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 topic, 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].
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 dimethylfor-mamide 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 hyper-sensitivity 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 ob-served—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, immuno-logically 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 hemol-ysis, 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.
Table 1 Common Occupational Disorders
|
|
Disorders |
Examples of Causal Factors |
|
Respiratory tract |
Pneumoconiosis Asthma Allergic alveolitis Metal fume fever |
Coal, silica, asbestos Latex, polyurethane Vegetable matter, machining fluids Metal fumes |
|
Skin |
Contact dermatitis Acne Urticaria |
Oils, rubber, metals Herbicides, oils, friction Latex |
|
Urinary tract |
Glomerular disease Tubulointerstitial disease |
Organic solvents, mercury 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 |
|
|
Parkinsonism |
Manganese |
|
|
Peripheral neuropathy |
Solvents, lead, acrylamide, arsenic |
|
|
Acute encephalopathy |
Organic solvents, asphyxiants |
|
|
Nervous system |
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 |
|
|
Hemolysis |
Lead, organic nitrites |
|
|
Accelerated red cell destruction |
||
|
Acute hemolysis |
Nitro and amine compounds |
|
|
Subacute hemolysis |
Lead |
|
|
Disorders of oxygen transport |
||
|
Hematologic conditions |
Methemoglobinemia |
Nitro and amine compounds |
|
Carboxyhemoglobinemia |
Carbon monoxide |
|
|
Disorders of red cell production |
||
|
Hyperplastic anemia |
Lead |
|
|
Aplastic anemia, hypoplastic anemia Myelodysplasia |
Ethylene glycol ethers, benzene, arsenic, ionizing radiation Benzene, ionizing radiation |
|
|
Polycythemia |
Cobalt |
|
|
Hepatitis B, C |
Health care |
|
|
Infectious |
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
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].
Table 2 Common Occupational Hazards for Which There Are Widely Available Biologic Tests of Exposure
|
Hazard |
Comments |
|
Metals Arsenic |
Hair sampling can detect historic exposures |
|
Cadmium |
Detectable in urine for many years if there is renal injury |
|
Fluorides Lead Mercury |
Transient in urine Half-life 40 days in blood 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 |
PCBs—polychlorinated biphenyls
RAST—radioallergosorbent test
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.
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.
