Three sensory systems are uniquely constructed to monitor contact with environmental substances: olfaction (smell), taste (sweet, salty, sour, and bitter perception), and the common chemical sense (detection of irritation or pungency). Because they require stimulation by chemicals, they are termed “chemosensory” systems. Olfactory disorders consist of temporary or permanent: complete or partial smell loss (anosmia or hyposmia) and parosmias (perverted smells dysosmia or phantom smells phantosmia) (Mott and Leopold 1991; Mott, Grushka and Sessle 1993). After chemical exposures, some individuals describe a heightened sensitivity to chemical stimuli (hyperosmia). Flavour is the sensory experience generated by the interaction of the smell, taste and irritating components of food and beverages, as well as texture and temperature. Because most flavour is derived from the smell, or aroma, of ingestants, damage to the smell system is often reported as a problem with “taste”.

Chemosensory complaints are frequent in occupational settings and may result from a normal sensory system’s perceiving environmental chemicals. Conversely, they may also indicate an injured system: requisite contact with chemical substances renders these sensory systems uniquely vulnerable to damage. In the occupational setting, these systems can also be damaged by trauma to the head and agents other than chemicals (e.g., radiation). Pollutant-related environmental odours can exacerbate underlying medical conditions (e.g., asthma, rhinitis), precipitate development of odour aversions, or cause a stress-related type of illness. Malodors have been demonstrated to decrease complex task performance (Shusterman 1992).

Early identification of workers with olfactory loss is essential. Certain occupations, such as the culinary arts, wine making and the perfume industry, require a good sense of smell as a prerequisite. Many other occupations require normal olfaction for either good job performance or self-protection. For example, parents or day care workers generally rely on smell to determine children’s hygiene needs. Firefighters need to detect chemicals and smoke. Any worker with ongoing exposure to chemicals is at increased risk if olfactory ability is poor.

Olfaction provides an early warning system to many harmful environmental substances. Once this ability is lost, workers may not be aware of dangerous exposures until the concentration of the agent is high enough to be irritating, damaging to respiratory tissues or lethal. Prompt detection can prevent further olfactory damage through treatment of inflammation and reduction of subsequent exposure. Lastly, if loss is permanent and severe, it may be considered a disability requiring new job training and/or compensation.

Anatomy and Physiology

Olfaction

The primary olfactory receptors are located in patches of tissue, termed olfactory neuroepithelium, at the most superior portion of the nasal cavities (Mott and Leopold 1991). Unlike other sensory systems, the receptor is the nerve. One portion of an olfactory receptor cell is sent to the surface of the nasal lining, and the other end connects directly via a long axon to one of two olfactory bulbs in the brain. From here, the information travels to many other areas of the brain. Odorants are volatile chemicals that must contact the olfactory receptor for smell perception to occur. Odorant molecules are trapped by and then diffuse through mucus to attach to cilia at the ends of the olfactory receptor cells. It is not yet known how we are able to detect more than ten thousand odorants, discriminate from as many as 5,000, and judge varying odorant intensities. Recently, a multigene family was discovered that codes for odorant receptors on primary olfactory nerves (Ressler, Sullivan and Buck 1994). This has allowed investigation of how odours are detected and how the smell system is organized. Each neuron may respond broadly to high concentrations of a variety of odorants, but will respond to only one or a few odorants at low concentrations. Once stimulated, surface receptor proteins activate intracellular processes that translate sensory information into an electrical signal (transduction). It is not known what terminates the sensory signal despite continued odorant exposure. Soluble odorant binding proteins have been found, but their role is undetermined. Proteins that metabolize odorants may be involved or carrier proteins may transport odorants either away from the olfactory cilia or toward a catalytic site within the olfactory cells.

The portions of the olfactory receptors connecting directly to the brain are fine nerve filaments that travel through a plate of bone. The location and delicate structure of these filaments render them vulnerable to shear injury from blows to the head. Also, because the olfactory receptor is a nerve, physically contacts odorants, and connects directly to the brain, substances entering the olfactory cells can travel along the axon into the brain. Because of continued exposure to agents damaging to the olfactory receptor cells, olfactory ability might be lost early in the lifespan if it were not for a critical attribute: olfactory receptor nerves are capable of regeneration and may be replaced, provided the tissue has not been completely destroyed. If the damage to the system is more centrally located, however, the nerves can not be restored.

Common chemical sense

The common chemical sense is initiated by stimulation of mucosal, multiple, free nerve endings of the fifth (trigeminal) cranial nerve. It perceives the irritating properties of inhaled substances and triggers reflexes designed to limit exposure to dangerous agents: sneezing, mucus secretion, reduction of breathing rate or even breath-holding. Strong warning cues compel removal from the irritation as soon as possible. Although the pungency of substances vary, generally the odour of the substance is detected before irritation becomes apparent (Ruth 1986). Once irritation is detected, however, small increases in concentration enhance irritation more than odorant appreciation. Pungency may be evoked through either physical or chemical interactions with receptors (Cometto-Muñiz and Cain 1991). The warning properties of gases or vapours tend to correlate with their water solubilities (Shusterman 1992). Anosmics appear to require higher concentrations of pungent chemicals for detection (Cometto-Muñiz and Cain 1994), but thresholds of detection are not elevated as one ages (Stevens and Cain 1986).

Tolerance and adaptation

Perception of chemicals can be altered by previous encounters. Tolerance develops when exposure reduces the response to subsequent exposures. Adaptation occurs when a constant or rapidly repeated stimulus elicits a diminishing response. For example, short-term solvent exposure markedly, but temporarily, reduces solvent detection ability (Gagnon, Mergler and Lapare 1994). Adaptation can also occur when there has been prolonged exposure at low concentrations or rapidly, with some chemicals, when extremely high concentrations are present. The latter can lead to rapid and reversible olfactory “paralysis”. Nasal pungency typically shows less adaptation and development of tolerance than olfactory sensations. Mixtures of chemicals can also alter perceived intensities. Generally, when odorants are mixed, perceived odorant intensity is less than would be expected from adding the two intensities together (hypoadditivity). Nasal pungency, however, generally shows additivity with exposure to multiple chemicals, and summation of irritation over time (Cometto-Muñiz and Cain 1994). With odorants and irritants in the same mixture, the odour is always perceived as less intense. Because of tolerance, adaptation, and hypoadditivity, one must be careful to avoid relying on these sensory systems to gauge the concentration of chemicals in the environment.

Olfactory Disorders

General concepts

Olfaction is disrupted when odorants can not reach olfactory receptors, or when olfactory tissue is damaged. Swelling within the nose from rhinitis, sinusitis or polyps can preclude odorant accessibility. Damage can occur with: inflammation in the nasal cavities; destruction of the olfactory neuroepithelium by various agents; trauma to the head; and transmittal of agents via the olfactory nerves to the brain with subsequent injury to the smell portion of the central nervous system. Occupational settings contain varying amounts of potentially damaging agents and conditions (Amoore 1986; Cometto-Muñiz and Cain 1991; Shusterman 1992; Schiffman and Nagle 1992). Recently published data from 712,000 National Geographic Smell Survey respondents suggests that factory work impairs smell; male and female factory workers reported poorer senses of smell and demonstrated decreased olfaction on testing (Corwin, Loury and Gilbert 1995). Specifically, chemical exposures and head trauma were more frequently reported than by workers in other occupational settings.

When an occupational olfactory disorder is suspected, identification of the offending agent can be difficult. Current knowledge is largely derived from small series and case reports. It is of importance that few studies mention examination of the nose and sinuses. Most rely on patient history for olfactory status, rather than testing of the olfactory system. An additional complicating factor is the high prevalence of non-occupationally related olfactory disturbances in the general population, mostly due to viral infections, allergies, nasal polyps, sinusitis or head trauma. Some of these, however, are also more common in the work environment and will be discussed in detail here.

Rhinitis, sinusitis and polyposis

Individuals with olfactory disturbance must first be assessed for rhinitis, nasal polyps and sinusitis. It is estimated that 20% of the United States population, for example, has upper airway allergies. Environmental exposures can be unrelated, cause inflammation or exacerbate an underlying disorder. Rhinitis is associated with olfactory loss in occupational settings (Welch, Birchall and Stafford 1995). Some chemicals, such as isocyanates, acid anhydrides, platinum salts and reactive dyes (Coleman, Holliday and Dearman 1994), and metals (Nemery 1990) can be allergenic. There is also considerable evidence that chemicals and particles increase sensitivity to nonchemical allergens (Rusznak, Devalia and Davies 1994). Toxic agents alter the permeability of the nasal mucosa and allow greater penetration of allergens and enhanced symptoms, making it difficult to discriminate between rhinitis due to allergies and that due to exposure to toxic or particulate substances. If inflammation and/or obstruction in the nose or sinuses is demonstrated, return of normal olfactory function is possible with treatment. Options include topical corticosteroid sprays, systemic antihistamines and decongestants, antibiotics and polypectomy/sinus surgery. If inflammation or obstruction is not present or treatment does not secure improvement in olfactory function, olfactory tissue may have sustained permanent damage. Irrespective of cause, the individual must be protected from future contact with the offending substance or further injury to the olfactory system could occur.

Head trauma

Head trauma can alter olfaction through (1) nasal injury with scarring of the olfactory neuroepithelium, (2) nasal injury with mechanical obstruction to odours, (3) shearing of the olfactory filaments, and (4) bruising or destruction of the part of the brain responsible for smell sensations (Mott and Leopold 1991). Although trauma is a risk in many occupational settings (Corwin, Loury and Gilbert 1995), exposure to certain chemicals can increase this risk.

Smell loss occurs in 5% to 30% of head trauma patients and may ensue without any other nervous system abnormalities. Nasal obstruction to odorants may be surgically correctable, unless significant intranasal scarring has occurred. Otherwise, no treatment is available for smell disorders resulting from head trauma, although spontaneous improvement is possible. Rapid initial improvement may occur as swelling subsides in the area of injury. If olfactory filaments have been sheared, regrowth and gradual improvement of smell may also occur. Although this occurs in animals within 60 days, improvements in humans have been reported as long as seven years after injury. Parosmias developing as the patient recovers from injury may indicate regrowth of olfactory tissue and herald return of some normal smell function. Parosmias occurring at the time of injury or shortly thereafter are more likely due to brain tissue damage. Damage to the brain will not repair itself and improvement in smell ability would not be expected. Injury to the frontal lobe, the portion of the brain integral to emotion and thinking, may be more frequent in head trauma patients with smell loss. The resultant changes in socialization or thinking patterns may be subtle, though harmful to family and career. Formal neuropsychiatric testing and treatment may, therefore, be indicated in some patients.

Environmental agents

Environmental agents can gain access to the olfactory system through either the bloodstream or inspired air and have been reported to cause smell loss, parosmia and hyperosmia. Responsible agents include metallic compounds, metal dusts, nonmetallic inorganic compounds, organic compounds, wood dusts and substances present in various occupational environments, such as metallurgical and manufacturing processes (Amoore 1986; Schiffman and Nagle 1992 (table 1). Injury can occur both after acute and chronic exposures and can be either reversible or irreversible, depending on the interaction between host susceptibility and the damaging agent. Important substance attributes include bioactivity, concentration, irritant capacity, length of exposure, rate of clearance and potential synergism with other chemicals. Host susceptibility varies with genetic background and age. There are gender differences in olfaction, hormonal modulation of odorant metabolism and differences in specific anosmias. Tobacco use, allergies, asthma, nutritional status, pre-existing disease (e.g., Sjogren’s syndrome), physical exertion at time of exposure, nasal airflow patterns and possibly psychosocial factors influence individual differences (Brooks 1994). Resistance of the peripheral tissue to injury and presence of functioning olfactory nerves can alter susceptibility. For example, acute, severe exposure could decimate the olfactory neuroepithelium, effectively preventing spread of the toxin centrally. Conversely, long-term, low-level exposure might allow preservation of functioning peripheral tissue and slow, but steady-transit of damaging substances into the brain. Cadmium, for example, has a half-life of 15 to 30 years in humans, and its effects might not be apparent until years after exposure (Hastings 1990).

Table 1. Agents/processes associated with olfactory abnormalities

H = hyposmia; A = anosmia; P = parosmia; ID = odour identification ability

1 = Mott and Leopold 1991. 2 = Amoore 1986. 3 = Schiffman and Nagle 1992. 4 = Naus 1985. 5 = Callendar et al. 1993.

Specific smell disturbances are as stated in the articles referenced.

Nasal passages are ventilated by 10,000 to 20,000 litres of air per day, containing varying amounts of potentially harmful agents. The upper airways almost totally absorb or clear highly reactive or soluble gases, and particles larger than 2 mm (Evans and Hastings 1992). Fortunately, a number of mechanisms exist to protect tissue damage. Nasal tissues are enriched with blood vessels, nerves, specialized cells with cilia capable of synchronous movement, and mucus-producing glands. Defensive functions include filtration and clearing of particles, scrubbing of water soluble gases, and early identification of harmful agents through olfaction and mucosal detection of irritants that can initiate an alarm and removal of the individual from further exposure (Witek 1993). Low levels of chemicals are absorbed by the mucus layer, swept away by functioning cilia (mucociliary clearance) and swallowed. Chemicals can bind to proteins or be rapidly metabolized to less damaging products. Many metabolizing enzymes reside in the nasal mucosa and olfactory tissues (Bonnefoi, Monticello and Morgan 1991; Schiffman and Nagle 1992; Evans et al. 1995). Olfactory neuroepithelium, for example, contains cytochrome P-450 enzymes which play a major role in the detoxification of foreign substances (Gresham, Molgaard and Smith 1993). This system may protect the primary olfactory cells and also detoxify substances that would otherwise enter the central nervous system through olfactory nerves. There is also some evidence that intact olfactory neuroepithelium can prevent invasion by some organisms (e.g., cryptococcus; see Lima and Vital 1994). At the level of the olfactory bulb, there may also be protective mechanisms preventing transport of toxic substances centrally. For example, it has been recently shown that the olfactory bulb contains metallothioneins, proteins which have a protective effect against toxins (Choudhuri et al. 1995).

Exceeding protective capacities can precipitate a worsening cycle of injury. For example, loss of olfactory ability halts early warning of the hazard and allows continued exposure. Increase in nasal blood flow and blood vessel permeability causes swelling and odorant obstruction. Cilial function, necessary for both mucociliary clearance and normal smell, may be impaired. Change in clearance will increase contact time between injurious agents and nasal mucosa. Intranasal mucus abnormalities alter absorption of odorants or irritant molecules. Overpowering the ability to metabolize toxins allows tissue damage, increased absorption of toxins, and possibly enhanced systemic toxicity. Damaged epithelial tissue is more vulnerable to subsequent exposures. There are also more direct effects on olfactory receptors. Toxins can alter the turnover rate of olfactory receptor cells (normally 30 to 60 days), injure receptor cell membrane lipids, or change the internal or external environment of the receptor cells. Although regeneration can occur, damaged olfactory tissue can exhibit permanent changes of atrophy or replacement of olfactory tissue with nonsensory tissue.

The olfactory nerves provide a direct connection to the central nervous system and may serve as a route of entry for a variety of exogenous substances, including viruses, solvents and some metals (Evans and Hastings 1992). This mechanism may contribute to some of the olfactory-related dementias (Monteagudo, Cassidy and Folb 1989; Bonnefoi, Monticello and Morgan 1991) through, for example, transmittal of aluminium centrally. Intranasally, but not intraperitoneally or intracheally, applied cadmium can be detected in the ipsilateral olfactory bulb (Evans and Hastings 1992). There is further evidence that substances may be preferentially taken up by olfactory tissue irrespective of the site of initial exposure (e.g., systemic versus inhalation). Mercury, for example, has been found in high concentrations in the olfactory brain region in subjects with dental amalgams (Siblerud 1990). On electroencephalography, the olfactory bulb demonstrates sensitivity to many atmospheric pollutants, such as acetone, benzene, ammonia, formaldehyde and ozone (Bokina et al. 1976). Because of central nervous system effects of some hydrocarbon solvents, exposed individuals might not readily recognize and distance themselves from the danger, thereby prolonging exposure. Recently, Callender and colleagues (1993) obtained a 94% frequency of abnormal SPECT scans, which assess regional cerebral blood flow, in subjects with neurotoxin exposures and a high frequency of olfactory identification disorders. The location of abnormalities on SPECT scanning was consistent with distribution of toxin through olfactory pathways.

The site of injury within the olfactory system differs with various agents (Cometto-Muñiz and Cain 1991). For example, ethyl acrylate and nitroethane selectively damage olfactory tissue while the respiratory tissue within the nose is preserved (Miller et al. 1985). Formaldehyde alters the consistency, and sulphuric acid the pH of nasal mucus. Many gases, cadmium salts, dimethylamine and cigarette smoke alter ciliary function. Diethyl ether causes leakage of some molecules from the junctions between cells (Schiffman and Nagle 1992). Solvents, such as toluene, styrene and xylene change olfactory cilia; they also appear to be transmitted into the brain by the olfactory receptor (Hotz et al. 1992). Hydrogen sulphide is not only irritating to mucosa, but highly neurotoxic, effectively depriving cells of oxygen, and inducing rapid olfactory nerve paralysis (Guidotti 1994). Nickel directly damages cell membranes and also interferes with protective enzymes (Evans et al. 1995). Dissolved copper is thought to directly interfere with different stages of transduction at the olfactory receptor level (Winberg et al. 1992). Mercuric chloride selectively distributes to olfactory tissue, and may interfere with neuronal function through alteration of neurotransmitter levels (Lakshmana, Desiraju and Raju 1993). After injection into the bloodstream, pesticides are taken up by nasal mucosa (Brittebo, Hogman and Brandt 1987), and can cause nasal congestion. The garlic odour noted with organophosphorus pesticides is not due to damaged tissue, but to detection of butylmercaptan, however.

Although smoking can inflame the lining of the nose and reduce smell ability, it may also confer protection from other damaging agents. Chemicals within the smoke may induce microsomal cytochrome P450 enzyme systems (Gresham, Molgaard and Smith 1993), which would accelerate metabolism of toxic chemicals before they can injure the olfactory neuroepithelium. Conversely, some drugs, for example tricyclic antidepressants and antimalarial drugs, can inhibit cytochrome P450.

Olfactory loss after exposure to wood and fibre board dusts (Innocenti et al. 1985; Holmström, Rosén and Wilhelmsson 1991; Mott and Leopold 1991) may be due to diverse mechanisms. Allergic and nonallergic rhinitis can result in obstruction to odorants or inflammation. Mucosal changes can be severe, dysplasia has been documented (Boysen and Solberg 1982) and adenocarcinoma may result, especially in the area of the ethmoid sinuses near the olfactory neuroepithelium. Carcinoma associated with hard woods may be related to a high tannin content (Innocenti et al. 1985). Inability to effectively clear nasal mucus has been reported and may be related to an increased frequency of colds (Andersen, Andersen and Solgaard 1977); resultant viral infection could further damage the olfactory system. Olfactory loss may also be due to chemicals associated with woodworking, including varnishes and stains. Medium-density fibre board contains formaldehyde, a known respiratory tissue irritant that impairs mucociliary clearance, causes olfactory loss, and is associated with a high incidence of oral, nasal and pharyngeal cancer (Council on Scientific Affairs 1989), all of which could contribute to an understanding of formaldehyde-induced olfactory losses.

Radiation therapy has been reported to cause olfactory abnormalities (Mott and Leopold 1991), but little information is available about occupational exposures. Rapidly regenerating tissue, such as olfactory receptor cells, would be expected to be vulnerable. Mice exposed to radiation in a spaceflight demonstrated smell tissue abnormalities, while the rest of the nasal lining remained normal (Schiffman and Nagle 1992).

After chemical exposures, some individuals describe a heightened sensitivity to odorants. “Multiple chemical sensitivities” or “environmental illness” are labels used to describe disorders typified by “hypersensitivity” to diverse environmental chemicals, often in low concentrations (Cullen 1987; Miller 1992; Bell 1994). Thus far, however, lower thresholds to odorants have not been demonstrated.

Non-occupational causes of olfactory problems

Ageing and smoking decrease olfactory ability. Upper respiratory viral damage, idiopathic (“unknown”), head trauma, and diseases of the nose and sinuses appear to be the four leading causes of smell problems in the United States (Mott and Leopold 1991) and must be considered as part of the differential diagnosis in any individual presenting with possible environmental exposures. Congenital inabilities to detect certain substances are common. For example, 40 to 50% of the population can not detect androsterone, a steroid found in sweat.

Testing of chemosensation

Psychophysics is the measurement of a response to an applied sensory stimulus. “Threshold” tests, tests that determine the minimum concentration that can be reliably perceived, are frequently used. Separate thresholds can be obtained for detection of odorants and identification of odorants. Suprathreshold tests assess ability of the system to function at levels above threshold and also provide useful information. Discrimination tasks, telling the difference between substances, can elicit subtle changes in sensory ability. Identification tasks may yield different results than threshold tasks in the same individual. For example, a person with central nervous system injury may be able to detect odorants at usual threshold levels, but may not be able to identify common odorants.

Summary

The nasal passages are ventilated by 10,000 to 20,000 litres of air per day, which may be contaminated by possibly hazardous materials in varying degrees. The olfactory system is especially vulnerable to damage because of requisite direct contact with volatile chemicals for odorant perception. Olfactory loss, tolerance and adaptation prevent recognition of the proximity of dangerous chemicals and may contribute to local injury or systemic toxicity. Early identification of olfactory disorders can prompt protective strategies, ensure appropriate treatment and prevent further damage. Occupational smell disorders can manifest themselves as temporary or permanent anosmia or hyposmia, as well as distorted smell perception. Identifiable causes to be considered in the occupational setting include rhinitis, sinusitis, head trauma, radiation exposure and tissue injury from metallic compounds, metal dusts, nonmetallic inorganic compounds, organic compounds, wood dusts, and substances present in metallurgical and manufacturing processes. Substances differ in their site of interference with the olfactory system. Powerful mechanisms for trapping, removing and detoxifying foreign nasal substances serve to protect olfactory function and also prevent spread of damaging agents into the brain from the olfactory system. Exceeding protective capacities can precipitate a worsening cycle of injury, ultimately leading to greater severity of impairment and extension of sites of injury, and converting temporary reversible effects into permanent damage.

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Cutaneous sensitivity shares the main elements of all the basic senses. Properties of the external world, such as colour, sound, or vibration, are received by specialized nerve cell endings called sensory receptors, which convert external data into nervous impulses. These signals are then conveyed to the central nervous system, where they become the basis for interpreting the world around us.

It is useful to recognize three essential points about these processes. First, energy, and changes in energy levels, can be perceived only by a sense organ capable of detecting the specific type of energy in question. (This is why microwaves, x rays, and ultraviolet light are all dangerous; we are not equipped to detect them, so that even at lethal levels they are not perceived.) Second, our perceptions are necessarily imperfect shadows of reality, as our central nervous system is limited to reconstructing an incomplete image from the signals conveyed by its sensory receptors. Third, our sensory systems provide us with more accurate information about changes in our environment than about static conditions. We are well-equipped with sensory receptors sensitive to flickering lights, for example, or to the tiny fluctuations of temperature provoked by a slight breeze; we are less well-equipped to receive information about a steady temperature, say, or a constant pressure on the skin.

Traditionally the skin senses are divided into two categories: cutaneous and deep. While deep sensitivity relies on receptors located in muscle, tendons, joints, and the periosteum (membrane surrounding the bones), cutaneous sensitivity, with which we are concerned here, deals with information received by receptors in the skin: specifically, the various classes of cutaneous receptors that are located in or near the junction of the dermis and the epidermis.

All sensory nerves linking cutaneous receptors to the central nervous system have roughly the same structure. The cell’s large body resides in a cluster of other nerve cell bodies, called a ganglion, located near the spinal cord and connected to it by a narrow branch of the cell’s trunk, called its axon. Most nerve cells, or neurons, that originate at the spinal cord send axons to bones, muscle, joints, or, in the case of cutaneous sensitivity, to the skin. Just like an insulated wire, each axon is covered along its course and at its endings with protective layers of cells known as Schwann cells. These Schwann cells produce a substance known as myelin, which coats the axon like a sheath. At intervals along the way are tiny breaks in the myelin, known as nodes of Ranvier. Finally, at the end of the axon are found the components that specialize in receiving and retransmitting information about the external environment: the sensory receptors (Mountcastle 1974).

The different classes of cutaneous receptors, like all sensory receptors, are defined in two ways: by their anatomical structures, and by the type of electrical signals they send along their nerve fibres. Distinctly structured receptors are usually named after their discoverers. The relatively few classes of sensory receptors found in the skin can be divided into three main categories: mechanoreceptors, thermal receptors, and nociceptors.

All of these receptors can convey information about a particular stimulus only after they have first encoded it in a type of electrochemical neural language. These neural codes use varying frequencies and patterns of nerve impulses that scientists have only just begun to decipher. Indeed, an important branch of neurophysiological research is devoted entirely to the study of sensory receptors and the ways in which they translate energy states in the environment into neural codes. Once the codes are generated, they are conveyed centrally along afferent fibres, the nerve cells that serve receptors by conveying the signals to the central nervous system.

The messages produced by receptors can be subdivided on the basis of the response given to a continuous, unvarying stimulation: slowly adapting receptors send electrochemical impulses to the central nervous system for the duration of a constant stimulus, whereas rapidly adapting receptors gradually reduce their discharges in the presence of a steady stimulus until they reach a low baseline level or cease entirely, thereupon ceasing to inform the central nervous system about the continuing presence of the stimulus.

The distinctly different sensations of pain, warmth, cold, pressure, and vibration are thus produced by activity in distinct classes of sensory receptors and their associated nerve fibres. The terms “flutter” and “vibration,” for example, are used to distinguish two slightly different vibratory sensations encoded by two different classes of vibration-sensitive receptors (Mountcastle et al. 1967). The three important categories of pain sensation known as pricking pain, burning pain, and aching pain have each been associated with a distinct class of nociceptive afferent fibre. This is not to say, however, that a specific sensation necessarily involves only one class of receptor; more than one receptor class may contribute to a given sensation, and, in fact, sensations may differ depending on the relative contribution of different receptor classes (Sinclair 1981).

The preceding summary is based on the specificity hypothesis of cutaneous sensory function, first formulated by a German physician named Von Frey in 1906. Although at least two other theories of equal or perhaps greater popularity have been proposed during the past century, Von Frey’s hypothesis has now been strongly supported by factual evidence.

Receptors that Respond to Constant Skin Pressure

In the hand, relatively large myelinated fibres (5 to 15 mm in diameter) emerge from a subcutaneous nerve network called the subpapillary nerve plexus and end in a spray of nerve terminals at the junction of the dermis and the epidermis (figure 1). In hairy skin, these nerve endings culminate in visible surface structures known as touch domes; in glabrous, or hairless, skin, the nerve endings are found at the base of skin ridges (such as those forming the fingerprints). There, in the touch dome, each nerve fibre tip, or neurite, is enclosed by a specialized epithelial cell known as a Merkel cell (see figures 2 and 3).

Figure 1. A schematic illustration of a cross-section of the skin

Figure 2. The touch dome on each raised region of skin contains 30 to 70 Merkel cells.

Figure 3. At a higher magnification available with the electron microscope, the Merkel cell, a specialized epithelial cell, is seen to be attached to the basement membrane that separates the epidermis from the dermis.

The Merkel cell neurite complex transduces mechanical energy into nerve impulses. While little is known about the cell’s role or about its mechanism of transduction, it has been identified as a slowly adapting receptor. This means that pressure on a touch dome containing Merkel cells causes the receptors to produce nerve impulses for the duration of the stimulus. These impulses rise in frequency in proportion to the intensity of the stimulus, thereby informing the brain of the duration and magnitude of pressure on the skin.

Like the Merkel cell, a second slowly adapting receptor also serves the skin by signalling the magnitude and duration of steady skin pressures. Visible only through a microscope, this receptor, known as the Ruffini receptor, consists of a group of neurites emerging from a myelinated fibre and encapsulated by connective tissue cells. Within the capsule structure are fibres that apparently transmit local skin distortions to the neurites, which in turn produce the messages sent along the neural highway to the central nervous system. Pressure on the skin causes a sustained discharge of nerve impulses; as with the Merkel cell, the frequency of nerve impulses is proportional to the intensity of the stimulus.

Despite their similarities, there is one outstanding difference between Merkel cells and Ruffini receptors. Whereas sensation results when Ruffini receptors are stimulated, stimulation of touch domes housing Merkel cells produces no conscious sensation; the touch dome is thus a mystery receptor, for its actual role in neural function remains unknown. Ruffini receptors, then, are believed to be the only receptors capable of providing the neural signals necessary for the sensory experience of pressure, or constant touch. In addition, it has been shown that the slowly adapting Ruffini receptors account for the ability of humans to rate cutaneous pressure on a scale of intensity.

Receptors that Respond to Vibration and Skin Movement

In contrast with slowly adapting mechanoreceptors, rapidly adapting receptors remain silent during sustained skin indentation. They are, however, well-suited to signal vibration and skin movement. Two general categories are noted: those in hairy skin, which are associated with individual hairs; and those which form corpuscular endings in glabrous, or hairless, skin.

Receptors serving hairs

A typical hair is enveloped by a network of nerve terminals branching from five to nine large myelinated axons (figure 4). In primates, these terminals fall into three categories: lanceolate endings, spindle-like terminals, and papillary endings. All three are rapidly adapting, such that a steady deflection of the hair causes nerve impulses only while movement occurs. Thus, these receptors are exquisitely sensitive to moving or vibratory stimuli, but provide little or no information about pressure, or constant touch.

Figure 4. The shafts of hairs are a platform for nerve terminals that detect movements.

Lanceolate endings arise from a heavily myelinated fibre that forms a network around the hair. The terminal neurites lose their usual coverage of Schwann cells and work their way among the cells at the base of the hair.

Spindle-like terminals are formed by axon terminals surrounded by Schwann cells. The terminals ascend to the sloping hair shaft and end in a semicircular cluster just below a sebaceous, or oil-producing, gland. Papillary endings differ from spindle-like terminals because instead of ending on the hair shaft, they terminate as free nerve endings around the orifice of the hair.

There are, presumably, functional differences among the receptor types found on hairs. This can be inferred in part from structural differences in the way the nerves end on the hair shaft and in part from differences in the diameter of axons, as axons of different diameters connect to different central relay regions. Still, the functions of receptors in hairy skin remains an area for study.

Receptors in glabrous skin

The correlation of a receptor’s anatomical structure with the neural signals it generates is most pronounced in large and easily manipulable receptors with corpuscular, or encapsulated, endings. Particularly well understood are the pacininan and Meissner corpuscles, which, like the nerve endings in hairs discussed above, convey sensations of vibration.

The pacinian corpuscle is large enough to be seen with the naked eye, making it easy to link the receptor with a specific neural response. Located in the dermis, usually around tendons or joints, it is an onion-like structure, measuring 0.5 × 1.0 mm. It is served by one of the body’s largest afferent fibres, having a diameter of 8 to 13 μm and conducting at 50 to 80 metres per second. Its anatomy, well-studied by both light and electron microscopy, is well known.

The principal component of the corpuscle is an outer core formed of cellular material enclosing fluid-filled spaces. The outer core itself is then surrounded by a capsule that is penetrated by a central canal and a capillary network. Passing through the canal is a single myelinated nerve fibre 7 to 11 mm in diameter, which becomes a long, nonmyelinated nerve terminal that probes deep into the centre of the corpuscle. The terminal axon is elliptical, with branch-like processes.

The pacinian corpuscle is a rapidly adapting receptor. When subjected to sustained pressure, it thus produces an impulse only at the beginning and the end of the stimulus. It responds to high-frequency vibrations (80 to 400 Hz) and is most sensitive to vibrations around 250 Hz. Often, these receptors respond to vibrations transmitted along bones and tendons, and because of their extreme sensitivity, they may be activated by as little as a puff of air on the hand (Martin 1985).

In addition to the pacinian corpuscle, there is another rapidly adapting receptor in glabrous skin. Most researchers believe it to be the Meissner corpuscle, located in the dermal papillae of the skin. Responsive to low-frequency vibrations of 2 to 40 Hz, this receptor consists of the terminal branches of a medium-sized myelinated nerve fibre enveloped in one or several layers of what appear to be modified Schwann cells, called laminar cells. The receptor’s neurites and laminar cells may connect to a basal cell in the epidermis (figure 5).

Figure 5. The Meissner corpuscle is a loosely encapsulated sensory receptor in the dermal papillae of glabrous skin.

If the Meissner corpuscle is selectively inactivated by the injection of a local anaesthetic through the skin, the sense of flutter or low-frequency vibration is lost. This suggests that it functionally complements the high frequency capacity of the pacinian corpuscles. Together, these two receptors provide neural signals sufficient to account for human sensibility to a full range of vibrations (Mountcastle et al. 1967).

Cutaneous Receptors Associated with Free Nerve Endings

Many still unidentifiable myelinated and unmyelinated fibres are found in the dermis. A large number are only passing through, on their way to skin, muscles, or periosteum, while others (both myelinated and unmyelinated) appear to end in the dermis. With a few exceptions, such as the pacinian corpuscle, most fibres in the dermis appear to end in poorly defined ways or simply as free nerve endings.

While more anatomical study is needed to differentiate these ill-defined endings, physiological research has clearly shown that these fibres encode a variety of environmental events. For example, free nerve endings found at the junction between the dermis and epidermis are responsible for encoding the environmental stimuli that will be interpreted as cold, warmth, heat, pain, itch, and tickle. It is not yet known which of these different classes of small fibres convey particular sensations.

The apparent anatomical similarity of these free nerve endings is probably due to the limitations of our investigative techniques, since structural differences among free nerve endings are slowly coming to light. For example, in glabrous skin, two different terminal modes of free nerve endings have been distinguished: a thick, short pattern and a long, thin one. Studies of human hairy skin have demonstrated histochemically recognizable nerve endings that terminate at the dermal-epidermal junction: the penicillate and papillary endings. The former arise from unmyelinated fibres and form a network of endings; in contrast, the latter arise from myelinated fibres and end around the hair orifices, as mentioned earlier. Presumably, these structural disparities correspond to functional differences.

Although it is not yet possible to assign specific functions to individual structural entities, it is clear from physiological experiments that there exist functionally different categories of free nerve endings. One small myelinated fibre has been found to respond to cold in humans. Another unmyelinated fibre serving free nerve endings responds to warmth. How one class of free nerve endings can respond selectively to a drop in temperature, while an increase of skin temperature can provoke another class to signal warmth is unknown. Studies show that activation of one small fibre with a free ending may be responsible for itching or tickling sensations, while there are believed to be two classes of small fibres specifically sensitive to noxious mechanical and noxious chemical or thermal stimuli, providing the neural basis for pricking and burning pain (Keele 1964).

The definitive correlation between anatomy and physiological response awaits the development of more advanced techniques. This is one of the major stumbling blocks in the management of disorders such as causalgia, paraesthesia, and hyperpathia, which continue to present a dilemma to the physician.

Peripheral Nerve Injury

Neural function can be divided into two categories: sensory and motor. Peripheral nerve injury, usually resulting from the crushing or severing of a nerve, can impair either function or both, depending on the types of fibres in the damaged nerve. Certain aspects of motor loss tend to be misinterpreted or overlooked, as these signals do not go to muscles but rather affect autonomic vascular control, temperature regulation, the nature and thickness of the epidermis, and the condition of cutaneous mechano-receptors. The loss of motor innervation will not be discussed here, nor will the loss of innervation affecting senses other than those responsible for cutaneous sensation.

The loss of sensory innervation to the skin creates a vulnerability to further injury, as it leaves an anaesthetic surface that is incapable of signalling potentially harmful stimuli. Once injured, anaesthetized skin surfaces are slow to heal, perhaps in part on account of the lack of autonomic innervation that normally regulates such key factors as temperature regulation and cellular nutrition.

Over a period of several weeks, denervated cutaneous sensory receptors begin to atrophy, a process which is easy to observe in large encapsulated receptors such as pacinian and Meissner corpuscles. If regeneration of the axons can occur, recovery of function may follow, but the quality of the recovered function will depend upon the nature of the original injury and upon the duration of denervation (McKinnon and Dellon 1988).

Recovery following a nerve crush is more rapid, much more complete and more functional than is recovery after a nerve is severed. Two factors explain the favourable prognosis for a nerve crush. First, more axons may again achieve contact with the skin than after a transection; second, the connections are guided back to their original site by Schwann cells and linings known as basement membranes, both of which remain intact in a crushed nerve, whereas after a nerve transection the nerves often travel to incorrect regions of the skin surface by following the wrong Schwann cell paths. The latter situation results in distorted spatial information being sent to the somatosensory cortex of the brain. In both cases, however, regenerating axons appear capable of finding their way back to the same class of sensory receptors that they previously served.

The reinnervation of a cutaneous receptor is a gradual process. As the growing axon reaches the skin surface, receptive fields are smaller than normal, while the threshold is higher. These receptive points expand with time and gradually coalesce into larger fields. Sensitivity to mechanical stimuli becomes greater and often approaches the sensitivity of normal sensory receptors of that class. Studies using the stimuli of constant touch, moving touch, and vibration have shown that the sensory modalities attributed to different types of receptors return to anaesthetic areas at different rates.

Viewed under a microscope, denervated glabrous skin is seen to be thinner than normal, having flattened epidermal ridges and fewer layers of cells. This confirms that nerves have a trophic, or nutritional, influence on skin. Soon after innervation returns, the dermal ridges become better developed, the epidermis becomes thicker, and axons can be found penetrating the basement membrane. As the axon comes back to the Meissner corpuscle, the corpuscle begins to increase in size, and the previously flattened, atrophic structure returns to its original form. If the denervation has been of long duration, a new corpuscle may form adjacent to the original atrophic skeleton, which remains denervated (Dellon 1981).

As can be seen, an understanding of the consequences of peripheral nerve injury requires knowledge of normal function as well as the degrees of functional recovery. While this information is available for certain nerve cells, others require further investigation, leaving a number of murky areas in our grasp of the role of cutaneous nerves in health and disease.

Back

The growth of industry, agriculture, mining and manufacturing has been paralleled by the development of occupational diseases of the skin. The earliest reported harmful effects were ulcerations of the skin from metal salts in mining. As populations and cultures have expanded the uses of new materials, new skills and new processes have emerged. Such technological advances brought changes to the work environment and during each period some aspect of the technical change has impaired workers’ health. Occupational diseases, in general and skin diseases, in particular, have long been an unplanned by-product of industrial achievement.

Fifty years ago in the United States, for example, occupational diseases of the skin accounted for no less than 65-70% of all reported occupational diseases. Recently, statistics collected by the United States Department of Labor indicate a drop in frequency to approximately 34%. This decreased number of cases is said to have resulted from increased automation, from enclosure of industrial processes and from better education of management, supervisors and workers in the prevention of occupational diseases in general. Without doubt such preventive measures have benefited the workforce in many larger plants where good preventive services may be available, but many people are still employed in conditions which are conducive to occupational diseases. Unfortunately, there is no accurate assessment of the number of cases, causal factors, time lost or actual cost of occupational skin disease in most countries.

General terms, such as industrial or occupational dermatitis or professional eczema, are used for occupational skin diseases but names related both to cause and effect are also commonly used. Cement dermatitis, chrome holes, chloracne, fibreglass itch, oil bumps and rubber rash are some examples. Because of the variety of skin changes induced by agents or conditions at work, these diseases are appropriately called occupational dermatoses—a term which includes any abnormality resulting directly from, or aggravated by, the work environment. The skin can also serve as an avenue of entry for certain toxicants which cause chemical poisoning via percutaneous absorption.

Cutaneous Defence

From experience we know that the skin can react to a large number of mechanical, physical, biological and chemical agents, acting alone or in combination. Despite this vulnerability, occupational dermatitis is not an inevitable accompaniment of work. The majority of the workforce manages to remain free of disabling occupational skin problems, due in part to the inherent protection provided by the skin’s design and function, and in part due to the daily use of personal protective measures directed towards minimizing skin contact with known skin hazards at the worksite. Hopefully, the absence of disease in the majority of workers may also be due to jobs which have been designed to minimize exposure to conditions hazardous to the skin.

The skin

Human skin, except for palms and soles, is quite thin and of variable thickness. It has two layers: the epidermis (outer) and dermis (inner). Collagen and elastic components in the dermis allow it to function as a flexible barrier. The skin provides a unique shield which protects within limits against mechanical forces, or penetration by various chemical agents. The skin limits water loss from the body and guards against the effects of natural and artificial light, heat and cold. Intact skin and its secretions provide a fairly effective defence zone against micro-organisms, providing mechanical or chemical injury does not impair this defence. Figure 1 provides an illustration of the skin and description of its physiological functions.

Figure 1. Schematic representation of the skin.

The outer epidermal layer of dead cells (keratin) provides a shield against elements in the outside world. These cells, if exposed to frictional pressures, can form a protective callus and can thicken after ultraviolet exposure. Keratin cells are normally arranged in 15 or 16 shingle-like layers and provide a barrier, though limited, against water, water-soluble materials and mild acids. They are less able to act as a defence against repeated or prolonged contact with even low concentrations of organic or inorganic alkaline compounds. Alkaline materials soften but do not totally dissolve the keratin cells. The softening disturbs their inner structure enough to weaken cellular cohesiveness. The integrity of the keratin layer is allied to its water content which, in turn, influences its pliability. Lowered temperatures and humidity, dehydrating chemicals such as acids, alkali, strong cleaners and solvents, cause water loss from the keratin layer, which, in turn, causes the cells to curl and crack. This weakens                                                                                                                       its ability to serve as a barrier and compromises its defence                                                                                                                             against water loss from the body and entry of various agents                                                                                                                             from outside.

Cutaneous defence systems are effective only within limits. Anything which breaches one or more of the links endangers the entire defence chain. For example, percutaneous absorption is enhanced when the continuity of the skin has been altered by physical or chemical injury or by mechanical abrasion of the keratin layer. Toxic materials can be absorbed not only through the skin, but also through the hair follicules, sweat orifices and ducts. These latter routes are not as important as transepidermal absorption. A number of chemicals used in industry and in farming have caused systemic toxicity by absorption through the skin. Some well established examples are mercury, tetraethyllead, aromatic and amino nitro compounds and certain organophosphates and chlorinated hydrocarbon pesticides. It should be noted that for many substances, systemic toxicity generally arises through inhalation but percutaneous absorption is possible and should not be overlooked.

A remarkable feature of cutaneous defence is the ability of the skin to continually replace the basal cells which provide the epidermis with its own built-in replication and repair system.

The skin’s ability to act as a heat exchanger is essential to life. Sweat gland function, vascular dilation and constriction under nervous control are vital to regulating body heat, as is evaporation of surface water on skin. Constriction of the blood vessels protects against cold exposures by preserving central body heat. Multiple nerve endings within the skin act as sensors for heat, cold and other excitants by relaying the presence of the stimulant to the nervous system which responds to the provoking agent.

A major deterrent against injury from ultraviolet radiation, a potentially harmful component of sunlight and some forms of artificial light is the pigment (melanin) manufactured by the melanocytes located in the basal cell layer of the epidermis. Melanin granules are picked up by the epidermal cells and serve to add protection against the rays of natural or artificial light which penetrate the skin. Additional protection, though less in degree, is furnished by the keratin cell layer which thickens following ultraviolet exposure. (As discussed below, for those whose worksites are outdoors it is essential to protect exposed skin with a sun-screen coating agent having a protective against UV-A and against UV-B (rating of 15 or greater) together with appropriate clothing to provide a high level of shielding against sun light injury.)

Types of Occupational Skin Diseases

Occupational dermatoses vary both in their appearance (morphology) and severity. The effect of an occupational exposure may range from the slightest erythema (reddening) or discoloration of the skin to a far more complex change, as a malignancy. Despite the wide range of substances that are known to cause skin effects, in practice it is difficult to associate a specific lesion with exposure to a specific material. However, certain chemical groups are associated with characteristic reaction patterns. The nature of the lesions and their location may provide a strong clue as to causality.

A number of chemicals with or without direct toxic effect on the skin can also cause systemic intoxication following absorption through the skin. In order to act as a systemic toxin, the agent must pass through the keratin and the epidermal cell layers, then through the epidermal-dermal junction. At this point it has ready access to the bloodstream and the lymphatic system and can now be carried to vulnerable target organs.

Acute contact dermatitis (irritant or allergic).

Acute contact eczematous dermatitis can be caused by hundreds of irritant and sensitizing chemicals, plants and photoreactive agents. Most occupational allergic dermatoses can be classified as acute eczematous contact dermatitis. Clinical signs are heat, redness, swelling, vesiculation and oozing. Symptoms include itch, burning and general discomfort. The back of the hands, the inner wrists and the forearms are the usual sites of attack, but acute contact dermatitis can occur anywhere on the skin. If the dermatosis occurs on the forehead, the eyelids, the ears, the face or the neck, it is logical to suspect that a dust or a vapour may be involved in the reaction. When there is a generalized contact dermatitis, not restricted to one or a few specific sites, it is usually caused by a more extensive exposure, such as the wearing of contaminated clothing, or by autosensitization from a pre-existing dermatitis. Severe blistering or destruction of tissue generally indicates the action of an absolute or strong irritant. The exposure history, which is taken as part of the medical control of occupational dermatitis, may reveal the suspected causative agent. An accompanying article in this chapter provides more details on contact dermatitis.

Sub-acute contact dermatitis

Through a cumulative effect repeated contact with both weak and moderate irritants can cause a sub-active form of contact dermatitis characterized by dry, red plaques. If the exposure continues, the dermatitis will become chronic.

Chronic eczematous contact dermatitis

When a dermatitis recurs over an extended period of time it is called chronic eczematous contact dermatitis. The hands, fingers, wrists and forearms are the sites most often affected by chronic eczematous lesions, characterized by dry, thickened and scaly skin. Cracking and fissuring of the fingers and the palms may be present. Chronic nail dystrophy is also commonly found. Frequently, the lesions will begin to ooze (sometimes called “weeping”) because of re-exposure to the responsible agent or by imprudent treatment and care. Many materials not responsible for the original dermatosis will sustain this chronic recurrent skin problem.

Photosensitivity dermatitis (phototoxic or photoallergic)

Most photoreactions on the skin are phototoxic. Either natural and artificial light sources alone or in combination with various chemicals, plants or drugs can induce a phototoxic or photosensitive response. Phototoxic reaction is generally limited to light-exposed areas while photosensitive reaction can develop frequently on non-exposed body surfaces. Some examples of photoreactive chemicals are coal tar distillation products, such as creosote, pitch and anthracene. Members of the plant family Umbelliferae are well known photoreactors. Family members include cow parsnip, celery, wild carrot, fennel and dill. The reactive agent in these plants are psoralens.

Folliculitis and acneform dermatoses, including chloracne

Workers with dirty jobs often develop lesions involving the follicular openings. Comedones (blackheads) may be the only obvious effect of the exposure, but often a secondary infection of the follicle may ensure. Poor personal hygiene and ineffective cleansing habits can add to the problem. Follicular lesions generally occur on the forearms and less often on the thighs and buttocks, but they can occur anywhere except on the palms and soles.

Follicular and acneform lesions are caused by overexposure to insoluble cutting fluids, to various tar products, paraffin, and certain aromatic chlorinated hydrocarbons. The acne caused by any of the above agents can be extensive. Chloracne is the most serious form, not only because it can lead to disfigurement (hyperpigmentation and scarring) but also because of the potential liver damage, including porphyria cutanea tarda and other systemic effects that the chemicals can cause. Chloronaphthalenes, chlorodi-phenyls, chlorotriphenyls, hexachlorodibenzo-p-dioxin, tetrachloroazoxybenzene and tetrachlorodibenzodioxin (TCDD), are among the chloracne-causing chemicals. The blackheads and cystic lesions of chloracne often appear first on the sides of the forehead and the eyelids. If exposure continues, lesions may occur over widespread areas of the body, except for the palms and soles.

Sweat-induced reactions

Many types of work involve exposure to heat and where there is too much heat and sweating, followed by too little evaporation of the sweat from the skin, prickly heat can develop. When there is chafing of the affected area by skin rubbing against skin, a secondary bacterial or fungal infection may frequently occur. This happens particularly in the underarm area, under the breast, in the groin and between the buttocks.

Pigment change

Occupationally induced changes in skin colour can be caused by dyes, heavy metals, explosives, certain chlorinated hydrocarbons, tars and sunlight. The change in skin colour may be the result of a chemical reaction within the keratin, as for example, when the keratin is stained by metaphenylene-diamine or methylene blue or trinitrotoluene. Sometimes permanent discoloration may occur more deeply in the skin as with argyria or traumatic tattoo. Increased pigmentation induced by chlorinated hydrocarbons, tar compounds, heavy metals and petroleum oils generally results from melanin stimulation and overproduction. Hypopigmentation or depigmentation at selected sites can be caused by a previous burn, contact dermatitis, contact with certain hydroquinone compounds or other antioxidant agents used in selected adhesives and sanitizing products. Among the latter are tertiary amyl phenol, tertiary butyl catechol and tertiary butyl phenol.

New growths

Neoplastic lesions of occupational origin may be malignant or benign (cancerous or non-cancerous). Melanoma and non-melanocytic skin cancer are discussed in two other articles in this chapter. Traumatic cysts, fibromata, asbestos, petroleum and tar warts and keratoacanthoma, are typical benign new growths. Keratoacanthomas can be associated with excessive exposure to sunlight and also have been ascribed to contact with petroleum, pitch and tar.

Ulcerative changes

Chromic acid, concentrated potassium dichromate, arsenic trioxide, calcium oxide, calcium nitrate and calcium carbide are documented ulcerogenic chemicals. Favourite attack sites are the fingers, hands, folds and palmar creases. Several of these agents also cause perforation of the nasal septum.

Chemical or thermal burns, blunt injury or infections resulting from bacteria and fungi may result in ulcerous excavations on the affected part.

Granulomas

Granulomas can arise from many occupational sources if the appropriate circumstances are present. Granulomas can be caused by occupational exposures to bacteria, fungi, viruses or parasites. Inanimate substances, such as bone fragments, wood splinters, cinders, coral and gravel, and minerals such as beryllium, silica and zirconium, can also cause granulomas after skin embedment.

Other conditions

Occupational contact dermatitis accounts for at least 80% of all cases of occupational skin diseases. However, a number of other changes that affect the skin, hair and nails are not included in the foregoing classification. Hair loss caused by burns, or mechanical trauma or certain chemical exposures, is one example. A facial flush that follows the combination of drinking alcohol and inhaling certain chemicals, such as trichlorethylene and disulfuram, is another. Acroosteolysis, a type of bony disturbance of the digits, plus vascular changes of the hands and forearm (with or without Raynaud’s syndrome) has been reported among polyvinyl chloride polymerization tank cleaners. Nail changes are covered in a separate article in this chapter.

Physiopathology or Mechanismsof Occupational Skin Diseases

The mechanisms by which primary irritants act are understood only in part—for instance, vesicant or blister gases (nitrogen mustard or bromomethane and Lewisite, etc.)—interfere with certain enzymes and thereby block selective phases in the metabolism of carbohydrates, fats and proteins. Why and how the blister results is not clearly understood but observations of how chemicals react outside the body yield some ideas about possible biological mechanisms.

In brief, because alkali reacts with acid or lipid or protein, it has been presumed that it also reacts with skin lipid and protein. In so doing, surface lipids are changed and keratin structure becomes disturbed. Organic and inorganic solvents dissolve fats and oils and have the same effect on cutaneous lipids. Additionally, however, it appears that solvents abstract some substance or change the skin in such a way that the keratin layer dehydrates and the skin’s defence is no longer intact. Continued insult results in an inflammatory reaction eventuating in contact dermatitis.

Certain chemicals readily combine with the water within skin or on the surface of the skin, and cause a vigorous chemical reaction. Calcium compounds, such as calcium oxide and calcium chloride, produce their irritant effect in this way.

Substances such as coal tar pitch, creosote, crude petroleum, certain aromatic chlorinated hydrocarbons, in combination with sunlight exposure, stimulate the pigment-producing cells to over function, leading to hyperpigmentation. Acute dermatitis also may give rise to hyperpigmentation after healing. Conversely, burns, mechanical trauma, chronic contact dermatitis, contact with monobenzyl ether of hydroquinone or certain phenolics can induce hypo- or de-pigmented skin.

Arsenic trioxide, coal tar pitch, sunlight and ionizing radiation, among other agents, can damage the skin cells so that abnormal cell growth results in cancerous change of the exposed skin.

Unlike primary irritation, allergic sensitization is the result of a specifically acquired alteration in the capacity to react, brought about by T-cell activation. For several years it has been agreed that contact allergic eczematous dermatitis accounts for about 20% of all the occupational dermatoses. This figure is probably too conservative in view of the continued introduction of new chemicals, many of which have been shown to cause allergic contact dermatitis.

Causes of Occupational Skin Diseases

Materials or conditions known to cause occupational skin disease are unlimited. They are currently divided into mechanical, physical, biological and chemical categories, which continue to grow in number each year.

Mechanical

Friction, pressure or other forms of more forceful trauma may induce changes ranging from callus and blisters to myositis, tenosynovitis, osseous injury, nerve damage, laceration, shearing of tissue or abrasion. Lacerations, abrasions, tissue disruption and blisters additionally pave the way for secondary infection by bacteria or, less often, fungi to set in. Almost everyone is exposed each day to one or more forms of mechanical trauma which may be mild or moderate in degree. However, those who use pneumatic riveters, chippers, drills and hammers are at greater risk of suffering neurovascular, soft tissue, fibrous or bone injury to the hands and forearms. because of the repetitive trauma from the tool. The use of vibration-producing tools which operate in a certain frequency range can induce painful spasms in the fingers of the tool-holding hand. Transfer to other work, where possible, generally provides relief. Modern equipment is designed to reduce vibration and thus obviate the problems.

Physical agents

Heat, cold, electricity, sunlight, artificial ultraviolet, laser radiation and high energy sources such as x rays, radium and other radioactive substances are potentially injurious to skin and to the entire body. High temperature and humidity at work or in a tropical work environment can impair the sweat mechanism and cause systemic effects known as sweat retention syndrome. Milder exposure to heat may induce prickly heat, intertrigo (chafing), skin maceration and supervening bacterial or fungal infection, particularly in overweight and diabetic individuals.

Thermal burns are frequently experienced by electric furnace operators, lead burners, welders, laboratory chemists, pipe-line workers, road repairmen, roofers and tar plant workers contacting liquid tar. Prolonged exposure to cold water or lowered temperatures causes mild to severe injury ranging from erythema to blistering, ulceration and gangrene. Frostbite affecting the nose, ears, fingers and toes of construction workers, firemen, postal workers, military personnel and other outdoor workers is a common form of cold injury.

Electricity exposure resulting from contact with short circuits, bare wires or defective electrical apparatus cause burns of the skin and destruction of deeper tissue.

Few workers are without exposure to sunlight and some individuals with repeated exposure incur severe actinic damage to skin. Modern industry also has many sources of potentially injurious artificial ultraviolet wavelengths, such as in welding, metal burning, molten-metal pouring, glass blowing, electric furnace tending, plasma torch burning and laser beam operations. Apart from the natural capacity of ultraviolet rays in natural or artificial light to injure skin, coal tar and several of its by-products, including certain dyes, selected light-receptive components of plants and fruits and a number of topical and parenteral medications contain harmful chemicals which are activated by certain wavelengths of ultraviolet rays. Such photoreaction effects may operate by either phototoxic or photoallergic mechanisms.

High-intensity electromagnetic energy associated with laser beams is well able to injure human tissue, notably the eye. Skin damage is less of a risk but can occur.

Biological

Occupational exposures to bacteria, fungi, viruses or parasites may cause primary or secondary infections of the skin. Prior to the advent of modern antibiotic therapy, bacterial and fungal infections were more commonly encountered and associated with disabling illness and even death. While bacterial infections can occur in any kind of work setting, certain jobs, such as animal breeders and handlers, farmers, fishermen, food processors and hide handlers have greater exposure potential. Similarly, fungal (yeast) infections are common among bakers, bartenders, cannery workers, cooks, dishwashers, child-care workers and food processors. Dermatoses due to parasitic infections are not common, but when they do occur they are seen most often among agricultural and livestock workers, grain handlers and harvesters, longshoremen and silo workers.

Cutaneous viral infections caused by work are few in number, yet some, such as milker’s nodules among dairyworkers, herpes simplex among medical and dental personnel and sheep pox among livestock handlers continue to be reported.

Chemicals

Organic and inorganic chemicals are the major source of hazards to the skin. Hundreds of new agents enter the work environment each year and many of these will cause cutaneous injury by acting as primary skin irritants or allergic sensitizers. It has been estimated that 75% of the occupational dermatitis cases are caused by primary irritant chemicals. However, in clinics where the diagnostic patch test is commonly used, the frequency of occupational allergic contact dermatitis is increased. By definition, a primary irritant is a chemical substance which will injure every person’s skin if sufficient exposure takes place. Irritants can be rapidly destructive (strong or absolute) as would occur with concentrated acids, alkalis, metallic salts, certain solvents and some gases. Such toxic effects can be observed within a few minutes, depending upon the concentration of the contactant and the length of contact which occurs. Conversely, dilute acids and alkalis, including alkaline dusts, various solvents and soluble cutting fluids, among other agents, may require several days of repeated contact to produce observable effects. These materials are termed “marginal or weak irritants”.

Plants and woods

Plants and woods are often classified as a separate cause of skin disease, but they can also be correctly included in the chemical grouping. Many plants cause mechanical and chemical irritation and allergic sensitization, while others have gained attention because of their photoreactive capacity. The family Anacardiaceae, which includes poison ivy, poison oak, poison sumac, cashew-nut shell oil and the Indian marking nut, is a well-known cause of occupational dermatitis due to its active ingredients (polyhydric phenols). Poison ivy, oak and sumac are common causes of allergic contact dermatitis. Other plants associated with occupational and non-occupational contact dermatitis include castor bean, chrysanthemum, hops, jute, oleander, pineapple, primrose, ragweed, hyacinth and tulip bulbs. Fruits and vegetables, including asparagus, carrots, celery, chicory, citrus fruits, garlic and onions, have been reported as causing contact dermatitis in harvesters, food packing and food preparation workers.

Several varieties of wood have been named as causes of occupational dermatoses among lumberers, sawyers, carpenters and other wood craftspeople. However, the frequency of skin disease is much less than is experienced from contact with poisonous plants. It is likely that some of the chemicals used for preserving the wood cause more dermatitic reactions than the oleoresins contained in wood. Among the preservative chemicals used to protect against insects, fungi and deterioration from soil and moisture are chlorinated diphenyls, chlorinated naphthalenes, copper naphthenate, creosote, fluorides, organic mercurials, tar and certain arsenical compounds, all known causes of occupational skin diseases.

Non-Occupational Factors in OccupationalSkin Disease

Considering the numerous direct causes of occupational skin disease cited above, it can be readily understood that practically any job has obvious and often hidden hazards. Indirect or predisposing factors may also merit attention. A predisposition can be inherited and related to skin colour and type or it may represent a skin defect acquired from other exposures. Whatever the reason, some workers have lower tolerance to materials or conditions in the work environment. In large industrial plants, medical and hygiene programmes can provide the opportunity for placement of such employees in work situations that will not further impair their health. In small plants, however, predisposing or indirect causal factors may not be given proper medical attention.

Pre-existing skin conditions

Several non-occupational diseases affecting the skin can be worsened by various occupational influences.

Acne. Adolescent acne in employees is generally made worse by machine tool, garage and tar exposures. Insoluble oils, various tar fractions, greases and chloracnegenic chemicals are definite hazards to these people.

Chronic eczemas. Detecting the cause of chronic eczema affecting the hands and sometimes distant sites can be elusive. Allergic dermatitis, pompholyx, atopic eczema, pustular psoriasis and fungal infections are some examples. Whatever the condition, any number of irritant chemicals, including plastics, solvents, cutting fluids, industrial cleansers and prolonged moisture, can worsen the eruption. Employees who must continue to work will do so with much discomfort and probably lowered efficiency.

Dermatomycosis. Fungal infections can be worsened at work. When fingernails become involved it may be difficult to assess the role of chemicals or trauma in the nail involvement. Chronic tinea of the feet is subject to periodic worsening, particularly when heavy footgear is required.

Hyperhidrosis. Excessive sweating of the palms and soles can soften the skin (maceration), particularly when impervious gloves or protective footgear are required. This will increase a person’s vulnerability to the effects of other exposures.

Miscellaneous conditions. Employees with polymorphous light eruption, chronic discoid lupus erythematous, porphyria or vitiligo are definitely at greater risk, particularly if there is simultaneous exposure to natural or artificial ultraviolet radiation.

Skin type and pigmentation

Redheads and blue-eyed blondes, particularly those of Celtic origin, have less tolerance to sunlight than people of darker skin type. Such skin is also less able to tolerate exposures to photoreactive chemicals and plants and is suspected of being more susceptible to the action of primary irritant chemicals, including solvents. In general, black skin has a superior tolerance to sunlight and photoreactive chemicals and is less prone to the induction of cutaneous cancer. However, darker skin tends to respond to mechanical, physical or chemical trauma by displaying post-inflammatory pigmentation. It is also more prone to develop keloids following trauma.

Certain skin types, such as hairy, oily, swarthy skins, are more likely to incur folliculitis and acne. Employees with dry skin and those with ichthyoses are at a disadvantage if they must work in low humidity environments or with chemical agents which dehydrate skin. For those workers who sweat profusely, a need to wear impervious protective gear will add to their discomfort. Similarly, overweight individuals usually experience prickly heat during the warm months in hot working environments or in tropical climates. While sweat can be helpful in cooling the skin, it can also hydrolyze certain chemicals that will act as skin irritants.

Diagnosing Occupational Skin Diseases

Cause and effect of occupational skin disease can be best ascertained through a detailed history, which should cover the past and present health and work status of the employee. Family history, particularly of allergies, personal illness in childhood and the past, is important. The title of the job, the nature of the work, the materials handled, how long the job has been done, should be noted. It is important to know when and where on the skin the rash appeared, the behaviour of the rash away from work, whether other employees were affected, what was used to cleanse and protect the skin, and what has been used for treatment (both self-medication and prescribed medication); as well as whether the employee has had dry skin or chronic hand eczema or psoriasis or other skin problems; what drugs, if any, have been used for any particular disease; and finally, which materials have been used in home hobbies such as the garden or woodworking or painting.

The following elements are important parts of the clinical diagnosis:

• Appearance of the lesions. Acute or chronic eczematous contact dermatosis are most common. Follicular, acneform, pigmentary, neoplastic, ulcerative granulomatous lesions and conditions such as Raynaud’s syndrome and contact urticaria can occur.
• Sites involved. The hands, the digits, the wrists and the forearms are the most common sites affected. Exposure to dusts and fumes usually cause the dermatosis to appear on the forehead, face, and V of the neck. Widespread dermatitis can result from autosensitization (spread) of an occupational or nonoccupational dermatosis.
• Diagnostic tests. Laboratory tests should be employed when necessary for the detection of bacteria, fungi and parasites. When allergic reactions are suspect, diagnostic patch tests can be used to detect occupational as well as non-occupational allergies, including photosensitization. Patch tests are a highly useful procedure and are discussed in an accompanying article in this chapter. At times, useful information can be obtained through the use of analytical chemical examination of blood, urine, or tissue (skin, hair, nails).
• Course. Of all the cutaneous changes induced by agents or certain conditions at work, acute and chronic eczematous contact dermatoses are foremost in number. Next in frequency are follicular and acneform eruptions. The other categories, including chloracne, constitute a smaller but still important group because of their chronic nature and the scarring and disfigurement which may be present.

An occupationally induced acute contact eczematous dermatitis tends to improve upon cessation of contact. Additionally, modern therapeutic agents can facilitate the period of recovery. However, if a worker returns to work and to the same conditions, without proper preventive measures undertaken by the employer and necessary precautions explained and understood by the worker, it is probable that the dermatosis will recur soon after re-exposure.

Chronic eczematous dermatoses, acneform lesions and pigmentary changes are less responsive to treatment even when contact is eliminated. Ulcerations usually improve with elimination of the source. With granulomatous and tumour lesions, eliminating contact with the offending agent may prevent future lesions but will not dramatically change already existing disease.

When a patient with a suspected occupational dermatosis has not improved within two months after no longer having contact with the suspected agent, other reasons for the persistence of the disease should be explored. However, dermatoses caused by metals such as nickel or chrome have a notoriously prolonged course partly because of their ubiquitous nature. Even removal from work cannot eliminate the workplace as the source of the disease. If these and other potential allergens have been eliminated as causal, it is reasonable to conclude that the dermatitis is either non-occupational or is being perpetuated by non-occupational contacts, such as maintenance and repair of automobiles and boats, tile setting glues, garden plants or including even medical therapy, prescribed or otherwise.

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There are three histological types of non-melanocytic skin cancers (NMSC) (ICD-9: 173; ICD-10: C44): basal cell carcinoma, squamous cell carcinoma and rare soft tissue sarcomas involving the skin, subcutaneous tissue, sweat glands, sebaceous glands and hair follicles.

Basal cell carcinoma is the most common NMSC in white populations, representing 75 to 80% of them. It develops usually on the face, grows slowly and has little tendency to metastasize.

Squamous cell cancers account for 20 to 25% of reported NMSCs. They can occur on any part of the body, but especially on the hands and legs and can metastasize. In darkly pigmented populations squamous cell cancers are the most common NMSC.

Multiple primary NMSCs are common. The bulk of the NMSCs occur on the head and neck, in contrast with most of the melanomas which occur on the trunk and limbs. The localization of NMSCs reflects clothing patterns.

NMSCs are treated by various methods of excision, radiation and topical chemotherapy. They respond well to treatment and over 95% are cured by excision (IARC 1990).

The incidence of NMSCs is hard to estimate because of gross underreporting and since many cancer registries do not record these tumours. The number of new cases in the US was estimated at 900,000 to 1,200,000 in 1994, a frequency comparable to the total number of all non-cutaneous cancers (Miller & Weinstock 1994). The reported incidences vary widely and are increasing in a number of populations, e.g., in Switzerland and the US. The highest annual rates have been reported for Tasmania (167/100,000 in men and 89/100,000 in women) and the lowest for Asia and Africa (overall 1/100,000 in men and 5/100,000 in women). NMSC is the most common cancer in Caucasians. NMSC is about ten times as common in White as in non-White populations. The lethality is very low (Higginson et al. 1992).

Susceptibility to skin cancer is inversely related to the degree of melanin pigmentation, which is thought to protect by buffering against the carcinogenic action of solar ultraviolet (UV) radiation. Non-melanoma risk in white-skinned populations increases with the proximity to the equator.

In 1992, the International Agency for Research on Cancer (IARC 1992b) evaluated the carcinogenicity of solar radiation and concluded that there is sufficient evidence in humans for the carcinogenicity of solar radiation and that solar radiation causes cutaneous malignant melanoma and NMSC.

Reduction of exposure to sunlight would probably reduce the incidence of NMSCs. In Whites, 90 to 95% of NMSCs are attributable to solar radiation (IARC 1990).

NMSCs may develop in areas of chronic inflammation, irritation and scars from burns. Traumas and chronic ulcers of the skin are important risk factors for squamous cell skin cancers, particularly in Africa.

Radiation therapy, chemotherapy with nitrogen mustard, immunosuppressive therapy, psoralen treatment combined with UV-A radiation and coal tar preparations applied on skin lesions have been associated with an increased risk of NMSC. Environmental exposure to arsenic trivalent and arsenical compounds have been confirmed to be associated with skin cancer excess in humans (IARC 1987). Arsenicism can give rise to palmar or plantar arsenical keratoses, epidermoid carcinoma and superficial basal cell carcinoma.

Hereditary conditions such as lack of enzymes required to repair the DNA damaged by UV radiation may increase the risk of NMSC. Xeroderma pigmentosum represents such a hereditary condition.

A historical example of an occupational skin cancer is scrotal cancer that Sir Percival Pott described in chimney sweeps in 1775. The cause of these cancers was soot. In the early 1900s, scrotal cancers were observed in mulespinners in cotton textile factories where they were exposed to shale oil, which was used as a lubricant for cotton spindles. The scrotal cancers in both chimney sweeps and mulespinners were later associated with polycyclic aromatic hydrocarbons (PAHs), many of which are animal carcinogens, particularly some 3-, 4- and 5-ring PAHs such as benz(a)pyrene and dibenz(a,h)anthracene (IARC 1983, 1984a, 1984b, 1985a). In addition to mixtures that readily contain carcinogenic PAHs, carcinogenic compounds may be formed by cracking when organic compounds are heated.

Further occupations with which PAH-related excesses of NMSC have been associated include: aluminium reduction workers, coal gasification workers, coke oven workers, glass blowers, locomotive engineers, road pavers and highway maintenance workers, shale oil workers, tool fitters and tool setters (see table 1). Coal tars, coal-based pitches, other coal-derived products, anthracene oil, creosote oil, cutting oils and lubricating oils are some of the materials and mixtures that contain carcinogenic PAHs.

Table 1. Occupations at risk

Additional job titles that have been associated with increased NMSC risk include jute processors, outdoor workers, pharmacy technicians, sawmill workers, shale oil workers, sheep-dip workers, fishermen, tool setters, vineyard workers and watermen. The excess for watermen (who are primarily involved in traditional fishing tasks) was noticed in Maryland, USA and was confined to squamous cell cancers. Solar radiation probably explains fishermen’s, outdoor workers’, vineyard workers’ and watermen’s excess risks. Fishermen also may be exposed to oils and tar and inorganic arsenic from the consumed fish, which may contribute to the observed excess, which was threefold in a Swedish study, as compared with the county-specific rates (Hagmar et al. 1992). The excess in sheep dip workers may be explained by arsenical compounds, which induce skin cancers through ingestion rather than through skin contact. While farmers have slightly increased risk of melanoma, they do not appear to have increased risk of NMSC, based on epidemiological observations in Denmark, Sweden and the USA (Blair et al. 1992).

Ionizing radiation has caused skin cancer in early radiologists and workers who handled radium. In both situations, the exposures were long-lasting and massive. Occupational accidents involving skin lesions or long-term cutaneous irritation may increase the risk on NMSC.

Prevention (of Non-Melanocytic OccupationalSkin Cancer)

The use of appropriate clothing and a sunscreen having a protective UV-B factor of 15 or greater will help protect outdoor workers exposed to ultraviolet radiation. Further, the replacement of carcinogenic materials (such as feed stocks) by non-carcinogenic alternatives is another obvious protective measure which may, however, not always be possible. The degree of exposure to carcinogenic materials can be reduced by the use of protective shields on equipment, protective clothing and hygienic measures.

Of overriding importance is the education of the workforce about the nature of the hazard and the reasons for and value of the protective measures.

Finally, skin cancers usually take many years to develop and many of them pass through several premalignant stages before achieving their full malignant potential such as arsenic keratoses and actinic keratoses. These early stages are readily detectable by visual inspection. For this reason, skin cancers offer the real possibility that regular screening could reduce mortality among those known to have been exposed to any skin carcinogen.

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