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Environmental Sensitivities: The Dose is the Poison.

Mr. A was 50 years old when he was referred to me because of his "environmental sensitivity" (ES), also called Multiple Chemical Sensitivity (MCS) or Idiopathic Environmental Intolerance (IEI). Over the previous five years he had developed distressing symptoms when exposed to very short exposures of many common smells, especially perfume, but also many others, such as paint, gasoline or smoke inhaled when walking past the knot of smokers outside his office building. He had attended a clinic that specialized in ES and was advised that he must avoid this exposure. He considered quitting work and moving to a Muskoka cottage. (More about Mr. A later.)

Ms. X was a school teacher who developed headaches and other distressing symptoms attributed to the recent introduction of Wi-Fi in the school. She quit her job but continued to have similar distress when near electronic or information technology equipment, a cell phone tower or walking under overhead electric wiring. She visited the ES clinic and was advised that she suffered from ES due to electromagnetic fields (EMF). The advice was to avoid these exposures.

In the past 50 years, an increasing number of patients report severe ES. How should the general public and evidence-based medicine, in particular, understand this phenomenon and respond to it?

When evaluating the possible adverse effects on a person due to exposure to multiple occupational or environmental agents or stimuli (chemical, physical or biological), there are two fundamental principles that must be considered. The first is: "The dose is the poison." The second is a corollary to the first: "If you can't count it, it is not science."

The dose received by a person is the amount or concentration of the product multiplied by the duration of exposure. Both these factors must be measured.

Even "good" things can have serious adverse effects on a person. For example, if a person inhales 100% oxygen consistently for 3 weeks, it can be fatal or cause serious irreversible disease. Prolonged therapeutic oxygen is rarely administered in a concentration greater than 60%. However, short-term high oxygen treatment for "the bends" after prolonged scuba diving at excessive depths is safe and effective. There are many other medical indications for short-duration oxygen treatment occasionally under high oxygen pressure.

Pure distilled water is "good" but when it was ingested excessively by some inexperienced runners during a very hot and humid Boston Marathon, some developed serious brain damage. (Excessive sweating depleted the blood of salts and water. The water was frequently replaced by drinks supplied by friends "on route," but the diluted very low blood salt level resulted in serious brain damage.) Currently, replacement of evaporated sweat is by drinks containing the required salt and other nutrients.

In contrast, high-dose "bad" products can be fatal, but if the dose is sufficiently small, the product may be beneficial. A good example is Botulinum toxin, one of the most toxic food contaminants due to the growth of Botulinum bacteria in improperly sterilized or bottled preservatives. The toxin paralyzes the consumers' nerves, including those needed for respiration, and can be fatal. A recent outbreak of "botulism" occurred due to contaminated carrot juice that was improperly bottled and contained no antibacterial preservatives.

However, Botulinum toxin in extremely low doses is botox, which has many therapeutic benefits (for example, in spastic neuromuscular disease such as paraplegia) and in cosmetic treatments.

Obviously, a person's general health status due either to genetic or acquired disease or other factors will modify the effect and the intensity of the dose but the principle is still true.

Allergic or immunological reactions can be caused by very small doses of the offending agent but much smaller doses used in desensitization treatment protocols are usually safe and effective. For example, a single honeybee sting, which contains 50 ug of venom, can be fatal to a person allergic to the venom, but an effective, well-tolerated desensitization program may begin with a dose that is l/50th or 1/100th the strength of the sting. This dose is gradually built up with weekly injections increasing it to a dose of 100 [micro]g which is then maintained monthly for about 3 years and provides protection to the vulnerable patient. Similarly, a sufficiently small initial dose of a food allergen to a person with such an allergy may lead (after multiple incremental doses) to tolerance. However this latter program is not always successful.

For most drugs or normal environmental agents, there is a range of doses between toxicity and tolerability. Most therapeutic drugs have an upper dose beyond which a recipient may encounter serious adverse reactions, while a dose that is too low may be safe but ineffective. The same is true for environmental agents. It is important to know the range of this separation. For many drugs, the range between a toxic dose and a safe dose (the therapeutic window) is relatively narrow, usually 10 times or less, compared to a similar population sample such as previously healthy occidental adults. For example, the effective dose of the cardiac drug digoxin is 0.25 mg daily, but a dose of 0.80 mg could be very toxic and a dose less than 0.08 mg daily has no beneficial or adverse effect. The range is 10 times. This range is true for many other drugs used in different treatments.

When considering environmental sensitivity, it is important to know the tolerance range of common environmental or ingested agents in comparable "control" populations when evaluating a patient with complaints of specific or Multiple Chemical Sensitivity (MCS or IEI). For example, consider the range of adverse reactions (sunburn) experienced by healthy adult occidental people on a sunny Miami beach on June 21st. High ultraviolet light sun rays are reinforced by reflection from the ocean. More than 50% of normal healthy people who are continuously on the beach for 3 hours without sunscreen will experience distressing sunburn, developing after an interval of several hours. Some more vulnerable people, without sunscreen, may get similar sunburn after 1 hour and a very pale blonde blue-eyed Swede may react after 30 minutes. The range of vulnerability to the above exposure would be 6 times. Under very special conditions, for example, for an albino person, who might react after 10 minutes of sun exposure, the range would be 18 times normal. However, if a healthy person attributed a sunburn-like rash after less than 10 minutes exposure, it might lead me to suspect a different cause for his or her itchy symptoms such as food allergy, virus infection or insect bites.

Similar reasoning can be used to explain a person's vulnerability to alcohol. Some women and Asian peoples are indeed more vulnerable than Caucasian males but I would not want to drive in a car driven by a male who had consumed three full glasses of wine in one hour. The range of vulnerability to alcohol would rarely exceed 20 times. A frequent heavy drinker like Churchill may tolerate three full glasses without significant impairment, whereas some genetically vulnerable Asiatic women may become impaired after one glass or less.

The important principle is that we must compare, relative to physically similar normal "control populations," the quantitative dose range of a claimant's "sensitivity or vulnerability" to environmental stimuli (i.e., Multiple Chemical Sensitivity (MCS) or sensitivity to electromagnetic fields).

Many people like Mr. A or Ms. X complain of the rapid development of distressing symptoms upon exposure to extremely small doses of several or many common environmental agents. For MCS these are usually perceived by their smell, but other stimuli such as the sight of a person smoking a cigarette or a neighbour's barbeque may trigger the symptoms. EMF-sensitive persons develop similar symptoms following exposure to very weak EMF sources or sources that they believe emit electromagnetic fields. The most common complaints are headaches, dizziness without vertigo, weakness, cough or choking feelings or shortness of breath. These symptoms are rarely accompanied by objective evidence of disease or dysfunction but a medical exam may detect the patient's cough, rapid breathing without wheezing, or rapid heart rate. Objective tests may reveal vocal cord dysfunction (VCD) which is often triggered by psychopathology or low carbon dioxide blood levels due to hyperventilation.

Challenge tests with the environmental "chemical" such as low-dose perfume reproduce the patients' symptoms only when they can smell or otherwise detect the presence of the chemical product. However, when the chemical is presented (in a "blind" challenge study) at the same dose, but his or her detection of the indexed chemical is blocked by the addition of a much stronger "good" smell (identified by the patient such as "all natural" peppermint or vanilla), he or she cannot identify whether the test chemical, such as perfume, is present or absent in the challenge study. Dr. Des Manchi and colleagues reviewed "Provocative Studies of Persons Reporting Multiple Chemical Sensitivities," in the Journal of Allergy and Clinical Immunology. They concluded that persons with MCS react to chemical challenges only "when they can discern differences between active and sham challenges."

Similar challenge studies show that when the EMF stimulus is blind or masked, EMF-sensitive patients like Ms. X cannot distinguish between their reported causative stimulus and the blind fake challenge.

The classical symptoms and the occasionally detected objective findings (i.e., vocal cord dysfunction) are typically triggered by strong belief, and phobic or panic stimulation in patients with these psychological problems, suggesting that the mechanism of the distressing symptoms is not specific to the chemical itself and may be related to expectations and prior belief.

A quantitative analysis of the dose of the environmental agent triggering the patient's symptoms (compared to appropriate "control" populations) can be even more useful in understanding the patient's "environmental sensitivity" to "chemicals" or electromagnetic field stimuli (i.e., Wi-Fi).

Unfortunately, in many patients with ES on whom I have consulted, almost never has the dose of an identified adverse stimulus been compared quantitatively to the dose tolerated by normal "control" people. The claimants describe how they become "very" distressed because of extreme "sensitivity," but neither word is scientific or quantitative.

For example, consider Patient Y, who cannot work because of chemical sensitivity. Even though there is a "scent-free" policy in the workplace, Y can detect the smell of perfumed "Bounce" used in the dryer of a colleague's clothing, or perfume from the occasional transient visitor. Y cannot enter the lobby of the building if it had been painted one week previously, shop in the detergent aisle of the supermarket or enter a department store via the entrance near the perfume centre. Y cannot fill the gas tank of the car, attend a friend's wedding or attend a movie. In Y's home, vinegar is the only cleaning product that is used. His or her life is seriously compromised.

When I interviewed Y in a scent-free office, Y sat across the desk from me about 6 feet from the closed door. I presented Y with the following scenario: "A heavily-scented perfumed woman, who has just patronized the beauty salon across the street, opens the door and asks if Dr. Brown is here. I advise her that Dr. Brown's office is down the hall and she is gone in a minute."

I then ask Y, "In such a situation can you detect the cosmetic smell?" The answer invariably is "yes."

I then ask Y, "How long does it take for you to detect the smell and begin to have unpleasant symptoms?"

The typical answer is "immediately," which the patient explains (in response to my next inquiry) is usually "30 seconds to 1 minute." With this information, I can compare the dose tolerated by normal "control" people (i.e., salon workers, workers who demonstrate perfumes and cosmetics at the department store, painters, technicians in a hospital pathology lab, traffic police working at the busiest intersection in the city, or the woman or man who wears perfume all day). These and many other "normals" are free of symptoms despite 8 hours daily of scent exposure.

Therefore, the time comparison between the "chemically sensitive patient" and normal controls is 1 minute versus 8 hours of exposure, equal to 480 times.

However, many of these normals (the painter, the lab technician treating pathology slides with formaldehyde or toluene, the salon worker and others) have their noses 1 foot away from the smell source, while Y is 6 feet away. When light, sound or smell is disseminated in all directions from a single source, the concentration falls off as the square of the distance from the source. Compared to the 1 foot nasal distance from the scent source in the "controls," Y's exposure 6 feet away is 6 squared or 36 times less than the control subjects. Therefore, Y's purported chemical sensitivity (480 x 36) is more than 17,000 times that of the control normal subjects.

Considering the normal ranges of vulnerability to exposures to toxins or other environmental stimuli, the exposure doses to which Y attributes his or her "sensitivity" cannot possibly be biologically toxic.

Y's "sensitivity" or intolerance is not an allergic reaction. Allergies, in general, are specific and can be confirmed on allergy testing or "blind" challenges. Y's environmental triggers are multiple and non-specific and even too weak to qualify for common allergic reactions. Furthermore, an allergic tendency is not a requirement for ES to chemicals and is not relevant to electromagnetic sensitivity. Most patients like Y have tested negatively for a presumed allergic cause of their symptoms and for "physical allergies" like cold sensitivity.

People who develop symptoms quickly upon exposure to electromagnetic fields exhibit similar symptoms to those with Multiple Chemical Sensitivity. The most common exposures relate to Wi-Fi or other IT systems such as cell phone use, proximity to cell phone towers, microwave ovens, overhead street wiring, etc.

A patient on whom I consulted developed distressing symptoms when he entered his teenage son's bedroom when he was doing school homework on his computer. Several teachers experienced symptoms when Wi-Fi was introduced in the school.

When a patient with EMF intolerance is presented with placebo-controlled blinded challenges, he or she could not distinguish between the real EMF stimulus and the dummy placebo.

The symptoms described by patients with environmental sensitivity (ES) are consistent with entrenched beliefs or psychological anxiety, panic or phobic reactions, clinically and quantitatively. This has been confirmed by extensive research published in respected medical journals.

Unfortunately, the unscientific and irrational aspects of ES are not recognized by a small number of physicians or medical clinics dedicated to ES. They accept the ES diagnosis and generally recommend treatment that reinforces a patient's avoidance behaviour. This compromises the patient's ability to work and constricts his or her life experience in many ways. Various medications may be prescribed in these clinics.

A very effective treatment in many cases is intensive "Hands On" cognitive behavioural therapy (CBT). If the patient tries CBT on Monday and Wednesday but follows the previous advice on Tuesday and Thursday, he or she will never improve.

I close this discussion by describing a specific patient whom I saw in consultation, but followed up personally. I advised CBT which was very successful.

The above patient was Mr. A, described in the first paragraph of this essay. His major symptoms following exposure to the various triggers were the feeling that his throat was closing, a throaty cough, shortness of breath and dizziness. Allergy tests had been done previously and were negative.

At the scent-free St. Michael's Hospital Occupational Health Clinic consultation, I could find no evidence of other significant disease of Mr. A that could explain his symptoms. Throat and chest exam and pulmonary function tests were normal. He agreed to be challenged with perfume. In a small closed room he sat on an armchair next to a table. I placed a few drops of perfume on a Kleenex tissue on the table. In less than 2 minutes he began to cough and choke and to breathe rapidly with no audible wheezing. I looked at his mouth and throat which were normal and gave him a mirror and flashlight to observe his own throat which was normal. On the breathing test (pulmonary function test), his respiratory flow rate was slightly reduced but I could see that he unconsciously made a reduced effort. The flow rate became normal with a full expiratory effort.

I suggested to him that I believed his symptoms were due to strong belief or other psychological problems "triggered" (not "caused") by the perfume smell which was non-toxic and did not cause allergy.

The above experience was Phase I of the cognitive part of CBT which is just the beginning of the CBT process. He understood but accepted that this was just the early insufficient phase of CBT.

I was 75 years old at that time and took one hour for lunch. I suggested that we try the behavioural phase of CBT therapy Monday at noon. We met in front of the Queen Street entrance to the Hudson's Bay department store, which was close to St. Michael's Hospital and to Mr. A's office.

On the sidewalk outside of "The Bay," Mr. A observed his normal-appearing throat using a mirror and flashlight and measurement of his peak expiratory flow rate with a handheld peak flow meter was normal.

I then held his hand and entered the perfume-cosmetic area of The Bay.

After 5 minutes, Mr. A was extremely distressed and stated he must exit. He repeated his throat exam and peak expiratory flow (with my encouragement for maximal effort). Both were normal.

On Tuesday noon we repeated the trial (still holding hands). Mr. A lasted 10 minutes in the perfume cosmetic area. On returning to the sidewalk, mirror and peak flow exams were normal.

On Wednesday, the handholding pair ventured further into the cosmetic department with a needed symptomatic 15-minute exit. Tests were normal.

On Thursday, Mr. A and I spent a relatively comfortable 20 minutes in the cosmetic area followed by normal sidewalk tests.

On Friday (still holding hands), we spent a happy and comfortable 30 minutes in the department. Mr. A allowed a sales person to demonstrate a scented cosmetic cream on his forearm with no adverse symptoms. Some of the sales personnel snickered as the handholding pair walked by. The sidewalk tests were normal.

Mr. A's environmental sensitivity had been cured!! He was overjoyed. His "sensitivity" did not return.

CBT usually takes much longer, with sessions 2 or 3 times weekly by younger "behavioural therapists" who do not have the "authority" and presence of a senior St. Michael's Hospital physician, but their methods may be similar, always guided by the patient's personal problems and circumstances.

The bottom line is that quantitative analysis (because the dose is the poison) should be a part of the investigation of patients with the ES syndromes.

Allergic, immunological or toxic reactions to specific or excessive doses of occupational or other exposures are quite different and very common. These are well studied and treated in occupational health clinics, by dermatologists, respiratory, allergy and immunology clinics and other scientifically based medical services.

In conclusion, for environmental sensitivity symptoms, MCS or IEI, and electromagnetic field sensitivity, challenge tests or a history of challenge tests and quantitative analysis (the dose is the poison) can demonstrate that these syndromes are not due to toxic or allergic mechanisms. Many patients respond well to CBT.

Arthur Leznoff, MD, FRCP (C) is a semi-retired honorary consultant in medicine at St. Michael's Hospital, Toronto. Prior to his present status, he had been head of the Allergy and Clinical Immunology Division and Associate Professor of Medicine at the University of Toronto. Currently he consults in environmental medicine, electromagnetic sensitivity and mould-related disease.
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Author:Leznoff, Arthur
Publication:Humanist Perspectives
Date:Dec 22, 2019
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