Environmentally Triggered Small Vessel Vasculitis William J. Rea, MD, Clinical Assistant Professor of Thoracic and Cardiovascular Surgery, The University of Texas Southwest Medical School, Dallas, TX, Director of the Brookhaven Environmental Unit.

Abstract: Ten randomly selected patients with recurrent nonspecific small vessel vasculitis (edema, petechiae, spontaneous bruising, peripheral cyanosis) were studied under rigid environmental control. All cleared their symptoms without medications. All patients had their vasculitis reproduced after direct challenge with numerous individual foods and chemicals. Multiple incitants were found in each patient.

Source: Annals of Allergy, 38: 245-251, Apr. 1977.
 
  Vasculitis has long been an ill defined clinical entity until recently. Studies are sparse and most dissertations on the subject are vague. It has become apparent that there is a whole spectrum of vasculitis stretching from very minor vessel involvement to devastating organ necrosis. Triggering agents are generally unknown outside of a few bacterial infections and drug induced inflammation. Various other clinical entities such as some arthritis, nephritis, lupus erythematosus and periarteritis are known to have vasculitis as part of their individual syndromes, but their triggering agents are also unknown. Other types of vasculitis are apparently nonspecific but also have no known etiology. A randomly selected group of patients with nonspecific vasculitis of unknown etiology was chosen for this prospective study to see whether triggering agents could be more specifically found and the clinical course more clearly defined.
 
 
MATERIALS AND METHODS Ten consecutive patients with nonspecific vasculitis (petechiae, spontaneous bruising, vascular spasm, and recurrent edema) from this author=s cardiovascular practice were selected as they presented. This paper deals with the patients with small blood vessel involvement in contrast to a future series where the large vessels are involved.

Detailed lifelong ecological histories were taken by Randolph=s1 method, searching for other parts of the environmental maladaptation syndrome. Specific symptom complexes and recurrent inflammation such as sinusitis, laryngitis, hoarseness, bronchitis, cystitis, spastic colon, enteritis, colitis, migraine or vascular headaches, myalgia, arthritis, arthralgia, depression, cardiac arrhythmia or phlebitis of unknown etiology were recorded.

An attempt was made to create an environment that was as free as possible from inhaled and ingested contaminations and where triggering agents could be clearly defined. Thus, cause and effect could be established.

Rooms were specially constructed. Walls were made of glass and cement blocks. The blocks were painted with a low outgassing paint that was allowed to dry from six months to one year so as to eliminate any volatile petrochemicals. Floors were of stone (terrazzo) or hard vinyl (also allowed to age). Ceilings were of mineral rock. Lighting was fluorescent, hanging from the ceiling, with metal shades. Beds and furniture were all metal or hard wood and void of volatile plastics. Mattresses were of chemically less treated 100% cotton with all the plastic removed. All bed linen and curtains were chemically less contaminated 100% cotton that had been laundered in pure nondetergent vegetable or animal soap. The heat and air conditioning were local electric, using air blown over steel coils containing water. Filters of activated charcoal and alumina-oxide impregnated with potassium permanganate were placed at the entrance to rapidly eliminate extraneous fumes, odors, and particles that might come through the doors. No offensive synthetic or natural odors were allowed in the rooms. The rooms were as totally devoid as possible of volatile petrochemicals and dust, as judged by susceptible humans acting as monitors and as registered on the synthetic odor detector. No smoking was allowed. Rooms were cleaned with borax, nonchlorinated cleaner, and water.

Food used for testing was grown, transported, stored, and prepared in the relative absence of petrochemicals. Only natural fertilizers were used to grow the food, and no insect sprays, herbicides or preservatives were used. Storage was in glass jars or nonpetroleum-based cellophane bags. Preparation was in glass or stainless steel utensils, heated by electricity. The eating utensils were glass or stainless steel, and the drinking water was filtered through activated charcoal so as to remove chlorine and pesticide residues.

All patients, during the course of diagnosis and treatment, were kept in the rooms for at least a 16-day period. Patients were required to remove all hair sprays, cosmetics, perfumes, and polyester clothing before entering the room and to wear chemically less treated 100% cotton. Upon entering the room, patients stopped all medications, including anticoagulants and steroids. Once the patients reached the symptom free basal state, they could act as their own controls. No medications were given during the stay in the unit with the exception of oral or intravenous bicarbonate of soda and oxygen. Pulses, blood pressure, temperature, bruising, petechiae, and color changes were monitored every four hours. After the patient was in a basal state free of signs and symptoms, including absence of petechiae and bruises, with normal pulses and a rate below 80, able to sleep all night and had lost his hunger, challenge with single chemically less contaminated source food (an individual pure food whose origin is known, i.e., wheat, oats, cane sugar, beet sugar, chicken, duck, turkey, etc.) was begun. The food was selected individually and randomly. In order not to miss delayed reactions, no more than four source foods were tested in one 24-hr period. As many as 60 individual source foods were tested sequentially during the period in environmental control. Pulses were recorded five minutes before and at 5-, 20-, 40-, and 60-minute intervals after meals. Electrocardiograms were taken with the onset of any arrhythmia. The time of onset after the challenge was noted. All signs and symptoms were recorded. Testing of the next food was not begun until all previous reactions had subsided.

After totally tolerated foods were found the patients were retested with these same nonreactive foods but this time obtained from the commercial market. The commercial foods were naturally contaminated by synthetic sprays, herbicides, preservatives, artificial colorings and sweeteners, wax and plastic wrappings, or other additives occurring during their production and processing. These were cooked on gas stoves in synthetic cookware. Individual and cumulative reactions from one to six consecutive meals were observed and recorded.

Testing of odors was done in the following manner: Each patient was given a timed exposure of one to sixty minutes to the flames of natural gas, cigarette smoke, chlorine, perfume, pine-scented floor wash, ethyl alcohol, formaldehyde, phenol, and pesticides. In addition, challenge to the fumes of common odor producing material such as home carpet, foam pillows, polyester clothes, which the individual breathed daily in the home and work environment, was done. Each exposure was at a distance of 20 inches with a constant flow of the vapor. All odors tested were of a double-blind nature in that neither the examiner nor the patient knew the content of the container until after the test. Saline was used as a control.

The following laboratory tests were performed. Complete blood count, sodium, potassium, chloride, carbon dioxide, blood urea nitrogen, serum protein, protein electrophoresis, immunoglobulins (IGE, IGG, IGA, IGM), total hemolytic and serum complements (C3 and C4), prothrombin time, partial thromboplastin time, platelets, Lee and White clotting time, calcium, phosphorus, fibrinogen, fibrinolysins, fibrin split products, glucose, uric acid, alkaline phosphatase, serum glutamic oxalo-acetic transaminase, lactic dehydrogenase, alpha 1 antitrypsin, and C1 esterase inhibitor were obtained upon entrance into room and at the beginning and end of testing. C3 and C4 were done daily during the period of fasting. Biopsies were taken of the spontaneous bruises and petechial hemorrhages.
 
 

RESULTS As shown by Table 1, there was an impressive number of associated signs and symptoms related to the environmental maladaptation syndrome occurring during the patient=s lifetime. Each patient averaged more than ten distinct recurrent signs and symptoms. Few episodes of vasculitis required hospitalization but usually rendered the patient incapacitated for the duration, which was usually four to five days. The average time of onset of the disease to the time of diagnosis was about 20 years. Four patients had lifelong problems with recurring symptomatology related to the respiratory, gastrointestinal, and genitourinary systems. Prior to development of the vasculitis, all patients gave histories of being supersensitive to odors of things like car exhausts, perfumes, fabric stores, natural gas, etc. They usually also reacted adversely to medications. The difficulty in making the diagnosis was manifested by the fact that each patient had seen at least 10 physicians prior to being admitted to the environmental control unit.

Table 1

Associated Signs & Symptoms

Recurrent spontaneous bruising and/or petechiae
10
Recurrent edema
10
Recurrent nasal stuffiness
10
Extremity vascular spasm
10
Cold susceptibility
10
Tonsillectomy
9
Increased sense of smell
9
Adult acne
8
Recurrent myalgia
7
Recurrent sinusitis
6
Recurrent headaches
6
Spastic colon and/or nonspecific colitis
5
Recurrent nonspecific chest pain
5
Recurrent bronchitis or bronchopneumonia
5
Recurrent overwhelming fatigue 
5
Recurrent sore throats
5
Asthma
4
Recurrent arrhythmias
4
Recurrent cystitis
4
Recurrent depression
2

  Once under environmental control, all 10 patients cleared their active symptoms, including their ongoing vasculitis, in three to seven days. Frequently, symptoms were accentuated the first two to three days. Most patients underwent withdrawals just as patients with phlebitis described in a previous report.2 Each patient initially had hunger followed by complaints of Anervousness,@ Ajitters@ and headaches. There were observable signs of agitation, trembling, and depression. Insomnia or disturbed sleep were the rule the first night, which was followed by assorted symptoms such as nausea, diarrhea, wheezing, and/or headaches. Finally, backaches, sometimes excruciating, usually signaled the termination of the symptoms. At this time all tenderness, bruises, petechiae, extremity discoloration, and other associated signs and symptoms were gone. Patients were asymptomatic, and all stated that they had not been that well in years. This feeling of well being was confirmed by observable signs of animation, walking or even riding a stationary bicycle. None had previously been able to do this because of uncontrollable fatigue.

After testing started, it became quite obvious that reactions fell into three categories. The first consisted of unmistakable signs, such as rhinorrhea, nasal stuffiness, hoarseness, cough, wheezes, peripheral blanching, cyanosis, swelling or loss of pulses, bruising, polyuria, fever, increased pulse rate, blood pressureCdecreased or elevated, arrhythmia, petechiae, bruising, and phlebitis. The second category consisted of equivocal signs and the third category of no observed reactions. The latter two were lumped together for statistical purposes and considered as having no observed reactions.

All ten patients clearly had their vasculitis reproduced on at least three separate occasions. Usually, there was a sequential progression of symptoms of color change of the hands, feet, nose, and skin followed by pulse alteration, periorbital and peripheral edema, petechia, and/or spontaneous bruising. It is evident by the data shown in Table II that many different susceptibilities existed in each patient. Also, it was observed that some individual incidents would produce only portions while others would produce all the patient=s original signs and symptoms. These reactions were further substantiated by the benign asymptomatic course after ingestion or inhalation of nonreactive foods and food odors plus the reproducibility of signs by retesting of reacting foods. Of the reactions that occurred within the first four hours, 95% started within the first five minutes after ingestion, leaving no doubt in the minds of observing personnel and patients that there was a cause and effect relationship. The severe reactions lasted up to 48 hours with lesser effects lasting up to five days. The moderate reactions lasted four to eight hours while the mild ones were terminated within a four-hour period. Of the associated signs and symptoms, 100% were reproduced.

Table 2

Offending Agents Associated Signs & Symptoms Reproduced Vasculitis Reproduced
1. Beef, chicken, cigarette smoke, shrimp, pork, gas heat, ingested chemicals Diarrhea, pulse increase 30 b/m, nasal stuffiness, bigeminy, multifocal PVCs Pork, inhaled chemicals, wheat
2. Wheat, rice, inhaled chemicals Vomiting, pulse increase 40 b/m, catatonia Wheat, rice, inhaled chemicals
3. Corn, cane sugar, eggs, inhaled chemicals, milk Wheezing, rhinorrhea, red nose, nasal stuffiness, tender muscles, cystitis Corn, inhaled chemicals, milk
4. Beef, potatoes, ingested chemicals, wheat, corn Peripheral pulse from 4 to 1+, tachypnea, shortness of breath, cyanosis, belching Beef, wheat, corn, inhaled chemicals
5. Pork, pork fumes, ingested chemicals, inhaled chemicals Generalized edema, tender muscles, colitis, dizziness, headaches Pork, shrimp, inhaled chemicals
6. Legumes, seafood, cane sugar, wheat, chicken, cigarette smoke, ingested chemicals, inhaled chemicals Syncope, wheezing, muscle tenderness, hives, paroxysmal atrial tachycardia, headaches Cigarette smoke, ingested chemicals, inhaled chemicals, seafood, corn
7. Beef, chicken, lettuce, inhaled petrochemicals, corn, milk G.I. bloating, belching, diarrhea, PVCs, ventricular tachycardia Wheat, corn, milk, ingested chemicals
8. Turkey, chicken, peas, cigarette smoke, beef, inhaled chemicals Decrease in pulseCleft arm only, left neck and arm tenderness, tender over arm veins Chicken, beef, inhaled chemicals
9. Coffee, peanut butter, cane sugar, ingested chemicals, wheat, rice, turkey Dyspnea, wheezing, eyes watering, hoarse, pulse increase 50 b/m Apples, rice, turkey, inhaled chemicals
10. Corn, wheat, beef, eggs, inhaled chemicals, chicken, peanut butter Cystitis, diarrhea, skin rash, itching, dyspnea, pulse increase Chicken, wheat, peanut butter, inhaled chemicals

  Testing for ingested chemicals resulted in symptoms and signs after the initial meal in two patients while eight patients took from two to six meals to produce signs, although symptoms were often produced at least one meal earlier.

All reactions to inhalant chemicals were within the first one and a half hours and their after-effects lasted up to 48 hours although most terminated within a four-hour period. Ten patients reacted to the fumes of the flame of the gas pilot, reproducing assorted signs and symptoms in all patients and reproducing the vascular signs in six. The most striking examples were those of 33-year-old and 34-year-old females who had a 15-second exposure to the natural gas pilot. Patient A developed immediate dizziness, staggering, and then premature ventricular contractions followed by severe leg pain and bruises over both extremities. Recovery took 36 hours. Patient B developed immediate abdominal cramps, irritability, chills, and vascular spasm of hands and feet vessels followed by spontaneous bruising and depression. Recovery took 48 hours under oxygen with the patient writhing in pain and complaining of abdominal cramps most of this time.

Double-blind exposures to the various inhaled chemicals are seen in Table III. One can see the widespread involvement of susceptibilities to these chemicals. Not shown is the fact that the transient exposures produced spontaneous bruising in all patients at least on two different occasions. Vascular spasm with cyanosis was seen in all patients frequently, as were petechiae and periorbital edema.

Table 3

Reaction to Double-Blind Exposure to the Fumes of Chemicals ( 1 to 15 minute Exposure)

Patient
Saline control
Petroleum Alcohol
Phenol
Chlorine
Mixture (Pesticides)
Pine-Scented Floor Wash
Formaldehyde
1
-
+
+
+
+
+
+
2
-
+
-
+
+
+
+
3
-
+
+
-
+
-
+
4
-
+
-
-
+
+
+
5
-
+
+
+
-
-
+
6
-
-
+
+
+
+
+
7
-
-
-
+
+
+
+
8
-
+
+
+
+
+
+
9
-
+
+
+
+
-
-
10
-
+
+
+
+
+
+
Skin biopsies of the bruises and petechiae on occurrence showed the following: A. Spontaneous bruises: precapillary arteriole involvement with monocellular infiltrate and either rupture or leak of red blood cells outside the vessel. B. Petechiae showed intradermal hemorrhage of a capillary.

Laboratory DataCTable IV

Table IV shows a tendency for the white blood count to be depressed. Immunoglobulins generally were within normal limits. Alterations in total serum hemolytic complements were seen in only one patient and presumably this was due to abnormality in one of the unmeasured components. All C3's were abnormally lower, but mildly so, in all cases. C4's were altered in only two patients, both being slightly elevated in one. Bleeding studies were all normal.

Table 4

Control

10 Patients

5-10,000

WBC

10-200

IGE

800-1800

IGG

90-450

IGA

60-280

IGM

90-100%

THC

80-120

C-3

20-40

C-4

50-200

Total Eosinophil

1
6000
15
920
231
84
90
67
25
67
2
3500
30
1560
474
116
93
62
30
150
3
4500
60
1540
201
460
91
68
28
300
4
4700
40
1420
273
266
95
70
40
75
5
5000
120
1127
210
100
80
65
47
90
6
3800
80
1290
220
124
93
58
45
140
7
4200
20
1060
290
160
91
59
36
200
8
4100
25
1580
158
160
99
60
39
66
9
5500
38
1140
104
143
96
63
29
190
10
2800
40
1040
254
240
90
61
40
88

 

DISCUSSION

Environmentally triggered vasculitis has been alluded to in reports from many observers, starting in the early 1900's. Hare3 first observed peripheral vasoactive phenomena when he withdrew and rechallenged certain foods. Later Harkavy4 in the 1930's was able to link some arterial disease to sensitivity to cigarette smoke as well as induce cardiac arrhythmias with isolated food challenges in susceptible individuals. In 1970 Taylor5 reported a fatal arrhythmia due to inhalation of aerosolized fluorocarbon. Randolph6 performed the first studies under environmentally controlled conditions, showing that the whole spectrum of arrhythmias could be triggered by inhaled and ingested chemicals. Recently, Yevick7 reported further evidence of chemically triggered vasculitis when he demonstrated inflammation and fibrosis of the cardiovascular system in sea life exposed to oil spills. Nour-Elden8 further substantiated this phenomena by showing that arteries have 15 times more affinity for phenol than any other tissue in the body. In 1976 Stewart9 reported a case of fatal triggering of a myocardial infarction by furniture refinishing solution. Last, a series of environmentally triggered phlebitis was described by this author. This series of patients fits the general pattern described by these aforementioned observers although distinguished by their wide variety of symptoms involving many of the major organ systems. Also, in addition to frequent peripheral vasospasm, all had the spontaneous cutaneous bruising and/or petechiae, plus facial and/or peripheral edema, indicating inflamed blood vessels. These vascular responses apparently act as mirrors to the pathology occurring internally, thus explaining the occurrence of unusual and even bizarre symptoms. Since these symptoms were reproducible with repeated, known, blind and double-blind challenges, vascular involvement of that specific area of the body would be the logical explanation of underlying pathophysiological response. Frequently, they did indeed correspond with the visible bruising, purpura, petechiae, and edema. Usually, if the pathologic responses could not be explained or correspond with the vascular involvement, other components of the smooth muscle systems such as the respiratory, gastrointestinal or genitourinary systems were involved.

In viewing the life-long histories it is difficult to say when the vasculitis started. However, several facts were evident. Most patients had symptoms due to abnormal responses to environmental stimuli in early childhood. These increased insidiously over many years before exhibiting the full vasculitis syndrome. Many could clearly relate accentuation of their allergic manifestations with apparent spreading of intolerance to commonly used foods and outgassing objects such as newsprint, perfume, plastics, etc. very early in life. Frequently, precipitating overexposure episodes such as having the house fumigated would trigger the cascade of spreading intolerance to both foods and chemicals. This spreading phenomena seemed to occur in patients with a background of susceptibility though two patients on careful scrutiny were totally asymptomatic at the time of the precipitating exposure. A careful review of the clinical course in these patients revealed three or four of the smooth muscle systems to be involved, indicating widespread disease. This multisystem involvement clearly distinguishes the patient with environmentally triggered disease from the average atopic patient. Even though the patients presented with multisystem complaints due to apparent spreading of intolerance many isolated clues were present years before the onset of the vasculitis. Ninety-plus percent had tonsillectomies, indicating involvement of the respiratory and immune systems in early childhood and even infancy, thereby pointing out the importance of obtaining this information early in life. Family histories were also very important in that 60% had ancestors who suffered and eventually died from a nonarteriosclerotic cardiovascular entity. Finally, most patients had isolated chemical intolerance with years of complaints of a hypersensitive sense of smell to these. Usually, odors of various chemicals such as chlorine, newsprint, fabric stores, pesticides, etc. would cause them to be nauseated or ill. All gave histories of being able to smell natural gas when others could not.

Water quality apparently plays a significant role in the development and treatment of vasculitis. Eighty percent of the patients in this series were tried on at least four different nonchlorinated spring and filtered waters before their symptoms cleared. One hundred percent of the patients reacted strongly to a blind challenge of chlorinated water. It repeatedly became apparent that use of well water was hazardous due to wiidespread permeation of the water table with pesticides. As pointed out by Randolph,10 the patient=s water intolerance must be solved or symptoms will not clear and other testing results will be suspect.

Food as a trigger to pathological responses has been mentioned by past generations of food allergists. Its importance in the pathogenesis of disease has been overlooked recently. Responses to food testing have frequently been confusing for numerous reasons, including alteration of reactions by extraneous environmental insults and the so-called delayed food reactions. Apparently, food reactions in susceptible individuals are influenced by many factors, including the quantity and frequency of ingestion, temperatures of the foods, multiplicity of ingested synthetic elements in the food, the ambient inhaled air quality including temperature, humidity, barometric pressure, amount of ionization, the number and type of pollutants, the quality of ingested water, cyclical hormone influences and the state of nutritional balance of the individual. This complexity explains why few triggering agents have previously been found with certainty. The controlled environment decreases the complexity and adds to the clear definition of foods as one facet of the triggering agent for vasculitis and possibly many other diseases of unknown etiology.

In a controlled environment it becomes clear that most food reactions are immediate rather than delayed. However, many reactions are insidious and start with relatively minor symptoms such as transient nasal stuffiness, malaise, hoarseness, depression, or belching. Later, they frequently crescendo into devastating symptomatology. Once the physician and patient observe this sequential phenomena under controlled conditions, they are able to dissect out other influential environmental triggering agents.

One factor is dominant in testing food and that is the food must be as uncontaminated as possible. With the environment steadily deteriorating, the difficulty of acquiring pure food is at times almost overwhelming. Food is contaminated from the point of growing by artificial fertilizers, pesticides, and herbicides. Further contamination continues during processing by the different washes, additives, preservatives, stabilizers, polyvinyl chloride wrappings, etc. Cooking with gas in synthetic cookware adds more contamination. Because of this chemical adulteration of food it was necessary to develop a network of food growers who farmed without the use of synthetics. Then, one must be sure that the food was not contaminated during transportation or preparation. Once this detail was managed, testing results were reproducible in the 95% range. Food monitoring by treated chemically susceptible individuals appears to be the best mode of monitoring at present and is a necessity.

The increase in the ambient air pollution further adds to the difficulty of defining triggering agents. There appear to be two types of effects from inhaled pollution. One is an overall depressant effect which is very subtle. This appears to be a volume load effect and may account for the fact that certain symptoms are accentuated in days when there is more air pollution with all other facets remaining constant. These observations were first observed by Randolph11 and were later supported by analytical studies of ambient air by Whitby et al.,12 who measured air in various areas of the world. They found that sea air had the fewest fumes and particles (excluding salt). Comparable standards for clean continental air showed a tenfold increase in pollution while air blowing from cities, but still on continental areas, increased pollution at least 35 times. The city on a good day had 150-fold more pollution while on bad days it increased 1,000 to 4,000 times. The abnormal responses of patients to food in this series were more frequent and accentuated when they were taken out of the environmental control unit to areas of higher nonspecific air pollution. This was further evidenced when the same patients went to areas of the country with less air pollution and found reactions to certain foods to be much less or even absent in a few instances. With less ambient air pollution they also found ingested chemicals, formerly intolerable, to be less harmful. Because of this effect, it became clear that patients had to have 10 to 12 hours in a less polluted environment to keep their vasculitis under control out of the hospital. This necessitated cleaning up the home by removing the high outgassing plastics (polyvinyls, polyethylene, polyurathane, foam rubber, etc.) and other synthetics (oil base paints, natural gas, etc.) as well as eliminating particle producing materials. Most of all, none got well until their natural gas appliances, including heating, were removed.

While developing instrumentation for the orbital space laboratory Poehlmann et al.13 observed that the fine tuning of instruments was initially distorted, giving disastrous results. They measured outgassing potentials of all materials and found glass, steel, metal, and stone to be inert while the soft plastics, such as polyvinyl chloride, polyethylene, polyurethane, and silicone, to be constantly fuming. Some of the hardest synthetics like masonite, polycarbonate, and Formica had initial fuming but little thereafter. Knowledge of these phenomena is crucial in diagnosing and treating a chemically susceptible vasculitis patient. This nonspecific pollution effect usually explains why patients are not clearing all symptoms periodically and also explains sudden susceptibility to formerly safe foods.

The second type of response to air pollution followed the more classic allergic reactions with a sudden precipitating onset followed by the usual sequence of symptoms. This was also present to the same incitants and was easily reproducible. In addition to occasional pollen, dust, and mold triggering incitants were mainly due to halogenated petrochemicals such as pesticides, floor cleaning compounds, and/or metals like copper, aluminum, cadmium, and nickel. This effect was always most evident if the patient=s ambient overall pollution level was low.

Environmentally triggered small vessel vascular disease is probably part of a spectrum of inflammatory diseases of all sizes of arteries since smooth muscle appears to be the sensitized system involved. This particular group of patients had blood vessel involvement at the precapillary arteriole level and/or small arteries of the intra-organ type. At times, there were large vessel responses but minimal in this group of patients.

The pathologic vascular damage seen in this series fell into the mild to moderate categories and would be considered to be stage I and II responses. As seen in all pathologic sections this resulted in mild vessel damage resulting in localized or mild generalized edema. This appeared to be reversible even when the vasculitis had been long standing. Also, rupture of the capillaries was present, manifested by bruising and petechiae. Frequently, noninflammatory purpura was seen, and it seemingly reflected a more severe, but still reversible, clinical course. The pathologic involvement fell short of organ necrosis, apparently because of the size of vessels involved and the lack of intravascular coagulation. This probably accounted for the diversity of symptoms and multiple complaints of the patients.

Laboratory data were unremarkable other than the change in the serum complements. Immunoglobulins were not elevated and did not change much. The fact that patients did have immediate type I reactions (Gell & Combes) with some challenges makes one suspect that there was alteration of IGE at the local level. However, as shown recently in allergic lung diseases this response may be more a reflection of IGG alteration.14 Direct triggering of the kinin and complement systems bypassing the a-a reactions also apparently occurs. The complement mechanism is involved in producing the inflammation, since all patients had mild depression of the C3 and some elevation of the C4. It would have been interesting to measure kinin levels, but these were unavailable in our laboratory at the time of these studies. Many of the clinical characteristics in this series are similar to those of Garner and Diamond,15 who found kinin elevation associated with bruising but thought the triggering was due to autoerythrocyte sensitization, and by Leibe,16 who actually introduced bruising by kinin injection in a single patient.

The intrinsic mechanism of the environmentally triggered arteritis is unclear but probably encompasses a variety of mechanisms. Some incitants probably trigger the deposition of antigen-antibody complexes in the vessel walls. Another possible mechanism which occurs in other vasculitis would be the alteration of a native component of the vessel so that it becomes antigenic and induces hormonal or cellular immunity. Deposition of an antigenic foreign substance within the vessel should also be considered in some patients. Finally, an alteration of a vessel wall component so that it directly induces an inflammatory response surely occurs in other patients. Regardless of these different pathways for the final production of vasculitis, it is now possible to define a multiplicity of incitants in any given patient, thus allowing us the opportunity to remove the triggering agent.
 
 

SUMMARY 1. Ten randomly selected patients with recurrent, nonspecific small vessel vasculitis of unknown etiology were placed in a therapeutic diagnostic environmental control unit.

2. All patients had multiple recurrent symptoms in addition to their vasculitis, including such complexes as sinusitis, colitis, bronchitis, asthma, myalgia, arrhythmias, depression, and otitis.

3. All patients were cleared of their symptoms, including their vasculitis, without medications while in the unit.

4. With each patient acting as his own control, the whole spectrum of associated symptoms could be reproduced by direct challenge with individual foods and chemicals immediately and repeatedly.

5. Ten patients had a direct cause-and-effect relationship demonstrated by challenge with individual foods and chemicals causing reproduction of their vasculitis. Multiple individual incitants were found to trigger the vasculitis in each of 10 patients.
 
 

REFERENCES 1. Randolph TG: Human Ecology & Susceptibility to the Chemical Environment. Springfield, IL: Chas. C. Thomas, 1962, pp. 2-40. 2. Rea WJ: Environmentally triggered thrombophlebitis. Ann Allerg 37:101, 1976.

3. Hare F: The Food Factor in Disease. London: Longmans, 1905, p. 274.

4. Harkavy J: Vascular Allergy & Its Systemic Manifestations. Washington: Butterworth, 1963, pp. 152-155. 5. Taylor GS and Herns WS: Cardiac toxicity to aerosol propellants. JAMA 219:8, 1970.

6. Randolph TG: Personal communication.

7. Yevick P: Oil pollutants in marine life. Eighth Advanced Seminar. Society of Clinical Ecology; Instatape, Tape II, 1975. 8. Nour-Elden F: Uptake of phenol by vascular and brain tissue. Microvascular Res 2:224, 1970.

9. Steward RD and Hake CL: Paint remover hazard. JAMA 235: 398, 1976.

10. Randolph TG: Personal communication.

11. Randolph TG: Human Ecology & Susceptibility to the Chemical Environment. Springfield, IL: Chas. C. Thomas, 1962.

12. Willeke and Whitby: Atmospheric aerosols: Size distribution interpretation. J Air Poll Control Assoc 25:529, 1975.

13. Poehlmann HC: General aspects of outgassing & contamination. In Proceedings of the Symposium on Long Life Hardware for Space. Huntsville, AL, Vol. 2, 1969.

14. Patterson R, Roberts M, Roberts R, Emanul D, and Franks J: Antibodies of different immunoglobulins. Classes against antigens causing Farmers Lung. Am Rev Resp Dis 114:315, 1976.

15. Garner FH and Diamond LK: Auto erythrocyte sensitization, a form of purpura producing painful bruising following auto sensitization to RBC in certain women=s blood. Blood 10:675, 1955.

16. Leibe H, Almag CH, Kaufman S, and Edery H: Possible role of bradykinins in a patient with recurrent ecchymosis (DNA sensitization). Israel State Med 8:67, 1972.