gms | German Medical Science

GMS Current Topics in Otorhinolaryngology - Head and Neck Surgery

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V. (DGHNOKHC)

ISSN 1865-1011

Multiple Chemical Sensitivity (MCS) : Scientific and Public-Health Aspects

Review Article

Suche in Medline nach

GMS Current Topics in Otorhinolaryngology - Head and Neck Surgery 2004;3:Doc05

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter:

Veröffentlicht: 28. Dezember 2004

© 2004 Schwenk.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Multiple Chemical Sensitivity (MCS) is a phenomenon which the ENT-doctor should be familiar with. It has its roots in the description of a syndrome in 1987. A worker spilled chemicals at his workplace and from then on he reacted highly sensitive to chemicals. Today, there are many people who explain their complaints with self-suspected MCS. Various pathopysiological models have been proposed, including toxicological, immunological or behaviorial models. But no-one could be proved so far. Since controlled provocation tests have also provided unclear results, an increasing number of doctors assumes today, that MCS reflects a psychic condition. In 1996, an expert team of the WHO has suggested the renaming of MCS to "idiopathic environmental illness" (IEI). However, other doctors still assume a chemical cause. Since there are neither straightforward diagnostic methods to proof MCS, nor reliable therapeutic concepts, treatment of MCS-patients is usually difficult. The MCS-debate (somatic vs psychic causes) seems to reflect the dilemma of the medical profession today, that somatic disorders of known origin can be well treated, whereas the increasing number of psychosomatic/ somatoform disorders is often resistant to medical help. The ENT-doctor should pay attention to changes of the nasal mucous membrane, nasal resistance and the sense of smell. Moreover he should know about the peculiarities of MCS-patients. The manuscript describes the present knowledge and state of discussion with special regard to the situation in Germany.

Keywords: Multiple Chemical Sensitivity, ENT, MCS, idiopathic environmental illness, IEI, pathogenesis, psychosomatic

1. Introduction

The ENT-doctor has frequently to work with illnesses which are triggered by environmental influences (e.g. airway infection, tinnitus, esophagus cancer..). In the last decade a new environmental illness came up: Multiple Chemical Sensitivity (MCS). If individuals protect their apartments with plastic foils from environmental poisons, they are probably MCS-patients. Until now, the phenomenon isn't defined explicitly. It is even controversial, whether the illness exists at all. An association with the function of the olfactory organ is often assumed. Therefore it is important for the ENT-doctor to know the actual state of discussion. This may enable him to better understand and advise patients.

1.1 History of MCS

The term "chemical sensitivity" has been introduced by T.G. Randolph in 1954. Randolph was allergist in Chicago and is considered to be the founder of the clinical ecology movement [1]. He believed that the uptake of common environmental chemicals can overload the adaptive mechanisms in sensitive persons and thus lead to disease. This became the basic assumption of clinical ecologists [2], an American variant of alternative medicine. However, it was declined by the majority of academic physicians. Only after Mark R. Cullen introduced the term "multiple chemical sensitivity" in journals of occupational medicine in 1987 [3], [4], [5], a long-lasting debate over chemical sensitivities started, which has not ended jet. This was triggered by the following observation of Cullen [3]: "Little more than a few months after the occupational medical clinic began at Yale, in 1979, the staff was confronted with a problem none of us had ever seen before nor heard about. A middle-aged man was referred because of a delayed recovery from an episode of pneumonia that had resulted from a chemical spill on the job. As his x-ray cleared, he had become not better, but worse. Particularly striking was the history that exposure to chemical odors would markedly exacerbate baseline dyspnea and chest pain. Upon return to work he "passed out" on several occasions after a whiff of fume. Disability leave, however, did not resolve the situation. Increasingly, even common household products and environmental contaminants induced debilitating respiratory and constitutional symptoms, reducing his formerly vigorous life to a pitiful existence at home. In response we exhaustively investigated his list of chemical precipitants in search for some way to tie these toxicologically with his prior pneumonia, but without success. Equally unrevealing were results of extensive clinical tests undertaken to define his "lesion" pathophysiologically. Therapeutically, it would be generous to say that we accomplished very little. There were other cases too."

Cullen assumed, that there are people, who react about 100-fold more sensitive to multiple chemicals than the average population. This means that the dose-response curve would be shifted to the left [Fig. 1]. On basis of this publication a controversy started [6], [7]. The original hypothesis assumes a chemical hypersensitivity (somatic model) which can be treated by avoiding exposures. The contrary hypothesis assumes a primary psychic cause e.g. on the basis of phobia towards chemical exposures (psychosomatic model), which can be treated by searching exposure sources. In Germany the discussion about MCS started about in the year 1994 [8], [9], [10], [11], [12].

1.2 Criteria for MCS

Cullen defined classification criteria [3], [4], [5], according to which patients should be selected for further scientific investigations of MCS [Fig. 2]. These criteria have been applied in many studies. In short, the results were often not reproducible and it was impossible to identify individual solvents or other chemicals as the cause for the problems of the patients. Therefore several proposals have been made to revise the classification criteria [13].

1.3 WHO-definition

In 1996, an expert group of the WHO/ICPS has suggested to use as an appropriate descriptor of MCS the broader term "idiopathic environmental intolerances" (IEI), in order to incorporate a number or disorders, sharing similar symptoms [14]. Although the existence of a disease of unclear pathogenesis was accepted, it was declined that the condition was simply caused by chemical exposures. The expert group proposed the following diagnostic criteria:

• IEI is an acquired disorder with multiple relapsing symptoms.

• The symptoms are in close relationship to multiple environmental influences which are well tolerated by the majority of the population.

• The symptom complex cannot be explained by a known clinical or psychic disorder.

The meeting also underlined the importance of research. Although many research results supported the view of the WHO-experts, various physicians continued to use the old MCS-classification criteria. As a consequence, the term "MCS-patient" today is not clearly defined. It describes in the wider sense a person, who believes that he suffers from chemical hypersensitivities (self-reported MCS), or who has been diagnosed by his doctor as having MCS. It describes in the closer sense patients, who match to MCS-criteria. This manuscript uses the term MCS, although many authors prefer "IEI" today.

1.4 Delimitation of similar diseases

MCS partly overlaps with some other environmental diseases with regard to symptomatic, triggers and diagnostic uncertainties. These other diseases include the "sick building syndrome" and the "chronic fatigue syndrome" [15], [16], [17], [18]. Sick building syndrome (SBS) is the collective name for complaints, which appear simultaneously in several persons in a building. Very often this occurs after a renovation. Typical complaints are headache, decreased impulsion and irritation of the mucous membranes. There is a wide range of possible triggers such as poorly run air-conditioning systems, emission of chemicals from building materials, bad odors, infrasound or unfavorable illumination. It is usually difficult to uncover the cause. It is also difficult to find out to which extent dissatisfaction of the affected persons with their (new) working rooms or working conditions plays a role. In contrast to MCS, several persons are affected in SBS and complains usually disappear, when causes are eliminated.

Chronic fatigue syndrome (CFS) is a disease which goes along with increased exhaustion and fatigue that exists for more than six month. It often starts in mid-life rather abruptly without a known cause. For many of the patients it is impossible to continue their occupational or domestic work. Physical exercise deteriorates the condition. The symptoms are similar to those of a common cold, however the diagnostic outcome does not give an indication to an infectious disease. Compared to MCS, the CFS-patient is less committed to the hypothesis of a chemical cause, and spontaneous recoveries after longer periods of illness are not infrequent.

1.5 State of the expert discussion

Since Cullen gave the first definitions of MCS, two parties formed within the medical profession. On the one hand those doctors, who think that a somatic genesis has been proven, who diagnose MCS and who often apply unconventional therapies. On the other side those, who are scientifically oriented. They think that their doubts in the MCS-hypothesis have been proven by the various unclear/negative findings in provocative tests [19], and believe that MCS is a wrong diagnosis. They usually consider MCS as a primary psychic problem. Both groups appear equally interested to uncover the causes of the severe complains of the affected persons. More than 500 publications on MCS have appeared in the last 15 years in established scientific journals.

The different approaches in the medical profession are also reflected in the outcome of the German multi-center MCS-study [20]: One of the centers considered environmental influences as important causes for the health situation of their patients with self-assumed MCS. However this was much less or not at all the case in the other centers [Fig. 3]. This underlines the existing classification problem which has been described already years ago by an American Colleague [21]: "It may be the only ailment in existence in which the patient defines both the cause and the manifestations of his own condition."

In order to assure the medical quality in this situation, the German center of disease control (Robert-Koch Institute) called an expert committee "Methods and quality assurance in environmental medicine". It works out recommendations in environmental medicine [22].

1.6 State of discussion in the public

In parallel with the scientific discussion and in part with the same stakeholders, there has been a polarized discussion in the public. The persons affected and their supporters fight for the view that MCS is solely caused by chemicals, and they do that in magazines and on web sites. The number of patients with self-reported MCS has considerably grown in the 90ies. Some media reported that more than one million people in Germany were affected [20]. The persons affected and their organizations asked for far-reaching consequences in prevention, diagnostics and treatment.

2. Triggers and symptoms

2.1 Chemicals that have been assumed to trigger MCS

According to Cullen, volatile compounds and mixtures are considered as the main triggers of the complains [3], [4], [5]. These include solvents, car emissions and pesticides, as well as emissions from building materials, furniture, carpets, adhesives, clothing and electrical apparatuses. Indoor compounds are emitted at higher concentrations when the products are new or freshly renovated.

2.2 Symptoms of MCS

The disease usually starts in the middle of life. MCS-patients typically have multiple, somatic und psychic symptoms [Fig. 4]. CNS-problems such as dizziness, difficulties to concentrate and headache are often reported. Irritations of the eyes, nose and throat are common [23], [24]. Often the case history reveals an earlier exposure to different chemicals, e.g. in connection with a poor room climate or preceding renovation works. The health problems arise at person-specific sites, including the home, the street-side traffic, the vicinity of laundries or freshly cleaned public buildings. Some patients have reported about an alcohol intolerance [25]. Characteristically patients are sensitive towards smells. Patients may be debilitated to an extent that they cannot live a normal life [26]. The avoidance of exposures becomes their major aim. At the same time they suffer from the lack of understanding of their fellow citizens.

This can be exemplified by the report of an affected person [27]: "Within a few days, and despite this "protective" outfit, my sensitivity to the odors from journals, books, and particularly newspapers, dramatically increased. Newspapers now had an intense, objectionable odor best described as a stench, and I could not remain in the same room with one. My sensitivity to books now had increased to the point that just walking past a shelf full of books triggered of the familiar sensation of slinging and burning pain on my face and eyelids. ....Because of my increasing sensitivity, work was not only frustrating - it seemed impossible to continue on a full-time basis. I found, as a patient with MCS, many routine tasks of social interactions now became an environmental encounter, and there came a feeling of social isolation. Going into a hardware store, drugstore, or supermarket was now a physically uncomfortable, irritating experience replete with characteristic odors..."

3. Pathomechanistic models

Since the first publications of Cullen in 1987, many theories and hypothesis have been developed to explain the pathogenesis of MCS. Most of these theories tend to break down into concepts involving: (1) disruption in immunological/allergy processes; (2) alteration in nervous system function; (3) changes in biochemical or biotransformation capacity; (4) changes in psychological/neurobehavioural function [28]. In detail, the following explanations have been given in the literature: allergy; autosuggestion; cacosomia; conditioned response; immunological; impairment of biochemical pathways involved in energy production; impairment of neurochemical pathways; illness belief system; limbic kindling; olfactory threshold sensitivity; panic disorder; psychosomatic condition; malingering; neurogenic inflammation; overload of biotransformation pathways (also linked with free radical production); psychological or psychiatric illness; airway reactivity; sensitisation of the neurological system; time dependent sensitisation, toxicant induced loss of tolerance.

3.1 Models of clinical ecology

Physicians who are devoted to clinical ecology postulate, that MCS is caused by an overload of the organism with environmental chemicals (environmental overload) [2], [29]. During the first contact with the chemical there are fugitive symptoms. These can be compensated by adaptive biochemical and immunological processes. This leads to a decreased ability to compensate additional environmental stress. As a result of repeated re-exposure an individual summation dose will be reached, when the adaptive processes of the organism get overloaded. This is the beginning of the disease. Later on, a shift of symptoms may occur, especially in those cases when the chemicals persist in the body.

Clinical ecologists apply some specific methods. These include food rotation and the provocation-neutralization method [29]. The American College of Physicians [30] and of the Councils on Scientific Affairs [31] came to the conclusion that "no scientific evidence supports the contention that the diagnostic tests and the treatments used by clinical ecology have any therapeutic value."

3.2 Toxicologic models

Many toxicologist believe, that a toxic mechanism can hardly play a role since neither the common dose-response relationship, nor the toxicant-specific organotropies are maintained [32]. Moreover MCS-like complaints are not known in occupational medicine, and inhalative provocation tests in MCS-patients did not deliver reproducible results. Finally, MCS is not observed in animal studies.

On the other hand it has been described earlier that a single life-threatening exposure to high concentrations of hydrogen sulfide may lead to lifelong hypersensitivity towards very low concentrations of the compound [33]. Recent controlled studies with solvent-exposure of healthy volunteers showed, that somatic effects (on the respiratory rate) may occur at concentrations below the present threshold levels [34], [35]. Finally, various diseases are known, which may be accompanied with an increased hypersensitivity to common concentrations of airborne compounds (hyperreactive respiratory system, alpha-1 antitrypsin-deficiency, inflammation of the mucus membrane). Taken altogether there is a need for further assessment of threshold levels in very sensitive persons [36].

3.3 Nasal mucous membrane and sense of smell

It is characteristic for MCS patients that they suffer from the smells in their environment. They cannot tolerate the cigarette smoke of other people, the car emissions at the roadside, or the perfume that has been used by the doctor in the clinic. Sometimes they barricade in their sterile home to avoid exposures and averting odors. Because of that some researchers have focused their interest on the sense of smell [24], [37], [38], [39], [40], [41]. An experimental problem with this kind of studies consists in the fact, that a blind provocation with odors cannot be done [40].

In the multi-center MCS-study [20] most MCS patients reported an increased sense of smell. However, when testing with odor sticks, an increased sensitivity was usually not verified. Moreover in a small subgroup of 19 MCS-suspicious patients the further olfactometric investigation did not support the idea that there was an impairment of the olfactory function.

Olfactory stimuli are processed in the limbic system and have a considerable influence on the emotional state and behavior [26], [37], [42]. In the animal kingdom, odors have a function to find sexual partners and to delineate districts. In humans the same odor can induce nausea in one situation but well-being in another. Chemosensory event-related potentials are detectable near the olfactory threshold value [26]. It appears conceivable that signal processing may occur already at concentrations below the threshold of odor perception and induces emotional reactions. The respective results of the German MCS study suggest that there may be differences in the chemosensory event-related potentials between volunteers and MCS patients.

Rhinolaryngoscopic findings were often abnormal in MCS-patients; edema, excessive mucus, a cobblestone appearance of the posterior pharynx and base of the tongue, and mucous membrane injection were observed frequently [43]. MCS was also associated with increased nasal airflow resistance [44]. Subjects with MCS had a significant decrease in the flow value in anterior rhinomanometry [41]. Taken altogether there are several indications, suggesting that a considerable proportion of MCS-patients suffers from an altered nasal mucous membrane and odor sensitivity.

3.4 Immunological models

"My immune system has collapsed" is a common remark among MCS-patients. But in contrast to earlier reports, the immunologic laboratory parameters of these patients are not specifically changed [45]. Therefore, changes of immunological parameters cannot be taken as an indication for MCS. But nevertheless, recent immunological findings deliver interesting new explanation models:

3.4.1 Psychoneuroimmunologic mechanisms

The immune system produces signaling compounds such as cytokines, which affect the function of nerves and of the CNS. Moreover, the immune system as well as the nerve system and the hormone system are affected by the brain and its emotional state. These interactions are described by the young discipline of psychoneuroimmunology. Environmental influences on one of the systems may therefore have consequences for the others. Those symptoms of MCS-patients, which resemble the symptoms of infectious diseases (fatigue, soft tissue pain, difficulties to concentrate) might theoretically be explained by psychoneuroimmunologic mechanisms [46].

3.4.2 Neurogic Inflammation

Neurogenic inflammation occurs, when chemicals irritate nerve endings of sensory fibers (C-fibers). These fibers are present in the mucous membranes of the eyes, nose, mouth or lower airways. Upon binding, an excitation signal is transduced to the brain ("it burns, it hurts"). At the same time mediators, such as substance P, are released from the irritated nerve endings [Fig. 5]. These mediators induce a local inflammation by attracting inflammatory cells, activating mast cells to degranulate, and induce a widening of the adjacent capillaries. Substances like tear gas or pepper-ingredients (capsaicin) act in this way. In the nasal mucous membrane, the olfactorius nerve transduces the odor-selective and sensitive sense of smell, whereas the trigeminus nerve is responsible for the general chemical sense, which recognizes the itching and biting part of chemicals (non-selective, poorly sensitive). The nerve endings of the trigeminus can thus answer a chemical stimulus with a local neurogenic inflammation. Repeated exposures may perpetuate an increased mucous membrane sensitivity and bad feeling. The pathogenetic basis might be an increased susceptibility of the trigeminus nerve endings to irritants in MCS-patients [47], [48], [49], [50]. This could be due to a defective epithelial barrier or a reduced activity of the peptidases, which destroy the released neuropeptides.

3.4.3 Inflammation processes in the brain

Non-infectious inflammations play a significant role in various pathologic processes of the brain. Cerebral ischaemia for example is followed by inflammation reactions of the glia, which leads to a loss of neuronal function. Moreover, autoimmune reactions of the brain are currently intensively investigated. They appear to play an important role in multiple sclerosis and are presently discussed as possible causes for various behaviour disorders [51]. Whether such mechanisms are involved in cases of MCS has to be awaited.

3.5 Psychiatric Models

Today it is increasingly recognized, that psychiatric morbidity is high in patients presenting to specialized centers for environmental medicine. Somatoform disorders are the leading diagnostic category [52], [53]. The environment is blamed for the unpleasant mental situation. The patients are often under emotional pressure from their social environment. As they are fixed to the hypothesis to be poisoned, they strictly decline the idea of a psychiatric cause as well as a psychotherapeutic treatment.

In the MCS-study, MCS-patients showed much higher values for somatization, compulsive disorders, depression, anxiety and social uncertainty compared to controls [20]. Aggressiveness and phobic anxiety were also elevated. Other studies found similar results [53], as well as associations with trauma, abuse in the childhood [54] and panic attacks [55]. Psychiatrist thus generally assume, that MCS is primarily a psychic disorder.

3.6 Pavlovian conditioning

Several authors have suggested that the development of MCS in some individuals may be due, at least in part, to Pavlovian conditioning processes in which the expression of overt symptoms to certain substances reflects classically conditioned somatic responses to previously neutral olfactory and contextual stimuli [56], [57]. An initial annoying exposure causes a facilitation, subsequent low exposures elicit the acquired somatic reaction. Such a conditioning system has similarities with the better known odor-induced vomiting in pregnancy, which may be triggered by the mere imagination of the bad odors.

The hypothesis, that chemical sensitivity may be conditioned was tested by van den Bergh and coworkers [58], [59], [60], [61]. Healthy volunteers were exposed in successive tests to air (baseline), then to odors (ammonia or butyric acid) in the absence or presence of 7,4% CO2 (causes somatic reactions) [Fig. 6]. 7,4% CO2 caused an increased respiration rate and bad feeling independent of the added odors. After this conditioning phase, a test phase followed. It showed, that odors alone could now elicit the CO 2 -specific symptoms. In a final extinction phase, five extinction trials were sufficient to reduce the level of acquired symptoms. This study underlines the plausibility of a Pavlovian conditioning hypothesis to explain the pathogenesis of MCS.

3.7 Risk factor model

According to this model, MCS might be a multifactorial process in which several of the above mentioned mechanisms add up. This would be in analogy to various other diseases such as coronary heart disease or diabetes mellitus. Moreover, in analogy to alcohol intolerance, combined exposures and disposition might play a role: Alcohol intolerance symptoms may originate from a genetic disposition (asian), from psychic factors (stress), illnesses (carcinoid) or co-exposure to chemicals (lime-nitrogen fertilizer). It is also evident, that various disorders may cause an increased sensitivity to various chemical exposures in daily life [Fig. 7]. A combined action of various risk factors would explain, why it is so difficult to get reproducible results in clinical investigations on MCS.

4. Diagnostic possibilities

Patients who consult the environmental practice have often suffered a long history of illness. Usually they have consulted several specialists previously, and often they bring along the findings of the earlier investigations. It is not uncommon that the earlier physicans gave conflicting diagnoses. If a patient has previously received the diagnosis "MCS" he will usually decline any other attempts of explanation. This is one of the reasons why it appears unwise, today, to tell the patient that he possibly suffers from MCS. This can bring about a fixation to unproved causes. It is also important to recognize that patients try to control the diagnostic process. The doctor should be aware that quite common existential fear is involved, as well as the silent hope, that the acknowledgment of a disease will help to receive medical and social support.

The diagnostic process includes a detailed case history and a physical examination. Depending on the circumstances, these are completed by laboratory investigations, organ function tests, biomonitoring and sometimes inspection of the patient's housing conditions. Suggestions for the procedure have been defined [62].

4.1 Case history

Case history is considered to be the main part of the diagnostic process in environmental medicine. A detailed first conversation typically lasts two hours. It is important to establish an atmosphere of confidence. The patient should be allowed to finish speaking and the doctor should actively listen. Relevant information about the time pattern of complaints and of possible connections to annoying exposures should be written down. The following questions are important : Where? (exposure site); wherefrom? (source); how? (exposure path); what? (chemical); which? (symptom). Information about smoking, drugs and nutrition complete the case history.

It appears often helpful, that the doctor accepts the explanations on the patient even if they are not compatible with his own. However the doctor should never overlook symptoms that indicate a non-environmental disease. The judgment about the importance of the reported exposures requires a lot of knowledge and experience with environmental medicine and chemistry. In special cases the patient should engage an institute, which analyzes suspicious sources in his house. Misinterpretations by the doctor or by the measuring institutes are not uncommon. They are however extremely harmful, as they may cause long-lasting fear and unnecessary but expensive renovations.

Because of the complexity, the diagnostic process should be done in a team, consisting of the specialist in environmental medicine, an internist, allergist, psychiatrist and other specialists.

4.2 Clinical finding

MCS patients often report burning of the skin and mucous membranes, fatigue, difficulties to concentrate, dizziness and dyspnoea. Disturbed sleep and soft tissue pain are also common. Occasionally, there is a change of the nasal mucous membrane and of the sense of smell. However the physical examination, organ function tests and laboratory diagnosis are not specifically changed [Fig. 8]. In addition the immunological and allergologial diagnosis cannot be expected to deviate from normal [63]. Imaging diagnostics such as CT and NMR show no specific changes [64] and SPECT and PET have not been sufficiently validated for these patients [65].

4.3 Laboratory tests and organ function tests

It is reasonable to apply simple and inexpensive methods first and to adhere to the following guidance of the German expert group for environmental medicine [62]:

• Incorporation of laboratory diagnostics into a diagnostic program (case history, clinical investigation, laboratory diagnostic, environmental analytics),

• No unaimed diagnosis,

• Highly specialized procedures should not be used in the beginning and not without a specific indication (e,g, SPECT only after conventional neurological diagnosis),

• Only established methods with approved analytic and diagnostic quality,

• Only methods where reference values for the interpretation are available,

• Critical interpretation of the findings,

• Influencing factors have to be taken into account (e.g. drinking-, smoking-, and nutritional habits, drug intake),

• It has to be clarified initially, who pays the cost of the various investigations (especially chemical analysis in body fluids or in indoor air are usually covered by patient).

The flowing simple basal program has been proposed (it can be modified depending on the question, the age and the health condition of the patient): [Tab. 1]

On basis of this program, a further differential diagnosis should be considered [25], with special regard to: Serology (borreliosis, HIV, EBV, rheumatic factor..); ENT-investigation to exclude sinusitis and abnormal odor sense; allergologic diagnostics including the possibility of food-intolerance; exclusion of a sleep apnea syndrome; exclusion of a consumptive illness. Those methods, which have a high rate of false-positive or false-negative results (e.g. mould-IgE, cytokines, lympocyte-transformation test) have to be interpreted with greatest caution [63], [66]. Characterization of polymorphism of drug metabolizing enzymes is at present without any diagnostic value, since it can neither predict risks nor has it a relationship to MCS [67].

4.4 Human biomonitoring

Occasionally the doctor is demanded to study environmental chemicals in body fluids of the patient in order to prove an assumed relationship between an environmental exposure and his complaints. Before considering such an investigation, the following questions should be clarified [62]:

• is an exposure of the postulated kind conceivable?

• are the compounds compatible with the complaints?

• is a method available to study the compound at low concentrations in body fluids?

• which body fluid is best suited?

• how must the sample be collected, stored and sent?

Moreover, it is most important to consider in advance whether the results will be interpretable. A minimum requirement is the existence of stable reference values. Reference values give no information on a toxic threshold, but reflect the background concentration in the population. Fortunately the toxic thresholds are usually far above the reference values [68]. Therefore, patient´s results that are moderately above reference values, must not be interpreted as health risk. Such wrong interpretations have fixed many patients to the false diagnosis "poisoned".

4.5 Environmental monitoring

Sources are usually assumed at home. One should not only think of chemicals, but also of indoor allergens (mould, cat, mite..). The expert for home exposures starts with a visual inspection of the rooms. Housing situation, hygienic standard, odors, ventilation, moisture, mold growth and so on are registered. Air samples or dust samples may be taken for chemical, allergological or biological analysis.

Whereas 15 years ago high concentrations of volatile compounds, including formaldehyde and other irritants were not uncommon in homes and public buildings, the situation has dramatically improved since then. Elevated concentrations that are suitable to affect health, are now rarely seen in German homes.

5. Therapy

A principal therapeutic method is the doctor-patient conversation. If an increased exposure or a hypersensitivity has been diagnosed, the primary therapy is the avoidance of the compounds (allergens, irritants..). If, however, diagnosis points to toxiphobia, an avoidance of compounds should not be recommended, since it may fix the situation. Of the various unconventional and conventional therapies that are characteristically employed, some are described below.

5.1 Unconventional methods

5.1.1 Neutralization

A characteristic method in clinical ecology is the provocation-neutralization method. The suspicious chemical is administered in rising doses by the subcutaneous, intracutaneous or sublingual route. This provocation has the purpose to find the diagnosis and the proper therapeutic dose. The "neutralization" is the treatment with the proper dose of the suspected chemical, analogous to allergic desensitization. From the viewpoint of academic medicine, the method has not been validated [30], and there is no known biochemical-pharmacological principal of explanation (for non-allergens).

5.1.2 Orthomolecular therapy and other methods

Orthomolecular therapy is the administration of high doses of essential vitamins and trace elements with the assumption, that the substitution would reconstitute the normal balance in a chemically overloaded organism. Fatty acids and antioxidants are also given. Moreover methods of naturopathy, sauna, physical examinations and fasting may be included. Although such therapeutic approaches may be useful to some patients, they are not at all specific for MCS. Unfortunately it also occurs, that the safe upper limits for the intake of essential compounds [69] are exceeded.

5.1.3 Elimination therapy

Chelating agents are used with the aim to induce the elimination of heavy metals, especially mercury. In some cases fat-binding oils such as paraffin were orally applied in order to accelerate the fecal elimination of persistent chemicals (DDT, PCB, HCB etc). In general, these methods may lead to a desired decrease of the body burden. However they are accompanied with some risks, such as redistribution of the chemicals between the organs. Therefore, the large majority of clinical toxicologist believe that these methods should not be employed, unless the threshold of clinical intoxication is exceeded.

5.2 Psychotherapeutic approaches and desensitization

It is important to find ways, by which the patient starts to be interested in things other than his poisoning [70]. In the case of anxiety disorders, behavior therapy often brings good results. In the case of drug abuse a specific therapy should be started, followed by self-help groups.

Psychic desensitization is a method, where confrontation with the suspected trigger is searched. It can be exercised initially in the patient's imagination and later in reality. A desensitization is indicated in the case of toxicophobia. But it might also be helpful in the case of a real hypersensitivity, if symptoms still persist after all chemical exposures are avoided [61].

5.3 Therapeutic successes

The therapeutic success has been described by one of the leading MCS-researchers as follows [54]: "Despite the significant therapeutic effort expanded, some patients who are imprisoned by a closed belief system about the harmful effects of chemical sensitivities are resigned to travel down the path which ultimately leads to despair and depression, social isolation, and even death."

6. The MCS-patient in the ENT-practice

The ENT-doctor should make a profound environmental case history in order to get hints on possible chemical or allergic exposures [Fig. 9]. Knowledge of the social situation of the patient will help to understand his expectations (healing, understanding, compensation). The investigation should include an inspection of the nasal mucous membrane, nasal resistance and smell test (which may be difficult to perform because of an increased odor aversion). In the doctor-patient-relationship, the doctor has to be aware, that the patient may have a profound suspicion of medical expertise and physicians.

7. Public Health aspects

The MCS-discussion shows clearly, that there are profound differences between the approaches of ecologically oriented environmental doctors and their colleagues in academia. Today there is hardly any contact between the two parties in Germany. The MCS-study [20] tried to build bridges, but was not very successful in this regard. Moreover, its results could not support the hypothesis of a chemical cause. It can not be entirely excluded however, that 15 years earlier, the results would have been positive, because human exposure to environmental chemicals in buildings (and in food) was much higher in 1987, when Cullen reported his observations. In those times, exposures (e.g. formaldehyde) in houses sometimes exceeded the known threshold values of complaints.

7.1 Fashionable complaints

The cover story of a leading German magazine in 2003 read "the disease-makers -how doctors and the pharmaceutical industry invent new illnesses" [71]. Although MCS does not belong to the invented diseases, it has been assumed, that in many cases it is an imagined disease. This would be analogous to fashionable complaints in earlier times such as neurasthenia or autointoxication, 100 years ago [72]. A scientist from the American National Institute of Health, who organized a MCS-symposium in 1993, expressed this the following way [73]: "In every era people have suffered varieties of symptoms not readily explained by "known" diseases of the day. To provide explanations and treatment approaches, individuals with symptom complexes were frequently provided a unifying disease label. At the turn of the 20th century, that label was autointoxication. Today, it is multiple chemical sensitivities (MCS)".

7.2 Regulatory aspects

There is hope, that the MCS-problematic will help to find better medical solutions for the patients affected [74]. In addition it has propagated the concept, that guideline values for environmental chemicals should be made not only for the healthy majority, but for the susceptible people such as pregnant women, children, elderly people or otherwise sensitive persons. However, there will always remain limits. In cases of hypersensitivity to nutrients (e.g. celiac disease) or essential food ingredients (e.g. phenylketonuria, nickel allergy), the persons affected have to protect themselves by individual measures today and in the future.

It should also be mentioned, that intensified regulation of environmental chemicals will only be favorable, if at the same time intentional and high exposures to (environmental) tobacco smoke, odorants and other emissions are kept low, at least in the public. Today, the widespread use of odorants makes it difficult for people with odor-aversion to move in the public.

7.3 Health political aspects

An important health political aspect of MCS is the following: Although many organ-diseases can be well treated today, there is a continuous increase in the number of people with psychosomatic and somatoform disorders. Modern environmental influences (working condition, family, social situation, physical inactivity, overeating..) are evident risk factors. The MCS-debate (somatic vs psychic) is an example how the medical profession today searches for suitable answers to this arising challenges.

7.4 Medical care

Concerning the medical care, the situation must be confusing for MCS-patients: representatives of the medical societies usually decline a MCS-diagnosis from the beginning, whereas many environmentally oriented physicians may accept such a diagnosis, and ecologically oriented doctors consider MCS as an established disorder.

Independent of that, the majority of doctors who work with MCS-patients are convinced, that the complaints are serious. No matter whether the somatic or the psychosomatic hypothesis applies to the individual patient, it is desirable that he can receive help. Hopefully, the controversial discussion and the necessary research will finally lead to a better understanding of the MCS.


Randolph TG, Moss RW, eds. Allergien, Folgen von Umwelt und Ernährung. Chronische Erkrankung aus der Sicht der Klinischen Ökologie. Karlsruhe: Müller; 1991.
Rea WJ, ed. Chemical Sensitivity. Boca Raton: Lewis; 1992.
Cullen MR. The worker with multiple chemical sensitivities: an overview. Occup Med 1987; 2: 655-61.
Cullen MR. Multiple chemical sensitivities: summary and directions for future investigators. Occup Med 1987; 2: 801-4.
Cullen MR. Occupational medicine - Workers with multiple chemical sensitivities, in Hanley and Belfus, Inc., Medical Publishers, P.o. Box . 1987.
Gots RE, Hamosh TD, Flamm WG, Carr CJ. Multiple chemical sensitivities: a symposium on the state of the science. Regul Toxicol Pharmacol 1993; 18: 61-78.
Gots RE. Multiple chemical sensitivities: distinguishing between psychogenic and toxicodynamic. Regul Toxicol Pharmacol 1996; 24: S8-15.
Altenkirch H. Multiple chemical sensitivity syndrome. Gesundheitswesen 1995; 57: 661-6.
Remmer H. Die Umwelt als Ursache von Erkrankungen. Deutsches Ärzteblatt 1994; 91, Heft 27-A: 1884-8.
Schimmelpfennig W. Begutachtung umweltbedingter toxischer Gesundheitsschäden. Bundesgesundheitsblatt 1994;9:377-85.
Wolf C. Umweltallergie - Multiple Chemical Sensitivity. Allergologie 1995; 18: 420-4.
Zober A. Multiple Chemical Sensitivity (MCS) oder Vielfach-Chemikalien-Unverträglichkeit (VCU) und die Multiplikation in der Bundesrepublik Deutschland. Arbeitsmedizin, Sozialmedizin, Umweltmedizin 1996; 31: 141-4.
Multiple chemical sensitivity: a 1999 consensus. Arch Environ Health 1999; 54: 147-9.
Lukassowitz I. Ursachen, Diagnostik und Therapie der vielfach Chemikalienüberempfindlichkeit (MCS) stellen Wissenschaft und Ärzte vor Probleme. Bundesinstitut für gesundheitlichen Verbraucherschutz und Veterinärmedizin, Berlin, Pressemitteilung 1996; 28. Februar 1996:
Fiedler N, Kipen H, Natelson B, Ottenweller J. Chemical sensitivities and the Gulf War: Department of Veterans Affairs Research Center in basic and clinical science studies of environmental hazards. Regul Toxicol Pharmacol 1996; 24: S129-38.
Bell IR, Warg-Damiani L, Baldwin CM, Walsh ME, Schwartz GE. Self-reported chemical sensitivity and wartime chemical exposures in Gulf War veterans with and without decreased global health ratings. Mil Med 1998; 163: 725-32.
Kipen HM, Fiedler N. The role of environmental factors in medically unexplained symptoms and related syndromes: conference summary and recommendations. Environ Health Perspect 2002; 110: 591-5.
Meggs WJ. Gulf War Syndrome, Chronic Fatigue Syndrome, and the Multiple Chemical Sensitivity Syndrome: stirring the cauldron of confusion. Arch Environ Health 1999; 54: 309-11.
Staudenmayer H, Selner JC, Buhr MP. Double-blind provocation chamber challenges in 20 patients presenting with "multiple chemical sensitivity". Regul Toxicol Pharmacol 1993; 18: 44-53.
Robert Koch Institut, Berichtband von der Projektgruppe des MCS-Forschungsverbundes. 2002;
Gots RE. Multiple chemical sensitivities--public policy [editorial]. J Toxicol Clin Toxicol 1995; 33: 111-3.
RKI-Kommission. Umweltmedizin, Grundsätze der Bewertung von umweltmedizinischen Methoden. Bundesgesundheitsbl - Gesundheitsforsch - Gesundheitsschutz 2001; 44: 519-22.
Miller CS. Chemical sensitivity: symptom, syndrome or mechanism for disease? Toxicology 1996; 111: 69-86.
Miller AN, Ashford NA. Chemical Exposures. New York: Van Nostrand Reinhold; 1991.
Lacour M, Dettenkofer M, Daschner F, Schwenk M. Multiple Chemical Sensitivity (MCS). Internist 1998; 39: 105-9.
Kobal G, Hummel T. Olfactory (chemosensory) event-related potentials. Toxicol Ind Health 1994; 10: 587-96.
Klubes P. An encounter with the syndrome of multiple chemical sensitivities: reflections of a pharmacologist. Perspect Biol Med 1991; 34: 355-64.
Winder C. Mechanisms of multiple chemical sensitivity. Toxicol Lett 2002; 128: 85-97.
Runow K-D, ed. Klinische Ökologie: Umweltkrankheiten- neue Wege in Diagnose und Therapie. Stuttgart: Hippokrates; 1987.
ACP. Clinical ecology. American College of Physicians. Ann Intern Med 1989;111(2):168-78.
Council on Scientific Affairs, American Medical Association. Clinical ecology. JAMA. 1992;268(24):3465-7.
Cohn JR. Multiple chemical sensitivity or multi-organ dysesthesia [editorial]. J Allergy Clin Immunol 1994; 93: 953-4.
Wirth KE, Gloxhuber C. Toxikologie. Stuttgart: Thieme; 1994
Fiedler N, Kipen HM. Controlled exposures to volatile organic compounds in sensitive groups. Ann N Y Acad Sci 2001; 933: 24-37.
Haumann K, Kiesswetter E, van Thriel C, Blaszkewicz M, Golka K, Seeber A. Breathing and heart rate during experimental solvent exposure of young adults with self-reported multiple chemical sensitivity (sMCS). Neurotoxicology 2003; 24: 179-86.
Bolt HM, Kiesswetter E. Is multiple chemical sensitivity a clinically defined entity? Toxicol Lett 2002; 128: 99-106.
Bell IR, Miller CS, Schwartz GE. An olfactory-limbic model of multiple chemical sensitivity syndrome: possible relationships to kindling and affective spectrum disorders. Biol Psychiatry 1992; 32: 218-42.
Bell IR, Schwartz GE, Bootzin RR, Wyatt JK. Time-dependent sensitization of heart rate and blood pressure over multiple laboratory sessions in elderly individuals with chemical odor intolerance. Arch Environ Health 1997; 52: 6-17.
Amundsen MA, Hanson NP, Bruce BK, Lantz TD, Schwartz MS, Lukach BM. Odor aversion of multiple chemical sensitivities: recommendation for a name change and description of successful behavioral medicine treatment. Regul Toxicol Pharmacol 1996; 24: S116-8.
van Thriel C, Kiesswetter E, Blaszkewicz M, Golka K, Seeber A. Neurobehavioral effects during experimental exposure to 1-octanol and isopropanol. Scand J Work Environ Health 2003; 29: 143-51.
Wiesmuller GA, Van Thriel C, Steup A, Bachert C, Clinic EN, Blaszkewicz M, Golka K, Kiesswetter E, Seeber A. Nasal function in self-reported chemically intolerant individuals. Arch Environ Health 2002; 57: 247-54.
Otto T, Giardino ND. Pavlovian conditioning of emotional responses to olfactory and contextual stimuli: a potential model for the development and expression of chemical intolerance. Ann N Y Acad Sci 2001; 933: 291-309.
Meggs WJ, Cleveland CJ. Rhinolaryngoscopic examination of patients with the multiple chemical sensitivity syndrome. Arch Environ Health 1993; 48: 14-8.
Doty RL. Olfaction and multiple chemical sensitivity. Toxicol Ind Health 1994; 10: 359-68.
Fiedler N, Maccia C, Kipen H. Evaluation of chemically sensitive patients. J Occup Med 1992; 34: 529-38.
Cohen N, Kehrl H, Berglund B, O'Leary A, Ross G, Seltzer J, Weisel C. Psychoneuroimmunology. Environ Health Perspect 1997; 105: 527-9.
Meggs WJ. Mechanisms of allergy and chemical sensitivity. Toxicol Ind Health 1999; 15: 331-8.
Ternesten-Hasseus E, Bende M, Millqvist E. Increased capsaicin cough sensitivity in patients with multiple chemical sensitivity. J Occup Environ Med 2002; 44: 1012-7.
Bascom R, Meggs WJ, Frampton M, Hudnell K, Killburn K, Kobal G, Medinsky M, Rea W. Neurogenic inflammation: with additional discussion of central and perceptual integration of nonneurogenic inflammation. Environ Health Perspect 1997; 105: 531-7.
Renner B. Sachbericht - MCS und neurogene Entzündung. 2002;
Lang B, Dale RC, Vincent A. New autoantibody mediated disorders of the central nervous system. Curr Opin Neurol 2003; 16: 351-7.
Hausteiner C, Bornschein S, Förstl H, Zilker T. Leidet Ihr Patient an Umweltgiften oder an der Seele? MMW-Fortschr.Med 2003; 145 (33-34): 31-4.
Bornschein S, Hausteiner C, Zilker T, Forstl H. Psychiatric and somatic disorders and multiple chemical sensitivity (MCS) in 264 'environmental patients'. Psychol Med 2002; 32: 1387-94.
Staudenmayer H. Clinical consequences of the EI/MCS "diagnosis": two paths. Regul Toxicol Pharmacol 1996; 24: S96-110.
Kurt TL. Multiple chemical sensitivities--a syndrome of pseudotoxicity manifest as exposure perceived symptoms. J Toxicol Clin Toxicol 1995; 33: 101-5.
Miller CS. The compelling anomaly of chemical intolerance. Ann N Y Acad Sci 2001; 933: 1-23.
Sorg BA, Newlin DB. Sensitization as a mechanism for multiple chemical sensitivity: relationship to evolutionary theory. Scand J Psychol 2002; 43: 161-7.
Van den Bergh O, Stegen K, Van Diest I, Raes C, Stulens P, Eelen P, Veulemans H, Van de Woestijne KP, Nemery B. Acquisition and extinction of somatic symptoms in response to odours: a Pavlovian paradigm relevant to multiple chemical sensitivity. Occup Environ Med 1999; 56: 295-301.
Van den Bergh O, Devriese S, Winters W, Veulemans H, Nemery B, Eelen P, Van de Woestijne KP. Acquiring symptoms in response to odors: a learning perspective on multiple chemical sensitivity. Ann N Y Acad Sci 2001; 933: 278-90.
Van den Bergh O, Stegen K, Van de Woestijne KP. Learning to have psychosomatic complaints: conditioning of respiratory behavior and somatic complaints in psychosomatic patients. Psychosom Med 1997; 59: 13-23.
Strehl U. Lerntheoretische Überlegungen zur Entstehung von vermuteten Umwelterkrankungen. Med Sach 2000; 97: 117-80.
RKI-Kommission, Umweltmedizin. Untersuchungsgang in der Umweltmedizin. Bundesgesundheitsbl -Gesundheitsforsch - Gesundheitsschutz 2001; 44 : 1209-16
RKI-Kommission, Umweltmedizin. Einsatz immunologischer Untersuchungsverfahren in der Umweltmedizin - Eine Einführung. Bundesgesundheitsbl - Gesundheitsforsch - Gesundheitsschutz 2002; 45: 740-4.
Simon TR, Hickey DC, Fincher CE, Johnson AR, Ross GH, Rea WJ. Single photon emission computed tomography of the brain in patients with chemical sensitivities. Toxicol Ind Health 1994; 10: 573-7.
Bartenstein P, Grunwald F, Herholz K, Kuwert T, Tatsch K, Sabri O, Weiller C. [Role of positron emission tomography (PET) and single photon emission tomography (SPECT) in so-called "multiple chemical sensitivity"]. Nuklearmedizin 1999; 38: 297-301.
RKI-Kommission, Umweltmedizin. Diagnostische Relevanz des Lymphozytentransformationstestes in der Umweltmedizin. Bundesgesundheitsbl - Gesundheitsforsch - Gesundheitsschutz 2002;745-9.
Schulz T, Degen G, Foth H, Kahl R, Kramer P-J, Lilienblum W, Schrenk D, Schweinfurth H. Zur Bedeutung von genetischen Polymorphismen von Fremdstoff-metabolisierenden Enzymen in der Toxikologie. Umweltmedizin in Forschung und Praxis 2002; 7: 232-46.
Human-Biomonitoring-Kommission. Konzept der Referenz- und Human-Biomonitoring-Werte (HBM) in der Umweltmedizin. Bundesgesundhbl 1996; 39: 221-4.
DGE, DACH, ÖGE. Referenzwerte für die Nährstoffzufuhr. Frankfurt am Main: Umschau Braus; 2000
Bornschein S, Forstl H, Zilker T. Idiopathic environmental intolerances (formerly multiple chemical sensitivity) psychiatric perspectives. J Intern Med 2001; 250: 309-21.
Blech J. Die Krankmacher - Wie Ärzte und Pharmaindustrie neue Krankheiten erfinden. Der Spiegel 2003; 33: 11.8.2003.
Schafer ML. On the history of the concept neurasthenia and its modern variants chronic-fatigue-syndrome, fibromyalgia and multiple chemical sensitivities. Fortschr Neurol Psychiatr 2002; 70: 570-82.
Gots RE. Medical hypothesis and medical practice: autointoxication and multiple chemical sensitivities. Regul Toxicol Pharmacol 1993; 18: 2-12.
Brown AE. Developing a pesticide policy for individuals with multiple chemical sensitivity: considerations for institutions. Toxicol Ind Health 1999; 15: 432-7.