Medical Evaluation and Treatment of Patients with
Chemical Injury and Sensitivity
by
Grace Ziem,
M.D., Dr. P.H.,
Conference Sponsored
by the
National Institute of Environmental Health Sciences
August 13-15, 2001
Medical Evaluation and Treatment of Patients with Chemical Injury and Sensitivity
Abstract
Medical testing was conducted on 30 consecutive toxic injury new patients seen in the author’s medical practice. These patients typically had toxic encephalophathy with reactive airways disease. Other abnormalities were quantified by testing, and included adrenal cortisol changes with frequent deficiency; protein deficiency with greatest deficiency in detoxification-related amino acids; changes in Phase II detoxification following challenge, with deficiency of glutathione and superoxide dismutase and increase of lipid peroxides and other free radicals; changes in cell membrane lipid composition to a proinflammatory status; Secretory IgA deficiency with frequent parasites and/or Candida; pancreatic digestive enzyme (chymotrypsin) deficiency; food intolerances; intracellular essential mineral deficiency; reduced antioxidant function; altered energy metabolism; and other nutrient defiency, the most prevalent being B12 (involved with myelin synthesis). Toxic exposures inducing illness were symptomatic (and repeated, except one patient from a massive propane leak). Other causal agents were solvents, pesticides (organophosphates, pyrethroid, chlordane, benzyl benzoate, other), vehicle exhaust in a building, “sick building” volatiles, adhesives, inorganic chlorines, formaldehyde and glutaraldehyde.
Introduction
Toxic
exposure to a variety of petrochemical compounds or combustion products can
induce permanent heightened intolerance to chemicals.[1]
Toxic induced brain damage, also called toxic encephalopathy, can also
induce chemical intolerance.[2],[3] Even
relatively short term exposure to petrochemical compounds can cause a
significant heightened intolerance to future chemical exposures.3 Short-term intermittent exposures at even
modest levels are capable of causing heightened neural (brain) sensitization by
means of the mechanism of time dependent sensitization.[4],[5]
Toxic
Encephalopathy
Many petrochemical
compounds have been shown to cause chronic changes in brain function as
documented by testing.[6],[7],[8],[9],[10],[11],[12],[13],[14]
Industrial accidents and exposures, sick building exposure and
environmental overexposure's are all capable of causing toxic encephalopathy.[15]
Persisting brain damage can be caused by either repeated or single acute
symptomatic exposure to combustion products, pesticides, volatile organic
compounds, solvents, inorganic and organic chlorines, hydrogen sulfide, and a
wide range of petrochemicals.15,[16],[17],[18] Even
low-level exposure to volatile petrochemical compounds can cause changes in
brain function.[19]
Short-term exposure can also cause toxic encephalopathy.3 Numerous studies document toxic
encephalopathy resulting from low level chronic exposure.[20],[21],[22],[23]
Further exposure after brain damage begins causes additional damage,[24] demonstrating the need for early detection
and focusing on neurologic symptoms with exposure at an early stage, such as
impaired attention span, reduced memory and/or concentration, headache, balance
disturbance or impaired coordination, because these can become permanent10,11,13,14,[25],[26] unless the individual is removed from
exposure and/or the exposures promptly controlled to below a symptomatic level.
Because petrochemical
compounds are often lipid soluble, they are readily taken up into the brain and
concentrate in the lipid part of the brain.[27]
Toxic compounds are also capable of entering the brain directly through
the nose.[28],[29] The
brain also has a special vulnerability to toxic damage because of other
factors, including the long shape of nerve cells and the high metabolic rate of
the brain so that even minutes of adverse changes in brain metabolism can cause
brain cell death.28 The
relatively small number of neurons which utilize the neurotransmitters dopamine
or acetylcholine creates increased
vulnerability to causing, respectively, profound reductions in coordination and
memory.28 Further, brain cells are unable to regenerate, so that
death of a brain cell is usually permanent.28 Impairment of energy metabolism increases
the risk of brain and nerve cell damage.28 Such impairment is
common.[30]
Impaired energy metabolism is found in the vast majority of chronically
ill toxic injury
patients.30 Petrochemicals are also able to attack the
membranes of nerve cells, causing damage.[31]
SPECT brain
scans on individuals with chronic symptoms following toxic exposure to various
petrochemical compounds compared to healthy control subjects show reduced blood
flow to the brain and reduced ability of the brain to take up the tracer
substance in the early phase of injection.[32],[33],[34] This
is often not evident in the late phase of injection with SPECT scan testing,
emphasizing the need for such scanning to focus on the early phase of
injection, which is not always done when this scanning is performed for
evaluation of other neurologic conditions.
Changes seen in these SPECT brain scans studies involve the frontal,
temporal and limbic brain areas.
Because of the well known relationship of the limbic brain to emotions,
those lacking thorough knowledge of toxic encephalopathy can confuse
toxic-induced brain effects with a psychologic condition. However, mood and personality changes which
are long-standing have been documented in patients with toxic encephalopathy.10,11,13,14,25,26 A study which evaluated symptoms in toxic
encephalopathy patients secondary to long-term exposure to organic solvents
found chronic persisting symptoms of fatigue (90%), impaired short-term memory
(94%), reduced concentration (88%), irritability (84%), headaches (81%) and
other neuropsychiatric effects.17
Reactive
Airways
Another
mechanism by which toxic injury can cause heightened future sensitivity to
chemical exposure is reactive airway disease.
Repeated modest or even "tolerable" level exposure to
irritants,[35],[36] higher dose single36 or repeated[37] exposure to irritants can cause permanent
reactive airway disease. This induces
significant increased respiratory sensitivity to irritant exposures in the
future.35,37 Irritants cause
reactive airway disease of upper and/or lower airways by release of the
inflammatory substance P and the mechanism called neurogenic inflammation.[38]
Biopsy study has confirmed that irritant exposure can cause loss of the
protective nasal epithelial cells, increased permeability (which could allow
future irritants to enter more readily),
chronic
inflammatory changes, and an increase in the number of nerve
fiber endings
of the olfactory nerve in the nose.[39] These
changes would not only affect the respiratory system but would increase the
risk of toxins entering the brain directly through the nose. Other scientists have independently
confirmed that reactive airway disease can involve the upper as well as the lower
airways.[40]
Reactive
airway disease can be induced by volatile organic compounds.[41]
These compounds as well as virtually all other petrochemicals are
irritants[42],[43] Non petrochemicals such as ammonia and
chlorine[44],[45] are also irritants. Reactive airway disease can be induced by
solvents,39 pesticides,39
indoor air pollutants,[46] and inorganic irritants.39,14
Reactive airway disease is considered a long-standing or permanent phenomenon
even after the initial causal exposure has been discontinued.[47],[48],[49]
Respiratory
irritation in humans at even low levels of exposure to a mixture of irritants
and/or volatile chemicals shows more than additive effect.44,45 The degree of hyperadditivity increases with
the number of substances present and also with the fat soluability of the
chemicals.41 Prior irritant
exposure increases the irritant effect of subsequent irritant exposure.44 Longer duration of low level exposures
and/or higher levels of chemical mixtures increases both adverse response of
symptoms as well as sensitization.[50] A
key feature of reactive airway disease is heightened respiratory symptoms with
exposure to irritants.35,36,37,41
Nonrespiratory symptoms are also increased following irritant exposure
with reactive airway disease,41 which is consistent with the
inflammatory response and release of inflammatory substances (which increase
fatigue, aching, etc.) as well as the reduction of the protective nasal
epithelium and thus increased ability for toxins to enter the brain.
Intolerance
to chemical irritants has also been reported in persons with asthma39,[51] and in those with rhinitis.39 Additionally, a community based
epidemiologic study of individuals diagnosed with asthma found a higher level
of illness exacerbation from irritants such as new carpets, scented products
and cleaning products compared to nonasthmatics.[52]
Persons with a diagnosis of hay fever also experience frequent illness
exacerbation from irritants such as pesticides and vehicle exhaust.42
Asthmatics and individuals with hay fever also have significant exacerbation
from irritants such as drying paint and passive smoke.42
A study of
non smoking individuals with reactive airway disease/airway hyperreactivity to
irritants showed that testing such as methacholine challenge, chest x-rays and
lung function tests were not reliable predictors of reactivity, that symptoms
typically involved the upper and lower airways and often failed to respond to
(beta 2 agonist) bronchodilators or steroids, and were commonly accompanied by
symptoms such as fatigue, headache and/or musculoskeletal aching.[53] When
these patients were challenged tested, the authors found that the hyper
reactivity involved not only the upper and lower airways but also the
eyes. Perfume challenge testing below
the smell level exacerbated symptoms of airway hyperreactivity in the upper and
lower respiratory tract as well as causing headache and fatigue.50,[54]
This challenge testing also exacerbated eye symptoms. Psychologic causation was ruled out.50,54 Eye irritation also occurs with irritant
exposure at even low levels, and with mixtures of irritants shows more than
additive effect on eye irritation in humans.41
Evaluation
of Chemical Exposure
The author has
long been a treating physician for hundreds of toxic injury patients. This paper reflects that experiences as well
as the medical literature.
A basic
principle of toxicology is that lowering exposure reduces the risk of adverse
health effects.[55] When
determining what exposure controls are most appropriate to a particular
patient, it is useful to evaluate whether they have toxic related organ changes
(see discussion below) and their response to commonly encountered exposures to
irritants and other toxins. A
questionnaire which is excellent for characterizing the dose response
relationship of a particular individual for exacerbating exposures was
developed at the Johns Hopkins School
of Hygiene
and Public Health by Dr. Davidoff and colleagues and has
been validated in
the peer-review medical literature.[56] The author has used this questionnaire1
for many years in evaluation of toxic injury patients because it describes the
duration of exposure, characterizes an exposure in readily understandable
language that helps to assess its intensity, and characterizes the response. It
is also useful to ask the question:
“how long does it usually take to feel as good as you did before” to assess
recovery time from exacerbations. Another useful assessment instrument which
the author has utilized was developed by Dr. Kipen and colleagues[57] (Appendix I). This assessment instrument is particularly useful to determine
which specific exposures and products are problematic in the home, school or
workplace.
Careful
evaluation of the home environment is important because of the amount of time
individuals spend in the home. The
author utilizes a home questionnaire section (Appendix II) and reviews the responses with the patient, obtaining
further information as indicated. It
has been the author’s consistent experience that individuals who have chemical
exposures in their community sufficient to exacerbate symptoms on a recurring
basis experience significant health improvement by relocating unless the
community exposure can be controlled below levels which exacerbate symptoms,
eg., when opening windows, being outside near the home.
If the
individual is working or attending school, it is important to evaluate whether
the workplace or school has exposures which exacerbate symptoms. For occupational exposures, many principles
of an occupational exposure history apply.
These include the timing of symptoms relative to exposure, such as
whether the individual is more symptomatic at home or at work, particularly
early in the course of illness. For
individuals who have become chronically ill, significant improvement may not
occur with being away from exposure for only hours or a few days, so for these
individuals information about symptom levels when the individual is away for
longer periods of time such as several weeks or more is particularly
helpful. It is useful to obtain
information about the tasks being performed, with sufficient detail to allow a
mental image of the exposure in relation to the individual. Asking the person to provide a diagram is
also a helpful aid in clarifying the exposure.
Material safety data sheets or other means of obtaining the chemical
identity of exposures is useful, and the health care provider can obtain this
information with the patient’s consent through the OSHA Hazard Communication
Standard: 29 CFR 1910.1200. Results
from workplace medical monitoring can be obtained through the OSHA Access to
Medical Records provision: 29 CFR 1910.0020.
This allows the health provider or other designated representative, with
the patient’s consent, access to any workplace study and personal and/or
medical monitoring for which the employer has a copy, thus allowing access for
information conducted by consultants as well as in-house studies. Information about the heating, ventilation
and air-conditioning (HVAC) system is also useful. Exposure is more likely to affect the individual in work areas
that share a common air supply through the air handling system. Air monitoring, HVAC studies etc. are often
done after some corrective measures have been taken: this makes them
nonrepresentative of original exposures.
Common use areas such as entryways, hallways, meeting rooms and
restrooms should also be evaluated.
Similar principles apply to the school environment, although students,
unlike teachers and other school employees, do not have OSHA protection
regarding information access. It
is often possible to obtain needed
exposure information through the individual and/or school administration.
Exposure
Control
It is been
the author’s consistent experience with toxic-induced chronic illness that the
most significant factor for future health is the extent to which exposures can
be controlled below symptomatic levels. There are four studies in the medical
literature which confirm that reduced exposure is the major factor in the
long-term outcome of patients who have developed chemical intolerance: Dr. Lax,[58] an occupational medicine physician, found
that his patients who had environmental controls did much better than patients
without adequate environmental controls.
A survey of 305 persons with chemical sensitivity by DePaul University[59] found that they experienced much greater
relief from environmental controls and reducing exposure than with any other
form of treatment, and that the use of tranquilizing agents was actually less
effective than meditation or prayer.
Another study by Dr. Jason[60] found that individuals were chemically
sensitive and had relatively nontoxic housing had much better long term health
than those that did not have adequate environmental controls in their
housing. This is because once chemical
sensitivity is induced, it can be exacerbated by exposures at work, at home, or
elsewhere. A fourth study of 206
chemically hypersensitive patients by Dr. Miller and colleagues[61] found that reducing exposure to chemicals
was very helpful for 71%, but only 17% of the patients who used psychological
or psychiatric services/treatment found those to be very helpful. It is
important to focus on exposure control in the environments where the person
spends the most time: work, school, and home.
Current
occupational exposure limits (TLVs) have shown no statistical correlation with
health effects.[62]
Adverse health effects are often reported in the medical literature
below these exposure limits.[63] Thus
they are often not a reliable guide of the health status of a working
environment even for workers without toxic injury, and are thus likely to be
less protective for workers who have already developed work-related symptoms.
Accomodation
If the individual has symptoms with a medical condition which
significantly interferes with major life activities, they can be considered to
have a qualifying condition under various disability legislation and
regulations. The most effective
approach is to discuss with the individual the exposure situations, utilize
knowledge of the health care provider and/or other information sources, and
then formulate a request for reasonable accommodation which is planned
according to the types of exposures and the degree of severity of the
exacerbated response, also taking into consideration the known toxic properties
of the substance(s).
Nontoxic and
least toxic pest control methods have been developed for virtually all weeds
and pests,[64],[65] and should be requested for persons with any
disabling symptoms or symptoms which are exacerbated in that environment and/or
frequent symptoms. It is the author’s
experience that pesticide residue, even when weeks old, can exacerbate illness
in individuals who have toxic-induced illness and/or heightened intolerance to
pesticide residue by history. The
reasonable accommodation provision regarding nontoxic pest control would
probably not apply to agricultural situations in which the crop is an important
source of livelihood, but advance notification can then be utilized. This provides much less protection but still
allows the individual to take some preventive precautions as described below. In the author’s experience, chronically ill
persons near agricultural pesticide use have significant difficulty achieving
significant improvement, despite other medical interventions (which can slow or
limit deterioration).
Reasonable
accommodation can also be requested and provided for cleaning agents, air
fresheners and less toxic renovation and repair products. These also have alternatives which are
effective and far less likely to exacerbate symptoms.[66]
Individuals
can also be requested to refrain from the use of scented products if they are
in an environment sufficiently close to an affected individual to exacerbate
symptoms. Because scented product use
is often a personal behavior, compliance is often much more successful if
persons understand the nature of scented products (Appendix III). Illness
reactions in the general population are common to scented products, involving
20 percent or more of the population.[67],[68] Illness reactions can cause migraine
headaches, sinus congestion, hoarseness and/or asthma reactions. Further, scented products residue can cling
to hair and clothing for many hours at levels sufficient to exacerbate illness
hours later. Like the issue of smoking and passive smoke, altering personal
habits may initially be resisted by some individuals, but in the author’s
experience, when users have adequate knowledge and when decision makers set a
positive example and tone, reasonable accommodation can often be achieved.
Other
reasonable accommodations for the workplace can include
changes in
work schedule to reduce exposure to rush hour traffic; and for all
environments, conducting the activity in an area with a window that can be
opened if the exterior environment is less polluted than the interior
environment. Advance notification is also needed for painting or pest control
procedures, since even less toxic products may cause a problem, albeit of less
severity, for certain individuals.
Flexi-place accommodations can be used for home, work and school
environments and are medically necessary if the individual’s health declines or
symptoms aggravated despite attempts to achieve reasonable accommodation or if
adequate accommodation is not achievable or not undertaken.
Once the affected individual and their health care provider and/or other information sources have adequately discussed which accommodations are needed and appropriate, a recommended format is that the individual request in writing the accommodations and the health care provider confirms the meme if the individual’s health declines or symptoms aggravated despite attempts to achieve reasonable accommodation or if adequate accommodation is not achievable or not undertaken.
Once the affected
individual and their health care provider and/or other information sources have
adequately discussed which accommodations are needed and appropriate, a
recommended format is that the individual request in writing the accommodations
and the health care provider confirms the meecision makers set a positive
example and tone, reasonable accommodation can often be achieved.
Other
reasonable accommodations for the workplace can include
changes in
work schedule to reduce exposure to rush hour traffic; and for all
environments, conducting the activity in an area with a window that can be
opened if the exterior environment is less polluted than the interior
environment. Advance notification is also needed for painting or pest control
procedures, since even less toxic products may cause a problem, albeit of less
severity, for certain individuals.
Flexi-place Patients who experience exacerbation
of symptoms in traffic should utilize an automobile activated charcoal
filter. Devices which generate ions are
not medically recommended because of their ability to create airway irritants.
Care should
be taken in recommending specific filtration devices. Areas with a moisture problem should utilize a device with a HEPA
filter, since this is needed to capture mold particles. When mold is not a problem, HEPA filters may
be unnecessary and some HEPA filters can create some exacerbation in certain
individuals because of their glues. Consideration should be given to the noise level of the device to reduce the risk
of gradual hearing loss. Whole house filtration can also reduce noise if
properly located. The device also needs to be adequate for the space and
contaminant level. Thus for workplaces
it is often useful to use a smaller office.
For the home, it is helpful to have such filtration at least in the
individual’s bedroom and major living areas.
In many environments it is more effective to leave the filter device
running so that pollutants do not build up in the individual’s absence. This also avoids the need to turn the device
on high, creating a higher noise level during occupant use.
Some
individuals experience symptom exacerbation from water which is used for
cooking, drinking or shower. This is
more common for chlorinated water, since chlorine reacts with organic debris to
form chloroform. Individuals with wells
near areas of pesticide application also need activated charcoal filtration for
shower/bathing and may wish to consider bottled spring water for drinking and
cooking. Chronically affected
individuals can benefit from whole house activated charcoal water filtration to
control chloroform, pesticides etc., which can be used with backup activated
charcoal filters on shower and cooking/drinking water for optimal control. The investment in filtration devices may
well be offset by a reduction in medical expense and disability. Periodic filter changes are needed, with
frequency according to contaminant levels
and illness severity.
Home Controls
If relocation
is needed or if the individual plans to move, a relatively
nontoxic
house with electric heat and appliances is recommended. Other important features include relatively
nontoxic flooring such as hardwood or tile, a substantial buffer of land,
ideally wooded or a body of water, location preferably not closer than one mile
from agricultural pesticide use, not closer than one-quarter mile from a major
highway, and not close enough to an industrial or other commercial emission
source to notice any detectable odor or particulate. Ideally the house should be free standing and under the control
of the patient, because of the problem of chemical use in an apartment or
condominium. If the house has an
attached garage, an impermeable barrier between the garage and house is
recommended. Windows that open easily in the bedroom, kitchen and other major
living areas are important. Ceiling
fans can be utilized to help reduce the need to close the house during much of
the summer. Very major improvement in health occurs with such housing in the
author’s experience.
Because of
the amount of time spent in the bedroom, often about 60 hours per week, extra
caution in bedroom exposures typically results in reduced respiratory
irritation, fatigue, neurologic symptoms, etc.. Controls here, especially for
individuals with frequent symptoms, are recommended to include mattresses or
futons without petrochemical flame retardants (which may require a physician’s
prescription) and without pesticides, which are common in mattresses as mold
control agents. Mold can be controlled
with a very tightly woven mattress and pillow enclosure called barrier
cloth. Because cotton is often grown using
a significant amount of pesticides, bedding and mattresses using cotton grown
without pesticides often results in reduced symptoms. Because pillows are close to the breathing zone for many hours
daily, even small amounts of offgassing from a pillow can exacerbate
respiratory symptoms, and affected individuals typically improve noticeably
when synthetic pillows are replaced with those containing natural fibers. Patients report that wool containing pillows
are more comfortable than those with cotton. If down is utilized, barrier cloth is essential as is ensuring
that the individual does not have allergies. New onset allergies are not
uncommon in chronically affected individuals and down pillows could potentially
initiate allergy to dander, especially if used without a barrier cloth pillow
case.
Individuals
who experience respiratory congestion with newsprint can utilize a reading box
with proper ventilation to reduce illness exacerbation. Non-toxic airtight
containers to store printed matter in the house reduces exposure. Some affected individuals experience skin
irritation with synthetic clothing and need to utilize clothing made from
natural fibers. Storage of food in containers
made from glass, metal, or wood derived cellophane can reduce food contamination.
Individuals with frequent symptoms following toxic exposure improve when eating
foods not grown with pesticides. This
avoids the ingestion of pesticide residue, which the body must detoxify.
The author
does not recommend or urge affected individuals to remain housebound. Human beings are social beings and have a
need for personal interaction. Some
individuals are so severely affected that until their body can detoxify better,
they will voluntarily choose to limit their social excursions, and should not
be coerced out. Social interaction can
be improved by the use of a proper car filter, by educating friends and social
contacts regarding medical needs, and of course when society implements
reasonable accommodation in public places, such as least toxic pest control,
cleaning agents, and eliminating “air fresheners” from public places,
particularly since these are often odor masking agents and commonly contain
irritants and/or toxins.
Medical
Measures
As an added
measure but not a substitute for exposure control, individuals who experience
symptom exacerbation with an exposure can take measures to reduce intensity and
severity of exacerbations. The author provides a factsheet to patients
(Appendix IV) describing actions they
can take. Due to difficulty with memory in toxic injury, written information is
especially important. Micellized agents
are useful because of the reduced pancreatic enzymes commonly present.30
It is common during significant exacerbations for the body to become more
acidic. pH strips to self test urine
can be used to determine whether this occurs.
Such patients experience improved symptoms with a bisalt or trisalt
mixture, such as two parts of sodium bicarbonate to one part of potassium
bicarbonate (a drop in potassium levels is also common and determining
potassium levels during exacerbation is useful to assess whether this
occurs). Patients who experience
neurologic, respiratory or cardiovascular symptoms during exacerbations often
benefit from oxygen at 3-4 liters per minute using a ceramic mask and Tygon
2075 tubing (to reduce exposure to plasticizing chemicals) until significant
symptom improvement occurs. Body
temperature can drop further; a well tolerated way to assist this is a yutampo
(metal “hot water bottle” in quilted cotton sack.[69] It
should be filled from tap water, not water heated on the stove, to avoid burns.
The author
also recommends a baseline daily broad range antioxidant protection, often 1-11 gm of buffered C powder in water, vitamin E
at 300-400 IU, micellized A at 5,000 IU, and broad spectrum bioflavinoids. Improved pH can be achieved by testing and
dietary information on foods (Appendix V).
Glutathione
The proper
use of glutathione can significantly reduce the severity of exacerbations in the
author’s experience. Glutathione is the
most important intracellular antioxidant in the body. It is ier cloth pillow case.
Individuals
who experience respiratory congestion with newsprint can utilize a reading box
with proper ventilation to reduce illness exacerbation. Non-toxic airtight
containers to store printed matter in the house reduces exposure. Some affected individuals experience skin
irritation with synthetic clothing and need to utilize clothing made from
natural fibers. Storage of food in
containers made from glass, metal, or wood derived cellophane can reduce food
contamination. Individuals with frequent symptoms following toxic exposure
improve when eating foods not grown with pesticides. This avoids the ingestion of pesticide residue, which the body
must detoxify.
The author
does not recommend or urge affected individuals to remain housebound. Human beings are social beings and have a
need for personal interaction. Some
individuals are so severely affected that until their body can detoxify better,
they will voluntarily choose to limit their social excursions, and should not
be coerced out. Social interaction can
be improved by the use of a proper car filter, by educating friends and social contacts
regarding medical needs, and of course when society implements reasonable
accommodation in public places, such as least toxic pest control, cleaning
agents, and eliminating “air fresheners” from public places, particularly since
these are often odor masking agents and commonly contain irritants and/or
toxins.
As an added
measure but not a substitute for exposure control, individuals who experience
symptom exacerbation with an exposure can take measures to reduce intensity and
severity of exacerbations. The author provides a factsheet to patients
(Appendix IV) describing actions they can take. Due to difficulty with memory
in toxic injury, written information is especially important. Micellized agents are useful because of the
reduced pancreatic enzymes commonly present.30 It is common during significant
exacerbations for the body to become more acidic. pH strips to self test urine can be used to determine whether
this occurs. Such patients experience
improved symptoms with a bisalt or trisalt mixture, such as two parts of
sodium bicarbonate to one part of potassium bicarbonate (a drop in
potassium levels is also common and determining potassium levels during
exacerbation is useful to assess whether this occurs). Patients who experience neurologic,
respiratory or cardiovascular symptoms during exacerbations often benefit from
oxygen at 3-4 liters per minute using a ceramic mask and Tygon 2075 tubing (to
reduce exposure to plasticizing chemicals) until significant symptom
improvement occurs. Body temperature
can drop further; a well tolerated way to assist this is a yutampo (metal “hot
water bottle” in quilted cotton sack._
It should be filled from tap water, not water heated on the stove, to
avoid burns.
The author
also recommends a baseline daily broad range antioxidant protection, often 1-11
gm of buffered C powder in water, vitamin E at 300-400 IU, micellized A at
5,000 IU, and broad spectrum bioflavinoids.
Improved pH can be achieved by testing and dietary information on foods
(Appendix V).
The proper
use of glutathione can significantly reduce the severity of exacerbations in
the author’s experience. Glutathione is
the most important intracellular antioxidant in the body. It is s are close to the breathing zone for
many hours daily, of brands and insulation is critical, since glues, certain
woods, some insulation materials and various other construction substances can
be heated up and actually exacerbate symptoms in these patients. A sauna in
which the patient is laying down has more risk of falling asleep. If the patient has such a sauna, it is
essential that it never be used without an effective timer and ideally with
another individual who would awaken the person.
Petrochemicals
are stored in fatty tissues of the body, creating a specific body burden. These chemicals are in equilibrium with
blood levels through principles of toxicokinetics such that increased fat
levels result in higher levels in blood and other body tissue. Reducing body burden can help improve
detoxification. Further, reducing body
burden is associated with reduced risk of adverse effects because of the
dose-response principle of toxicology.55
Multiple
epidemiologic studies and clinical case reports confirm both clinical
improvement and reduced body burden of various petrochemical and combustion
products with use of sauna for chemical injury. Unlike some metals, chelation is not used, but reduced body
burden is the common principle. Chronic illness following PCB overexposure
resulted in liver abnormalities and chloracne.
Following sauna therapy, symptoms improved and fat levels dropped by
over 50%.[70]
Seven individuals ill following PCB exposure were given intensive sauna
therapy for an average of 20 days.
There was an average reduction of 21.3% in fat levels of 16 organochlorines
tested.
Testing 4
months later revealed a drop of 42.4% from original levels, indicating that the
initial drop was not just a shift to other body areas.[71]
Electrical workers exposed to PCB’s and other biopersistent
organochlorines were given sauna therapy and organochlorines compared before
and after therapy with electrical workers not undergoing sauna treatment. Treated workers had a mean reduction in
organochlorine pesticides of 7.8% after treatment which by 3 months later
dropped 21.2% compared to before treatment.
Levels in untreated controls actually rose slightly (4.2%).[72]
A study of
103 patients undergoing sauna therapy used a control group of 19 persons
untreated but undergoing comparable testing.
Neurocognitive function revealed a mean increase in IQ in the treated
group of 6.7 points. Symptoms of body
aching improved in 11 of 11 persons affected, irritable bowel symptoms in 8 of
9 affected; dermatitis in 7 of 8 affected; migraine in 3 of 4 affected;
thyromegaly in 3 of 4 affected, etc.[73]
Fourteen firefighters with PCB and combustion product overexposure
showed significant impairment with sauna treatment in neurocognitive testing
for memory, visual images, block design, culture fair, trails, reaction time,
motor speed, and digits backward compared to unexposed firefighters.[74]
Eleven capacitor workers with PCB and other chemical exposure were given
sauna therapy and testing compared with untreated co-workers. Following treatment with sauna, PCB levels
in serum and fat dropped by 42% and 30% in those without concurrent disease (6
patients) and 10% in fat in those with disease. Levels in untreated controls actually increased during the same
interval. Following treatment, there
was significant improvement in symptom severity using a standard rating scale
for chloracne, other dermatologic problems, headache, and eye, respiratory,
gastrointestinal, musculoskeletal and neurologic symptoms.There was no symptom
improvement in the untreated group.71
Clinical
improvement following sauna therapy has also been documented with case reports
in several peer reviewed medical articles.
A disabled woman following soot and fire ash overexposure had severe
adenopathy, extreme fatigue, pustular acne, sleep disturbance and chronic
respiratory symptoms. During sauna
treatment a black substance began to daily exude from her pores. Following sauna therapy the acne and
adenopathy largely cleared, fatigue and respiratory symptoms greatly improved
and sleep returned to normal.73 There is also some legal precedent
that patients cannot be denied reimbursement for sauna when no traditional
therapy has been shown to be effective in reducing body burden of petrochemical
compounds.[75]
Symptom
Log
For individuals
who have waxing and waning of symptoms and/or exacerbations, a log of these
occurrences can help to identify the particular situations, exposures or other
circumstances chronologically preceding an exacerbation. This log of illness exacerbation may not be
needed long term but is helpful until exacerbating factors have been better
identified. The illness log should
focus on exposures/places/situations in the 6 to 8 hours before the onset of
symptoms or before symptom exacerbation.
Over time, review of this log can assist both the individual and the
health care provider to identify exposures and other situations which precede
symptom exacerbation. This facilitates
an information-based means of developing strategies to reduce exposures using
means described above.
Medical
Evaluation and Care
Neurologic
Evaluation
It is
recommended that patients who describe neurologic symptoms including but not
limited to confusion, disorientation, reduced memory and/or concentration,
difficulty thinking quickly or clearly, balance disturbance and/or
numbness/tingling be evaluated for neurologic and neurocognitive changes. Dr. Kilburn14 has carefully
described evaluation of brain and neurologic function from toxic exposure and
that discussion will not be duplicated here.
It is important to seriously consider his recommendations, because they
were based upon significant experience and careful epidemiologic design
evaluating many hundreds of individuals with frequent symptoms following toxic
exposures such as hydrogen sulfide, chlorine, hydrogen chloride, arsenic,
chlordane, polychlorinated biphenyls, trichloroethylene, diesel exhaust,
combustion products with a toluene rich vapor, and vinyl chloride and other
contaminants. He found Culture Fair
testing of intelligence (2A) and Trail Making B to be the most sensitive of the
neurocognitive testing. He also found
that neurophysiologic testing was often more sensitive than neurocognitive
testing, and that the most sensitive neurophysiologic testing to assess toxic
injury was balance testing (he quantitated by sway speed), blink reflex
latency, visual fields, and simple and choice reaction time. Not all toxins will affect the brain in an
identical way nor cause identical changes on testing, but review of his findings
from epidemiologic studies of the above exposure situations provides vital
guidelines for selecting the most sensitive testing approach. Sensitive testing is important to detect
brain and neurologic injury at the earliest stage to avoid further damage.
Neurocognitive
tests results can be utilized as a basis for focusing cognitive
rehabilitation. This can help the
patient to better cope with damaged brain functions and utilize less affected
areas. This is obviously not a
substitute for controlling exposure and early detection. Following
principles of occupational medicine,[76] when individuals describe cognitive,
neurologic or other symptoms which may be related to exposure, exposure removal
is recommended to ascertain whether symptoms improve. If this principle is widely implemented early in symptom onset,
much chronic and disabling toxic injury can be prevented.
Hyperbaric
Oxygen Treatment
Toxic brain
injury, also called toxic encephalopathy, is associated with reduced blood flow
to the brain[77],[78],[79],[80],[81] on SPECT scan and therefore brain
ischemia. HBOT therapy has
been shown to reduce ischemia and its damage in a wide range of tissues,
including but not limited to the nervous system.[82] Increased lipid peroxides are present in the
majority of toxic injury patients.[83]
Hyperbaric oxygen therapy (HBOT) reduces lipid peroxides.[84] It
also facilitates healing of damaged nerves in the brain as well in the
peripheral nervous system.85
Increased formation of lipid peroxides occurs with toxic injury
(directly through detoxification changes[85] with increased free radical production and
indirectly through inflammation). Cytochromes are essential to detoxification
and can be disturbed by toxic exposure. Cytochrome disturbances can improve
with hyperbaric oxygen therapy.85 Superoxide dismutase is an enzyme
important for clearing toxins from the body and is commonly reduced in toxic
injury patients.84
HBOT helps stimulate production of this enzyme.85
It has been
the author’s experience that significant and long-lasting improvement in brain
function typically occurs with HBOT which often also acts to improve multiple
other symptoms. For improvement to occur, HBOT must be properly
administered. Ideally, the chamber
should be metal rather than plastic or other synthetic material. Pressure levels of 1.3 to 1.5 atmospheres
are recommended except for patients with a history of seizures, for whom 1.25
atmospheres is preferred. No
significant complications have been described at these pressure levels in the
hyperbaric literature.81,83
To avoid exacerbation, for patients with heightened intolerance it is
necessary to utilize a chamber that does not use disinfectants which are
irritants or petrochemicals or leave any such residue. Many hyperbaric chambers are now used for
the treatment of resistant infections, utilizing significantly higher pressure
levels as well as disinfectants. A
toxic encephalopathy patient of the author who mistakenly sought treatment in
such a chamber experienced no improvement, in contrast to significant
improvement seen in all patients treated in a nontoxic chamber and relatively
nontoxic facility. This patient
experienced significant improvement with treatment at 1.5 Atm without
germicidal use in the chamber.
A treatment
of one hour duration can be conducted daily.
Follow-up is recommended during the course of therapy: after a few
treatments to ensure that improvement is occurring and there are no problems
with the treatment or facility, occasional follow-up during the course of
therapy to assess ongoing progress, (which should be occurring if the treatment
is effective), and follow-up before the treatment is terminated. Severely
affected patients may require up to two months of treatment, with lesser
duration needed for more mildly affected individuals. Once the physician can be sure that maximum improvement has been
reached, treatment can be discontinued.
In the author’s experience, benefits are typically long-lasting unless a
significant exposure occurs (an exposure sufficient to exacerbate symptoms for
weeks or months).
It is also
important to insure that the patient will be returning to a relatively nontoxic
home environment, since benefits of hyperbaric treatment can be lost if there
is significant contamination in or near the home or if significant workplace or
school exposures have not been corrected.
It may also be useful to time the hyperbaric treatment after some
reduction in body burden and after treatment for the treatable complications of
toxic injury as described below.
Hyperbaric-like
oxygen
Prior to use
of the hyperbaric chamber treatment, the author used an approach designed to
create increased oxygen availability for toxic brain injury. Blood plasma is capable of carrying oxygen
at levels which are equal to those which can be carried by the red blood cell,82,83
if sufficient oxygen is available. This
technique includes a mask designed by a respiratory therapist, with metal for
the mask and tygon tubing for the face seal.
Other equipment includes tygon 2075 tubing, a glass jar as a water
reservoir, and a wood-derived cellophane humidity mixing chamber.[86]
Oxygen is given at 6 liters per minute for two hours daily, which
requires added humidity to avoid drying the respiratory passages. On the first day, an arterial oxygen blood
draw is recommended while the oxygen is running and after one hour of oxygen
running at 6 liters per minute. The
author recommends an arterial paO2 of 250 mm of mercury for optimal effect:
oximetry testing is not satisfactory for this assessment. Virtually all patients with toxic brain
effects treated in this manner by the author for 6 to 8 weeks experienced
sustained improvement in cognitive function, but the extent of improvement was
less than that seen with the above described HBOT chamber treatment. The author feels that HBOT by chamber is
preferred when possible, but this alternative is better than no measures to
increase brain blood flow. A longer
duration may be needed for more severely affected patients.
Patient
characteristics for subsequent data discussion
One of the
most exciting developments for the author has been the growing understanding
that some aspects of toxic injury are treatable and that such treatment can be
scientific, i.e., test-based. To further
illustrate abnormalities which are more common with toxic injury, all available
test data was analyzed for 30 consecutively tested new patients who had
chronic illness, defined as two or more daily symptoms following toxic
exposure. The toxic cause of exposure
was evaluated with these criteria: 1) the patient was relatively healthy, able
to work/conduct daily activities prior to exposure; 2) symptomatic exposure with symptoms occurring during exposure
and improving away from exposure on multiple occasions (except for one patient
with a single massive propane leak exposure who had only one exposure
incident); 3) symptoms consistent with
the type of exposure; and 4) onset of
chronic illness within hours or days of a symptomatic exposure to the toxin(s). There is no overlap between these patients
and those for whom test data was described earlier by this author.30
Of these 30
patients, the most common situation of exposure was sick building/building
related, involving 9 patients. Two of
the sick building exposures involved mold and could have also involved chemical
agents to remediate mold exposure. Mold
is capable of
releasing
volatile compounds not unlike those encountered in other sick building
environments.[87],[88],[89],[90]
The most
common chemical class was pesticides, involving 9 patients and including
organophosphates chlorpyrifos (two patients), and diazinon; the synthetic
pyrethroid resmethrin; a benzyl benzoate containing dust mite spray which was
utilized on four (symptomatic) occasions by the patient to spray home carpet;
disinfectant glutaraldehyde and occupational handling of plants which had been
pesticide treated. Two of the pesticide
exposed patients involved chlordane, although they came from a very large
family where chlordane had been illegally used to treat the home by a
nonprofessional applicator. To avoid
skewing the data results, I randomly selected two individuals from the
family.
Solvent
exposure was involved with 7 patients, two of whom work in laboratories (one of
whom also had exposure to sterilizing agents and formaldehyde). Two patients were secondary to inorganic
chlorine compounds. One of these
involved passive occupational exposure to a 10% solution of chlorox used to
clean floors. The other was exposed to
sodium hypochlorite in a poultry processing operation. She was one of fourteen individuals exposed
and chronically ill from working in the evisceration department of the same
plant. Two patients were exposed to
adhesives: one a carpet adhesive, the other a drywall adhesive containing
n-hexane. Three patients were exposed
to vehicle exhaust: two to diesel exhaust entering into a building while idling
at open warehouse loading doors and one with gasoline powered vehicles used in
a building.
One of the
patients was exposed to ultraviolet inks containing acrylates and epoxies. This patient has the most severe
exacerbation by light of any patient the author has ever encountered, verified
both by history and testing. Even his
balance testing when facing the window with blinds pulled and wearing
sunglasses was much more impaired than when facing away from the window. This is strongly suggestive of a persisting
body burden. One of the patients was
exposed to medical cleaning towlettes used occupationally in a health care
setting. Some patients had multiple
symptomatic causal exposures to toxins that met the above criteria. Of the 30 patients, 25 (83%) were of
occupational origin, four were a consequence of home contamination and one was
a consequence of removing contaminated items from an office involving diazinon
treatment in an office of a chronically ill family member (who is also the
author’s patient).
Adrenal
Function Testing and Treatment
Reactive
airway disease as well as chemical sensitivity are associated with increased
inflammation.30,40 Petrochemicals when metabolized generate free
radicals[91] which can perpetuate inflammation. Inflammation often causes pain, which
induces cortisol release from the adrenal gland. Inflammation on a chronic basis can deplete adrenal reserve,
leading to adrenal insufficiency.
Like other
hormones, the vast proportion of cortisol is protein-bound when assessed in the
blood. The bound portion is not only
less active but can be affected by other factors such as the protein status,
often deficient in toxic injury patients.30 Blood assessment also
involves venipuncture, which can induce stress and may thus alter results. The cortisol daily rhythm is clinically
important as a basis for medical decisions, making venipuncture impractical for
assessing the rhythm beginning in the early morning and concluding at bedtime.
Fortunately, salivary cortisol levels show excellent correlation with plasma
levels[92],[93],[94] Salivary cortisol is collected by placing a
cotton pad in the mouth to pick up saliva as excreted without sucking motion
(since sucking can alter the composition of saliva) at 7-8 am; 11 am to noon;
4-5 pm and 11 pm to midnight, with one sample collected during each of those
four time intervals.
Of the 22
consecutively tested new patients in this group described above
(Table1), a total of 15 (68%) had reduction of morning cortisol with 9 (41%)
having changes suggesting significant adrenal insufficiency. Of the remaining five individuals, three had
elevations of two or more daily cortisol levels, one had a single modest
elevation and only one had a normal rhythm. This is further evidence of
involvement of the hypothalamic-pituitary-adrenal axis. HPA impairment makes the individual more
susceptible to physical and psychologic stressors.[95]