per year.

In addition, the air in cities of 50,000 population or more has an outside air pollution gradient as compared to sea air of 150 good days to 2,000-4,000 on average to bad days(35) (Table IV).

The average home appears to be the most polluted place in our environment. The fact that homes are being built more airtight tends to increase pollutant contaminants. They contain high outgassing synthetics such as dyed nylons, polyesters, foam rubber beds, chairs, floor mats, etc. and, in addition, many have gas or oil heat, which further complicates pollution (Table V).



Sea Air __ 0 (Excluding Salt Particles)
Desert Air __ 10X
Towns (over 2,500) __ 35X
Urban __ days

150X good

1,000- avg. & bad





Least Outgassing to most














The summation of all these facts, plus a polluted work environment, makes a massive increase in body load that the individual has to handle just to function daily. This often becomes too great in people with certain hereditary and acquired tendencies resulting in individual susceptibility, thus allowing inflammatory diseases to occur. This chemical overload often distorts the food handling mechanism to the point that no foods are safe for some individuals. Often, people with chemical overload will also become quite sensitive to pollens, dusts, and molds.

The third principle is that of masking or adaptation where a person comes into contact with a substance and perceives no harm because there is not an immediate reaction.

Alarm - Resistance - Exhaustion
Non-adapted - Adapted - Maladapted
Unmasked - Masked - Overload

This occurs if he is exposed daily or more often. In contrast, if he avoids the substance for four days, he becomes unmasked. Then, if he takes the suspected substance into his body, he will have an immediate and clearly definable reaction if it is harmful to him. In this way, cause and effect is easy to establish. Often, food sensitivity is missed because the individual is eating the offending food daily or more often, thus causing symptoms to be masked. This masking principle is commonly understood in the individual who is addicted to drugs. Here, in order to feel better, the individual often takes drugs whenever he has symptoms. If he omits them for four or five days, he has severe withdrawals. Some painters and battery workers say that the substances they work around bother them after returning from vacation until they get "used" to the offending substance again. Once they are "used" or masked they do not perceive the harmful effects any longer and they do well until they eventually develop inflammatory disease. At this time, then, since they are masked, they do not perceive the cause of their disease. We have seen several patients who exhibited this phenomenon while in the environmental unit.

The fourth concept is that of bipolarity. Often, the individual will have a stimulatory reaction and perceives the substance as not harming him initially, but actually making him feel good. However, after a period of time, be it minutes to years, his body's defenses break down and he has harmful disabling withdrawal symptoms. This is a well-recognized principle in cigarette, narcotic or alcohol addicts but not well known, yet just as prevalent, in plastic workers, painters, food addicts, and many other individuals who constantly inhale or digest toxic substances.


Once the aforementioned facts and principles are understood, study for incitant susceptibility must be done in meticulous detail in order to discriminate and clearly define particular triggering agents.

Each category of air, food and water will be discussed separately in order to consider all parameters. It should be pointed out that one must consider all parameters of equal importance in order to successfully diagnose and treat patients with environmentally triggered inflammatory vascular disease. Failure to consider all parameters usually results in a continuation of the disease processes, and eventual failure of overall treatment. This, though usually blatantly evident, may take years to perceive in some patients.


This parameter is the most difficult to assess because little attention has been directed toward air analysis of indoor pollution and because the outside air in the United States has become so polluted. According to some authorities, there has been no fresh air in this country in fifteen years.(36)

In order to study the environmental problems better, the Brookhaven Environmental Unit was created, taking into consideration the aforementioned facts and principles while using material constructed with meticulous detail. A description of the unit follows so the physician can use the principles in his office practice. Inattention to controlling the ambient air of an office will often result in misdiagnosis and, therefore, inappropriate treatment of many individuals.

Outside air is analyzed for the major pollutants such as nitrous oxide, sulphur dioxide, ozone, chlorine dioxide, cyanide carbon monoxide, and carbon dioxide.

A wing of the hospital was used to exclude contaminants from other parts of the hospital. A firewall was used in order to exclude all possible pollutants. Double doors were used so that an air lock could be obtained to stop outside air in the adjacent building. Air conditioning is local window units using all metal coolers. Heat is of local nature and presented a much more difficult problem since so many chemically susceptible people are sensitive to many types and sources. We have found that approximately ninety percent of 400 consecutive chemically susceptible patients are sensitive to the fumes of natural gas. This correlates with Randolph's findings. In addition, many patients are also sensitive to the fumes emanating from different electric devices. Copper radiators with aluminum fins are only satisfactory for fifty percent of our patients. Steel and cast iron radiators appear better but have a central blower which presents a problem. Radiant glass and ceramic are also available and are tolerable to many individuals. High temperature wires appear to be the most offensive form of electric heat (Table VI). Solar heat, when available directly, appears to be very acceptable.







With Motor



Without Motor

Copper &



With Glass

1 + + + + 0
2 + + + + 0
3 + + + + +
4 + + + + +
5 + 0 0 + +
6 + + 0 + +
7 + 0 0 + +
8 + + + 0 +
9 + + + 0 +
10 + + + + +

Bedding and draperies are cotton, linen and/or silk. No synthetics are allowed because of their high fuming properties.

Air depollution devices are used intermittently to clean outside pollutants. Unfortunately, these cannot be left on at all times because many patients are sensitive to the substances which emanate from the units.

Materials in these devices should be inert, preferably of metal and stone. Electronic filters are not advisable unless other filters are used distal toward the room. They should be rated to remove the ozone and phosgene which occur with the electronic filters.

HEPA filters seem to be the most toxic of the filters, apparently because of the glues that are used to hold paper together.

Currently, we are using sequences of filtration such as cotton or fiberglass as a prefilter followed by aluminum oxide impregnated with potassium permanganate. Then, a loose charcoal filter is used as the final pathway. These should all be in metal cages. Many patients have become sensitive to charcoal from either the pure coconut or bituminous coal origin. Ideally, cotton, marbles, and dechlorinated water should be used to remove the charcoal particles.

Basically, rooms can be made from any inert material. However, only four or five are easily available.

Air in the rooms is assessed by several parameters. The first is whether environmentally susceptible patients clear their symptoms in the rooms, and secondly, whether their abnormal laboratory tests return to control level without medication. The third parameter is direct analysis obtained by using gas chromotography and mass spectrometry. Unfortunately, not all parameters are easily available for air analysis. Some easily measured parameters are shown in FIGS. 15, 16, 17, 18 and 19, while changes in patients' serum returning to normal without medications are shown in FIGS. 20, 21, 22 and 23. It is even more important to stress the measurement of organics such as aldehydes, pesticides, phenols, benzenes, etc., since these are common contaminants of indoor air pollution. Failure to properly access these organics appear to be the single most common error in attempting to create a controlled environment, whether in the hospital, home, or office. A large proportion of the diagnosis and treatment of inflammatory disease falls into a lack of appreciation of these facts. Particulate counts, barometric pressure and relative humidity are constantly monitored.


Since there are now large amounts of additives, preservatives, pesticides and herbicides in commercial food, testing must be done with less chemically contaminated foods. In our center, an organization had to be started to foster the acquisition of such food. Farmers were contracted to grow the food in a safe manner. No herbicides, pesticides, or artificial fertilizers are used in growing this food. Food must be stored in uncoated cellophane and glass in order to prevent contamination.

Cooperatives are necessary in order to have available safe food and also to monitor the food to ensure a less chemically contaminated form. We have seen several examples of contaminated food found by this method. One time, many individuals began reacting to pork. The individuals knew they were safe on pork and that it must be contaminated. The farmer was contacted and informed us that he had acquired six-week-old pigs from another farmer and placed them on our usual feeding regime. Apparently, the gestation time and first six weeks feeding on chemically contaminated food was enough to severely contaminate these pigs. A second example was when many people were reacting to cantaloupe from a recent lot. Chemical analysis showed two parts per billion of dieldrin and chlordane. By using such a network of analysis, one can constantly monitor and help prevent food contamination.

Food for testing must be cooked in the patient's water, using either steel, iron or glass cookware in order to prevent further contamination.


It has become evident that many people are becoming increasingly sensitive to minute water contaminants. Recent studies show that most of our largest cities have severely chemically contaminated water supplies. We are now at the point of chemical contamination in water where we were 75 years ago with bacteria before the onset of chlorination. Little is recognized of the potential harmful effects of the chemical contamination of the water supply by the average layman or physician. In the Environment Unit, acute cause and effect for water contaminants can be ascertained in approximately two days. Double-blind studies using tap, charcoal filtered, numerous spring and distilled waters has revealed approximately ninety percent of the chemically sensitive patients to be intolerant of tap water. Some patients are very sensitive to distilled water while others may be sensitive to many of the spring waters:

Waters Tested:

a) Chlorine

b) Distilled

c) Spring - 10

d) Filtered

Spring water appears to be the best of the alternate waters. This correlates well with Randolph's studies. In an office practice, use of spring water in glass bottles can be a practical necessity in working out patients' problems. Care must be taken that they are not contaminated by forced chlorination induced by local authorities due to fear of bacterial contamination.

It is important that the clinician perceive these facts and concepts in order to advance our knowledge in inflammatory vascular disease, to help patients who were formerly unsalvageable, and to prevent devastating effects of advanced disease. This, in the long term, will allow a much longer proportion of the clinician's time to be used for preventive medicine and markedly reduce the costs in medicine.


Cucu, F.: Carbon monoxide and its implications in atherosclerosis etiopathogeny. Med Interne 16(3):229, Jul-Sep 1978.

Caputo, R.V. and Solomon, L.M.: Vascular reactive diseases. Major Probl Clin Pediatr 19:404, 1978.

Aviado, D.M.: Physiological and biochemical responses to specific group of inhalants: concluding remarks. Fed Proc 37 (11):2508, Sep 1978.

Callen, J. P., et al.: Cutaneous angiitis (vasculitis). Int J Dermatol 17(2):105, Mar 1978.

Cream, J.J.: Mechanisms involved in clinical allergic vasculitis. Experimental Models of Chronic Inflammatory Diseases. Berlin, Springer, 1977.

Parish, W.E.: Features of human spontaneous vasculitis reproduced experimentally in animals. Effects of antiglobulins, C-reactive protein and fibrin. Experimental Models of Chronic Inflammatory Diseases. Berlin, Springer, 1977.

Haynes, B.F., et al.: The ocular manifestations of Wegener's granulomatosis. Fifteen years experience and review of the literature. Am J Med 63(1):131, July 1977.

Sharrett, A. R.: Water hardness and cardiovascular disease. Elements in water and human tissues. Sci Total Environ 7:217, May 1977.

Mustacchi, P.: The interface of the work environment and hypertension. Med Clin North Am 61:531, May 1977.

Keller, R.H., et al.: Ataxia telangiectasia, immunodeficiency, and AFP: Is there a relationship? UCLA Forum Med Sci 20:27, 1978

Hyer, F.H. and Gottlieb, N.L.: Rheumatic disorders associated with viral infection. Semin Arthritis Rheum 8:17, Aug 1978

Henson, P.M.: Immune complex diseases: cellular mediators and the pathogenesis of inflammatory tissue injury produced by immune complexes. Experimental Models of Chronic Inflammatory Diseases. Berlin, Springer, 1977.

Duomonde, D.C.: Experimental models of rheumatoid inflammation. Experimental Models of Chronic Inflammatory Diseases. Berlin, Springer, 1977

Schur, P.H.: Complement testing in the diagnosis of immune and autoimmune diseases. Am J Clin Path 68:647, Nov 1977.

Alarcon, S.D.: The necrotizing vasculitides. A new pathogenetic classification. Med Clin North Am 61:241, Mar 1977.

Sacca, J. D.: Hereditary angioedema (HAE). Ann Allergy 42:88, Feb 1979.

Bretza, J. and Novey, H.S.: Hereditary angioedema and the Mallory-Weiss syndrome. Ann Allergy 42:83, Feb.1979

Romanski, B., et al.: The immunologic response to tobacco antigens in smokers: II. Specific precipitins against tobacco antigens in the serum of smoker suffering from coronary heart disease. Allergol Immunopathol 6:383, Sep-Oct, 1978.

Lockwood, C.M., et al.: Reversal of impaired splenic function in patients with nephritis or vasculitis (or both) by plasma exchange. N Engl J Med 300:524, 8 Mar 1979.

Treatment of hereditary angioedema (editorial) Lancet 1:417, 24 Feb 1979.

Szuler, I.M., et al.: Massive variceal hemorrhage secondary to presinusoidal portal hypertension due to arsenic poisoning. Can Med Assoc J 120:168, 20 Jan 1979.

Gammon, W.R. and Wheeler, C.E.: Urticarial vasculitis: report of a case and review of the literature. Arch Dermatol 115:76, Jan 1979.

Roizen, M. F. and Stevens, W.C.: Multiform ventricular tachycardia due to the interaction of aminophylline and halothane. Anesth Analg 57:738, Nov-Dec 1978.

Cockett, F.B.: Ulcers of the leg. Adv. Surg 12:327, 1978.

Czarny, D.: Urticaria and angioedema. Med J. Aust 2:11, 2 Dec 1978.

Fukushima, S., et al.: Blood pressure in stroke-prone SHR (SHRSP) exposed to unusual environmental temperature. Jpn Heart J 19:618, Jul 1978.

Zvaifler, N.J.: Vasculitides: classification and pathogenesis. Aust NZ J Med 8 Suppl 1:134, 1978.

Dicken, C.H. and Winkelmann, R.K.: The Churg-Strauss granuloma: cutaneous, necrotizing, palisading granuloma in vasculitis syndromes. Arch Pathol Lab Med 102:576, Nov. 1978.

Weiss, E.B., et al.: Allopurinol-induced arteritis in partial HGPRTase deficiency. Atypical seizure manifestation. Arch Intern Med 138:1743, Nov 1978.

Fauci, A.S., et al.: The spectrum of vasculitis: clinical, pathologic, immunologic, and therapeutic considerations, Ann Intern Med 89:660, Nov. 1978.

Agostoni, A., et al.: Hepatic function and fibrinolysis in patients with hereditary angioedema undergoing long-term treatment with tranexamic acid. Allergy 33:216, Aug 1978.

Delfino, J.J.: Management of a patient with hereditary angioneurotic edema. J. Oral Surg 36:890, Nov 1978.

Pitts, J.S., et al.: Remissions induced in hereditary angioneurotic edema with an attenuated androgen (danazol): correlation between concentrations of C1-inhibitor and the fourth and second components of complement. J Lab Clin Med 92:501, Oct 1978.

Gero, S., et al.: Immunological factors in vascular diseases. International symposium: State of Prevention and Therapy in Human Arteriosclerosis and in Animal Models. Opladen, Westdeutscher Verlag. 1978.

Harkavy, J.: Harkavy syndrome, bronchial asthma, recurring pulmonary eosinophilia, and periarteritis nodosa. J Allergy Clin Immunol 62:378, Dec 1978.

Hurley, J.E. and Rayden, M.R.: Hereditary angioedema in relation to dentistry. Br J Oral Surg 16:26, Jul 1978.

Nwaefuna, A.: Angioneurotic edema caused by sensitivity to herbal hair dye - a case report. Niger Med J 8:272, May 1978.

Frith, P., et al.: Life-threatening asthma, urticaria, and angioedema after ketoprofen. Lancet 2:847, 14 Oct 1978.

Reiann, H.A.: Hereditary angioedema. JAMA 240:2155, 10 Nov 1978.

Cohen, S.H., et al.: Acquired angioedema associated with rectal carcinoma and its response to danazol therapy. Acquired angioedema treated with danazol. J Allergy Clin Immunol 62:217, Oct 1978

Herman, J.E. and Fleischmann, P.: Unusual evidence of myocardial involvement during a hypersensitivity reaction to oral penicillin. Isr J. Med Sci 14:848, Aug 1978.

Eady, R. A., et al.: Cold urticaria vasculitis. Br. J Dermatol 99.9, July 1978.

Cheesbrough, M.J.: Angioedema - acquired C1 esterase inhibitor deficiency. Br. J Dermatol 99.39, July 1978.

Cheesbrough, M.J.: Familial angioedema - C1 esterase inhibitor deficiency. Br. J Dermatol 99.38, July 1978.

Parbtani, A. and Cameron, J.S.: Platelets, serotonin, migraine, and immune-complex disease. Lancet 2:679, 23 Sep 1978.

Lyell, A., et al.: Repeated failure of nickel-containing prosthetic heart valves in a patient allergic to nickel. Lancet 2: 657, 23, Sep 1978.

Marasini, B., et al.: Treatment of hereditary angioedema. Klin Wochenschr 56:819, 15 Aug 1978.

Jarvinen, P., et al.: Streptokinase and concomitant oral anticoagulants in the treatment of deep venous thrombosis. Klin Wochenschr 56:801, 15 Aug 1978.

Fishelson, G. and Graves, P.: Air pollution and morbidity: SO2 damages. J Air Pollut Control Assoc 28:785, Aug 1978.

Fernandez, P.G., et al.: Hereditary angioneurotic edema and Charcot-Marie-Tooth disease in the same family. Can Med Assoc J 119:455, 9 Sep 1978.

Laurberg, G.: Plasma kinin activation in tranexamic acid treated patients with hereditary angioneurotic edema. Arch DermatolRes 262:153, 28 Jul 1978.

Pollak, E.W.: The choice of test for diagnosis of venous thrombosis. Vas Surg 11:219, Jul-Aug, 1977.

Sugimoto, K., et al.: Studies on angiopathy due to carbon disulfide. Retinopathy and index of exposure dosages. Scand J Work Environ Health 4:151, June 1978.

Grant, E. C.: Oral contraceptives, smoking, migraine, and food allergy. Lancet 2:581, 9 Sept 1978.

Passive smoking and angina (editorial). Lancet 2:413, 19 Aug 1978.

Wolff, H.H., et al.: Immunoelectron microscopic examination of early lesions in histamine-induced immune complex vasculitis in man. Br. J Dermatol 99.13, July 1978.

Kumar, M.K. and Philip, M.P.: Hypersensitivity vasculitis. J Indian Med Assoc 70:87, 16 Feb 1978.

Geltner, D., et al.: Allergic vasculitis following injection of 113mIn. Isr J Med Sci 14:486, Apr 1978.

Kurt, T.L., et al.: Association of the frequency of acute cardiorespiratory complaints with ambient levels of carbon monoxide. Chest 74:10. July 1978.

Aronow, W.S.: Effect of ambient level of carbon monoxide on cardiopulmonary disease. Chest 74.1, July 1978.

Soter, N.A., et al.: Cutaneous necrotizing venulitis: a sequential analysis of the morphological alterations occurring after mast cell degranulation in a patient with a unique syndrome. Clin Exp Immunol 32:46, Apr 1978.

Ostergaard, K.: Renal cadmium concentration in relation to smoking habits and blood pressure. Acta Med Scand 203:379, 1978.

Griswold, W.R., et al.: Vasculitis associated with propylthiouracil. Evidence of immune complex pathogenesis and response to therapy. West J Med 128:543, Jun 1978.

Aronow, W.S.: Effect of passive smoking on angina pectoris. N. Engl J. Med 299:21, 6 Jul 1978.

Weston, W. L.: EPP masquerading as angioedema. J Allergy Clin Immunol 61:408, Jun 1978.

Millikan, L.E., and Duvall, J.M.: Cutaneous vasculitis. Cutis 21:819, Jun 1978.

Vertin, P.G.: Incidence of cardiovascular diseases in the Dutch viscose rayon industry. JOM 20:346, May 1978.

Schele, R., et al.: Physical characteristics and allergic history in young men with migraine and other headaches. Headache 18:80, May 1978.

Rosenberg, J.L., et al.: Liver disease and vasculitis in a patient taking cromolyn. Arch Intern Med 138:989, Jun 1978.

Donaldson, V.H., et al.: Rose of the second component of complement (C2) and plasmin in kinin release in hereditary angioneurotic edema (H.A.N.E.) plasma. Trans Assoc Am Physicians 90:174, 1977.

Kirdaly, K., et al.: Immunofluorescence in cutaneous vasculitis. Panminerva Med 20:23, Jan-Mar 1978.

Gould, D.J., et al.: Anabolic steroids in hereditary angioedema. Lancet 1:770, 8 Apr 1978.

Schocket, A. L., et al.: Immune complex vasculitis as a cause of ascites and pleural effusions in systemic lupus erythematosus. J Rheumatol 5:33, Spring 1978.

Matson, J.R., et al.: Mycardial ischemia complicating the use of isoproterenol in asthmatic children. J. Pediatr 92:776, May 1978.

Jackson, C.E., et al.: Evidence of nonlinkage of genes for HLA and hereditary angioedema. J Allergy Clin Immunol 61:331, May 1978.

Van Mieghem, W., et al.: Ephedrine-induced cardiopathy. Br Med J 1:816, 1 Apr 1978.

Secher, L., et al.: Immunofluorescence of the skin in allergic diseases: an investigation of patients with contact dermatitis, allergic vasculitis, and atopic dermatitis. Acta Derm Venereol 58:117, 1978.

Marshall, M. and Hess, H.: New findings concerning pathogenesis and non-surgical treatment of peripheral arterial diseases. Vasa 7:49, 1978.

Education "effect" in hypertension. Data on possible environmental poisons. Penicillin alternatives in gonorrhea. JAMA 239:1485, 14 Apr 1978.

McCluskey, R.T., et al.: Immune complex mediated diseases. Hum Pathol 9:71, Jan 1978.

Davis, J.A., et al.: Vascular disease in infective endocarditis, Report of immune-mediated events in skin and brain. Arch Intern Med 138:480, Mar 1978.

Cooper, B.J., et al.: Allergic angiitis and granulomatosis. Prolonged remission induced by combined prednisone-azathioprine therapy. Arch Intern Med 138:367, Mar 1978.

Wishart, J.M.: Hereditary angioedema. NZ Med J 85:521, 22 June 1977.

Agostoni, A., et al.: Intermittent therapy with danazol in hereditary angioedema. Lancet 1:453:, 25 Feb 1978.

Eady, R.A. and Greaves, M.V.: Induction of cutaneous vasculitis by repeated cold challenge in cold urticaria. Lancet 1:336. 11 Feb 1978.

Nakao, M., et al.: Experimental studies on etiology of portal hypertension in allergic aspect. Jpn J Surg 7:269, Dec 1977.

Macfarlane, D.G. and Bacon, P.A.: Levamisole-induced vasculitis due to circulating immune complexes. Br Med J 1:407, 18 Feb 1978.

Saihan, E.M. and Warin, R.P.: Treatment of hereditary angioneurotic edema with methadienone. Br Med J 1:367, 11 Feb 1978.

Ishihara, H., et al.: Sensitivity to diethyl-ester as a possible cause of repeated cardiac arrest. Anaesthsist 26:670, Dec 1977.

Spragg, J.: Specific functional and immunologic assay of plasma plasminogen in hereditary angioedema, in hereditary angioedema treated with tranexamic acid, and in normal subjects. J Immunol 120:592, Feb 1978.

Starr, J. C. and Brasher, G.W.: Wasp sting anaphylaxis with cerebral infarction. Ann Allergy 39:431, Dec 1977.

Plaza, J., et al.: Hereditary angioedema with mesangiocapillary glomerulonephritis. Postgrad Med J 53:627, Oct 1977.

Senges, J., et al.: Ventricular arrhythmias in cardiac anaphylaxis. Naunyn Schmiedebergs Arch Pharmacol 300:115, 10 Nov 1977.

Hedstrand, H., et al.: Noise and blood pressure. Lancet 2:1291, 17 Dec 1977.

Knipschild, P.: V. Medical effects of aircraft noise: community cardiovascular survey. Int Arch Occup Environ Health 40:185, 29 Nov 1977.

Gajaraj, A., et al.: Obscure stenosing aortitis and arteritis associated with peri-vascular lymphadenitis - combined angiographic and lymphographic evaluation. Clin Radiol 28:555, Sep 1977.

Cogen, F.C., et al.: Chronic eosinophilic pneumonia followed by polyarteritis nodosa complicating the course of bronchial asthma. Report of a case. J Allergy Clin Immunol 60:377, Dec 1977.

Harris, B.K.: Myocardial infarction after a gold-induced nitritoid reaction. Arthritis Rheum 20:1561, Nov-Dec 1977.

Stewart, M.M.: MAO inhibitors and foods-reality and mythology. Neuropharmacology 16:527, Jul-Aug 1977.

Kalden, J.R., et al.: Immune mechanisms in Gardner-Diamond syndrome. N Engl J Med 297-1350, 15 Dec 1977.

Obesity in children. Environment or genes? New treatment for hereditary angioedema. JAMA 238-2009, 7 Nov 1977.

Kaplan, A.P.: Mediators of urticaria and angioedema. J Allergy Clin Immunol 60:324, Nov 1977.

Heft, M.W., and Flynn, P.M.: Hereditary angioedema: review of literature and dental treatment. J Am Dent Assoc 95: 986, Nov 1977.

Blackmore, W.P.: Danazol in the treatment of hereditary angio-neurotic edema. J Int Med Res 3:38, 1977.

Tucker, G.F.: Pulmonary migraine. Ann Otol Rhinol Laryngol 86:671, Sep-Oct 1977.

Sasagawa, S., et al.: Rearing of SHRSP in a different environmental temperature. Jpn Heart J 18:523, Jul 1977.

Gower, R.G., et al.: Leukocytoclastic vasculitis: sequential appearance of immunoreactants and cellular changes in serial biopsies. J Invest Dermatol 69:477, Nov 1977.

Phanuphak, P., et al.: Urticarial vasculitis. N Engl J Med 297:948, 27 Oct 1977.

Dalton, K.: Migraine. Avoiding triggering factors. Nurs Mirror 145:18, 11 Aug 1977.

Ashford, R., et al.: Cutaneous vasculitis due to acebutolol. Lancet 2:462, 27 Aug 1977.

Conn, D.L.: Immune deposits in normal skin in infective endocarditis. JAMA 238:1182, 12 Sep 1977.

Rubenfeld, S., and Min, K.W.: Leukocytoclastic angiitis in subacute bacterial endocarditis. Arch Dermatol 113:1073, Aug 1977.

Laurell, A.B., et al.: Studies of C1 subcomponents in chronic urticaria and angioedema. Int Arch Allergy Appl Immunol 54: 434, 1977.

Warin, R.P.: Familial vasculitis (life-long morbilliform urticaria, neurological changes and arthritis). Br J Dermatol 97 Suppl 15:30, Jul 1977.

Zeit, R.M.: Angioneurotic edema following ingestion of iocetamic acid. Radiology 123:590, Jun 1977.

Chumbley, L.C., et al.: Allergic granulomatosis and angiitis (Churg-Strauss syndrome). Report and analysis of 30 cases. Mayo Clin Proc 52:477, Aug 1977.

Gibbs, P.S., et al.: The anesthetic and peri-operative management of a patient with documented hereditary angioneurotic edema. Anesth Analg 56:571, Jul-Aug 1977.

Weiller, P.J. and Mongin, M.: Hereditary angioedema. N Engl J Med 297:399, 18 Aug 1977.

Sheffer, A.L., et al.: Tranexamic acid: preoperative prophylactic therapy for patients with hereditary angioneurotic edema. J Allergy Clin Immunol 60:38, Jul 1977.

Tanimoto, K., et al.: HLA types in two families with hereditary angioneurotic edema. Clin Immunol Immunopathol 7:336, May 1977.

Molina, C., et al.: Diagnostic and therapeutic problems associated with hereditary deficiency of the C1 esterase inhibitor. Clin Allergy 7:127, March 1977.

Soter, N.A.: Chronic urticaria as a manifestation of necrotizing venulitis. N Engl J Med 296:1440, 23 Jun 1977.

Abada, R.P. and Owens, W.D.: Hereditary angioneurotic edema, an anesthetic dilemma. Anesthesiology 46:428, Jun 1977.

Frank, M., et al.: Epsilon aminocaproic acid for hereditary angioedema. N Engl J Med 296:1235, 26 May 1977.

Fauci, A.S. and Wolff, S.M.: Wegener's granulomatosis and related diseases. DM 23:1, Apr 1977.

Newman, S., et al.: Quantitative requirements for C3 to induce Forssman systemic shock and cutaneous hemorrhagic vasculitis in guinea pigs. J Allergy Clin Immunol 59:327, Apr 1977.

Hamilton, A.G., et al.: Laryngeal edema due to hereditary angioedema. Anaesthesia 32:265, March 1977

Rissin, L.: Hereditary angioneurotic edema: report of case. J Am Dent Assoc 94:723, Apr 1977.

Soter, N.A. and Austen, F.: Urticaria, angioedema, and mediator release in humans in response to physical environmental stimuli. Fed Proc 36:1736, Apr 1977.

Tuffanelli, D.L.: Discoid lupus erythematosus and the variant form of hereditary angioedema. Arch Dermatol 113:374, Mar 1977.

Donaldson, V. H., et al.: Lupus erythematosus-like disease in three unrelated women with hereditary angioneurotic edema. Ann Intern Med 86:312, Mar 1977.

Sheffer, A. L., et al.: Methyltestosterone therapy in hereditary angioedema. Ann Intern Med 86:306, March 1977.

Ohela, K., et al.: Hereditary angioneurotic edema (HANE): Lack of close linkage between HAL haplotypes and C1 esterase inhibitor deficiency. Tissue Antigens 9:90, Feb 1977.

Brasher, G. W., C1q levels in hereditary angioedema. J Allergy Clin Immunol 59:263, Mar 1977.

Johsson, A. and Hansson, L.: Prolonged exposure to a stressful stimulus (noise) as a cause of raised blood pressure in man. Lancet 1:86, 8 Jan 1977.

Davies, D. and Howell, D.A.: Tranexamic acid and arterial thrombosis. Lancet 1:49, 1 Jan 1977.

Smolen, J.S., et al.: Autoimmunological aspects of thromboangiitis obliterans (Buerger's disease). Clin Immunol Immunopathol 11:168, Oct 1978.

Gammon, W. R. and Wheeler, C.E.: Urticarial vasculitis: report of a case and review of the literature. Arch Dermatol 115:76, Jan 1979.

Zvaifler, N.J.: Vasculitides: classification and pathogenesis. Aust NZ J Med 8 Suppl 1:134, 1978.

Markle, R.A., et al.: Reversal of renovascular hypertension by antibodies specific for angiotensin-converting enzyme. Proc Natl Acad Sci USA 75:5702, Nov 1978.

Kazmierowski, J.A. and Wuepper, K.D.: Erythema multiform: immune complex vasculitis of the superficial cutaneous microvasculature. J Invest Dermatol 71:366, Dec 1978.

Lord, G.D. and Duckworth, J. W.: Complement and immune complex studies in migraine. Headache 18:255, Nov 1978.

Gray, M.V., et al.: Immune mechanisms in patients with proven vascular disease. Atherosclerosis 31:377, Nov 1978.

Szondy, E., et al.: The effect of clofibrate and pyridinol carbamate on the circulating immune complexes and cellular immune response in experimental atherosclerosis. Atherosclerosis 31:251, Nov 1978.

Fauci, A.S., et al.: The spectrum of vasculitis: clinical, pathologic, immunologic and therapeutic considerations. Ann Intern Med 89:660, Nov 1978.

Becker, C.G.: The thrombotic process and atherogenesis in specific arterial injury. Summary of workshop 3b: immunologic injury. Adv Exp Med Biol 104:371, 1978.

Woolf, N.: Thrombosis and atherosclerosis. Adv Exp Med Biol 104:145, 1978.

Wilson, J.D., et al.: Autoantibodies in hypertension. Lancet 2:996, 4 Nov 1978.

Gero, S., et al.: Immunological factors in vascular diseases. International symposium: State of prevention and therapy in human arteriosclerosis and in animal models. Opladen, Westdeutscher Verlag, 1978.

Capron, J.P., et al.: False-positive Widal test in Hbs antigen-associated polyarteritis nodosa. Gastroenterology 75:770, Oct 1978.

Gallagher, P. J., et al.: Immunological aspects of arterial disease. Atherosclerosis 30:361, Aug 1978

Jick, H. and Porter, J.: Thrombophlebitis of the lower extremities and ABO blood type. Arch Intern Med 138:1566, Oct 1978.

Naito, S., et al.: Takayasu's disease: association with HLA-B5. Tissue Antigens 12:143, Aug 1978.

Cheesbrough, M.J.: Angioedema - acquired C1 esterase inhibitor deficiency. Br J Dermatol 99:39, Jul 1978.

Cheesbrough, M.J.: Familial angioedema - C1 esterase inhibitor deficiency.. Br J Dermatol 99:38, Jul 1978.

Finn, R. and Hill, C.A.: Oral contraceptives and subarachnoid hemorrhage. Lancet 2:582, 9 Sep 1978.

Immunogenetics and essential hypertension (editorial) Lancet 2:409, 19 Aug 1978.

Nieboer, C. and Kalsbeek, G.L.: Immunofluorescence studies in granuloma eosinophilicum faciale. J. Cutan Pathol 5:68, Apr 1978.

Dasgupta, A., et al.: Immunoglobulins and complement 3 in patients with thromboangiitis obliterans. Indian J Med Res 67:332, Feb 1978.

Wolff, H.H., et al.: Immunoelectron microscopic examination of early lesions in histamine-induced immune complex vasculitis in man. Br J Dermatol 99:13, Jul 1978.

Houston, K.A., et al.: Behcet's disease associated with a lymphoproliferative disorder mixed cryoglobulinemia, and an immune complex mediated vasculitis. J Rheumatol 5:217, Summer 1978.

Kudrow, L.: HL-A antigens in cluster headache and classical migraine. Headache 18:167, Jul 1978.

Brandrup, F. and Ostergaard, P.A.: Alpha 1-antitrypsin deficiency associated with persistent cutaneous vasculitis. Occurrence in a child with liver disease. Arch Dermatol 114:921, Jun 1978.

Alexander, N.J. and Clarkson, T.B.: Vasectomy increases the severity of diet-induced atherosclerosis in Macaca fascicularis. Science 201:538, 11 Aug 1978.

Bassler, T.J.: More on immunity to atherosclerosis in marathon runners. N Engl J. Med 299:301, 27 Jul 1978.

Yadav, N., et al.: Development of antibody mediated immune reaction in hyperlipidaemic atherosclerotic rabbits. Indian J Exp Biol 15:1206, Dec 1977.

Gupta, R.L. and Papiha, S.S.: ABO blood groups and serum proteins in thromboangiitis obliterans (Buerger's disease). Hum Hered 28:285, 1978.

Millikan, L.E. and Duval, J.M.: Cutaneous vasculitis. Cutis 21:819, Jun 1978.

Numano, F., et al: Takayasu's disease in twin sisters. Possible genetic factors. Circulation 58:173, Jul 1978.

Fust, G., et al.: Studies on the occurrence of circulating immune complexes in vascular complexes in vascular diseases. Atherosclerosis 29:181, Feb 1978.

1. Randolph, T. G.: The Ecologic Unit. Hospital Management, Part 1, 97-45, 1965; Part II, 97:46, 1965.

2. Zeek, P.M.: Periarteritis Nodosa and Other Forms of Necrotizing Angiitis, N Eng J Med, 248:764, 1953.

3. Parish, W. E.: Studies on Vasculitis, Immunoglobulins BIC, C-Reactive Protein and Bacterial Antigens in Cutaneous Vasculitis Lesions, Clin Allergy, 1:92, 1971.

4. Kohler, P.F., Panophak, P.: Recent Advances in Allergic Vasculitis, Advances in Asthma, Allergy and Pulmonary Disease, 5(2):19, 1978.

5. Gilliam, J.N.: Cutaneous Necrotizing Vasculitis and Related Disorders, Ann Allergy, 37:328, 1976.

6. Segovia, A.: The Necrotizing Vasculitides - A New Pathogenetic Classification, Med Clin North Am, 61:241-260, 1977.

7. Buisseret, P.D., Youlten, L.J.F., Heinzelmann, D.I. and Lessof, M.H.: Prostaglandin-synthesis inhibitors in Prophylaxis of Food Intolerance, Lancet, 1:906, 1978.

8. Bell, I.R.: A Unified Theory of Mechanism for Diseases Caused by Maladaptation to Exogenous Substances, Ph.D. Thesis, Stanford University Press, 1977.

9. Hare, F.: The Food Factor in Disease, Chapter X, London: Longmans, 1905.

10. Schofield, A.T.: A Case of Egg Poisoning, Lancet, 1:716, 1908

11. Harkavy, J.: Vascular Allergy and Its Systemic Manifestations, Washington: Butterworth, 1963, p. 93.

12. Rowe, A.H. and Rowe, A.H., Jr.: Food Allergy: Its Manifestation and Control and the Elimination Diets: A Compendium, Springfield, Il: Charles C Thomas, 1972.

13. Coca, A. F.: Familial Nonreagenic Food Allergy, 1st ed., Springfield, IL: Charles C Thomas, 1902.

14. Yevick, P.: Oil Pollutants in Marine Life - Eight Advanced Seminar, Society of Clinical Ecology, Instatape, Tape II, 1975.

15. Taylor, G.S. and Hern, W.S.: Cardiac Arrhythmias to Aerosol Propellants, JAMA, 219:8, 1970.

16. Spizer, F. E., Wegman, D. H., Ramires, A.: Palpitation Rate Associated with Fluorocarbon Exposure in a Hospital Setting, N Eng J Med, 292:624, 1975.

17. Stewart, M.M..: MAO inhibitors and Foods - Reality and Mythology (Proceedings). Neuropharmacology 16(7-8): 527-528, July-Aug 1977.

18. Boxer, R.E.: Cardiac Arrhythmias due to Foods, Clinical Ecology, Dickey, Springfield, Il: Charles C Thomas 1976.

19. Klotz, S.D.: Allergy and the Cardiovascular System, Clinical Ecology, Dickey, Springfield, Il: Charles C Thomas 1976.

20. Rea, W.J.: Environmentally Triggered Cardiac Disease, Ann Allergy, 40:243, 1978.

21. Finn, R.: Food Allergy, Lancet, 2:249, 1978

22. Levi, R.: Is Cardiac Anaphalyaxis a Cause of Sudden Death?, American Heart Association presentation, January 1979.

23. Dickey, James William, Jr.: Drifting Hematomas, Surgery Gynecology & Obstetrics, 148:209, 1979.

24. Rea, W.J.: Environmental Triggered Large Vessel Vasculitis, in press.

25. Grant, E.C.: Oral Contraceptives, Smoking, Migraine and Food Allergy, Lancet 2:581, 1978.

26. Parish, W.E.: Studies on Vasculitis, Immunoglobulins, BIC, C-Reactive Proteins and Bacterial Antigens in Cutaneous Vasculitis Lesions, Clin Allergy, 1:92, 1971.

27. Theorell, H., Blombock, M., Kockum, C.: Demonstration of Reactivity to Airborn and Food Antigen in Cutaneous Vasculitis by Variations in Fibrino Peptide A and Others, Blood Coagulation, Fibrinolysis and Complement Parameters, Thrombos Haemostus (Stuttz), 36:593, 1976.

28. Rea, W.J.: Environmentally Triggered Small Vessel Vasculitis, Ann Allergy, 38:245, 1977.

29. Austen, K.F.: Introduction to Connective Tissue Diseases ("Collagen Diseases") Other Than Rheumatoid Arthritis, Beeson & McDermott Textbook of Medicine, Philadelphia: Saunders, 14th Ed. 1975, p.123.

30. Connor, L.: Nelson's Loose Leaf Medicine, Vol. 4, 1920, Philadelphia, Pa: Saunders, 1920.

31. Harkavy, J.: Vascular Allergy and Its Systemic Manifestations, Washington: Butterworth, 1963, 152-155.

32. Rea, W. J.: Environmentally Triggered Thrombophlebitis, Ann Allergy, 37:101, 1976.

33. EPA

34. Manske, D.D., Johnson, R.D.: Pesticide Residues in Total Diet Samples (X), Pesticides Monitoring Journal, 10:134, 1977.

35. Willeke and Whitby: Atmospheric Aerosols: Size Distribution Interpretation, J Air Poll Control Assoc 21:259, 1975.

36. Girsh, L.S.: Air Pollutants and Weather and Their Effect on Bronchial Asthma, Annual Review of Allergy, 1974, Frazier, Garden City, NY: Medical Examination Publishing Company, Inc., 1974, p. 214.


To buy products for the chemically sensitive see
For more information on medical treatment see
For more articles on the relationship of health and disease to environmental factors, see the list of available articles and other information available here.