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Multiple Chemical Sensitivity, MCS

6 Possible causes and mechanisms of illness

6.1 Immunological mechanisms
6.2 Mechanisms in the mucous membrane of the nose
6.3 Neurological mechanisms
     6.3.1 The olfactory-limbic system
     6.3.2 Other mechanisms related to the neurogenic mechanism
     6.3.3 Changes in the functioning of the brain
6.4 Psychological mechanisms
     6.4.1 Conditioned reflexes (Pavlov's reflex)
     6.4.2 Psychogenic factors
     6.4.3 Environmental somatization syndrome
6.5 Toxic-induced loss of tolerance (TILT)
6.6 Illness model based on clinical ecology
6.7 Discussion
6.8 Conclusion

Research into the illness mechanisms behind MCS concentrates on four main categories, three physiological ones and a psychological one:

1. Immunological mechanisms,
2. mechanisms in the mucous membrane of the nose,
3. neurological mechanisms, and
4. psychological mechanisms.

Another hypothesis is based on a new illness concept:

5. Toxic-induced loss of tolerance (TILT),

and, finally, the

6. illness model of clinical ecology

proposed by the American Academy of Environmental Medicine (AAEM).

All these mechanisms are still being discussed. The most important research results and arguments for pathogenesis are presented for each mechanism.

6.1 Immunological mechanisms

The immonological mechanism is the most cited physiological illness mechanism behind MCS. Clinical ecologists in the US are especially fond of this mechanism. Some, including Rea (1992), who works on the basis of the AAEM theory, have suggested that the cause of MCS is a chemically triggered disturbance of the immune system, which can influence other bodily functions. An example of this can be an interaction between the immunological and the neuro-endocrine systems (see section 6.3, neurological mechanisms) (Meggs, 1992; Levin, 1992). Others recognize similarities between immunological responses and inflammatory reactions and suggest, therefore, that an overlapping between the two mechanisms is responsible for MCS (Meggs, 1992).

These hypotheses have not been proven. Since the first years when MCS was described as a hypersensitivity illness, many have sought an MCS-typical immune response among the classic immune responses, in vain. Others have tried to detect an MCS-specific immunological biomarker. Rea (1992) and his colleagues from an eco-health centre, who have performed more than 5000 immunological tests, though not only for MCS patients, have published many results, which correlated well with MCS. They have discovered special subgroups of white blood cells, a special fraction of activated white blood cells, abnormal antibodies against the body's own cells, and new compounds consisting of chemicals bound to proteins. Other scientists have not been able to reproduce Rea's discoveries. This they attribute to differences in research methodologies and scientific demands concerning the blinding principle and reproducibility.

Thus, no clear pattern of impacts on the immune system has been shown to exist in connection with MCS, neither as an immunological weakening nor as a strengthening (Terr, 1986; Simon, 1993). Great differences with respect to methods and quality control in connection with the investigations is the most likely explanation of such a discrepancy between the results of Reas' group and of the others. When the demands on methods and quality have been strict, it has been impossible to discover any illness indicators among the immunological parameters.

Simon (1993) assessed the applicability of immunological tests as biomarkers in a carefully planned study of MCS patients and a control group (concerning biomarkers, see chapter 7). Laboratory tests were carried out in a special laboratory used by clinical ecologists. None of the tests used could identify persons with MCS. Double checks of the same blinded blood sample in this laboratory gave conflicting results (Simon 1993; Friedmann 1994).

Margolick and his associates have come to the same conclusion (Mitchell, 2001).

6.2 Mechanisms in the mucous membrane of the nose

Enhanced sensitivity to odours found in MCS patients has occasioned an investigation of this condition as a possible explanation of MCS.

The mucous membrane in the nose contains chemo-sensitive nerve fibres from two brain nerves: the olfactory nerve (nervus olfactorius) with nerve endings in the upper part of the nasal cavity, and the fifth brain nerve (nervus trigeminus) with nerve endings everywhere in the nasal cavity. Chemicals (odours) stimulate both nerves. Stimulation of the olfactory nerve fibres creates a sense of smell, while stimulation of nervus trigeminus creates a sense of irritation. The two brain nerves transport the impulses received along different paths to centres in the brain, creating different sensations.

Ørbæk (1998) performed provocation tests with odours and chemical irritants in high concentrations on people with toxic encephalopathy (TE) and on normal persons. As opposed to the normal persons, the persons with encephalopathy experienced the odours as extremely uncomfortable irritants. Before the tests, both groups were shown to have normal odour thresholds.

With a double-blind test, Hummel (1996) demonstrated that MCS patients have a non-specific over-reaction, expressing an altered pattern of reaction, when exposed to irritants.

Caccappolo (2000) and his associates tested the reactions of three patient groups 1) with MCS (Cullen's criteria), 2) with chronic fatigue syndrome, and 3) with asthma and some normal persons to chemicals, a pleasant odour and a disagreeable smell. All groups had the same odour threshold. But phenylethyl alcohol (pleasant odour) in concentrations above the odour threshold created a burning sensation and pain in MCS patients, whereas disagreeable smells did not create the same unpleasant sensations. The other groups did not react abnormally, although several persons with chronic fatigue syndrome showed the same reactions as the MCS group. The authors emphasize that the reactions of MCS patients to the odour test did not follow current neurophysiological mechanisms.

Another Swedish group has exposed housepainters with and without MCS to a scent substance with a pleasant odour (furfuryl mercaptan), to chemicals (acetone, VOC), and to combinations of these (Georgellis, 1999). The author did not expect the scent substance to create unpleasant reactions. The persons with MCS experienced the substance alone or in any combination as extremely unpleasant, whereas acetone and VOC by themselves were, by no means, unpleasant.

Meggs' group investigated hypotheses based on the possible role of special nerve fibres (C fibres) and inflammation of the mucous membranes of the respiratory tract. They studied nose and throat in ten MCS patients, of which nine had complaints from the nose. Chronic-inflammation-induced changes were found in all of them (Meggs, 1993). Meggs suggested that it could be a Reactive Upper airway Syndrome (RUDS), analogous to the Reactive Airways Dysfunction syndrome (RADS), an asthma-like condition, which develops from acute exposure to respiratory tract irritants.

Cain (2001) found that persons with recurrent inflammation of the mucous membrane of the nose had enhanced odour perceptibility when the membranes were inflamed, compared to when they were not. Bascom (1992) investigated the role of the mucous membrane of the nose in connection with the development of MCS, assuming that chemicals stimulate the C fibre-containing nerve cells, which are found everywhere in the mucous membrane of the respiratory tract. A stimulation of these fibres in laboratory animals caused substances (neuropeptids) to be released locally. These could cause contractions in the respiratory tract, increased production of mucus, dilation of blood vessels, and increased permeability.

Several other authors have based their hypotheses of the mechanisms behind MCS on inflammation of the C fibres of the nervous system. Substances (substance P) creating local inflammations, which can contribute to the development of MCS symptoms, are released from the nerve endings with C-fibres(Meggs, 1995).

Bascom (1992) described how chronic irritation of the surface of the mucous membrane creates inflammational changes in the nerve end. These changes lead to increased susceptibility to the chemical effects of various respiratory tract irritants. She maintains that a similar inflammatory reaction should be involved in other conditions such as migraine, headache, and to a lesser extent arthritis and fibromyalgia.

Two additional mechanisms in the mucous membrane are mentioned as possible contributory mechanisms. The first is the release of substances (interleukins), which influence the brain, from nerve cells. The other is a theory on “neural switching”, a type of “switching between nerve paths”, according to which a chemical stimulation of the mucous membrane of the nose creates a response from another organ, e.g., palpitation and headache (Meggs, 1995). As illustrations of “neural switching”, Meggs mentions, i.e., respiratory tract symptoms and nettle rash (urticaria) from food allergy and mucous membrane reactions in eyes and nose from eating strong spices. Stimulation of nerve fibres of the trigeminus nerve in the nose and throat can create a protective reaction from the heart with reduced heart rate and pumping action (Ashford & Miller, 1998).

Referring to animal experiments, Sparks (1994) mentions that the release of a nerve substance (interleukin) in relation to nerve tissue inflammation might explain how symptoms are created in various organs in connection with MCS.

6.3 Neurological mechanisms

6.3.1 The olfactory-limbic system

Bell (1992) and his associates are behind most of the research having to do with the hypothesis on an interaction between the olfactory nerve, the limbic system (the brain centre controlling emotions and behaviour), and hypothalamus (the brain centre for the autonomous and endocrine control of organ functions). Our physiological, cognitive, and behavioural reactions are integrated through this system, which also governs the immune response and the hormonal and autonomous control systems. An impact on the limbic system can create changes in most of the bodily functions and in all organs, which corresponds to the symptoms of MCS.

Bell describes how chemicals can enter the nervous system via the olfactory nerve, which is directly connected to the brain. The so-called blood-brain barrier surrounding the brain is circumvented in this way. Experiments with rats show that a substance is transferred from the nerve fibres in the nose to the point of entry of the olfactory nerve into the brain (bulbus olfactorius) and further to other parts of the brain. This mechanism of transport has not been found in humans, but in rats that have inhaled high concentrations of manganese (Brenneman, 2000). This way of access would explain how a chemical reaches the limbic structures in the brain as a starting point for the sensitisation theory.

Neural sensitisation (sensitisation of nerve tissue)

The limbic system consists of several structures, including “amygdala”, “basal ganglia”, “septum” and “hippocampus”, all of which are located in the brainstem. Experiments on animals have shown that amygdala can be sensitised relatively easily (Antelman, 1994). Sensitisation in this context is when repeated exposures to the same substance create an increased response in the organism at concentrations than that would normally not create any response at all. Neural sensitisation can be attained by both “kindling” and “non-kindling” mechanisms.

Kindling is an experimental method aimed at detecting a change in the reaction of the nervous system to external stimuli. Repeated chemical or electrical stimuli, in so low concentrations/doses that they do not provoke a reaction, can lower the threshold concentrations or doses creating cramps.

Non-kindling stimulation gradually increases the response of the animal to repeated chemical/non-chemical stimulations over time. Responses are neurochemical, immunological, hormonal or behavioural (Bell, 1997b).

Both mechanisms of neural sensitisation support a theoretical explanation of why patients with MCS complain of symptoms in several organs (Bell, 1995). According to Bell (1997a), the sensitisation mechanism differs from, e.g., the mechanism behind the conditioned reflex, the point of departure of which, is also the limbic system. But she hints that both mechanisms may help explain the mechanism behind MCS.

Several research groups have confirmed the neural sensitisation mechanism through experiments with animals (Sorg, 1994; Sorg, 1995; Bell, 1997c). Gilbert observed changes in the electrical brain activity and epileptic-like fits in rats after prolonged exposure to Lindan (a pesticide) in low concentrations, whereas nothing happened, when the rats were given a single cumulative dose of Lindan (Gilbert, 1995). Other experiments with animals support the hypothesis that reactivity to, e.g., chemical stimulation can be partly genetically based. A special strain of rats (“Flinders sensitive Line rats”) with additional nerve receptors and greater sensibility to the organophosphate diisopropylenefluorinephosphate (a pesticide) than other strains, has developed behavioural changes similar to those of depressed humans (Overstreet, 1996).

An experimental investigation has shown that medicine, which should not be able to enter the brain because of the existence of the blood-brain barrier, did so none the less, when the experimental animals were stressed (Friedmann, 1996). This observation can support the neural sensitisation hypothesis. That the substance could enter the brain during stress illustrates the hypothesis that a traumatic experience can contribute to or trigger MCS.

Bell and associates found a connection between a highly developed sense of smell and functional disturbances of the limbic system. This was expressed by increased psychological problems such as substance abuse, anxiety and depression in a group of students with increased odour sensitivity (cacosmia) compared to students with a normal sense of smell (Bell, 1996a).

Other symptoms, such as memory problems and prolonged reaction times during neurophysiological testing compared to control groups, which may also have been triggered via the limbic system, have been seen in soldiers from the Gulf War and in other persons with chemical intolerance respectively (Bell, 1996b; Bell, 1997c).

One investigation has tested the neural sensitisation theory on two patient groups with MCS and asthma respectively and a control group, using neurophysiological methods. Bell's theory, according to which MCS patients should have greater cognitive problems than the other two patient groups, could not be corroborated (Brown-DeGagne, 1999).

6.3.2 Other mechanisms related to the neurogenic mechanism

Arnetz' integrated model for MCS

Arnetz proposes a model based on the neural sensitisation theory, and which is more suited for a rational and co-ordinated research effort.

This concept is based on the assumption that sensitisation of the limbic system creates a change in the pattern of reaction, which can be measured by objective criteria. Both physiological and psychogenic factors can bring about this sensitisation (Arnetz, 1999).

The first step in the course of events consists of an initial exposure, which can be reversible, that is, the person being exposed recovers, or it can be irreversible, which means that the limbic system is sensitised; the person is sensitised.

As opposed to Bell, who assumes that a chemical or chemicals penetrate the olfactory-limbic system, Arnetz also sees other types of first-step influences causing sensitisation of the limbic system. These can, e.g., be strong psychosocial stress or a “life trauma” (e.g., so-called posttraumatic stress disorder).

The sensitised limbic system reacts to an enlarged selection of triggering influences – not chemicals and odours only, but also noise, electromagnetic fields, etc.

Arnetz expects to be able to document enhanced limbic sensitivity and reactivity as changes in neurophysiological, neuroendocrine, and endocrine parameters.

Arnetz' theory has been used by Georgellis (1999) in investigations involving Swedish housepainters with and without MCS. Painters with MCS experienced a pleasant odour as a very uncomfortable odour and reacted with stress, anxiety and reduced coping ability compared to painters without MCS. The MCS group also had significantly more symptoms from skin and mucous membranes and they were more tired than the control group. This implies that the changes observed in painters with MCS were due to a reaction in the limbic system.

Uncertainty and fear of being harmed when provoked can, however, have been the main cause of stress.

6.3.3 Changes in the functioning of the brain

Electroencephalograms (EEGs) and all modern electronic methods of examining the functioning of the brain (brain electrical activity mapping (BEAM), positron emission tomography (PET), single photon emission computed tomography (SPECT) have been used to investigate persons with MCS. Although several of the investigations mentioned have shown changes, Mayberg (1994) concludes that these changes are not the final proof, because all of the investigations were vitiated by methodological errors such as lack of standardization of the technical equipment, no control of reproducibility, and no use of control groups.

Heuser (1994) showed that the bloodflow through the brain of persons, who have been exposed to pesticides or organic solvents, has a different pattern than in persons, who have not experienced the same exposure, in depressed persons, and in persons with chronic fatigue syndrome. Unfortunately, the importance of the reported findings is weakened, since information on exposure and criteria for MCS is lacking. Lorig (1994) has shown that odours in low concentrations bring about changes in the electroencephalograms of normal people, which is an indirect objective indication of impact on the brain. Both of these investigations could be the first steps towards finding a biological indicator for MCS. Others should, therefore, look into them.

6.4 Psychological mechanisms

6.4.1 Conditioned reflexes (Pavlov's reflexes)

As an analogy to the mechanism behind the classic Pavlov's reflex, somatic symptoms are created as a response to influences, which normally do not create such symptoms. Many are of the opinion that this mechanism is the main cause of MCS. This is especially obvious when the symptoms occur as a result of exposure to chemicals, e.g., in connection with an accident (Siegel, 1997).

This corresponds to the situation in Denmark, where most MCS cases are reported from clinics of occupational medicine. Many Danish patients with chronic solvent poisoning have probably, to some degree, experienced their multiple episodes of poisoning as traumatic events.

The occupational physician Cullen (1992) does not consider MCS in people, who have been exposed to solvents, to be a conditioned reflex.

Traumatic childhood experiences (e.g., physical and sexual abuse) are emphasized as triggering or facilitating factors. One investigation showed that 60% of patients with chemical sensitivity had such experiences in their childhood, and that psychotherapy reduced MCS symptoms. This created the hypothesis that odours experienced in connection with traumatic events can trigger the conditioned reflex (Staudenmayer, 1993). The investigation suffers from several weaknesses, e.g., unclear criteria for selecting patients, which weaken the conclusions. This hypothesis has not been investigated further.

Other studies show that many people with multiple organic symptoms were abused in their childhood, and that persons who have experienced violent assaults, complain of minor symptoms more often than those who have not (Pennebaker, 1994). That psychotherapy helps in such cases can be taken as indirect proof of the causal hypothesis (Staudenmayer, 1993).

With a method using conditioned reflexes, a Belgian research group was able to create and later eliminate odour-related symptoms in healthy persons (Van den Bergh, 1999). The author concludes that the mechanism behind MCS can be explained, at least in part, as a Pavlov reflex.

6.4.2 Psychogenic factors

It is clear that many persons suffering from MCS complain of anxiety and depression, and many consider this to indicate that MCS has psychogenic causes. Many have mentioned the “iatrogenic” model, where the physician or therapist induces the patients to develop and sustain their symptoms and conception of illness (Black, 1995).

A group of persons were exposed to odours and the intensities of these and the symptoms and discomforts experienced were recorded. Prior to exposure, all of the subjects received information on the odours. One group received negative information and the other received positive or neutral information. The first group felt that the odours were intensified and created discomfort and health complaints, , whereas the other group did not have the same experience (Dalton, 2000; Hummel, 1996).

Many investigations of groups of people with environmental illnesses have shown that among these, more often than among others, are people predisposed for personality disturbances, depression and anxiety symptoms, and somatic and hypochondriac symptoms - all of which indicate that these people may have hidden emotional problems (Black, 1993). On the other hand, people with increased odour sensitivity (cacosmia) have been shown to be more susceptible to feeling anxiety or becoming depressed (Ashford & Miller, 1998).

Personality factors can have to do with the mechanism behind MCS. Women are quicker to develop physical symptoms in stressful surroundings than men. People with chronic anxiety experience all forms of pressure negatively, creating discomfort and health complaints.

These factors are also mentioned in connection with other illnesses, including environmental illnesses. These factors may be of importance as psychosomatic factors behind the pathogenesis of MCS.

Leznoff (2000) observed typical signs of fear reaction accompanied by hyperventilation when MCS patients were exposed to triggering substances. He makes reference to the fact that several triggering symptoms in connection with MCS can be explained by a physiological reaction in the blood circulation of the brain during hyperventilation.

7 out of 13 patients with environmental illnesses had experienced anxiety and depression before they became ill (Simon, 1990). In 38 out of 90 persons filing for compensation for an occupation-induced environmental illness (62 of these with multiple symptoms), psychiatric diagnoses such as depression, anxiety, stress, and psychosomatic symptoms were found. Several had more than one diagnosis. But none of these persons had a psychiatric diagnosis, before they acquired the environmental illness (Terr, 1989). The number and distribution of the psychiatric diagnoses were not reported.

Fiedler (1996) investigated the frequencies of psychiatric diagnoses among her patients on several occasions. In an investigation involving 36 persons with MCS or chemical sensitivity (CS) and 18 controls, several of the 36 had or had had a psychiatric illness. But more than half of the 36 had never had a psychiatric diagnosis. 96 persons with MCS, CS or chronic fatigue syndrome (CFS) and a control group were subjected to neurophysiological and standardized psychiatric tests. More abnormal test results indicating psychiatric illnesses were found in the three groups with MCS, CS, and CFS than in the control group. But 74% of the MCS patients, 38% of those with CS, and 61% of the ones with CFS had normal test results.

Out of ten investigations of the importance of psychogenic problems in connection with the emergence of MCS, considerable methodological problems were discovered in the nine, including the mixing of cause and causal relations in eight cross-sectional investigations (Davidoff, 1994). In a more recent investigation where 1166 persons were tested for MCS, Kutsogiannis and Davidoff (2001) found that psychological factors were not over-represented in persons fulfilling the MCS criteria, compared to the others.

6.4.3 Environmental somatization syndrome

The somatization syndrome, which is often cited in connection with environmental illnesses, including MCS, is based on a psychosomatic mechanism. The pattern of reaction is connected to a tendency in us all to connect illness with an outside agent, while many of us are also latently disposed to developing somatic symptoms in one form or another (headache, fatigue, insomnia, muscular pains (myalgia), etc.) when we are exposed to stress, have personal problems, or are anxious or depressive. The international name for this pattern of reaction is individual determined response (IDR)^[3].

In a chapter of a recently published textbook on environmental and occupational medicine, Rasmussen and Hildebrandt-Eriksen (2001) describe the Danish experience with odour hypersensitivity, which is grouped together with other environmentally determined somatization disorders. The authors consider the illness to be determined by an interaction between the personality structure of the patient and factors in the patient's physical and social environment. They also regard a conditioned reflex like the Pavlov reflex as a possible contributing factor in case of acute overexposure to irritating substances. The authors also mention, that “ … persons with injuries to the nervous system, e.g., toxic encephalopathy, experience enhanced sensitivity to organic solvents and also to non-neurotoxic chemicals in general. We are presumably dealing with other mechanisms than in otherwise healthy persons.”

Thus, the authors group odour hypersensitivity together with somatization disorders, while they suspect another illness mechanism to be behind MCS, when it occurs in persons with symptoms from exposure to solvents. The assumed illness mechanism associated with the latter patient group is not elaborated upon.

6.5 Toxic-induced loss of tolerance (TILT)

The hypothesis associated with TILT, developed by Miller (1997), chooses an induced weakness or the elimination of natural tolerance towards external stimuli (e.g., weakening of the defence mechanisms of certain organs, similar to the reduced tolerance to sugar of diabetics), where a response is triggered at very low concentrations, as a starting point.

This theory is based on a new concept of illness involving weakening or loss of tolerance. Miller also considers this mechanism to be the cause of other illnesses such as migraine. The definition of change in tolerance is the opposite of the change in tolerance connected to drug misuse, since TILT is associated with increasingly lower concentrations of the trigger substance(s) inducing the response. The mechanism behind the loss of tolerance is based on neural sensitisation.

TILT as a cause of MCS, proceeds in two phases: an initial phase involves exposure to chemicals (preferably pesticides, organic solvents or indoor VOC). Not all people exposed develop loss of tolerance. Some do not develop permanent symptoms following the first exposure and recover. Other more susceptible persons develop weakening/loss of tolerance.

During phase two involving exposure to the same or other chemicals or substances in very low concentrations, various organs react with a so-called “trigger response”. Different substances create different responses (e.g., diesel fumes create headaches, food odours lower the ability to concentrate, perfumes creates nausea, etc.). Several daily exposures can create overlapping symptoms from several organs, making it impossible to find the connection between symptom and trigger substance (masking). Exposure to several trigger substances over a number of days can perpetuate the symptoms. This state of affairs can be upheld by constant exposures to new trigger substances (habituation).

Miller sets the diagnosis by testing in a provocation chamber taking both masking and habituation into account. The patient must be free from trigger substances, before the provocation test is performed.

6.6 Illness model based on clinical ecology

This model uses concepts and definitions, which most physicians and researchers are unfamiliar with and usually do not use in connection with their research. The clinical ecologists consider this model and its concepts to offer a better understanding of the pathogenesis behind MCS, as well as other environmental illnesses (Rea, 1992).

According to the holistically oriented illness model for environmental illnesses, to which MCS belongs, many illnesses of hypersensitive people are based on a malfunctioning of one or more of the biological systems of the body: As part of a defence reaction against “environmental stressors”, described as a form of detoxification, an unbalance is created in the bodily homeostasis, followed by a reaction from the bodily organs. The mechanism of unbalance can be caused by defective enzyme systems or vitamin, trace element, etc. deficiency. Reactions from organs create symptoms. The defence mechanism has several aspects and is based on individual susceptibility, pattern of response and adaptation (AAEM, 1992) (see also definition of environmental illness in Annex A).

The following concepts are used to describe the model further:

All descriptions of investigations and research by the clinical ecologists are based on the principles listed above. The illnesses are documented by measurements of very specific organ and enzymatic functions and metabolic processes (e.g., glutathion metabolism), and by the lack of various trace elements. Accurate standard values for such measurements do not exist in general clinical medicine.

Dr. Kuklinski (2001), director of Ambulanz in Rostock (Centre for diagnosis and treatment of environment medical illnesses) is of the opinion that most physicians lack knowledge about the facts mentioned above and, therefore, are unable to diagnose illnesses like MCS.

It is surprising that the holistic illness model does not include the possibility of psychological factors being involved in the pathogenesis of the illness.

6.7 Discussion

The problem concerning the causal relationship between MCS and the mechanisms behind it resemble the well-known “black-box” situation. It is possible to describe:

1. What a person was exposed to initially and
2. what the symptoms are, when a person has MCS.

But what happens between A and B is not known: What mechanisms make a person develop the symptoms when exposed to a chemical, which he/she had no problems with before?

It seems that the course of events having to do with MCS proceeds in two phases. First there is the exposure phase, which for most of the exposed persons has no permanent effect (they do not become sensitive to chemicals). Then there is the trigger phase, where a few of the persons who were exposed initially, get symptoms when exposed to low concentrations of trigger substances. A few of the people afflicted can recover.

Conditions of exposure

Many researchers refer to the course of events described above, but no investigations segregate clearly between the two phases of development of possible illness mechanisms. This is remarkable, since what happens in the initial phase seems very different from what happens in the trigger phase. Certain persons develop a chemical intolerance in the initial phase. This can happen when exposed to high concentrations of a chemical or during a serious virus infection (e.g., mumps in adults) or through psychogenic shock or trauma. No research results describe mechanisms leading to chemical intolerance or discuss the significance of infection or shock/trauma.

During the trigger phase very low concentrations of chemicals create symptoms. The research reports dealt with in this chapter deal with mechanisms of the trigger phase.

According to Bell's theory, the effect created by initial exposure (chemical intolerance) can also be created by repeated exposures to smaller doses over a longer period of time. This hypothesis seems to be based on a combination of phenomena of the initial phase and of the trigger phase. Many researchers include a similar concept in their hypotheses for illness mechanisms behind MCS.

Mechanisms

One of the most plausible hypotheses for the MCS syndrome is: A complex reaction from main brain centres of the limbic system. Various mechanisms may be able to explain, how low concentrations of a chemical create this reaction in the brain.

An immunological mechanism is possible, but a comprehensive pattern of change is lacking, both among the individuals and in each individual.

A mechanism based on the mucous membrane of the nose and the odour-sensitive nerve fibres also seems likely. Several research results point at a reaction of the brain to nervous impulses from the olfactory sense or a mechanism based on the release of biologically active substances from nerve cells in the mucous membrane of the nose.

The theory on neural sensitisation in the olfactory-limbic system offers a plausible explanation of MCS – a chemical in small doses can, over an extended period of time, cause an increased and changed response from the limbic system of the brain. Bell's model on “limbic kindling” fits the description of MCS and corresponds to the neurophysiological functioning of the brain.

Finally, MCS may be based on a toxic mechanism. The literature on organic solvents includes descriptions of the limbic system of the brain being affected in persons with toxic encephalopathy, and a toxic mechanism is assumed to be involved. This chapter presents results from many research reports describing MCS or MCS-like conditions in persons who have been exposed to toxic doses of organic solvents.

It is difficult to prove or disprove that MCS in some persons has psychogenic causes or is due to a psychiatric ailment and, conversely, that MCS is the cause of psychogenic symptoms. Existing psychogenic problems can contribute to MCS. That psychological problems can increase the susceptibility of some persons to environmental impacts is well documented (individual increased susceptibility). This psychological factor plays a role during initial exposure as well as in the “trigger” phase of MCS patients.

This hypothesis entails, e.g., that persons predisposed to fear and depressions are in greater risk than others of acquiring MCS when exposed to chemicals.

A large group of MCS researchers agree that psychological mechanisms can sometimes trigger MCS, but most probably not in all cases. A connection exists between MCS and psychological factors, but this is not to say that there is a direct causal connection between the two (Graveling, 1999).

The conditioned reflex, especially the character and pattern of the response, does not correspond to an MCS response (e.g., the tunnel workers mentioned in subsection 4.1.1). It can be debated whether the mechanism behind the odour hypersensitivity of Danes having been exposed to solvents is due to a conditioned reflex. If so, then the exposure itself has been a traumatic experience.

This possibility exists and several Danish occupational physicians support this mechanism as an explanation of odour hypersensitivity. But no Danish investigations support this supposition. Ørbæk's (1998) investigation of two persons with toxic encephalopathy points to other mechanisms. Van den Bergh et al. (1999) consider the mechanism of MCS to be a conditioned reflex, but it is hardly the primary mechanism behind all cases of MCS.

Most people can accept a mixture of a psychogenic and a physical illness mechanism to be behind an illness. At present, several researchers refer to interactions between psychological, physiological and other (social) factors as mechanisms behind MCS.

Based on this hypothesis it is assumed that the pattern of symptoms connected to MCS is created by a physiological-psychological impact on the olfactory system and other brain centres (amygdala and hypothalamus). A combination of several mechanisms including primarily alterations in the nose, neural sensitisation, and psychological mechanisms must be contemplated as a mechanism of impact.

Various discoveries in persons with odour hypersensitivity could imply that a subgroup of people among us are born with or have acquired an ability to be sensitised by environmental factors. Bell (1995) is of the opinion that low concentrations of a chemical create physical and psychological symptoms in especially sensitive persons, who may be genetically predisposed for affective illnesses. This hypothesis has not been corroborated, but many research results support the theory indirectly.

If it is correct, one can expect that among a randomly chosen group of people exposed to the same chemical(s), some, belonging to this subgroup, will react more strongly than others. They will prove to be more susceptible to chemical impacts and thus candidates for developing MCS.

Olin (1999) is of the opinion that our modern age makes increasing numbers of people more susceptible to environmental impacts. The most important single factor of this change is that people are increasingly being bombarded with sense impulses and impressions, which are added to the impacts from chemical, technical, and psychogenic environmental factors already received. Many cannot adapt to the new impacts and develop the well-known unspecific health complaints associated with MCS. Olin considers the causes of these complaints to be biological rather than psychological.

6.8 Conclusion

Definite knowledge of and scientific documentation for causes and mechanisms of illness in connection with MCS still do not exist. None of the mechanisms described have been excluded beforehand.

At present, most researchers agree on the following:

1. The mechanism is based on an interaction between one or more physiological and psychological factors and
2. MCS is primarily seen in persons, who react more readily to external environmental impacts than others.

The following hypothesis can be put forward: The illness mechanism behind MCS involves both physiological and psychological impacts on certain brain centres in particularly predisposed persons.

Footnotes

[3]. Individual determined response (IDR): Somatic manifestation of an emotional response to an external or internal stimulus.

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