The ILO Encyclopeadia of Occupational Health and Safety is an authorative

text on matters relating to the workplace.

In its 1997 edition, it includes stuff on Systemic connditions, including

Sick Building Syndrome (SBS) and Multiple Chemical Sensitivity (MCS).

Below please find the stuff on MCS. Any errors are mine, as I have scanned

and reprocessed the original through character recognition software. If

you are interested in SBS, a separate article is available, although you

will need to go to the text to get it.

Encyclopaedia of Occupational Health and Safety

Ch 13 - Systemic Conditions

SYSTEMIC CONDITIONS: AN INTRODUCTION

Howard M. Kipen

The last edition of this Encyclopedia did not contain articles on either

sick building syndrome (SBS) or multiple chemical sensitivities (MCS) (the

latter term was coined by Cullen, 1987). Most practitioners of occupational

medicine are not comfortable with such symptomatically driven and

frequently psychologically related phenomena, at least partly for the

reason that patients with these syndromes do not respond reliably to the

standard means of occupational health intervention, namely, exposure

reduction. Non-occupational physicians in general medical practice also

react similarly: patients with little verifiable pathology, such as those

complaining of chronic fatigue syndrome or fibromyalgia, are regarded as

more difficult to treat (and generally regard themselves as more disabled)

than patients with deforming conditions such as rheumatoid arthritis. There

is clearly less regulatory imperative for sick building syndrome and

multiple chemical sensitivities than for the classic occupational syndromes

such as lead intoxication or silicosis. This discomfort on the part of

treating physicians and the lack of appropriate regulatory guidance is

unfortunate, however understandable it may be, because it leads to

minimization of the importance of these increasingly common, albeit largely

subjective and non-lethal complaints. Since many workers with these

conditions claim total disability, and few examples of cures can be found,

multiple chemical sensitivities and sick building syndrome present

important challenges to compensation systems.

In the developed world, since many classic occupational toxins are better

controlled, symptomatic syndromes, such as those under present scrutiny

that are associated with lower-level exposures, are assuming increasing

recognition as significant economic and health concerns. Managers are

frustrated by these conditions for a number of reasons. As there are no

clear-cut regulatory requirements in most jurisdictions which cover indoor

air or hypersusceptible individuals (with the important exception being

persons with recognized allergic disorders), it is impossible for

management to be certain whether or not they are in compliance.

Agent-specific contaminant levels developed for industrial settings, such

as the US Occupational Safety and Health Administration's (OSHA)

permissible exposure levels (PELs) or the American Conference of

Governmental Industrial Hygienists' (ACGIHs) threshold limit values (TLVs),

are clearly not able to prevent or predict symptomatic complaints in office

and school workers. Finally because of the apparent importance of

individual susceptibility and psychological factors as determinants of

response to low levels of contaminants, the impact of environmental

interventions is not as predictable as many would like before a decision is

taken to commit scarce building or maintenance resources. Often after

complaints arise, a potential culprit such as elevated volatile organic

compound levels with respect to outdoor air is found, and yet following

remediation, complaints persist or reoccur.

Employees who suffer from symptoms of either sick building syndrome or

multiple chemical sensitivities are often less productive and frequently

accusatory when management or government is reluctant to commit themselves

to interventions which cannot be reliably predicted to ameliorate symptoms.

Clearly occupational health providers are among the few key individuals who

may be able to facilitate reasonable middle ground outcomes to the

advantage of all concerned. This is true whether or not an underlying cause

is low levels of contaminants, or even in the rare case of true mass

hysteria, which may often have low-level environmental triggers. Using

skill and sensitivity to address, evaluate and incorporate a combination of

factors into solutions is an important approach to management.

Sick building syndrome is the more contained and definable of the two

conditions, and has even had definitions established by the World Health

Organization (1987). Although there is debate, both in general and in

specific instances, about whether a given lesion is more attributable to

individual workers or to the building, it is widely acknowledged, based on

controlled exposure studies with volatile organic compounds, as well as

survey epidemiology, that modifiable environmental factors do drive the

kinds of symptom which are subsumed under the following article entitled

Sick Building Syndrome. In that article, Michael Hodgson (1992) details the

triad of personal, work activity and building factors which may contribute

in various proportions to symptoms among a population of workers. A major

problem is in maintaining good employee-employer communication while

investigation and attempts at remediation take place. Health professionals

will usually require expert environmental consultation to assist in the

evaluation and remediation of identified outbreaks.

Multiple chemical sensitivities is a more problematic condition to define

than sick building syndrome. Some organized medical entities, including the

American Medical Association, have published position papers which question

the scientific basis of the diagnosis of this condition. Many physicians

who practise without a rigorous scientific basis have nevertheless

championed the validity of this diagnosis. They rely on unproven or

over-interpreted diagnostic tests such as lymphocyte activation or brain

imaging and may recommend treatments such as sauna therapies and megadoses

of vitamins, practices which have in large part engendered the animosity of

groups such as the American Medical Association. However, no one denies

char there is a group of patients who present with complaints of becoming

symptomatic in response to low levels of ambient chemicals. Their

constitutional symptoms overlap those of other subjective syndromes such as

chronic fatigue syndrome and fibromyalgia. These symptoms include pain,

fatigue and confusion, they worsen with low-level chemical exposure and

they are reported to be present in a substantial percentage of patients who

have been diagnosed with these other syndromes. Of great import, but still

unresolved, is the question whether chemical sensitivity symptoms are

acquired (and to what extent) because of a preceding chemical overexposure,

or whether - as in the commonly reported situation - they arise without a

major identified precipitating event.

Multiple chemical sensitivities is sometimes invoked as an outcome in

certain sick building syndrome outbreaks which are not resolved or

ameliorated after routine investigation and remediation. Here it is clear

that MCS afflicts an individual or small number of people, rarely a

population; it is the effect on a population that may even be a criterion

for the sick building syndrome by some definitions. MCS seems to be endemic

in populations, whereas sick building syndrome is often epidemic; however,

preliminary investigations suggest that some degree of chemical sensitivity

(and chronic fatigue) may occur in outbreaks, as was found among American

veterans of the Persian Gulf conflict. The controlled exposure studies

which have done much to clarify the role of volatile organic compounds and

irritants in sick building syndrome have yet to be performed in a

controlled manner for multiple chemical sensitivities.

Many practitioners claim to recognize MCS when they see it, but there is no

agreed-upon definition. It may well be included as a condition which

"overlaps" other non-occupational syndromes such as chronic fatigue

syndrome, fibromyalgia, somatization disorder and others. Sorting out its

relationship to both psychiatric diagnoses and to early reports suggests

that when the onset of the syndrome is fairly definable, there is a much

lower rate of diagnosable psychiatric co-morbidity (Fiedler et al. 1996).

The phenomenon of odor-triggered symptoms is distinctive, but clearly not

unique, and the extent to which this is an occupational condition at all is

debated. This is important because Dr Cullen's (1987) definition, like many

others, describes multiple chemical sensitivities as a sequel to a

better-characterized occupational or environmental disorder. However, as

stated above, symptoms following exposure to ambient levels of odorants are

common among individuals both with and without clinical diagnoses, and it

may be just as important to explore the similarities between .LICS and

other conditions as to define the differences (Kipen et al. 1995; Buchwald

and Garrity 1994).

MULTIPLE CHEMICAL SENSITIVITIES

Mark R Cullen

Introduction

Since the 1980s, a new clinical syndrome has been described in occupational

and environmental health practice characterized by the occurrence of

diverse symptoms after exposure to low levels of artificial chemicals,

although as yet it lacks a widely accepted definition. The disorder may

develop in individuals who have experienced a single episode, or recurring

episodes of a chemical injury such as solvent or pesticide poisoning.

Subsequently, many types of environmental contaminant in air, food or water

may elicit a wide range of symptoms at doses below those which produce

toxic reactions in others.

Although there may not be measurable impairment of specific organs, the

complaints are associated with dysfunction and disability. Although

idiosyncratic reactions to chemicals are probably not a new phenomenon, it

is believed that multiple chemical sensitivities (MCSs), as the syndrome is

now most frequently called, is being brought by patients to the attention

of medical practitioners far more commonly than in the past. This syndrome

is prevalent enough to have generated substantial public controversy as to

who should treat patients suffering with the disorder and who should pay

for the treatment, but research has yet to elucidate many scientific issues

relevant to the problem, such as its cause, pathogenesis, treatment and

prevention. Despite this, MCS clearly does occur and causes significant

morbidity in the work-force and general population. It is the purpose of

this article to elucidate what is known about it at this time in the hope

of enhancing its recognition and management in the face of uncertainty.

Definition and Diagnosis

Although there is no general consensus on a definition for MCS, certain

features allow it to be differentiated from other well-characterized

entities. These include the following:

¦ Symptoms typically occur after a definitely characterizable occupational

or environmental incident, such as an inhalation of noxious gases or

vapours or other toxic exposure. This "initiating" event may be a single

episode, such as an exposure to a pesticide spray, or a recurrent one, such

as frequent solvent overexposure. Often the effects of the apparently

precipitating event, or events, are mild and may merge without clear

demarcation into the syndrome which follows.

¦ Acute symptoms similar to those of the preceding exposure begin to occur

after re-exposures to lower levels of various materials, such as petroleum

derivatives, perfumes and other common work and household products.

¦ Symptoms are referable to multiple organ systems. Central nervous system

complaints, such as fatigue, confusion and headache, occur in almost every

case. Upper and lower respiratory, cardiac, dermal, gastrointestinal and

musculoskeletal symptoms are common.

¦ It is generally the case that very diverse agents may elicit the symptoms

at levels of exposure orders of magnitude below accepted TLVs or guidelines.

¦ Complaints of chronic symptomatology, such as fatigue, cognitive

difficulties, gastrointestinal and musculoskeletal imbances are common.

Such persistent symptoms may predominate over reactions to chemicals in

some cases.

¦ Objective impairment of the organs which would explain the pattern or

intensity of complaints is typically absent. Patients examined during acute

reactions may hyperventilate or demonstrate other manifestations of excess

sympathetic nervous system activity.

¦ No better established diagnosis easily explains the range of responses or

symptoms.

While not every patient precisely meets the criteria, each point should be

considered in the diagnosis of MCS. Each serves to rule out other clinical

disorders which MCS may resemble, such as somatization disorder,

sensitization to environmental antigens (as with occupational asthma), late

sequelae of organ system damage (e.g., reactive airways dysfunction

syndrome after a toxic inhalation) or a systemic disease (e.g., cancer). On

the other hand, MCS is not a diagnosis of exclusion and exhaustive testing

is nor required in most cases. While many variations occur, MCS is said to

have a recognizable character which facilitates diagnosis as much or more

than the specific criteria themselves.

In practice, diagnostic problems with MCS occur in two situations. The

first is with a patient early in the course of the condition in whom it is

often difficult to distinguish MCS from the more proximate occupational or

environmental health problem which precedes it. For example, patients who

have experienced symptomatic reactions to pesticide spraying indoors may

find that their reactions are persisting, even when they avoid direct

contact with the materials or spraying activities. In this situation a

clinician might assume that significant exposures are still occurring and

direct unwarranted effort to altering the environment further, which

generally does not relieve the recurrent symptoms. This is especially

troublesome in an office setting where MCS may develop as a complication of

sick building syndrome. Whereas most office workers will improve after

steps are taken to improve air quality, the patient who has acquired MCS

continues to experience symptoms, despite the lower exposures involved.

Efforts to improve the air quality further typically frustrate patient and

emplover.

Later in the course of MCS, diagnostic difficulty occurs because of the

chronic aspects of the illness. After many months, the MCS patient is often

depressed and anxious, as are other medical patients with new chronic

diseases. This may lead to an exaggeration of psychiatric manifestations,

which may predominate over chemically stimulated symptoms. Without

diminishing the importance of recognizing and treating these complications

of MCS, nor even the possibility that MCS itself is psychological in origin

(see below), the underlying MCS must be recognized in order to develop an

effective mode of management which is acceptable to the patient.

Pathogenesis

The pathogenic sequence which leads in certain people from a self-limited

episode or episodes of an environmental exposure to the development of MCS

is not known. There are several current theories. Clinical ecologists and

their adherents have published extensively to the effect that MCS

represents immune dysfunction caused by accumulation in the body of

exogenous chemicals (Bell 1982; Levin and Byers 1987). At least one

controlled study did not confirm immune abnormalities (Simon, Daniel and

Stockbridge 1993). Susceptibility factors under this hypothesis may include

nutritional deficiencies (e.g., lack of vitamins or antioxidants) or the

presence of subclinical infections such as candidiasis. In this theory, the

"initiating" illness is important because of its contribution to lifelong

chemical overload.

Less well developed, but still very biologically oriented, are the views

that MCS represents unusual biological sequelae of chemical injury. As

such, the disorder may represent a new form of neurotoxicity due to

solvents or pesticides, injury to the respiratory mucosae after an acute

inhalational episode or similar phenomena. In this view, MCS is seen as a

final common pathway of different primary disease mechanisms (Cullen 1994,

Bascom 1992).

A more recent biological perspective has focused on the relationship

between the mucosae of the upper respiratory tract and the limbic system,

especially with respect to the Linkage in the nose (Miller 1992). Under

this perspective, relatively small stimulants to the nasal epithelium could

produce an amplified limbic response, explaining the dramatic, and often

stereotypic, responses to low-dose exposures. This theory also may explain

the prominent role of highly odoriferous materials, such as perfumes, in

triggering responses in many patients.

Conversely, however, many experienced investigators and clinicians have

invoked psychological mechanisms to explain MCS, linking it to other

somatoform disorders (Brodskv 1983; Black, Ruth and Goldstein 1990).

Variations include the theory that MCS is a variant of post-traumatic

stress disorder (Schottenfeld and Cullen 1985) or a conditioned response to

an initial toxic experience (Bolle-Wilson, Wilson and Blecker 1988). One

group has hypothesized MCS as a late-life response to early childhood

traumas such as sexual abuse (Selner and Strudenmayer 1992). In each of

these theories, the precipitating illness plays a more symbolic than

biological role in the pathogenesis of MCS. Host factors are seen as very

important, especially the predisposition to somatocize psychological

distress.

Although there is much published literature on the subject, few clinical or

experimental studies have appeared to support strongly any of these views.

Investigators have not generally defined their study populations nor

compared them with appropriately matched groups of control subjects.

Observers have not been blinded to subject status or research hypotheses.

As a result, most available data are effectively descriptive. Furthermore,

the legitimate debate over the aetiology of MCS has been distorted by

dogma. Since major economic decisions (e.g., patient benefit entitlements

and physician reimbursement acceptance) may hinge upon the way in which

cases are viewed, many physicians have very strong opinions about the

illness, which limit the scientific value of their observations. Caring for

MCS patients requires a recognition of the fact that these theories are

often well known to patients, who may also have very strong views on the

matter.

Epidemiology

Detailed knowledge of the epidemiology of MCS is not available. Estimates

of its prevalence in the US population (from where most reports continue to

come) range as high as several percentage points, but the scientific basis

for these is obscure, and other evidence exists to suggest that MCS in its

clinically apparent form is rare (Cullen, Pace and Redlich 1992). Most

available data derive from case series by practitioners who treat MCS

patients. These shortcomings notwithstanding some general observations can

be made. Although patients of virtually all ages have been described, MCS

occurs most commonly among mid-life subjects. Workers in jobs of higher

socio-economic status seem disproportionately affected, while the

economically disadvantaged and non-White population seems underrepresented;

this may be an artifact of differential access or of clinician bias. Women

are more frequently affected than men. Epidemiological evidence strongly

implicates some host idiosyncrasy as a risk factor, since mass outbreaks

have been uncommon and only a small fraction of victims of chemical

accidents or overexposures appear to develop MCS as a sequela (Welch and

Sokas 1992; Simon 1992). Perhaps surprising in this regard is the fact that

common atopic allergic disorders do not appear to be a strong risk factor

for MCS among most groups.

Several groups of chemicals have been implicated in the majority of

initiating episodes, specifically organic solvents, pesticides and

respiratory irritants. This may be a function of the wide-spread usage of

these materials in the workplace. The other commonplace setting in which

many cases occur is in the sick building syndrome, some patients evolving

from typical SBS-type complaints into MCS. Although the two illnesses have

much in common, their epidemiological features should distinguish them.

Sick building syndrome typically affects most individuals sharing a common

environment, who improve in response to environmental remediation. MCS

occurs sporadically and does not respond predictably to modifications of

the office environment.

Finally, there is great interest in whether MCS is a new disorder or a new

presentation or perception of an old one. Views are divided according to

the proposed pathogenesis of MCS. Those favouring a biological role for

environmental agents, including the clinical ecologists, postulate that MCS

is a twentieth century disease with rising incidence related to increased

chemical usage (Ashford and Miller 1991). Those who support the role of

psychological mechanisms see MCS as an old somatoform illness with a new

societal metaphor (Brodsky 1993; Shorter 1992). According to this view, the

social perception of chemicals as agents of harm has resulted in the

evolution of new symbolic content to the historic problem of psychosomatic

disease.

Natural History

MCS has not yet been studied sufficiently to define its course or outcome.

Reports of large numbers of patients have provided some clues. First, the

general pattern of illness appears to be one of early progression as the

process of generalization develops, followed by less predictable periods of

incremental improvements and exacerbations. While these cycles may be

perceived by the patient to be due to environmental factors or treatment,

no scientific evidence for such relationships has been established.

Two important inferences follow. First, there is little evidence to suggest

that MCS is progressive. Patients do not deteriorate from year to year in

any measurable physical way nor have complications such as infections or

organ system failure resulted in the absence of intercurrent illness. There

is no evidence that MCS is potentially lethal, despite the perceptions of

the patients. While this may be the basis of a hopeful prognosis and

reassurance, it has been equally clear from clinical descriptions that

complete remissions are rare. While significant improvement occurs, this is

generally based on enhanced patient function and sense of well-being. The

underlying tendency to react to chemical exposures tends to persist,

although symptoms may become sufficiently bearable to allow the victim to

return to a normal lifestyle.

Clinical Management

Very little is known about the treatment of MCS. Many traditional and

non-traditional methods have been tried, though none has been subjected to

the usual scientific standards to confirm their efficacy. As with other

conditions, approaches to treatment have paralleled theories of

pathogenesis. Clinical ecologists and others, who believe that MCS is

caused by immune dysfunction due to high burdens of exogenous chemicals,

have focused attention on avoidance of artificial chemicals. This view has

been accompanied by use of diagnostic strategies to determine "specific"

sensitivities by various invalidated tests to "desensitize" patients.

Coupled with this have been strategies to enhance under-lying immunity with

dietary supplements, such as vitamins and antioxidants, and efforts to

eradicate yeasts or other commensal organisms. A most radical approach

involves efforts to eliminate toxins from the body by chelation or

accelerated turnover of fat where lipid-soluble pesticides, solvents and

other organic chemicals are stored.

Those inclined to a psychological view of MCS have tried appropriately

alternative approaches. Supportive individual or group therapies and more

classic behavioral modification techniques have been described, though the

efficacy of these approaches remains conjectural. Most observers have been

struck by the intolerance of the patients to pharmacological agents

typically employed for affective and anxiety disorders, an impression

supported by a small placebo-controlled double-blind trial with fluvoxamine

that was conducted by the author and aborted due to side effects in five of

the first eight enrollees.

The limitations of present knowledge notwithstanding, certain treatment

principles can be enunciated.

First, to the extent possible, the search for a specific "cause" of MCS in

the individual case should be minimized--it is fruitless and

counterproductive. Many patients have had considerable medical evaluation

by the time MCS is considered and equate testing with evidence of pathology

and the potential for a specific cure. Whatever the theoretical beliefs of

the clinician, it is vital that the existing knowledge and uncertainty

about MCS be explained to the patient, including specifically that its

cause is unknown. The patient should be reassured that consideration of

psychological issues does not make the illness less real, less serious or

less worthy of treatment. Patients can also be reassured that MCS is not

likely to be progressive or fatal, and they should be made to understand

that total cures are not likely with present modalities.

Uncertainty about pathogenesis aside, it is most often necessary to remove

the patient from components of their work environment which trigger

symptoms. Although radical avoidance is of course counterproductive to the

goal of enhancing the worker's functioning, regular and severe symptomatic

reactions should be controlled as far as possible as the basis for a strong

therapeutic relationship with the patient. Often this requires a job

change. Workers' compensation may be available, even in the absence of

detailed understanding of disease pathogenesis, MCS may correctly be

characterized as a complication of a work exposure which is more readily

identified (Cullen 1994).

The goal of all subsequent therapy is improvement of function.

Psychological problems, such as adjustment difficulties, anxiety and

depression should be treated, as should coexistent problems like typical

atopic allergies. Since MCS patients do not tolerate chemicals in general,

non-pharmacological approaches may be necessary. Most patients need

direction, counseling and reassurance to adjust to an illness without an

established treatment (Lewis 1987). To the extent possible, patients should

be encouraged to expand their activities and should be discouraged from

passivity and dependence, which are common responses to the disorder.

Prevention and Control

Obviously, primary prevention strategies cannot be developed given present

knowledge of the pathogenesis of the disorder or of its predisposing host

risk factors. On the other hand, reduction of opportunities in the

workplace for the uncontrolled acute exposures which precipitate MCS in

some hosts, such as those involving respiratory irritants, solvents and

pesticides, will likely reduce the occurrence of MCS. Proactive measures to

improve the air quality of poorly ventilated offices would also probably

help.

Secondary prevention would appear to offer a greater opportunity for

control, although no specific interventions have been studied. Since

psychological factors may play a role in victims of occupational

overexposures, careful and early management of exposed persons is advisable

even when the prognosis from the point of view of the exposure itself is

good. Patients seen in clinics or emergency rooms immediately after acute

exposures should be assessed for their reactions to the events and should

probably receive very close follow-up where undue concerns of long-term

effects or persistent symptoms are noted. Obviously efforts should be made

for such patients to ensure that preventable reoccurrences do not come

about, since this kind of exposure may be an important risk factor for MCS

regardless of the causal mechanism.