ACP medicine, 3rd Edition

Clinical Essentials

Occupational Medicine

Linda Rosenstock MD, MPH, FACP1

Mark R. Cullen MD2

1Dean, University of California, Los Angeles, School of Public Health

2Professor of Medicine and Public Health and Director, Occupational and Environmental Medicine Program, Yale University School of Medicine

Linda Rosenstock, M.D., M.P.H., F.A.C.P., has no commercial relationships with manufacturers of products or providers of services discussed in this chapter.

Mark R. Cullen, M.D., is a consultant for Alcoa, Inc.

November 2005

Awareness of the impact of the work environment on health has increased dramatically in the past few decades. Common clinical problems, such as carpal tunnel syndrome and respiratory irritation and allergy, are increasingly being related to physical, chemical, and biologic hazards at work.1 In this chapter, we cover some of the most common occupational disorders diagnosed in industrialized countries, and we present examples of known or suspected causes [see Table 1]. More extensive descriptions of specific disorders are presented in other chapters of ACP Medicine and in textbooks of occupational medicine.2,3,4 An increasing amount of information about occupational medicine is available on the Internet from the National Institute for Occupational Safety and Health (http://www.cdc.gov) and the Occupational Safety and Health Administration (http://www.osha.gov).

Table 1 Common Occupational Disorders

 

Disorders

Examples of Causal Factors

Respiratory tract

Pneumoconiosis

Coal, silica, asbestos

Asthma

Latex, polyurethane

Allergic alveolitis

Vegetable matter, machining fluids

Metal fume fever

Metal fumes

Skin

Contact dermatitis

Oils, rubber, metals

Acne

Herbicides, oils, friction

Urticaria

Latex

Urinary tract

Glomerular disease

Organic solvents, mercury

Tubulointerstitial disease

Cadmium, lead

Liver

Acute or subacute necrosis

Organic solvents, TNT, 2-nitropropane

Cholestatic hepatitis

Methylene dianiline

Acute and chronic hepatitis

Viruses (hepatitis B, C)

Steatosis

Organic solvents

Hepatoportal sclerosis

Vinyl chloride, arsenical compounds

Hepatocellular injury

Lead, arsenic, phosphorus, dioxin

Musculoskeletal

Carpal tunnel syndrome

Repetitive trauma

Raynaud phenomenon

Repetitive vibrations, vinyl chloride

Scleroderma

Coal mining

Nervous system

Parkinsonism

Manganese

Peripheral neuropathy

Solvents, lead, acrylamide, arsenic

Acute encephalopathy

Organic solvents, asphyxiants

Acute or subacute cholinergic crisis

Organophosphate and carbamate pesticides

Subacute encephalopathy

Mercury, lead, arsenic, manganese, carbon disulfide

Subacute peripheral neuropathy

Organophosphates

Chronic basal gangliar disorder

Manganese, carbon monoxide (postasphyxiation)

Chronic encephalopathy

Recurrent organic solvent exposures

Hematologic conditions

Hemolysis

Lead, organic nitrites

Accelerated red cell destruction

   Acute hemolysis

Nitro and amine compounds

   Subacute hemolysis

Lead

Disorders of oxygen transport

   Methemoglobinemia

Nitro and amine compounds

   Carboxyhemoglobinemia

Carbon monoxide

Disorders of red cell production

   Hyperplastic anemia

Lead

   Aplastic anemia, hypoplastic anemia

Ethylene glycol ethers, benzene, arsenic, ionizing radiation

   Myelodysplasia

Benzene, ionizing radiation

   Polycythemia

Cobalt

Infectious

Hepatitis B, C

Health care

Influenza A (H5N1)

Poultry workers

SARS

Health care

Anthrax

Animal handling

Endocrine and reproductive

Hypogonadism

Lead

Azoospermia, oligospermia

DBCP, ionizing radiation

Teratogenesis

Organic mercury, PCBs

DBCP—1,2-dibromo-3-chloropropane (pesticide)   PCBs—polychlorinated biphenyls   SARS—severe acute respiratory syndrome

Data on the frequency of occurrence of most occupational disorders are limited; however, data demonstrating the extent of the problem are available. Recent estimates are that each year, approximately 55,000 deaths result from occupational illness, and 3.8 million disabling occupation-related injuries occur.5 Costs of occupational deaths and related injuries have been estimated to be $125 billion to $155 billion a year.5,6 Occupational illness is common and has substantial clinical ramifications.

Basic Principles of Occupational Disease

It is important to debunk the widespread and erroneous perception that most occupational disorders are pathologically unique. Although some disorders, such as silicosis, do have distinguishing pathologic characteristics, the majority do not. Most occupational diseases—such as lung cancer induced by ionizing radiation, bladder cancer caused by fumes from coke ovens, asthma triggered by the inhalation of platinum salts, and fatty liver resulting from the absorption of the solvent dimethylformamide through the skin—are pathologically indistinguishable from disorders with more familiar causes. However, it is virtually always possible to differentiate occupational diseases from their nonoccupational counterparts. Laboratory testing and data gathering provide the best clues for the diagnosis of occupational disease, but to recognize these disorders, it is critical to ask appropriate questions when taking the medical history [see Clinical Evaluation, below].

Workplace toxins and hazards, when adequately studied, have predictable and discrete pathologic consequences. Although other diseases share common final pathways, the initial mechanisms of injury are generally highly specific for each agent. Aside from the possibility of idiosyncratic responses, as occur with pharmacologic agents, the actual potential effects of most toxins are few. For example, beryllium may cause an acute inflammatory pneumonia (acute beryllium disease) within hours after intense exposure, or it may cause a delayed hypersensitivity response with granulomatous lung disease (chronic beryllium disease [CBD]) in persons with recurrent or long-term exposures; no other form of nonmalignant lung disease is known to be caused by this metal or its salts.

Both the likelihood that workplace hazards will produce effects and the severity of those effects are determined by the amount of toxin to which the patient is exposed (hereafter referred to as dose). The nature of the relation between dose and response depends on the mechanism of action of the agent. For direct-acting toxins, which cause effects by directly disrupting cellular function or cell death at the target-organ level, there is usually a dose beneath which no biologic effects are observed—a so-called threshold level. Above this level, there is typically a sigma-shaped dose-response correlation as dose rises, until a lethal dose is reached. Similarly, an increasing percentage of the exposed population is affected as dose rises; eventually, everyone is affected. This is characteristic of heavy metals, organic solvents, and pesticides. For agents that cause allergic-type or idiosyncratic responses, such as latex and epoxy resins, which affect only susceptible people, dose contributes to the likelihood of sensitization, though not necessarily to the severity of the reaction. Further, once a worker has become sensitized, a very low dose may be sufficient to induce a full-blown clinical response. For mutagens and carcinogens, current knowledge presumes a linear dose-response model, with each increment in cumulative dose resulting in a proportional increase in the risk of cancer. The severity of the resultant cancer bears no predictable relation to the induction dose, though the time from exposure to onset generally is shorter when doses are higher.

The temporal relation between exposure and effect is highly predictable for each agent and each effect. For many direct toxins, effects occur within minutes or hours after exposure to an appropriate dose, such as the syndrome of cholinergic storm after organophosphate pesticide poisoning. Similarly, immunologically mediated responses, such as asthma and dermatitis, will occur within minutes or hours after exposure. Conversely, other effects are predictably delayed. Asbestos and silica rarely cause pneumoconiosis in less than 10 years after first exposure, except after very high exposure levels. Solid tumors, such as lung cancer associated with these same dusts, emerge, on average, 20 to 30 years after first exposure. Other effects occur in an intermediate time frame: some organophosphates cause a paralysis whose onset is delayed by weeks to months after an intense overexposure. The presentations of acute lead, mercury, or arsenic poisoning are insidious, coming after the poison accumulates to a dangerous level, usually after weeks or months of exposure.

When the clinician is approaching patients with new medical problems, consideration should be given to occupational causes. If the problem is acute, such as the relatively sudden onset of a rash or of liver function abnormalities or hemolysis, the search for a possible occupational cause should focus on recent events: Has there been a new or increased exposure to an agent that can cause such toxicity in the hours, days, or, at most, weeks before onset? On the other hand, for chronic disorders, such as pulmonary fibrosis and cancer, the search for causes should begin with a work history that goes back years.

With regard to work histories, it is important to note that host factors may modify temporal and dose-response correlations; all workers do not react alike to comparable exposures. In every workplace, some people appear to be immune to the effects of even the most toxic agents, and others seem to react to low doses, often lower than the threshold deemed toxic by regulatory authorities. These differences may be caused by genetic, dietary, or constitutional factors or by the preexistence of other illnesses.

In addition, many workplace hazards and toxins interact with one another and with nonoccupational factors to cause disease. Dose-response correlations for industrial hazards may be markedly shifted in the presence of other hazards, habits, or medications. An important example is the likelihood of disease resulting from thermal stress (i.e., heat or cold) in the presence of hemodynamically active agents, such as calcium channel blockers, autonomic agents, and diuretics.7 Likewise, the effects of vibration trauma on wrists and digits may be amplified by nicotine.8 The effects of one hazard may be significantly altered in the presence of another; for example, the combined effect of noise and solvents on hearing loss9 and of asbestos and smoking on lung cancer10 are greater than the effect of exposure to each hazard alone.

CLINICAL EVALUATION

Defining the Pathophysiologic Basis of the Patient's Complaints

When searching for the pathophysiologic basis of a patient's complaints, it is important to ascertain the following: Is the process an acute or relapsing process, with precipitous changes in physiologic status, reflecting a recent or ongoing exposure? Or is it a chronic process, more likely the result of noxious exposure in the distant past? Dysfunction of what organ or organs best explains symptoms? Is there evidence of physiologic disruption, or is the disorder predominantly one of subjective difficulties?

Taking the Occupational History

Every patient should be questioned regarding the essentials of occupation, including current and past workplaces, job type, and materials used. Open-ended questions are always appropriate (e.g., “Are there dangerous materials or hazards in your workplace?” and “Do you believe that your work is causing you any health problems?”).11 The exploration of work as the basis for a complaint or medical problem entails an incisive approach and depends on the nature of the clinical problem being investigated. Evidence suggests that physicians need to become more adept at assessing a patient's occupational history.12

Approach to the Patient with an Acute Disorder

The emphasis should be on new exposures, increased exposures, and accidental exposures. Has the patient recently begun a new job or task involving hazards? Were new materials recently introduced at work? Has there been a change in working conditions, such as a failure of the ventilation system? Has there been a leak, spill, or accident? If the answer to all of these questions is no, the likelihood is low that the acute illness is related to work processes or chemicals.

Other than acute effects that are immunologically mediated, most effects are not idiosyncratic and will follow a sigma-shaped dose-response correlation like that discussed for direct-acting toxins (see above). In such circumstances, it would be expected that a high proportion of exposed persons would be affected, although individual thresholds and dose responses may differ. Questions probing effects in other exposed persons are extremely helpful, as in the investigation of food poisoning or respiratory infections. Although a negative answer does not exclude a work-related effect, the suggestion of an outbreak or a cluster makes the probability of an association high and increases the urgency of a prompt, correct diagnosis.

Approach to the Patient with Recurrent Manifestations

A patient may have repeated or recurring manifestations, such as intermittent cough, rash, or nausea. Although the cause may be difficult to establish in some situations, especially when symptoms have been very persistent or chronic, the time course, particularly at the onset of recurring manifestations, is often extremely revealing. For example, a new asthma patient whose symptoms occur on vacations and weekends is unlikely to have an occupationally related disorder.

Approach to the Patient with Chronic Disease

When patients present with evidence of irreversible organ damage or malignancy, the approach is altogether different. Although the longer latency between initial exposure and disease onset is useful in determining whether occupational exposures have played an important role, questions directed at temporal associations between symptoms and exposures are not helpful. Rather, the first step is to establish a clear pathophysiologic picture of the disease process itself. Sometimes, knowledge of past exposures may assist in directing this evaluation. For example, a worker who has been exposed to asbestos and who presents with a malignant pleural effusion should be carefully evaluated for mesothelioma, which is otherwise an uncommon disorder.

Once the disease process is characterized, a role for occupational factors can be more seriously considered by obtaining a more detailed history of exposures. Because only a handful of agents are suspected of causing or have been proved to cause any single chronic disease, the goal of this history is to determine whether exposure to any of those agents has occurred and whether the exposure occurred at a time and dose that suggest a causal connection to the disease.

Approach to Subacute and Insidious Disease

The greatest diagnostic challenge in clinical occupational medicine is the clinical disorder of gradual onset over days to weeks for which none of the above approaches are effective. Examples include peripheral neuropathies, anemia, and a change in bowel habit in the absence of evidence of malignant or irreversible organ system damage. Often, in such cases, the search for the underlying pathophysiologic process and the search for its cause seem intricately related and must proceed simultaneously. Lessons from these paradigms may be helpful. If indeed the subacute process is toxic, it most likely reflects the effects of a recent exposure, typically of an agent that is accumulating slowly. Heavy metals, pesticides, and various toxic organic chemicals often accumulate in this fashion; under typical conditions of exposure, it may take weeks or months for these agents to accrue to levels of pathogenic significance. Although it is unnecessary to identify an accidental leak or spill to make a diagnosis in such cases, it is essential to note any enhanced opportunity for exposure or any novel exposure that may have occurred relatively recently. The distant exposure history is not likely to be helpful, because the subacute disorders almost always present at the point of maximal accumulation; once the worker is removed from the site of the exposure, latency or delay in onset is unusual.

CONFIRMING AND QUANTIFYING EXPOSURE

There are two basic approaches to obtaining additional exposure information. The first involves the collection of independent information about present or former work (depending on which is relevant). After the physician obtains consent from the patient (to ensure that the patient is protected from unwanted consequences), information about exposures is requested from the employer, a trade union, or a regulatory agency. Such information is usually reported through the use of a material safety data sheet (MSDS). The MSDS provides generic chemical names, compositions, and basic toxicity information of all materials used. In addition, employers may be able to provide evidence of objective sampling that may have been done to test air levels of hazardous substances. Job descriptions, results of medical tests performed at work, information about other workers with health problems, and the use of protective equipment or other methods to limit exposure may all be of value in assessing workplace exposures.

The second potential source of dose information is biologic testing. For a few hazards, testing of urine, blood, or hair may enable the physician to determine the body burden of the agent; the results of such testing correlate with current or recent levels and, less commonly, with remote exposures [see Table 2]. Most of these tests cannot detect chemicals that have been cleared from the body or deposited in bodily organs; this substantially limits their usefulness for diagnostic decision making. Of course, there are no simple tests for chemicals that cause topical injury to skin or respiratory mucosa but are not absorbed. For agents that act by immune sensitization, radioallergosorbent testing or skin-patch testing may be useful both for documenting exposure and for subsequent elicitation of an immune response.

Table 2 Common Occupational Hazards for Which There Are Widely Available Biologic Tests of Explosure

Hazard

Comments

Metals

 

  Arsenic

Hair sampling can detect historic exposures

  Cadmium

Detectable in urine for may years if there is renal injury

  Fluorides

Transient in urine

  Lead

Half-life 40 days in blood

  Mercury

Detectable in urine for days to weeks

Asphyxiants

 

  Carbon monoxide

Half-life 4 hr in blood

Pesticides

 

  Organophosphates

Detectable indirectly, by measurement of cholinesterase, which may be depressed for days to months

  Organochlorines (e.g., DDT, chlordane, dieldrin)

Persists in blood

Organic solvents

 

  Benzene and toluene

Metabolites transiently in urine

Antigens

IgE antibodies measurable by RAST

Miscellaneous

 

  PCBs

Persists in blood

RAST—radioallergosorbent test  PCBs—polychlorinated biphenyls

Most important of all is to remember that a test for exposure can be interpreted only in the context of the history and the clinical problem. It should not be directly interpreted as a test for disease, regardless of how the laboratory reports the data. For example, a whole blood lead level of 25 mg/dl is clear evidence of excess lead exposure. If the history indicated that the patient had recently been exposed for the first time, this level would suggest a modest, generally subtoxic dose of lead. If, however, the patient had worked around lead for many years and quit a year before the test was performed, this same value would suggest a very high previous exposure and might well be associated with health effects caused by high long-term exposure. Similarly, a large proportion of bakers working around flour dust may have IgE antibodies to wheat, rye, or other grain antigens, even though the vast majority of those bakers are symptom free and will most likely remain so. Given all these limitations, biologic testing plays only a limited role in occupational medicine and can never be a substitute for the occupational history.

DIAGNOSTIC DECISION MAKING

The determination that a patient's symptoms are work related often entails extensive ramifications for the patient's employer, as well as potentially serious public health and medicolegal implications. These may present a significant challenge to the clinician, because for many occupational disorders, there is no gold standard for diagnosis.

The decision-making process should address the following questions:

  1. Is the clinical illness—including the history, physical examination, and laboratory findings—consistent with other case descriptions?
  2. Is the timing between exposure and clinical onset compatible with the known biologic facts about the hazard?
  3. Is the exposure dose within the range of doses believed to cause such effects
  4. Are there special attributes of the particular patient that make it more or less likely that he or she would be so affected?
  5. Are there alternative ways of constructing the case that better fit the available facts?
  6. Where there remains significant uncertainty about the cause, how important is it to be certain?

Regarding the certainty of identifying the cause, the general legal standard for workers' compensation purposes is “more likely than not,” which is a relatively low hurdle of certainty (i.e., at least 50% certain). However, there may be other situations that demand a higher level of confidence, irrespective of the standard for obtaining compensation benefits. In general, problems involving current working conditions demand a far greater level of certainty than historical ones. For example, a diagnosis of occupational asthma in a spray painter would likely dictate removing the patient completely from exposure to the offending paint or constituent; correct identification of that agent might be crucial to saving his or her career. Similarly, if a surgeon presented with recurrent anaphylactic reactions, it would be very important to determine whether the reactions were to latex, an anesthetic agent, or some extrinsic factor.

In situations where a high level of certainty is needed, it is often worth the effort to refine the diagnostic impression by serial observations, usually while the patient remains exposed, or by utilizing diagnostic challenges of removal followed by reexposure. Using serial functional measurements, such as peak expiratory flow records or serial blood tests, a more certain judgment can be made. This may also be an appropriate circumstance for referral to occupational physicians who specialize in evaluating challenging cases.

Major Occupational Disorders in Developed Countries

The spectrum of occupational disorders of clinical importance is rapidly shifting as a result of several factors: these include changes in the economy, which have brought about a decline in traditional manufacturing and a rise in service-sector activities; better control of many hazards, such as mineral dusts (e.g., asbestos, silica, coal), heavy metals (e.g., lead, arsenic, mercury), and the most toxic solvents (e.g., benzene); rapid introduction of many new technologies whose health risks remain inadequately characterized; and changing demographics in the workplace, in which the proportion of women, minority, and older workers is increasing. In the sections that follow, the disorders that are most important in clinical practice in developed countries are briefly discussed by organ system.

OCCUPATIONAL CANCER

Only a small fraction of known chemical agents and a handful of physical and biologic hazards appear capable of inducing neoplastic change in mammalian tissues. In general, the risk of cancer being induced increases in direct proportion to total dose of toxin to which the person is exposed. Typically, the target organ is relatively specific and is determined by metabolism and transport of the agent. However, a few agents, including ionizing radiation and asbestos, appear to have potential to cause malignancy at more than one human site. There is invariably a long lag time between initial exposure and onset of clinical disease. Only a small number of hazards found in the workplace have been clearly established as carrying substantive cancer risk for workers. An additional group of hazards are suspected, but additional studies are needed. The list of potential carcinogens is expanding; for example, evidence suggests that exposure to cadmium may play a role in the development of prostate cancer.13 Studies provide some indication that workers in print shops, service-station employees, farm-product vendors, horticulturists, farmers, and aircraft mechanics are at increased risk for renal cell carcinoma14,15 [see Table 3].

Table 3 Established Occupational Carcinogens

Cancer Site

Hazard

Setting

Lung

Asbestos

Insulation, textiles

Ionizing radiation

Uranium mining

Arsenic

Refining

Polyaromatic hydrocarbons

Coke ovens

Nickel

Nickel refining

Chromium

Tanning, pigments

Alkylating agents

Chemical industry

Silica

Mining, stonecutting

Ceramic fibers

Insulation

Formaldehyde

Chemicals, plastics

Beryllium

Nuclear weapons, aerospace industry

Cadmium

Batteries

Acrylonitrile

Plastics

1,3-Butadiene

Rubber, plastics

Pleura and peritoneum

Asbestos

Construction materials

Upper respiratory tract

Wood dust

Carpentry

Nickel

Refining

Chromium

Plating

Asbestos

Friction products

Formaldehyde

Chemicals, plastics

Urinary bladder

Benzidine and related amines

Dyes, chemicals

Polyaromatic hydrocarbons

Aluminum reduction

Liver

Vinyl chloride monomer

Plastics

Arsenic

Pesticides

Upper GI tract

Asbestos

Shipbuilding

Coal dust

Mining

Acrylonitrile

Plastics

Hematologic system

Benzene

Chemicals, rubber

Ionizing radiation

Defense industry

Ethylene oxide

Chemicals, sterilizers

Soft tissue

Dioxin

Chemical industry

Brain

Vinyl chloride

Chemical industry

Formaldehyde

Chemical industry

RESPIRATORY TRACT DISORDERS

The respiratory tract is a frequent target of toxic effects. Complaints referable to the lungs or upper respiratory tract often require a careful evaluation for occupational causes. The presence of other possible causal factors, such as common allergy and smoking, does not exclude the possibility of an occupational cause and may, in fact, increase the likelihood of one.

Acute Disorders and Recurrent Disorders

The most prevalent acute effects—inflammatory reactions of the mucosae of the upper or lower airway system—are caused by environmental irritants.16 An extraordinary array of agents are irritating, including simple inorganic gases (e.g., ammonia and chlorine), organic solvents, acid and alkaline mists, metal fumes (i.e., tiny particles of metal and metal oxide that occur when vaporized metals hit cool air), mineral dusts (e.g., fibrous glass and coal), and almost all the pyrolytic products of combustion. The anatomic site of irritation for dusts, mists, and fumes depends on the deposition of particles; for gases, it depends on water solubility (i.e., the more water soluble the gas, the more it will dissolve in the upper respiratory tract). Expression of symptoms, from mild burning of the eyes, nose, and throat to small airway and alveolar injury associated with the acute respiratory distress syndrome, depends on dose, duration of exposure, and the potency and composition of the irritant; there is also substantial host variability. The period from the time of exposure to the onset of symptoms is very brief for the upper respiratory structures and can be from minutes to hours for lower structures.

Most of the consequences of acute irritation are self-limited; the upper respiratory tract is particularly resilient, although patients who work in areas of poor air quality will experience frequent recurrences, punctuated by commonplace complications such as sinusitis. Such cases require steps to modify exposure. More severe insults may result in fixed scarring of airways or lung parenchyma; late inflammatory sequelae such as bronchiolitis obliterans are occasionally reported. A newly recognized and probably common outcome of significant lower airway injury is the occurrence of persistent mucosal irritation and bronchospasm, a variant of asthma induced by a single exposure or repeated exposures to irritants. Initially dubbed reactive airways dysfunction syndrome,17 this disorder is best classified as nonimmune occupational asthma or simply asthma without latency. Unfortunately, the condition tends to be highly resistant to therapy, and patients derive only modest benefit from inhaled steroids or other bronchodilators. Typically, cough with some phlegm, chest discomfort, and occasionally even dyspnea persist despite early and intensive therapy. Reassurance and reduction of further exposures to irritants are the mainstays of treatment.

Occupational asthma, including the nonimmune- and the immune-mediated varieties, is prevalent.18 There are now over 200 established causes of presumed immune-mediated asthma19; these are usually categorized as proteins and other high-molecular-weight antigens (e.g., animal danders, latex antigens, and grains) and small molecules such as the isocyanates—the ubiquitous chemicals used in polyurethane products. Typically, the classic antigens differentially affect those with atopy and are associated with identifiable IgE antibody responses to the sensitizer.20 In such cases, the greatest diagnostic dilemma is distinguishing occupational sources from other causes of asthma, though the periodicity as documented by history or peak expiratory flow records (PEFR) aid in identifying a relation to work. Latex has become a particularly important cause, especially when rendered airborne in association with the use of powdered gloves.21,22 More troublesome are the low-molecular-weight agents such as toluene-2,4-diisocyanate (TDI) and other isocyanates, for which atopy is not a risk factor.19,23Onset is often insidious, with cough and chest discomfort relatively more common than in asthma of other causes. Far more often than with the IgE-mediated agents, symptoms may be delayed some hours after exposure, so patterns may include nocturnal complaints. Once the physiologic hallmarks of asthma are established, the history and PEFR are the keys to specific diagnosis. Studies have shown that detailed histories can be inconclusive; in some cases, objective measurements can establish the diagnosis of occupational asthma.24 Specific inhalation tests may be valuable, but they should be performed only under medical supervision.

Current evidence suggests that correct diagnosis of occupational asthma makes a difference. People who are removed early from further contact have a better likelihood of reducing their dependence on medication; many will become nonasthmatic over time.19,20 Most who remain exposed will develop persistent nonspecific bronchial hyperreactivity, as well as possible fixed obstructive changes. These patients will typically fail to recover after they are removed from contact with the agent, and their conditions may even worsen; this is the basis for an aggressive posture toward early evaluation and management.

Acute infectious diseases occur in an extraordinarily wide variety of workplaces, from health care to industrial and agricultural settings. Anthrax and other agents of bioterrorism, as well as emerging infectious diseases such as severe acute respiratory syndrome and influenza A (H5N1) are of particular concern to workers.25,26

Allergic alveolitis, with its more benign variants, such as humidifier fever, continues to occur sporadically in a wide range of settings. This disorder was traditionally associated with agricultural exposures to molds and bacilli. Cases are now reported to occur in manufacturing and other industrial settings because of the appearance of a few chemicals that appear capable of inducing the immune response (e.g., plastic resin constituents) and because of the contamination of many industrial processes with microorganisms.27 The office environment continues to be an occasional source of this condition as well, though the reservoir of causal microbes may be obscure; such organisms may potentially reside in heating and air-conditioning systems remote from the patient's work area.28

Chronic Conditions

The pneumoconioses continue to occur, in part because of their very long latency from first exposure and because pockets of very poor industrial conditions continue to exist even in developed countries. Construction activities have been particularly problematic. In general, asbestosis, silicosis, and coal workers' pneumoconiosis are diseases that occur after extensive work exposures. The diagnosis can usually be made on the basis of clinical findings and the history of exposure, once the patient's lifetime job history is obtained.

The granulomatous diseases, including CBD and so-called hard metal disease, are less common but important and increasingly recognized disorders of sensitization. CBD is clinically almost identical to idiopathic sarcoidosis except that all cases involve the lung and that the prognosis—even after the patient is removed from exposure to beryllium metal, compound, or fumes—is generally unfavorable. All patients with sarcoidosis should be asked if they work with metals, and the least suspicion should prompt specific testing; there is a highly sensitive test that can distinguish sarcoidosis from CBD on blood or bronchoalveolar lavage (BAL) fluid.29 Hard metal disease is a giant cell alveolitis induced through an idiosyncratic reaction in workers exposed to the metal cobalt.30 Most often, it occurs in workers making or using tungsten carbide, the very hard metal used for machine tools. Onset may be insidious and may include asthmatic symptoms, because cobalt is asthmogenic as well. Recognition of the parenchymal process by BAL or biopsy is crucial because hard metal disease is progressive, often refractory to treatment with steroids, and often lethal; there is anecdotal evidence favoring the use of cytotoxic drugs. Once hard metal disease is diagnosed, the patient should be promptly removed from any further exposure.

In 1998, a novel form of interstitial fibrosis related to an industrial exposure was reported: flock worker's lung, named after the nylon flocking used for making feltlike textiles.31 Cases of flock worker's lung are distinctive, with pathologic evidence of both parenchymal fibrosis and lymphocytic bronchiolitis. The reporting of flock worker's lung underscores a key principle of occupational medicine: that new occupational diseases and other clinical consequences of work continue to be uncovered.32

DERMATOLOGIC DISORDERS

Despite increased recognition of the need to reduce contact between the skin and the chemical and physical environment, dermal conditions remain responsible for significant morbidity in the workplace. Most disorders are caused by direct exposure of the skin to workplace irritants, sensitizers, pigments, carcinogens, and materials that interfere with normal dermal function by disrupting sebaceous and follicular secretions (e.g., oils that cause acne) or solvents that erode protective lipids. Trauma, foreign bodies, ionizing and nonionizing radiation, and extremes of temperature may modify or disrupt skin growth, vascular integrity, or both. On occasion, systemic exposure may have a dermal consequence, as in urticarial responses to inhaled antigens, pigmentary alterations from the deposition of metals (e.g., silver), and the much-described though rarely seen chloracne, a variant of acne induced by dioxins and related chemicals. Workers who are at increased risk for allergic contact dermatitis include tanners, cast-concrete product workers, leather-goods workers, footwear workers, machine and metal product assemblers, electrical and telecommunications equipment assemblers, print-shop workers, and machine and engine mechanics.33 Several excellent texts of occupational skin diseases are available.34,35,36

Overwhelmingly, the major skin problem in the workplace remains dermatitis, either irritant induced or caused by allergy. Many agents may be responsible, including organic and inorganic chemicals, plastics and rubber, oils and lubricants, metals and construction materials, paints, and coatings.37 Both allergic dermatitis and irritant-induced dermatitis are more likely to affect persons with atopic conditions, dry skin, or other dermal risk factors. Distinguishing between the two is less important than recognizing occupational precipitants in the first place; both are difficult to differentiate from other commonplace skin disorders, such as eczema. The key to correct diagnosis is the history of skin contact and the temporal relation between contact and manifestations. Unfortunately, there is seldom a perfect or obvious correlation between the two, and some sleuthing is necessary, especially to discern the extent to which chemical contact may spread to places like the groin or areas where hand contact occurs. Airborne exposure may cause lesions in apparently untouched areas, such as the face; such occurrences are signs of likely hypersensitivity. Vexingly, symptoms do not always abate dramatically over weekends or during short periods in which exposure is avoided; removing the patient from the toxin for a week or two may be necessary to observe response. This, combined with observation of the patient during reexposure, is often the most valuable diagnostic test. Patch testing, performed by an experienced clinician aware of the exposures of concern, may be useful in difficult cases, though the clinician should keep in mind that irritants may yield false negative results and that even many healthy atopic persons will experience reactions to common contactants, such as nickel.38 Often, complete isolation from offending agents is economically infeasible, and materials that previously were well tolerated become sources of irritation and exacerbation. Combinations of work modification, aggressive treatment of flares and complications, and careful attention to routine skin care are necessary to control disease.

DISORDERS OF THE URINARY TRACT

Although innumerable toxins are known to cause acute injury to the kidney, exposures to chemical and physical agents at concentrations found in the workplace rarely cause such effects (exceptions include cases involving overwhelming accidental overexposure or ingestion). Of far greater concern are recurring exposures to agents at more typical workplace exposure levels that have subclinical effects but can lead to late nephropathy. Although there remains a vast burden of unexplained nephro pathology in the population and despite epidemiologic data suggesting an occupational cause,39,40 chronic renal injury resulting from workplace exposures remains poorly characterized.

The best-established effects on the urinary tract are those caused by exposure to heavy metals, especially lead, mercury, and cadmium; each of these metals is associated with a unique pattern of effects. Workers whose jobs entail exposure to lead include traffic police, hazardous-waste incineration workers, industrial workers, and furniture strippers; workers at risk for exposure to mercury include gold-mine workers, workers at chloralkali plants, workers exposed to hazardous waste, and construction workers; workers at risk for exposure to cadmium include those involved in the manufacture of batteries. Long-standing heavy-lead exposure results in a pattern of injury difficult to distinguish pathologically and clinically from the effects of hypertension; signs and symptoms include nephrosclerosis and evidence of both glomerular and tubular defects. The ability to clear urate is impaired early in the course and may be a clue; saturnine gout may occur a decade later. There is debate about the possibility of low-level or brief exposures to lead predisposing to hypertension or enhancing the degree of renal injury associated with essential hypertension or gout.41,42 Proponents of this view stress the importance of assessment of lead exposure in patients with mild chronic renal insufficiency.43

Long-term occupational exposure to inorganic mercury—principally through exposure to mercury vapor—may result in renal alterations involving the tubules and glomeruli. The monitoring of urinary mercury is useful for controlling such risk.44

Cadmium exposure in jewelry making, battery production, and other metal-processing operations leads to bioaccumulation of cadmium in the kidney, which results in proximal tubular injury with excessive excretion of β2-microglobulin and other tubular proteins. Later, a pattern of renal tubular acidosis may occur, which subsequently may lead to the development of renal insufficiency. Because the tubular dysfunction is only partially reversible,45 it is important to carefully monitor cadmium exposure, which is best done with regular blood and urine cadmium testing.46 Renal damage can occur at relatively low levels of cadmium exposure.47

Organic solvents have been implicated in renal tubular and renal parenchymal injury48; despite uncertainty of their role in renal toxicity, growing evidence suggests the need for evaluation of these substances in all new cases of unexplained nephropathy.

LIVER DISEASE

The liver is highly sensitive to effects of numerous organic and inorganic substances used in the workplace [see Table 1]. Despite the impressive potential for harm, often at exposure levels not uncommon in the workplace, occupational liver diseases are rarely recognized except during outbreaks.49 This is almost certainly because the clinical presentation is nonspecific, most often consisting of unsuspected elevations of hepatocellular enzymes occasionally associated with mild gastrointestinal symptoms. The single exception to this is the now extremely rare vascular disorder resembling veno-occlusive disease that is caused by vinyl chloride.

The more common hepatic effects of occupational hazards—steatosis and nonspecific hepatocellular injury—have numerous causes and are prevalent in the general population; a given case may be readily attributed to infection, alcohol use, drug toxicity, biliary tract disease, diabetes, obesity, or weight change. When persistent elevations of hepatic enzymes prompt more extensive workup with radiographic studies and biopsy, results rarely provide specific evidence of an occupational cause. Only high suspicion of a workplace culprit, combined with evidence of exposure to a suspect agent, serves to distinguish etiology.

CENTRAL AND PERIPHERAL NERVOUS SYSTEMS

Most pesticides,50 organic solvents,51 and many metals52 are neurotoxic at doses that may be seen in the workplace [see Table 1]. A handful of other chemicals used in plastics, lubricating fluids, and chemical operations are also neurotoxic; most cases occur after accidental or unusual exposures. In addition, persons exposed to asphyxiants, such as carbon monoxide and cyanide, may present with acute or recurring central nervous system symptoms. Both acute and late effects may occur—the former typically occurring immediately after an intense exposure, the latter often after prolonged periods of exposure. Importantly, the late or chronic effects usually result from prolonged periods of bioaccumulation or recurrent mild or subclinical acute exposures or as sequelae of acute intoxication. A direct consequence of this toxicologic fact is that neurotoxicity almost invariably presents during the time of occupational exposure to the offending agent and not long afterward, as may occur with carcinogenic substances or dusts causing pneumoconiosis.

Because of the extraordinarily diverse range of clinical symptoms that may herald CNS toxicity, including subtle changes in cognitive and affective function, the evaluation of suspected cases follows the general principles for all occupational disease, with increased attention given to recent exposures. The acute disorders usually occur as mild alterations of CNS function,53 often with associated GI or other systemic effects; they are often recurrent, cycling with periods of work exposure, as might be seen in a painter (through exposure to solvents) or a pest-control worker. The key to recognition is the temporal pattern, with remission of symptoms occurring over a course of time consistent with the metabolism of the toxin. There may also be evidence of symptoms associated with withdrawal, similar to the effects associated with ethyl alcohol. For the subacute and chronic effects, the key to diagnosis is identification of evidence of substantial exposure occurring over a course of time consistent with the evolving neurotoxic picture. None of the neurologic disorders appear to involve allergy or idiosyncrasy; thus, the doses of exposure involved must be substantive.

In many cases, the exposure to the agent can be biologically confirmed with measurement of the levels of metal in the urine or blood, measurement of cholinesterase levels, or identification of a metabolite of an organic chemical in urine. There may also be some clinical or pathophysiologic clues. For example, the constellation of cerebellar ataxia, personality change, and salivary gland hypersecretion should prompt consideration of inorganic mercurialism, possibly with associated renal effects. An asymmetrical motor neuropathy should always raise the specter of lead poisoning. Insidious symmetrical distal sensory neuropathies, on the other hand, are far more common with solvents and acrylamide; electrophysiologic or pathologic evaluation reveals almost pure axonal degeneration, with minimal secondary demyelination—an important differential feature. Highly localized neuropathies, either unilateral or bilateral, should raise the possibility of a compressive etiology, not uncommon with repetitive work activities [see Musculoskeletal Disorders, below].54

Although diagnosis may be straightforward once the possibility of a workplace agent is considered, management remains challenging. Treatment of acute disorders involves ending the exposure and providing support where clinically necessary. Several hazards, such as certain cholinesterase inhibitors and cyanide, have specific antidotes that should be administered under medical supervision. The subacute and chronic conditions all require removal from further exposure. In addition, patients with heavy-metal exposure may be given chelation therapy when signs and symptoms of severe intoxication are evident; this, too, must be done under very close supervision in view of the risk of enhancing CNS effects early in treatment. Moreover, the possibility of rebound effects from reequilibration of metal into the nervous system must be anticipated when chelation is stopped. Most important, whatever strategy is chosen, physician and patient must be aware that the prognosis for full recovery from all but the most acute effects is somewhat guarded. Axons regrow very slowly, and higher integrative functions, such as affective or cognitive functions of the CNS, resolve even more slowly or not completely. Early efforts at functional rehabilitation, as may be used for trauma or stroke patients, are indicated when impairments limit work or other major life activities.

Possibly the most challenging diagnostic situation in occupational neurology is the worker who presents with CNS-related complaints that exhibit a temporal pattern consistent with a workplace origin but who does not have substantial exposure to neurotoxic agents. Such symptoms are a common part of the so-called sick-building syndrome, now referred to as nonspecific building-related illness, and are universal among persons who have acquired intolerance to low levels of chemicals (multiple chemical sensitivities).55 It is important to recognize early that these syndromes are different from the neurotoxic disorders discussed here with regard to evaluation, prognosis, and treatment. They are discussed more fully later in this chapter [see Clinical Problems Associated with Low-Level Environmental Exposures,below].

MUSCULOSKELETAL DISORDERS

There has been a marked increase in the awareness of the role that work factors play in musculoskeletal disorders, ranging from such well-defined clinical problems as arthropathies and nerve compression syndromes to the less well characterized ailments causing pain of the trunk and extremities.54,56 In developed countries, such disorders account for billions of dollars of costs in medical care and lost productivity. The overwhelming bulk of this epidemic relates to suspected consequences of physical stressors and trauma that occur at work. A number of systemic occupational disorders may also have expression in the muscles, bones, joints, and connective tissues; important examples of such disorders are the arthralgias and gouty consequences of lead intoxication, bony pain in association with systemic fluorosis, and the apparent increased risk of scleroderma in miners.57

It is clinically useful to divide potential occupational musculoskeletal disorders into those that have a well-defined anatomic structure of involvement, such as carpal tunnel syndrome, and those that lack such a clear-cut pattern, such as low back pain.58,59 Although extensive data suggest that physical aspects of work, such as overall force, repetition, awkward posture, and vibration, contribute in a cumulative fashion to the development of both localizable and nonspecific symptoms, the approach to diagnosis and treatment is somewhat different for each. There is also evidence that factors other than physical strain, such as work stress, work fatigue, and adverse relationships in the workplace, may be important contributory factors, partially explaining high rates of musculoskeletal disorders among certain white-collar workers.60,61

For disorders of new onset involving the trunk or extremities or for clinically mild disorders, the initial approach should be short-term palliation with minimal workup. Rest from physically demanding tasks, use of nonsteroidal anti-inflammatory drugs or other nonnarcotic pain relievers, reassurance, and follow-up after a few days of treatment are suggested; further evaluation is indicated only if suggested by physical findings. If conservative steps fail to alleviate symptoms rapidly, additional examination and laboratory evaluation may be appropriate to rule out an anatomically discrete lesion that could be amenable to treatment. Where specific lesions are identified, such as compression of a nerve or disk or tenosynovial inflammation, longer-term efforts at elimination of strain in the affected region combined with anti-inflammatory drugs or other therapies are appropriate, followed by surgical intervention should these fail. In such cases, it is crucial to remember that the work-related stressors that caused the problem will complicate recovery unless they are modified.62,63,64

The most perplexing problem is the management of patients whose complaints cannot be specifically localized by physical examination or, when necessary, electrophysiologic or radiologic evaluation. Such complaints are no less real than those that are more readily understood and treated. Modification of work activities is often necessary but is rarely sufficient to resolve the problem. Pain may be persistent and refractory to treatment, and the value of physical therapy or pain medications is questionable. Rather, it is important for the treating physician to establish early that the symptoms are troublesome but not the result of a progressive process and that the patient may have to adapt to them despite discomfort. Expectation of cure often leads to unnecessary treatment, prolonged (and clinically unhelpful) loss of work time, and, ultimately, frustration on the part of the employer, the insurance company, the patient, and the physician.

HEMATOLOGIC DISORDERS

A host of disturbances of red cell function, survival, and production have been attributed to workplace exposures, including acute, subacute, and chronic processes [see Table 1]. Effects involving other cell lines have seldom been reported and will not be discussed. In clinical practice, the biggest concerns are the risk of acute hemolysis in workers exposed to nitrogen-containing oxidant chemicals in pharmaceutical, chemical, and explosives manufacturing; the effects of lead, which remains ubiquitous in the work environment; and the potential for solvent-induced marrow injury. The problem of oxidant stressors is somewhat difficult. Although workers with marked deficiency of glucose-6-phosphate dehydrogenase (G6PD) should probably avoid significant contact with such chemicals, there is not a clear relation between any of the measurable enzyme levels and risk. It is prudent to periodically screen all exposed workers for subclinical evidence of hemolysis, as well as for subclinical accumulation of methemoglobin, which is often induced by the same agents; workers who show evidence of early effects should probably be removed from harm's way, irrespective of identifiable factors.65

The hematologic effects of lead are widely misunderstood.66,67 Although there is a dose-related inhibition of heme synthetase by lead that can be readily quantified by determining the accumulation of the precursor protoporphyrin (usually measured as whole blood zinc protoporphyrin), this biochemical effect of lead on blood hemoglobin or hematocrit is minimal until very high levels are reached, and there is almost no impact on red cell volume. In other words, anemia associated with hypoproliferation of red cells is very rare, and the absence of anemia should never be used to exclude a role for lead in causing toxicity to organs and systems that are far more sensitive, such as the nervous system and renal tubules. Furthermore, microcytosis can only occasionally be attributed to lead alone; when it is seen, especially in children, it most often signifies coincident iron deficiency. On the other hand, rapid accumulation of lead in acute lead poisoning, typically heralded clinically by the onset of abdominal pain, is almost always associated with evidence of rapid hemolysis; reticulocyte counts are in the range of 5% to 20%. In this setting, the notorious basophilic stipples are frequently seen as well, though they are by no means pathognomonic for lead toxicity. In general, this syndrome will occur only after lead levels have exceeded 60 mg/dl in whole blood. The hemolysis tends to abruptly stop after effective chelation therapy, which is usually indicated in this acute symptomatic form of lead poisoning.

The bone marrow effects of workplace chemicals are only slowly being unraveled, but certain conclusions seem warranted. Benzene, the aromatic constituent of petroleum products, was once widely prevalent in the work environment as a solvent and a component of gasoline. It can cause hypoplastic injury to the marrow, which may directly progress to a chronic blood dyscrasia (i.e., myelodysplasia or leukemia), or dyscrasia may occur after apparent recovery.68 In other words, an exposed worker may show depressed cell counts, be removed from the source of toxicity, improve, and years later (possibly long after exposure ceases) develop myelodysplasia or a myeloproliferative syndrome. It is likely that some workers will develop the obviously more serious dyscrasias without direct marrow injury having been recognized while exposure was ongoing. There are no hallmark features of either the hypoplastic state (occurring during ongoing exposure) or the myelodysplastic state (occurring later) that distinguish benzene toxicity from other causes of such disorders; this differentiation depends on the history of substantial benzene exposure, because the disorders are not believed to be idiosyncratic but dose related. Although there is some evidence that a few other solvents, such as the glycol ethers that are widely used in paints and coatings,69 may cause such injury, the vast majority of solvents, including many benzene congeners such as toluene and xylene, do not appear to have potential for marrow injury. For this reason, most products that formerly contained benzene that are used in developed countries have been modified, and benzene is not used directly except for specific purposes in the manufacture of chemicals and pharmaceuticals. Obviously, exposed persons should be carefully monitored for hematologic effects, the presence of which would be clear evidence of overexposure.

ENDOCRINE AND REPRODUCTIVE EFFECTS

Despite an exceptional upsurge in interest in the endocrine-disrupting effects of environmental contaminants, there is little evidence that occupational exposures to chemical hazards cause clinically relevant endocrinopathies in adults.70 Lead has been shown to impair hypothalamic-pituitary axis secretions and probably testosterone regulation in men heavily exposed, but the clinical relevance of these observations is unclear. Several compounds used in the pharmaceutical industry and other industries have been shown to have estrogenic activity, with predictable clinical consequences in both men and women.

The effects of work on male and female reproduction are a more formidable concern.71 Although data are far from complete because many chemicals have never been studied adequately, several substances at occupational levels of exposure have been proved to cause infertility and decreases in sperm counts; such substances include lead, the pesticides 1,2-dibromo-3-chloropropane (DBCP) and ethylene dibromide (EDB), ethylene glycol ethers, and carbon disulfide. Heat and ionizing radiation have also been associated with infertility and decreased sperm counts. In addition, a host of other metals, anesthetic agents, and plastic reagents have been shown to cause worrisome gonadal effects in toxicologic experiments on male animals. For this reason, infertile men should be carefully questioned about work exposures; they should be observed for signs of improvement for about 9 months (which equals four cycles of spermatogenesis) should suspicion of an occupational cause be entertained.

Female reproduction is harder to study for lack of a single body fluid to analyze and because of the absence of a simple animal model. There is evidence that several common exposures, including waste anesthetic gases, lead, glycol ethers, ethylene oxide, and antineoplastic drugs, have the potential to increase the risk of miscarriage. Lead, organic mercury, polychlorinated biphenyls (PCBs), heat, and ionizing radiation are established teratogens; organic solvents are also suspect on the basis of animal studies and new epidemiologic reports.72 Most of the agents that cause human cancer [see Table 3] are considered likely fetal hazards as well. In most cases, there is risk of adverse effects at doses considered acceptable in the workplace, because regulations have not traditionally been developed on the basis of reproductive concern. To a disturbing degree, knowledge of the reproductive effects of thousands of additional chemicals is unknown. Even the effects of hard physical work during pregnancy remain unclear, though there is evidence that excessive lifting and standing late in the third trimester may induce prematurity.

With the majority of women of reproductive age now in the workforce, many are questioning the safety of work during pregnancy, and clinicians are being confronted with trade-offs between fetal risks and the worker's economic security. Although each case must be studied individually, a reasonable guideline is to rigorously protect patients from the established teratogens or ensure the levels of exposure below those established for pregnancy. For others, reasonable steps can be taken to minimize exposure, including job transfer if the patient prefers and the employer has alternative work. For the patient for whom any risk represents an unacceptable psychological impediment, transfer or removal is probably in the best interest of all parties.

CLINICAL PROBLEMS ASSOCIATED WITH LOW-LEVEL ENVIRONMENTAL EXPOSURES

One of the most common problems emerging in developed countries is the constellation of respiratory and systemic complaints that are appearing with increasing frequency in office workers and others in what are traditionally considered safe jobs.73,74 Typical symptoms of sick-building syndrome, or nonspecific building-related illness, include upper and lower respiratory symptoms, often combined with neurologic problems, such as fatigue, headache, and cognitive deficits, as well as rashes and other nonspecific complaints.74 Usually, the patient will relate that others in the environment are experiencing similar difficulties and that the symptoms improve when the patient is away from work and return upon reexposure. Although in a minority of cases, investigation may reveal a specific allergy (e.g., in patients with asthma, rhinitis, or allergic alveolitis) or a specific hazard (e.g., fibrous glass released during a renovation or from a ventilation duct, causing pruritus), in the majority of cases, the environment is usually best described as poorly ventilated.74,75 At present, there is no specific treatment of this syndrome other than palliative care and reassurance that it is neither progressive nor life threatening.76,77Expensive testing of either the patient or the work environment is rarely necessary or beneficial.74 Ideally, remediation of both should be undertaken as soon as more dire possibilities are excluded by history and a walk-through of the workplace by an industrial hygienist or comparable environmental professional. In the vast majority of cases, improvement of ventilation will result in symptomatic improvement for most workers.74

On occasion, a patient in an affected building will start to experience similar discomfort in other situations, such as driving behind a bus, being in a store, or using a perfume or detergent.55 The net impression is that the patient has become reactive to everything that has an odor. Many also have fatigue or other asthenic symptoms between exposures. Symptoms reminiscent of those in panic disorder may also occur. Dubbed multiple chemical sensitivities (MCS), this disorder is not associated with measurable abnormalities of organ system function but may be highly disabling.55 Although there are many physical and psychological theories regarding the origin of MCS, present knowledge is limited. Patients do not easily tolerate pharmacologic agents and usually do not respond to treatment for anxiety or depression. Avoidance is equally fruitless, with shorter and more trivial exposures causing problems in those who quit work and minimize human contact. At present, the recommended treatment is supportive care coupled with moderate life modifications to avoid the most provocative exposures while preserving everyday functioning, including work if possible. Unrealistic expectations of cure or remission are as harmful as unwarranted fears of deterioration; neither outcome appears common among patients followed for many years.

References

  1. Palmer K, Coggon D: ABC of work related disorders: investigating suspected occupational illness and evaluating the workplace. BMJ 313:809, 1996
  2. Encyclopedia of Occupational Health and Safety 4th ed. Stellman JM, Ed. International Labor Office, Geneva, Switzerland, 1999
  3. Maxcy Rosenau Textbook of Public Health and Preventive Medicine 14th ed. Last WB, Ed. Appleton & Lange, Norwalk, Connecticut, 1998
  4. Textbook of Clinical Occupational and Environmental Medicine 2nd ed. Rosenstock L, Cullen M, Brodkin CA, et al, Eds. Elsevier Saunders, 2005
  5. Schulte P: Characterizing the burden of occupational injury and disease. J Occup Environ Med 47:607, 2005
  6. Injury Facts, 1998. National Safety Council. Itasca, Illinois, 1999
  7. Epstein Y, Albukrek D, Kalmovitc B, et al: Heat intolerance induced by antidepressants. Ann NY Acad Sci 813:553, 1997
  8. Tanaka S, Wild DK, Cameron LL, et al: Association of occupational and non-occupational risk factors with the prevalence of self-reported carpal tunnel syndrome in a national survey of the working population. Am J Ind Med 32:550, 1997
  9. Lataye R, Campo P: Combined effects of a simultaneous exposure to noise and toluene on hearing function. Neurotoxicol Teratol 19:373, 1997
  10. Erren TC, Jacobssen M, Piekarski C: Synergy between asbestos and smoking on lung cancer. Epidemiology 10:405, 1999
  11. Lax MB, Grant WD, Manetti FA, et al: Recognizing occupational disease: taking an effective occupational history. Am Fam Physician 58:935, 1998
  12. Politi BJ, Arena VC, Schwerha J, et al: Occupational medical history taking: how are today's physicians doing? A cross-sectional investigation of the frequency of occupational history taking by physicians in a major US teaching center. J Occup Environ Med 46:550, 2004
  13. Achanzar WE, Diwan BA, Liu J, et al: Cadmium-induced malignant transformation of human prostate epithelial cells. Cancer Res 61:455, 2001
  14. Parent ME, Hua Y, Siemiatycki J: Occupational risk factors for renal cell carcinoma in Montreal. Am J Ind Med 38:609, 2000
  15. Zhang Y, Cantor KP, Lynch CF, et al: A population-based case-control study of occupation and renal cell carcinoma risk in Iowa. J Occup Environ Med 46:235, 2004
  16. Baur X, Chen Z, Liebers V: Exposure-response relationships of occupational inhalative allergens. Clin Exp Allergy 28:537, 1998
  17. Brooks SM, Bernstein IL: Reactive airways dysfunction syndrome or irritant induced asthma. Asthma in the Workplace. Bernstein IL, Chan-Yeung M, Malo JL, et al, Eds. Marcel Dekker, New York, 1993, p 533
  18. Rabatin JT, Cowl CT: A guide to the diagnosis and treatment of occupational asthma. Mayo Clin Proc 76:633, 2001
  19. Chan-Yeung M, Malo JL: Occupational asthma. N Engl J Med 333:107, 1995
  20. Wild LG, Lopez M: Occupational asthma caused by high-molecular-weight substances. Immunol Allergy Clin North Am 23:235, 2003
  21. Liss GM, Sussman GL: Latex sensitization: occupational versus general population prevalence rates. Am J Ind Med 35:196, 1999
  22. Zeiss CR, Gomaa A, Murphy FM, et al: Latex hypersensitivity in Department of Veterans Affairs health care workers: glove use, symptoms, and sensitization. Ann Allergy Asthma Immunol 91:510, 2003
  23. Meredith SK, Bugler J, Clark RL: Isocyanate exposure and occupational asthma: a case-referent study. Occup Environ Med 57:830, 2000
  24. Malo JL, Chan-Yeung M: Occupational asthma. J Allergy Clin Immunol 108:317, 2001
  25. Drazen J: SARS: looking back over the first 100 days. N Engl J Med 349:319, 2003
  26. Bridges CB, Lim W, Hu-Primmer J, et al: Risk of influenza A (H5N1) infection among poultry workers. J Infect Dis 185:1005, 2002
  27. Hodgson MJ, Bracker A, Yang C, et al: Hypersensitivity pneumonitis in a metal-working environment. Am J Ind Med 39:616, 2001
  28. Hoffman RE, Wood RC, Kreiss K: Building-related asthma in Denver office workers. Am J Public Health 83:89, 1993
  29. Middleton DC: Chronic beryllium disease: uncommon disease, less common diagnosis. Environ Health Perspect 106:765, 1998
  30. Cugell DW: The hard metal diseases. Clin Chest Med 13:269, 1992
  31. Kern DG, Crausman RS, Durand KT, et al: Flock worker's lung: chronic interstitial lung disease in the nylon flocking industry. Ann Intern Med 129:261, 1998
  32. Kern DG, Kuhn C 3rd, Pransky GS, et al: Flock worker's lung: broadening the spectrum of clinicopathology, narrowing the spectrum of suspected etiologies. Chest 117:251, 2000
  33. Kanerva L, Jolanki R, Estlander T, et al: Incidence rates of occupational allergic contact dermatitis caused by metals. Am J Contact Dermat 11:155, 2000
  34. Hogan DJ: Occupational Skin Disorders. Igaku-Shoin, New York, 1994
  35. Adams R: Occupational Skin Disease 3rd ed. WB Saunders Co, Philadelphia, 1999
  36. Marks JG, DeLeo VA: Contact and Occupational Dermatology 3rd ed. Mosby, St. Louis, 2001
  37. Pratt MD, Belsito DV, DeLeo VA, et al: North American Contact Dermatitis Group patch-test results, 2001–2002 study period. Dermatitis 15:176, 2004
  38. Krob HA, Fleischer AB Jr, D'Agostino R Jr, et al: Prevalence and relevance of contact dermatitis allergens: a meta-analysis of 15 years of published T.R.U.E. test data. J Am Acad Dermatol 51:349, 2004
  39. de Broe ME, D'Haese PC, Nuyts GD, et al: Occupational renal diseases. Curr Opin Nephrol Hypertens 5:114, 1996
  40. Wedeen RP: Occupational and environmental renal disease. Semin Nephrol 17:46, 1997
  41. Batuman V, Landy E, Maesaka JK, et al: Contribution of lead to hypertension with renal impairment. N Engl J Med 309:17, 1983
  42. Lin JL, Lin-Tan DT, Hsu KH, et al: Environmental lead exposure and progression of chronic renal diseases in patients without diabetes. N Engl J Med 23:277, 2003
  43. Erhlich R, Robins T, Jordaan E, et al: Lead absorption and renal dysfunction in a South African battery factory. Occup Environ Med 55:453, 1998
  44. Roels HA, Hoet P, Lison D: Usefulness of biomarkers of exposure to inorganic mercury, lead, or cadmium in controlling occupational and environmental risks of nephrotoxicity. Ren Fail 21:251, 1999
  45. Roels HA, Van Assche FJ, Overstseyns M, et al: Reversibility of microproteinuria in cadmium workers with incipient tubular dysfunction after reduction of exposure. Am J Ind Med 31:645, 1997
  46. Jarup L, Persson B, Elinder CG: Blood cadmium as an indicator of dose in a long-term follow-up of workers previously exposed to cadmium. Scand J Work Environ Health 23:31, 1997
  47. Jarup L, Hellstrom L, Alfven T, et al: Low level exposure to cadmium and early kidney damage: the OSCAR study. Occup Environ Med 57:668, 2000
  48. Ravnskow U: Hydrocarbons may worsen renal function in glomerulonephritis. Am J Ind Med 37:599, 2000
  49. Hoet P, Graf MI, Bourdi M, et al: Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone-sparing substitutes of chlorofluorocarbons. Lancet 350:556, 1997
  50. Keifer MC, Mahurin RK: Chronic neurologic effects of pesticide overexposure. Occup Med 12:291, 1997
  51. Rutchik JS, Whittman RI: Neurologic issues with solvents. Clin Occup Environ Med 4:621, 2004
  52. Manzo L, Artigas F, Martinez E, et al: Biochemical markers of neurotoxicity: a review of mechanistic studies and applications. Hum Exp Toxicol 15(suppl):S20, 1996
  53. Stallones L, Beseler C: Pesticide illness, farm practices, and neurological symptoms among farm residents in Colorado. Environ Res 90:89, 2002
  54. Musculoskeletal Disorders and Workplace Factors: A Critical Review of Epidemiologic Evidence for Work-Related Musculoskeletal Disorders of the Neck Upper Extremity, and Low Back. Publication no. 97-141, U.S. Department of Health and Human Services. National Institute for Occupational Health and Safety, Cincinnati, Ohio, 1997 http://www.cdc.gov/niosh/ergosci1.html
  55. Cullen MR: Low-level environmental exposures. Textbook of Clinical Occupational and Environmental Medicine, 2nd ed. Rosenstock L, Cullen MR, Brodkin CA, et al, Eds. Elsevier Saunders 2005, p 1127
  56. Tanaka S, Petersen M, Cameron L: Prevalence and risk factors of tendinitis and related disorders of the distal upper extremity among U.S. workers: comparison to carpal tunnel syndrome. Am J Ind Med 39:328, 2001
  57. Katz JN, Brissot R, Liang MH: Systemic rheumatologic disorders. Textbook of Clinical Occupational and Environmental Medicine, 2nd ed. Rosenstock L, Cullen MR, Brodkin CA, Eds. WB Saunders Co, Philadelphia, 2005, p 533
  58. Pascarelli EF, Hsu YP: Understanding work-related upper extremity disorders: clinical findings in 485 computer users, musicians, and others. J Occup Rehabil 11:1, 2001
  59. Hoogendoorn WE, Bongers PM, de Vet HC, et al: Flexion and rotation of the trunk and lifting at work are risk factors for low back pain: results of a prospective cohort study. Spine 25:3087, 2000
  60. Macfarlane GJ, Hunt IM, Silman AJ: Role of mechanical and psychosocial factors in the onset of forearm pain: prospective population based study. BMJ 321:676, 2000
  61. Haufler AJ, Feuerstein M, Huang GD: Job stress, upper extremity pain and functional limitations in symptomatic computer users. Am J Ind Med 38:507, 2000
  62. Jayson MI: ABC of work related disorders: back pain. BMJ 313:355, 1996
  63. Hagberg M: ABC of work related disorders: neck and arm disorders. BMJ 313:419, 1996
  64. Buckle PW: Work factors and upper limb disorders. BMJ 315:1360, 1997
  65. Luster MI, Wierda D, Rosenthal GJ: Environmentally related disorders of the hematologic and immune systems. Med Clin North Am 74:425, 1990
  66. Nelson JC, Westwood M, Allen KR, et al: The ratio of erythrocyte zinc-protoporphyrin to protoporphyrin IX in disease and its significance in the mechanism of lead toxicity on haem synthesis (pt 3). Ann Clin Biochem 35:422, 1998
  67. Solliway BM, Schaffer A, Pratt H, et al: Effects of exposure to lead on selected biochemical and haematological variables. Pharmacol Toxicol 78:18, 1996
  68. Smith MT: Overview of benzene-induced aplastic anaemia. Eur J Haematol 57:107, 1996
  69. Cullen MR, Solomon L, Pace PE, et al: Morphologic, biochemical and cytogenetic studies of bone marrow and circulating blood cells in painters exposed to ethylene glycol ethers. Environ Res 59:250, 1992
  70. Cullen MR: Endocrine disorders. Textbook of Clinical Occupational and Environmental Medicine, 2nd ed. Rosenstock L, Cullen M, Brodkin CA, et al, Eds. WB Saunders Co, Philadelphia, 2005, p 609
  71. Reproductive Hazards. U.S. Department of Labor. Occupational Health and Safety Administraiton, Washington, DC, 2005http://www.osha.gov/SLTC/reproductivehazards
  72. Khattak S, Moghtader GK, McMartin K, et al: Pregnancy outcome following gestational exposure to organic solvents. JAMA 281:12, 1999
  73. Seltzer JM: Effects of the Indoor Environment on Health. Occupational Medicine: State of the Art Reviews, Vol 10, No 1. OEM Press, 1995
  74. Redlich CA, Sparer JS, Cullen MR: Sick building syndrome. Lancet 349:1013, 1997
  75. Mitchell LS, Donnay A, Hoover DA, et al: Immunologic parameters of multiple chemical sensitivity. Occup Med State Art Rev 15:539, 2000
  76. Husman T: Health effects of indoor-air microorganisms. Scand J Work Environ Health 22:5, 1996
  77. Bascom R, Kesavanathan J, Swift DL: Human susceptibility to indoor contaminants. Occup Med 10:119, 1995

Editors: Dale, David C.; Federman, Daniel D.