Introduction

There are two major forms of contact dermatitis: irritant and allergic. Irritant contact dermatitis (ICD) is a cutaneous inflammatory disorder resulting from activation of the innate immune system by direct cytotoxic effect of a chemical or physical agent, whereas allergic contact dermatitis is a delayed-type hypersensitivity immune reaction mediated by hapten-specific T cells .

Occupational contact dermatitis is a matter of public health importance , contributing to combined direct and indirect annual costs in the US of up to $1 billion when accounting for medical costs, workers’ compensation, and lost time from work . A recent National Health Interview Survey suggested that in 2010, 15 million Americans were affected by occupational dermatitis , a figure 100-fold higher than in prior reports by the US Bureau of Labor Statistics. Overall, the impact of occupational skin diseases on both society and the individual is formidable in light of both prevalence and economic factors.

History

One of the earliest documented irritant skin reactions is in the writings of Celsus around 100 AD, when he described skin ulceration resulting from corrosive metals . For the next several centuries, little attention was paid to the skin problems incurred by tradesmen. The first accounts of occupational skin diseases focused on ill health among miners, and in 1556, Georg Agricola detailed the deep ulcers observed among metal workers. Eleven years later, Paracelsus discussed the etiology, pathogenesis and therapy of skin changes caused by salt compounds. In 1700, Bernardino Ramazzini published a detailed treatise on the diseases of tradespeople in which he described skin disorders incurred by bath attendants, bakers, gilders, midwives, millers, and miners . Physicians began to more widely recognize occupational irritant dermatitis during the Industrial Revolution with the development of new materials and chemicals, both natural and synthetic, for both industrial and household use . Germany and France were the first to enact laws compensating workers for industrial skin diseases. Early prospective studies of ICD in 1919 involved experimentation with the irritant mustard gas dichloroethylsulfide .

Epidemiology

ICD is the most common form of occupational skin disease, estimated to constitute between 70% and 80% of all occupational skin disorders ( Table 15.1 ). Data from the North American Contact Dermatitis Group indicate that in groups of patients with contact dermatitis, ICD (as a primary diagnosis) accounts for 9–10% of those screened for allergic contact dermatitis via patch testing, and when hands are affected, ICD predominates over all other causes of contact dermatitis .

The US Bureau of Labor Statistics data show that occupational skin diseases accounted for a consistent 30–45% of all patients with occupational illnesses from the 1970s through the mid-1980s. However, occupational skin disease rates have since fallen dramatically, e.g. from an average rate of 16.2 events/10 000 full-time workers in 1972 to 2.8 events in 2013 . Although skin disease accounted for only 17% of all recorded non-fatal occupational illnesses in 2007 , it still ranks second and is only surpassed by musculoskeletal disorders. The incidence of occupational contact dermatitis in several other countries is similar to that in the US, with a range of 50 to 70 cases/100 000 workers/year . In 1996, the United Kingdom created a voluntary reporting system that combined information from the EPIDERM study with the occupational physicians’ reporting activity (OPRA). The annual incidence of occupational contact dermatitis reported by dermatologists was 0.9 per 10 000 workers, and for occupational physicians, it was 3.1 per 10 000 workers .

In 2010, the National Institutes of Occupational Safety and Health sponsored the National Health Interview Survey which utilized a sample cohort of 27 157 individuals (to represent 229 million US civilian adults), the majority of whom were employed or recently employed . The overall prevalence of dermatitis was 10.2%, ranging from 7.3% in those who never worked to 9.8% in currently employed workers to 11.8% in those recently, but not currently, employed.

In addition to manufacturing, industries with the highest non-adjusted and adjusted rates of dermatitis include healthcare and social assistance; arts, entertainment and recreation; and accommodations and food services. Rubber chemicals, soaps and cleansers, wet work, resins, acrylics, and nickel are some of the more common sources for irritant and allergic contact dermatitis. Additional high-risk occupations are discussed in Chapter 16 .

Clinical manifestations of ICD are determined by the properties of the irritating substance as well as host and environmental factors. These include concentration, pH, mechanical pressure, temperature, humidity, and duration of contact. Low ambient humidity and cold are important factors in decreasing the water content of the stratum corneum and, consequently, increasing the permeability to irritants such as soaps, detergents, acids, bases, and solvents. Cold alone may also reduce the plasticity of the horny layer, with consequent cracking of the stratum corneum. However, in one study, the application of cold had a protective effect on the development of ICD if applied during the provocative exposure, in this case to sodium lauryl sulfate . Occlusion, excessive humidity, and maceration increase the water content of the stratum corneum, with consequent enhanced percutaneous absorption of water-soluble substances ( Fig. 15.1 ). In addition, irritated skin may become more susceptible to superimposed allergic sensitization.

Bilateral irritant contact dermatitis of the feet and ankles due to chronic occlusive footwear.

Important predisposing characteristics of the individual include age, sex, pre-existing skin disease, anatomic region exposed, and sebaceous activity. There are age-associated changes in the skin that can alter the skin’s response to irritants. Both infants and the elderly are more often affected by ICD because of their less robust epidermal barrier, and they also develop more severe symptoms. While skin irritation may be seen more often on the upper extremities of women than men, this higher prevalence of ICD may be due to increased frequency of exposure rather than inherent gender differences. Genetic factors also play a role in the development of ICD, as shown in studies with monozygotic twins . Patients with a history of atopic dermatitis have a 13.5 times greater risk of developing occupational dermatitis , and a reduction in epidermal filaggrin can reduce the inflammatory threshold for irritants . Lastly, the most commonly affected sites are exposed areas such as the hands and the face, with hand involvement seen in ~80% of patients and facial involvement in 10% . Excessive exposure to water, soaps and detergents, common causes of ICD, play a critical role given that wet work (immersion in water for >2 hours, occlusive protective gear, and/or hand washing >20 times/day) represents one of the most important risk factors for developing irritant dermatitis .

Pathogenesis

Although the cellular mechanisms of ICD remain elusive, increasing evidence suggests that activated keratinocytes act as signal transducers in the control of host homeostatic responses to exogenous stimuli and they serve as key immunoregulators. An irritant chemical’s ability to induce cutaneous damage may serve to trigger pattern recognition receptors (PRR), including Toll-like receptors, providing the necessary impetus to activate the innate immune system . While other mediators such as prostaglandins, leukotrienes, and neuropeptides may possibly play a role, cytokines carry the most interest in ICD as they are the central mediators in T-cell recruitment and inflammation.

Several pathomechanisms have commonly been associated with ICD, including denaturation of epidermal keratins, disruption of the permeability barrier (see Ch. 124 ), damage to cell membranes, and direct cytotoxic effects, with different mechanisms at work with different irritants ( Table 15.2 ). The mechanisms involved in the acute and chronic phases of ICD are fundamentally different. Acute reactions involve direct cytotoxic damage to keratinocytes, while repeated exposures to solvents and surfactants cause slower damage to cell membranes by removing surface lipids and water-retaining substances.

The pathogenic pathway in the acute phase of ICD, common to many chemically unrelated irritants, begins with penetration of the irritant through the permeability barrier (stratum corneum), mild damage or stress to keratinocytes, and the release of mediators of inflammation with resultant T-cell activation. In this manner, once activation is initiated via epidermal cells, continuous T-cell activation independent of the exogenous agent may be maintained and barrier dysfunction perpetuated . Tumor necrosis factor-α (TNF-α) and interleukin (IL)-1α are the major mediators, and they are capable of inducing production of other cytokines, chemokines, and adhesion molecules, leading to leukocyte recruitment to the site. Specifically, TNF-α, IL-6, and IL-1β upregulate expression of intercellular adhesion molecule-1 (ICAM-1) . This is a predominant feature of ICD. In addition, IL-1 receptor antagonist (IL-1RA) and IL-8 increase substantially after exposure to the common irritant sodium lauryl sulfate.

In the chronic phase of ICD, the role of the stratum corneum as a barrier is disrupted. Damage to the stratum corneum lipids (which mediate barrier function) is associated with loss of cohesion of corneocytes, desquamation, and an increase in transepidermal water loss. Transepidermal water loss is one of the triggering stimuli that promote lipid synthesis, keratinocyte proliferation, and transient hyperkeratosis during the restoration of the cutaneous barrier. However, damage with a solvent can disrupt this protective mechanism by occlusion and blockage of water evaporation, thus halting lipid synthesis and barrier recovery. After chronic exposure, the result is increased epidermal turnover manifested clinically by the chronic eczematoid irritant reaction .

Clinical Features

Several different types of ICD have been described (see below). Consequences of the myriad forms of ICD range from postinflammatory pigmentary changes to poorly healing ulcers ( Table 15.3 ).

Pathology

The histopathologic features of ICD vary according to the nature of the irritant, but often include mild spongiosis, necrosis of keratinocytes, and an inflammatory infiltrate rich in neutrophils. The combination of a neutrophil-rich superficial perivascular infiltrate plus widely scattered necrotic keratinocytes is most typical; sometimes there is even full-thickness epidermal necrosis and subepidermal clefting. Mild ICD can resemble allergic contact dermatitis. Over time, additional histologic findings include acanthosis with mild hypergranulosis and hyperkeratosis. In aggregate, these elements are not specific, and they cannot be confidently differentiated from either chronic allergic contact dermatitis or other types of chronic eczemas.

Classification of Irritant Chemicals

Acids

A variety of both inorganic and organic acids can be corrosive to the skin. Acids cause epidermal damage via protein denaturation and cytotoxicity. Principally, all strong acids give the same clinical features, including erythema, vesication, and necrosis.

Inorganic acids are commonly used in industry, especially hydrofluoric, sulfuric, hydrochloric, chromic, nitric, and phosphoric acids ( Table 15.4 ). Hydrofluoric acid and sulfuric acid cause the most severe burns, even at low concentrations, and there can be significant absorption leading to systemic toxicity .

Table 15.4

Irritant chemicals: uses, properties and side effects.

Glycols/alcohols and detergents/cleansers are discussed in the text.

IRRITANT CHEMICALS: USES, PROPERTIES AND SIDE EFFECTS
Compound	Uses/exposures	Properties and side effects
Inorganic acids
Chromic acid	• Metal treatments (chrome plating, copper stripping, aluminum anodizing)	• Ulcerations known as “chrome holes” • Nasal septal perforation
Hydrochloric acid	• Production of fertilizers, dyes, paints, and soaps • Electroplating, oil refining, and food processing	• Erythema, vesication, and necrosis
Hydrofluoric acid	• Semiconductor industry (etching glass, metal, and stone; can dissolve silicon) • Household and commercial rust, stain, and lime-scale removers	• Extremely cytotoxic agent that can lead to severe tissue damage • Penetrates intact skin due to its limited dissociation constant • Painful penetration may continue for days after exposure • With low concentrations, the onset of symptoms may be delayed for up to a day • Intense pain is due to the capacity of fluoride ions to bind tissue calcium, thereby affecting nerve conduction • Hypomagnesemia and a fluoride-mediated increase in pulmonary vascular resistance may also play a role in toxicity
Nitric acid	• Production of fertilizers and explosives; metal etching and cleaning • Fuming nitric acid – a chemical intermediate used in rocket fuels and as a laboratory reagent	• Chemical burns • Irritant contact dermatitis • Distinctive yellow discoloration • Fuming nitric acid – highly corrosive
Phosphoric acid	• Phosphate fertilizer, pharmaceuticals, water treatment, animal feeds, soaps and detergents, and cotton dyeing	• Erythema, vesication, and necrosis
Sulfuric acid	• Manufacture of fertilizers, inorganic pigments, textile fibers, explosives, pulp, and paper • Occupational risk: jewelers, electroplaters, metal cleaners, and storage battery makers	• Erythema, vesication, and necrosis
Organic acids
Acrylic acid	• Monomer for acrylic plastics, synthetic resins, dentures, artificial nails, adhesives, and paints	• Highly irritating and corrosive • Capable of penetrating rubber gloves • Also allergic contact dermatitis
Formic acid	• Neutralizer in leather manufacturing, an antiseptic in brewing, and a coagulant in the production of natural latex	• Greatest corrosive potential of the organic acids
Alkalis
Cement (mixed with water)	• Construction	• Acute ulcerative damage as a result of the high alkalinity of wet cement (due to liberation of calcium hydroxide) • Necrotic skin changes appear 8–12 hours after exposure • Chronic irritant cement dermatitis – develops over months to years from continued exposure; can accompany allergic contact dermatitis to chromium • Most common locations – lower limbs (kneeling, contaminated footwear), hands (glove contamination)
Metal salts
Arsenic compounds (including arsenic trioxide)	• Aerosolized during the smelting of copper, gold, lead and other metals • Manufacture of pesticides and herbicides • Semiconductor industry and smelting operations	• Persistent folliculitis • Potential for systemic toxicity (see Ch. 88 )
Beryllium	• Production of hard, corrosion-resistant alloys	• Ulcerated granulomatous skin lesions (local reaction; see Ch. 94 ) • Sarcoidosis-like granulomas of the skin and lung (systemic reaction)
Calcium oxide (quicklime)	• Manufacture of pulp, steel, and paper	• Releases heat on contact with water, causing painful cutaneous ulcerations
Cobalt salts	• Alloys, ceramics, electroplating, electronics, magnets, paints, varnishes, and hair dyes	• Irritant and allergic contact dermatitis
Copper salts (e.g. sulfates, oxides, cyanides)	• Used as a biostatic surface and in wood preservatives and fungicides	• Impart a greenish-black color to hair, skin, and teeth if persistent exposure to dust forms • Inhalation of copper oxides (as well as magnesium and zinc oxides) can cause metal fume fever, a brief influenza-like illness usually associated with welding operations
Mercury, inorganic	• Products containing inorganic mercury have been banned since 1990; limited exposure possible from old cans of latex paint	• Bluish linear pigmentation of the tongue and gums, which may serve as a marker for systemic mercury poisoning
Mercury, organic	• Phenyl mercury salts are used as preservatives in cosmetics and vaccines, as fungicides, herbicides and pesticides in agriculture, and in dental restorative materials	• Although once used as skin disinfectants, both irritant and allergic contact dermatitis have restricted its use • Positive patch tests to mercury (as well as other metals such as gold) observed in patients with oral lichenoid reactions to dental materials (see Ch. 11 )
Selenium compounds (including sulfide)	• Therapeutic shampoo (selenium sulfide)	• Skin irritation, conjunctivitis
Thimerosal	• Topical medicaments, vaccines, and cosmetics	• Common cause of both allergic and irritant patch-test reactions
Solvents
Benzene	• Manufacture of polymers, plastics, resins, adhesives, rubber, lubricants, dyes, detergents, drugs, explosives, and pesticides	• Petechial eruption of the trunk, extremities, and mucous membranes • Petechiae considered to be a marker for aplastic anemia
Chlorinated hydrocarbons (e.g. carbon tetrachloride, trichloroethylene, tetrachloroethane, methylene chloride, ethylene chloride)	• Production of vinyl chloride, which is then converted to polyvinyl chloride • Pesticides • Dry cleaning	• Cutaneous irritation • Systemic effects: liver and kidney damage, CNS depression, and carcinogenesis • Methylene chloride can hydrolyze to form hydrochloric acid, thus leading to significant cutaneous irritation (see above) • “Degreaser’s flush” – sudden erythema in extensive areas of the face, neck, and shoulders; caused by alcohol ingestion shortly before or during inhalation of trichloroethylene
Coal tar derivatives (e.g. toluene, xylene, ethyl benzene, cumene)	• Medications • Solvents	• Skin drying and defatting • Exposure solely to vapors can cause xerosis
Petrochemicals (e.g. gasoline, hexane, kerosene, Stoddard solvent)	• Fuels • Insecticides • Dry cleaning • Hexanes – gasoline, glues, and for extraction of cooking oils from seeds	• Irritant contact dermatitis • Absorption of hexane via inhalation or percutaneously can cause paresthesias, hypoesthesia, and motor weakness
Disinfectants
Aldehydes (e.g. formaldehyde, glutaraldehyde, hexa-methylenetetramine)	• Disinfectants, biocides • Tissue fixative, embalming agent • Adhesives, resins	• More irritating than alcohols • Formaldehyde – high chemical reactivity with proteins; both allergen and irritant, even at low concentrations
Ethylene oxide	• Sterilization of medical equipment	• Oxidizing agent • Severe chemical burns
Halogens – Chlorines	• Disinfectants, including wounds * • Bleach (sodium hypochlorite) • Sanitizers for swimming pools, hot tubs	• Denature proteins via deaminating or chlorinating amino acids • Oxidizing agent (sodium hypochlorite) • Acute skin and mucosal irritant reactions, particularly at high temperatures
Halogens – Iodines	• Broad-spectrum antimicrobial and sporicidal agents • Surgical scrub, shampoo, and skin cleanser (povidone-iodine in a surfactant base)	• Inhibit DNA, RNA, and protein synthesis • Irritant contact dermatitis • Contact urticaria
Phenolic compounds (e.g. Lysol ® [cresol and soap solution], pentachlorophenol, chloroxylenol)	• Disinfectants • Preservative in over-the-counter products (baby powders, shampoos), especially chloroxylenol	• Irritant contact dermatitis • Chemical leukoderma (amyl- and butyl-phenol compounds; see Table 15.3 )
Quaternary ammonium salts (e.g. benzalkonium chloride)	• Cosmetics, medications (e.g. ophthalmic solutions) • Antiseptics (e.g. cleaning of surgical instruments) • Detergent	• Cationic surfactants that can precipitate or denature proteins and destroy microorganisms • Local skin irritation depends on the solution concentration • Benzalkonium chloride – irritant reactions frequent during patch testing (concentration, 0.1%); can also be an allergen (e.g. healthcare workers, leg ulcer patients) so clinical correlation required

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