Irritant Dermatitis

Chapter 23

Irritant Dermatitis Lisa E. Maier1, Howard I. Maibach2 and Michael O’Malley3 1

University of Michigan, Ann Arbor, Michigan, and Veterans Administration Medical Center, Ann Arbor, Michigan University of California, San Francisco, California 3 California Environmental Protection Agency, Sacramento, California, and University of California, Davis, California 2

23.1  Introduction

Irritant contact dermatitis (ICD) is defined as nonimmunologic skin inflammation after contact to a substance or physical factor. Although epidemiologic data are scarce, ICD appears to be an important cause of occupational and nonoccupational skin disease. The U.S. Bureau of Labor and Statistics estimated that 80% of occupational contact dermatitis cases were due to ICD in 1995 (Chew and Maibach, 2003). The burden of ICD in agricultural workers is unknown; however, it is likely high given the potential exposures to irritants in agriculture. This chapter discusses the factors influencing irritant potential, delineates general clinical presentations of irritant dermatitis, and addresses workup and treatment. In addition, it addresses methods of evaluating a chemical’s irritant potential and discusses the irritation potential of some agricultural chemicals and plants.

23.2  Factors influencing irritant potential

and balance or result in protein denaturation (Welss et al., 2004). These disruptions compromise skin barrier function, resulting in increased transepidermal water loss and inflammation. Beyond the effect on the stratum corneum, some irritants may directly damage cell membranes and cell proteins. Disruption of cell membranes triggers an inflammatory cascade that results in erythema and edema. Cell membrane damage may also result in abnormal signal transduction (Welss et al., 2004). Irritant potential is also dependent on the molar concentration (Tupker, 2003) and volume and duration of the exposure (Aramaki et al., 2001). As a general rule, increasing concentration and exposure time and frequency will increase irritant potential. Paradoxically, in some cases, repeated exposure results in improvement of the dermatitis. This is known as a “hardening” effect, in which the skin adapts to the topical irritant. The molecular mechanisms are not completely elucidated; however, changes in stratum corneum thickness and function, downregulation of the production of inflammatory mediators, and alteration in the production of stratum corneum lipids have been observed (Watkins and Maibach, 2009; Welfriend and Maibach, 2008).

23.2.1  Chemical Factors Various factors influence a chemical’s irritant potential. Intrinsic molecular properties such as molecular structure, size, ionization state, lipid solubility, and pKa (Berner et al., 1990; Welfriend and Maibach, 2008) determine the chemical’s interaction with the skin barrier and epidermal cells. For example, chemicals such as organic solvents can cause extraction of stratum corneum lipids (Fluhr et al., 2008). Other irritants may alter the lipid composition Hayes’ Handbook of Pesticide Toxicology Copyright © 2010 Elsevier Inc. All rights reserved

23.2.2  Physical Factors Physical factors such as extremes of temperature and humidity, as well as mechanical factors such as occlusion and friction, can enhance irritation of chemicals or act as irritants. Several studies evaluating irritancy of surfactants, perfumes, and detergents demonstrated increased irritation with increased temperature (Berardesca et al., 1995; Clarys 647

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et al., 1997; Fluhr et al., 2005; Rothenborg et al., 1977). High temperatures and humidity also promote sweating, which can increase penetration of the irritant chemical in the skin. Furthermore, sweat acts as an irritant if on the skin for prolonged periods (Slodownik et al., 2008). Experimentally, cold and dry weather increases the irritant potential of sodium lauryl sulfate (SLS) and sodium hydroxide on skin exposed to the environment (Agner and Serup, 1989; John and Uter, 2005; Loffler and Happle, 2003). Low humidity alone acts as an irritant, as evidenced by the common wintertime occurrence of asteatotic dermatitis (Robert, 2003). Occlusion possibly increases irritation by increasing percutaneous absorption of the irritant chemical and decreasing passive transepidermal water loss (TEWL) at the site (Van der Valk and Maibach, 1989). One clinical example is the prolonged, repeated use of occlusive gloves, which may promote abnormal barrier function and the development of cumulative irritant dermatitis (Ramsing and Agner, 1996). Lastly, mechanical friction and pressure can damage the skin barrier, resulting in greater irritation (McMullen and Gawkrodger, 2006). Farage (2006) developed a technique to assess the influence of friction on overall irritation potential by applying various products, including fabrics, menstrual pads, and lotion-coated samples, to the popliteal fossa using an elastic knee band. Normal movements in this location create friction at the test site, inducing mechanical irritation. In this study, the addition of mechanical irritation increased overall irritation of the products tested.

23.2.3  Endogenous Patient Characteristics Endogenous factors such as age, anatomical site, preexisting dermatologic conditions, and genetic background may influence an individual’s predisposition to irritant dermatitis. There is a decreased susceptibility of irritation with increasing age, with children younger that 8 years being most susceptible to skin irritation (Robinson, 1999, 2002; Welfriend and Maibach, 2008). The etiology of this difference is unknown, but changes in structural lipids, cell composition, and renewal have been hypothesized (Welfriend and Maibach, 2008). In addition, the anatomical site of irritant exposure may also influence the likelihood of reaction. In a study by Cua et al. (1990), measurements of TEWL were taken after exposure to SLS on various body sites. The most vulnerable site was the thigh, followed by the upper arm, abdomen, upper back, dorsal and volar forearm, postauricular skin, and ankle. The palm was the least affected. Another study employing the technique of corneosurfametry demonstrated the following regional differences: the forehead, back, neck, and dorsal foot were more easily irritated than the dorsal hand and volar forearm (Henry et al., 1997). The reason for these differences is unknown; however, several studies have demonstrated variable skin permeability

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based on location (Cronin and Stoughton, 1962; Feldmann and Maibach, 1967; Wester and Maibach, 1985). It is reasonable to assume this variation in permeability is responsible for differences in susceptibility to irritation; however, a direct correlation between permeability of the skin, skin thickness, and likelihood of irritation has not been demonstrated (Robinson, 2002). Preexisting dermatologic conditions may increase irritation susceptibility. Atopic dermatitis has frequently been cited as a predisposing condition for irritant dermatitis. Basketter et al. (1996) demonstrated increased irritant response to sodium dodecyl sulfate (SDS) in atopics over control subjects. Furthermore, up to 45% of adults who had atopic eczema in childhood develop hand eczema, which in most cases is irritant contact dermatitis (Thestrup-Pedersen, 2000). A constitutionally compromised skin barrier may be responsible for these findings (Thestrup-Pedersen, 2000). Fillagrin is a protein that plays an important role in stratum corneum architecture and function, and when abnormal or decreased it can result in compromise of skin barrier function. Not surprisingly, de Jongh et al. (2008) described an association with loss of function of the fillagrin gene and increased risk of chronic irritant dermatitis. Some atopic patients have defects in fillagrin, thus explaining the reported susceptibility to irritation. Moreover, another condition with a fillagrin mutation, ichthyosis vulgaris, may increase irritant susceptibility (Welfriend and Maibach, 2008). Despite these studies, some refute the association between atopy and irritation (Basketter et al., 1998; Santucci et al., 2003). Further studies should be undertaken with a variety of potential irritants and possibly separating atopic groups by fillagrin mutation classification. Other endogenous factors such as gender and race may influence irritant susceptibility, but multiple studies have had mixed results. No consistent difference has been noted between men and women or between various racial groups (Robinson, 2001, 2002; Welfriend and Maibach, 2008).

23.3  Identifying suspected irritants Although in theory any substance can cause irritation, some substances pose a greater hazard to human skin than others. To produce, transport, and use various chemicals safely, it is important to identify the irritant potential of chemicals. The majority of regulatory authorities rely on data from animal testing to assess irritant potential. Several methods have been described to identify and characterize possible irritants and quantify irritant potential; most commonly used is the Draize rabbit skin test. This and other animal tests are covered in Chapter 28. One obvious criticism of animal assays is the inherent difference between animal and human skin. Some chemicals cause more irritation in rabbits than humans and vice versa (Nixon et al.,

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1975; Phillips et al., 1972). Furthermore, animal studies such as Draize testing do not simulate “real-world” conditions such as cumulative exposure, high temperature, and compromised skin barrier – all factors that can change the irritant potential of a chemical. In addition, in recent years there has been increased concern for animal suffering. This has resulted in a ban on some animal testing for products in Europe (Brekelmans, 2007). Several human-based models have been described to address these issues, and they may serve as future approaches to best obtain this vital data on irritation.

23.3.1  Irritant Patch Testing In 1977, the National Academy of Sciences reported a human single application patch test procedure in which occlusive patches are applied on the intrascapular region of the back or dorsal forearms (National Academy of Sciences, 1977). The duration of exposure is variable depending on the desired study design. Irritation is graded on a visual scale similar to the Draize scale, and it is often compared to response of a reference material as a control. In a variant test, known as the 4-hour patch test (Robinson et al., 2001), 0.2 ml of the test liquid or 0.2 g of solid test material is applied in a Hill Top Chamber containing a Webril pad. Patches are then applied to the upper outer arm of approximately 30 subjects for initially short durations such as 15 or 30 min. Patches are left on for up to 4 h until a positive result occurs. The sites are then graded for degree of visual irritation (e.g., erythema and edema) immediately and 24, 48, and 72 h after patch removal. Irritation is graded as 0, , , or . A grade of  or higher is considered positive. The degree of irritation due to the test chemical is compared to irritation caused by a positive control, 20% SDS. The proportion of individuals with a positive irritant reaction to the test chemical after exposure up to 4 h is measured. If this proportion is significantly less than the proportion of positive irritant reactions to SDS, then the chemical is not classified as an irritant. If there is a similar or higher proportion of irritation, then the chemical is considered an irritant. It is essential to note that these irritant patch testing techniques are used for experimental purposes only. Known irritants should not be patch tested in the clinical setting to confirm irritant dermatitis.

23.3.2  Cumulative Irritation Testing Cumulative exposures to irritants are common; thus, assays to assess the long-term irritation potential of chemicals are important. Several cumulative irritation assays have been described. As described by Lanman et al. (1968) and Phillips et al. (1972), a 1-inch square of Webril is saturated with liquid or 0.5 g of a viscous substance and applied to a

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pad. This pad is then applied to the upper back with occlusive tape. Every 24 h the tape is removed and the test site is examined. This process is repeated for 21 days. Variants of these tests use different durations of exposure such as described by Robinson (2001) and Wigger-Alberti et al. (1997).

23.3.3  Chamber Scarification Test This test is designed to test the irritant potential of products on damaged skin (Frosch and Kligman, 1976). Artificial skin wounding is achieved by superficially scratching six to eight 1-mm sites on the volar forearm. Care is taken not to cause bleeding. Test material in a quantity of 0.1 g is placed in Durhing chambers (for solids) or fitted saturated pads (for liquids). These are placed on the scratched test sites once daily for 3 days. Once pads are removed, irritation is measured via a visual score of erythema and edema. This score can be compared to the product’s effect on intact skin by calculating a “scarification index.” This is the score of the scarified sites divided by the score of the intact sites. It is not known if this test is a reliable model for predicting response of routine use on damaged skin.

23.3.4  Immersion Tests These tests were devised to evaluate real-world use of potential irritants that are often used in “wet work” situations. The term wet work refers to prolonged exposure to liquids, occlusive gloves, hand washing, and water-soluble irritants (Diepgen and Coenraads, 1999). In one model described by Kooyman and Snyder, solutions of soap up to 3% were prepared in basins at 105°F. Subjects immersed one hand and forearm in each basin for 10–15 min, three times a day for 5 days or until irritation occurred (Levin and Maibach, 2008). Evidence of irritation on a visual scale was evaluated.

23.3.5  Bioengineering Approaches Bioengineering tools may allow a more sophisticated and precise assessment of irritation than a simple visual scale. These techniques include assessing for transepidermal water loss, laser Doppler flowmetry, laser Doppler perfusion imaging, capacitance, and chromametric analysis (Bashir and Maibach, 2001). Transepidermal water loss is the water that escapes from the skin surface as a normal process. This measurement has often been used as a method of indirectly assessing barrier function. It is thought that the higher the TEWL, the less effective the barrier. There is some concern about the accuracy and validity of TEWL as a marker for barrier function (Chilcott et al., 2002). Additional studies are needed to assess this

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issue. Laser Doppler flowmetry is a noninvasive technique that utilizes laser light to measure blood flow in the skin (Berardesca et al., 2002). In laser Doppler perfusion imaging, the investigator scans a skin area with a lowenergy laser to measure cutaneous perfusion. The results are projected on a computer screen (Aspres et al., 2003). Electrical skin capacitance is an indirect measurement of the stratum corneum hydration. Other bioengineering techniques exist and are discussed in more detail in other texts, such as Marzulli and Maibach’s Dermatotoxicology (Levin and Maibach, 2008). One other technique that deserves mention is corneosurfametry, which assesses the damage to corneocytes by surfactants. Cyanoacrylate skin surface strippings are harvested from various sites and then exposed to surfactant for 2 h. Subsequently, the stripping is stained with basic fuchsin and toluidine blue and measured by colorimetry. Reflectance colorimetry is used to measure color intensity. The intensity increases with increased irritation. This technique appears to have lower interindividual variability than patch testing and is reproducible (Piérard et al., 1994, 1995).

23.3.6  New Approaches Because of intraspecies disparity, concern for animal welfare, and a desire for more accurate testing methods, the U.S. National Research Council Committee on Toxicity Testing and Assessment of Environmental Agents has issued a statement that new approaches to toxicology testing should be developed. The hope is to move away from animal tests to more testing employing molecular technology, computer modeling, and computational biology (National Research Council, 2007). Some predictive modeling based on chemical structure is already in use, known as quantitative structure–activity relationship modeling (QSAR). QSAR predicts irritation based on the known structure of the molecule. One such system is known as DEREK, which is discussed more in Chapter 28.

23.4  Clinical patterns of irritant contact dermatitis The clinical morphology of ICD is heterogeneous. Acutely, contact with irritants may produce erythematous and edematous patches or plaques with possible vesiculation in the location of exposure. If exposure to strong acids and alkalis has occurred, there may also be cutaneous ulceration due to the corrosive properties of these chemicals. The risk of ulceration increases with larger volumes of exposure, preceding trauma, and concurrent friction. With chronic exposure to less intense irritants, the patient may exhibit dry, fissured, and lichenified plaques. Less common morphologies of ICD include granulomas, folliculitis,

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nonimmunologic urticaria (wheals), miliaria, and changes in pigmentation (Chew and Maibach, 2006). Chew and Maibach classified the more salient types of irritant contact dermatitis based on clinical presentation, chronology, and clinical course. A brief summary of these types follows.

23.4.1  Acute Irritant Dermatitis (Primary Irritation) This is the classic skin irritant response often seen as a result of exposure to a strong irritant such as a potent acid or alkaline solution. The skin responds immediately with erythema, edema, and possibly vesiculation, ulceration, and local necrosis (Slodownik et al., 2008; Welfriend and Maibach, 2008). Once the irritant is removed, the skin begins to heal. This is known as the decrescendo phenomenon. This is unlike allergic contact dermatitis, in which the inflammation increases after removal of the agent (crescendo phenomenon) before it eventually fades (Chew and Maibach, 2006).

23.4.2  Delayed, Acute Irritant Dermatitis This type of dermatitis is clinically similar to acute irritant dermatitis; however, it is characterized by a delayed onset of irritation after exposure. Generally, inflammation occurs 8–24 h after exposure and thus may mimic an allergic contact dermatitis (Chew and Maibach, 2006; Welfriend and Maibach, 2008). In these cases, thorough history, physical exam, and diagnostic patch testing can help distinguish between the two entities.

23.4.3  Irritant Reaction This type of reaction often arises in the first months of intense exposure to the irritant. Clinically, this condition is characterized by a monomorphous response. Individuals may display redness, scaling, vesicles, pustules, or erosions but not more than one characteristic. A classic example is occupations in which workers are exposed to wet work, such as beauty salon employees. Many of these workers have extensive water and soap exposures on a daily basis (i.e., during the shampooing process). Chronic exposures to the elements such as wind and cold can also result in an irritant reaction, such as dry lips on skiers. Often, this type of reaction heals without treatment (Chew and Maibach, 2006).

23.4.4  Subjective/Sensory Irritation In subjective/sensory irritation, there are symptoms of irritation such as stinging and burning without evidence of inflammation or damage clinically and histologically. The mechanism of this irritation is not known, although this

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must be differentiated from subclinical contact urticaria. One common chemical known to cause this phenomenon is lactic acid (Chew and Maibach, 2006; Welfriend and Maibach, 2008).

(Simon et al., 2001). This is also known as eczema craquele (Chew and Maibach, 2006).

23.4.5  Suberythematous Irritation

This dermatitis is characterized by erythema, scaling, and fissuring as a result of chronic low-grade friction. This should not be confused with skin thickening (i.e., callus formation or lichenification) that more commonly occurs due to chronic friction. Generally, these lesions improve with friction avoidance (Freeman, 2000).

This entity is characterized by early epidermal damage without visible inflammation. Clinically, the patient experiences burning, itching, and stinging (Chew and Maibach, 2006).

23.4.6  Cumulative Irritant Dermatitis This classification is likely one of the most prevalent morphologies seen by occupational physicians and dermatologists. Multiple exposures to weak irritants may eventually result in cutaneous irritation without an obvious acute dermatitis. The hallmark clinical features are erythema, dryness, scaliness, and eventual hyperkeratosis and skin fissures. Unlike acute irritant dermatitis, this dermatitis may arise over weeks to years. Patch testing helps separate this from its mimic, allergic contact dermatitis(Chew and Maibach, 2006).

23.4.7  Traumatic Irritant Dermatitis This peculiar type of irritant dermatitis occurs after acute trauma to the skin (Mathias, 1988). It may mimic cumulative irritant dermatitis or may present as nummular (coinshaped) erythematous patches and plaques (Welfriend and Maibach, 2008). A dyshidrotic eruption on the hands has also been described (Beukers and van der Valk, 2006). These lesions are often notably resistant to treatment, and they may take months to years to resolve (Mathias, 1988). The etiology is unknown, but in some cases it may be attributed to soaps and other topicals used to treat the wound (Slodownik et al., 2008).

23.4.8  Acneiform and Pustular Irritant Dermatitis Pustular irritant dermatitis often mimics the presentation of folliculitis or acne. Follicular-based erythematous papules and pustules occur in the area of irritant exposure. Classically, this response is seen after exposure to metals, oils, tar, asphalt, halogens, formaldehyde, aromatic hydrocarbons, chlorinated napththalene, and polyhalogenated naphthalene (Andersen and Petri, 1982; Chew and Maibach, 2006; Welfriend and Maibach, 2008).

23.4.9  Exsiccation Eczematoid Dry icthyosiform scaling, particularly in elderly individuals, is seen as a result of low humidity and cold temperatures

23.4.10  Friction Dermatitis

23.4.11  Airborne Irritant Dermatitis Airborne irritant dermatitis is similar to other types of acute and cumulative irritant dermatitis but has a characteristic clinical presentation. Because the irritant is in the air, the dermatitis generally involves uncovered skin, such as face, eyelids, arms, and V of the neck. This distribution is important to recognize in agricultural workers because aerosolized pesticides/fumigants may be cutaneous irritants (LaChapelle, 2006).

23.5  Diagnosis of irritant contact dermatitis The diagnosis of an acute corrosive-type irritant reaction is often self-evident. Generally, workers will recall exposure to a strong irritant chemical with immediate severe skin erythema, edema, vesiculation, or ulceration. Thus, the offending chemical is easily identified. Cases of cumulative irritant dermatitis are far more common in a clinical setting and more difficult to identify. These cases can be confused with allergic contact dermatitis, endogenous eczema, psoriasis, and other papulosquamous diseases. For these cases, thoughtful and complete history taking by the physician is crucial. One should inquire about the type of occupation and hobbies; daily activities within that occupation; and exposure to water, detergents, and other chemicals. Questions should be asked regarding exposure to physical irritants such as friction, low humidity, and heat. Attention to frequency and timing of these exposures is also important. Dermatitis that improves with time off from work suggests an occupational source. The distribution of lesions can be useful in identifying the source of the irritation. For example, an airborne irritant dermatitis such as a fumigant may present as a symmetric dermatitis on exposed areas of the body, especially eyelids and face (Dooms-Goossens et al., 1986), whereas harvesters may develop dermatitis on forearms and hands when in contact with irritant pesticide residues on foliage [Centers for Disease Control and Prevention (CDC), 1986]. Close physical inspection to exclude other common skin conditions, such as psoriasis, atopic dermatitis,

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and seborrheic dermatitis, is recommended. Table 23.1 presents the differential diagnosis of contact dermatitis and physical findings that are helpful in discriminating between these conditions. If an irritant or allergic contact dermatitis is suspected and one cannot distinguish between the two, patch testing is recommended. Patch testing is discussed in more detail in Chapter 25. Often, the diagnosis of ICD is one of exclusion – the clinical appearance suggestive of a contact dermatitis and negative patch tests for potentially relevant allergens favor a diagnosis of ICD.

23.6  Treatment of irritant contact dermatitis Identification and avoidance of the irritant is crucial in the treatment of irritant contact dermatitis. Use of protective devices such as gloves to prevent irritant exposure is an important preventive and treatment measure (Kwon et al., 2006). Corrosive reactions are best treated with irrigation (except in burning fragments of sodium, potassium, and lithium), specific antidotes for some chemicals, and local

wound/burn care. Having detailed knowledge of the product to which a person has been exposed can aid in the management of corrosive reactions (Bruze et al., 2006). For more cumulative ICD, emollients are often helpful when used frequently to improve skin barrier function. However, it appears that emollients may not be broadly effective in improving all patients with irritant dermatitis (Yokota and Maibach, 2006). Symptomatically, oral antihistamines may be helpful in preventing pruritus. For actively inflamed nonulcerated lesions, short courses of topical corticosteroids may be tried. Long-term treatment should be avoided to decrease the risk of skin atrophy and barrier dysfunction (Kao et al., 2003). The utility of topical corticosteroids for irritant dermatitis has been questioned. In one study of an acute experimental surfactant-induced irritant dermatitis, investigators found no improvement of lesions with use of low- and high-potency topical steroids (Levin et al., 2001). However, it is one author’s experience (L. M.) that short bursts of topical steroids are often worth an initial attempt to improve symptoms until avoidance strategies may be implemented. In addition, a few small studies suggest that topical calcineurin

Table 23.1  Differential Diagnosis of Contact Dermatitis Endogenous skin disease

Clinical features that may aid in diagnosis

References

Psoriasis

Well-demarcated scaly erythematous plaques on extensor surfaces, elbows, knees, scalp, and umbilicus Nail pitting Onycholysis and yellow nail discoloration Orange-yellow discoloration under nail (oil spots) Inflammatory arthritis and arthralgias

Griffiths and Barker (2007) Schon and Boehncke (2005)

Atopic dermatitis

Pruritic flexural erythematous papules, patches, and plaques Often located in popliteal fossae, antecubital fossa, and face Personal history of seasonal allergies or asthma Onset in early childhood Palmar hyperlinearity Icthyosis Nipple dermatitis Periorbital dermatitis with Dennie–Morgan line

Boguniewicz (2000)

Seborrheic dermatitis

Greasy or powdery scale in scalp, posterior auricular region, eyebrows, and nasolabial folds

Johnson and Nunley (2000)

Dermatophytosis

Scaly plaques that may be in an annular configuration Increased scale or pustules at leading edge Erythematous scaly plaques in moccasin distribution on feet Two plantar surfaces involved and one palm involved (two foot, one hand presentation) Yellowing and thickening of nails White crumbling nail surface Hyphal elements seen on potassium hydroxide preparation Culture positive for dermatophyte Hyphae seen with PAS stain on biopsy

Zuber and Baddam (2001)

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inhibitors may improve signs and symptoms of ICD (Engel et al., 2008; Mensing et al., 2008). For recalcitrant lesions, phototherapy or systemic immunosuppression with cyclosporine or azathioprine may be helpful (Cohen and Heidary, 2004).

23.7  ICD in agricultural workers 23.7.1  Acute Agricultural Irritant Dermatitis Agricultural work involves a complex and variable set of potential skin irritants. Depending on the season and climate and crop, these may include dust, heat, agricultural chemicals, and irritant chemicals derived from plants. For agricultural pest control workers, most of the irritant materials encountered may be synthetic pesticides and the hazard most obvious following accidental direct exposure. Between 1982 and 2006, the handler database included 1990 cases of possible, probable, and definite cases of skin reactions to single pesticide active ingredients in California pesticide handlers. (These included 653 skin reactions possibly related to pesticide application work, usually without direct exposure.) Although inert as well as active ingredients in pesticide formulations may cause skin irritation, for strongly irritant active ingredients the reported cases correlate with the results of experimental testing in animals and skin reactivity predicted from the DEREK model (see Chapter 28). SICRET (Skin Irritation Corrosion Rules Estimation Tool) is another model that helps predict the irritant potential of a chemical (Walker et al., 2005).

23.7.2  Acute Irritation from Pesticides (Fumigants and Insecticides) A large majority of the 149 reported definite and probable cases of irritant dermatitis associated with fumigants occurred in workers handling halogenated compounds and compounds releasing the irritant compound methyl isothiocyanate (MITC) (Table 23.2). There were 191 cases of probable and definite dermatitis associated with insecticide applications in California between 1982 and 2006. Data on two of the most frequently reported insecticides in this case series are given in Table 23.3. Propargite, despite institution of water-soluble bags during the 1970s, accounted for 47.6% of the cases. Its irritant properties are suggested by predictive modeling and also by results of animal tests. For the organophosphate chlorpyrifos, there were considerably fewer cases and less clear-cut results from Draize testing. It does not contain any of the reactive elements identified by the DEREK model. Additional data on the irritant properties of insecticides are discussed in Chapter 28.

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23.7.3  Cumulative Irritant Dermatitis from Pesticides As mentioned previously, because multiple exposures are required to manifest cumulative ICD, recognition of the offending agent may be challenging. Single case reports regarding potential pesticide-induced ICD have several potential explanations that require some effort to differentiate. Some cases might be reactions unique to a single crew member; some might be sentinel cases signifying the occurrence of an otherwise unrecognized outbreak; and some cases might prove to be nonwork-related skin conditions not expected, in most circumstances, to occur in coworkers. In investigating potential ICD cases and outbreaks, it is usually obvious whether the problem is work related. The central questions are whether the reported episode was related to pesticides and which material, among those reported, was principally responsible. A few examples of cumulative irritant dermatitis outbreaks have been described among fieldworkers in contact with pesticide residues on foliage. Repeated exposures to residues resulted in dermatitis. The persistence of pesticide residues depends on the amount of pesticide used, the halflife of the pesticide dissipation, the type of crop, and the type of work performed. Variation in residue dissipation is illustrated by data on propargite. Residue studies (Maddy et al., 1977, 1979) performed in a coastal area of California showed 1- or 2-day dissipation half-lives. Residue studies in California’s Central Valley typically showed half-lives of 5–7 days (Reeve et al., 1991), but some fields showed half-lives up to 11 days. Dissipation half-lives as long as 30 days have been measured in the context of outbreak investigations (O’Malley, 1998; O’Malley et al., 1989; Smith, 1991). To prevent exposure to an irritant residue, regulators must determine “safe-entry waiting periods” or the re-entry interval for the pesticide. The length of the required re-entry interval depends on both the irritant capacity of the individual compound but also on the level of initial residue deposition and the postapplication rate of residue dissipation. In 1988, an outbreak of dermatitis occurred among a crew of nectarine harvesters in Tulare County (Figure 23.1). Examination of a comparison group of workers who had dermatitis allowed an analysis of work history and residue history. This showed a strong correlation between cumulative exposure to propargite and the occurrence of dermatitis (Figure 23.2). A review of the work history for the group with dermatitis showed a peak exposure to propargite residues of 0.2 pg/cm2. This value was used as an estimated no-observed-effect residue level for purposes of determining a safe re-entry interval. The re-entry interval for harvesting tree fruit was lengthened to 21 days following the episode (O’Malley et al., 1990). In 1995, an outbreak of dermatitis on the chest, neck, arms, and face occurred among workers performing hand

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Table 23.2  Fumigant Irritants Probable definite cases in fumigant handlers, 1982–2006

No. of cases

Animal testing

Reactive structures identifiable based on DEREK and SICRET models

Halogenated fumigants

92

Methyl bromide

70

Reported as corrosive in public domain literature

1,3-Dichloropropene and D–D mixture

16

Multiple products (60.3% 1,3 dichloropropene and 3.2% chloropicrin; 81.2% 1,3-dichloropropene,16.5% chloropicrin) corrosive in the Draize assay; a 92% liquid formulation without chloropicrin caused minimal irritation

Ethylene dibromide

4

Reported as severe irritant in public domain literature

Methyl iodide

1

99.7% liquid technical material severe irritant in the Draize assay

MITC-releasing fumigants

51

Metam sodium

49

Five liquid products (32.7–43.8% metam sodium) corrosive in the Draize test; unexpected minimal irritation reported for three similar products (32.7–42.2% metam sodium)

Dazomet

2

24% liquid corrosive in Draize test; 2 20% liquid products and a 98.5% solid reported to cause minimal irritation

Other fumigants

7

Sulfuryl fluoride

5

Unable to perform Draize test because of physical properties of gas

Cases in applicators possibly related to rapid evaporation of liquid sulfuryl fluoride, akin to liquid nitrogen burns

Ethylene oxide

1

Unable to perform Draize test because of physical properties of gas

DEREK: IUNIQ ���������������������������� – Electrophile, generally no prolonged skin contact because of physical properties

DEREK IX: Reactive aliphatic halides, olefins SICRET: Halogenated alkanes and alkenes listed as potential skin irritants

DEREK: IUNIQ – Isocyanate strong nucleophile SICRET: Thiocyanates, cyanates not listed

SICRET: Epoxides considered potentially irritant or corrosive Aluminum phosphide

1

Unable to perform Draize test because of physical properties of phosphine gas

labor activities on a table grape ranch in northern Fresno County, California. Of 202 fieldworkers, 65 (32.2%) sought treatment for the dermatitis. The large number of workers involved suggested contact with an irritant rather than allergen. Several different pesticide residues were detected in these fields: sulfur, propargite, iprodione, myclobutanil, and dichloronitroaniline. Propargite was suspect because its direct irritant capacity was higher than that

Releases phosphine, weak base, electrophile relative to alkyl grignards (IUNIQ), but generally no prolonged skin contact because of physical properties

of other pesticides used on the field and it was found in higher than no-observed-effect levels. Some workers had a rapid onset of their dermatitis in relation to exposure, whereas others appeared to require a few days of cumulative exposure before the dermatitis developed. After further evaluation of propargite residue levels, it was presumed that slow dissipation of propargite was the cause of this outbreak (O’Malley, 1998).

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Table 23.3  Insecticide Irritants Probable definite cases in insecticide handlers, 1982–2006

No. of cases

Animal testing

Reactive structures identifiable based on DEREK and SICRET models

Propargite

91

Technical material (listed as 90.6% AI) and the liquid formulation used on cotton (73.86% AI) caused corrosion in the Draize assay. The emulsifiable concentrate (69.62% AI) caused severe irritation. Two powdered formulations (28.99% AI and 32% AI) nevertheless were reported to cause minimal irritation in the Draize assay

DEREK: Terminal propargyl group containing unsaturated olefin (triple bond) SICRET: Alpha-alkynes likely to cause skin irritation

Chlorpyrifos

12

Technical chlorpyrifos (97.6% AI) caused transient irritation; some EC formulations with 40% AI caused moderate to severe irritation; dilute formulations with 1% AI all caused minimal irritation

No identified reactive moieties

Another example of cumulative dermatitis related to pesticides occurred in 1986, when a dermatitis outbreak occurred among orange pickers in California. Based on physician reporting, 58% of 198 workers developed a dermatitis involving most commonly the neck and the chest. Workers often leaned into foliage to pick the oranges, thus explaining the distribution of the dermatitis and suggesting pesticide residues as a possible cause. The miticide OMITE-CR was the suspected cause of the dermatitis because no cases of dermatitis among workers occurred prior to the application of OMITE-CR. Furthermore, there was a positive correlation between OMITE-CR residue hours (estimated leaf residue multiplied by hours of exposure) and the development of dermatitis (CDC, 1986). Figure 23.1  Variable onset of cumulative irritation in a crew of nectarine harvesters, June 1988 (reprinted with permission from Hanley and Belfus, State of the Art Reviews in Occupational Medicine, 1997).

Figure 23.2  Increasing cumulative incidence of dermatitis with progressive exposure to propargite (reprinted from O’Malley, 1997, with permission from Hanley and Belfus).

23.7.4  Plants as Agricultural Irritants Plants may also cause irritant dermatitis in the agricultural worker. Mechanistically, irritant contact dermatitis may arise from chemical and/or mechanical injury from the plant. Physical irritants include thorns, sharp leaves, spines, and irritant “hairs,” and these may produce a variety of dermatologic lesion morphologies. For example, contact with cactus spines may result in a pruritic papular eruption in the location of contact. However, some spines and thorns lodged in the skin may result in persistent foreign body granulomas that resemble other granulomatous diseases such as granuloma annulare. Moreover, spines may be a conduit for inoculation of infectious organisms into the skin (Lovell, 1993). Chemical injury may occur from a variety of plant compounds. One frequent offending irritant, calcium oxalate, is found in many plants, including agave, dumb cane, daffodils, and other “bulb flowers” such as hyacinth

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(Bruynzeel et al., 1993; Julian and Bowers, 1997; Lovell, 1993). Workers exposed to agave harvested to produce tequila may develop cutaneous lesions commonly on the forearms, neck, and abdomen, known as “mal de agaveros” (agave worker’s sickness) (Salinas et al., 2001). Similarly, those exposed to calcium oxalate and alkaloids in daffodils may develop an eczematous or granulomatous dermatitis

that affects the wrist and the fingers known as “daffodil pickers’ rash” (Julian and Bowers, 1997). Pineapples contain bromelin, a proteolytic enzyme, as well as calcium oxalate in their juice, both of which may cause irritant dermatitis (Bruynzeel et al., 1993; Fisher and Mitchell, 2001). Table 23.4 lists some other plant families that may cause irritant dermatitis. Phytophotodermatitis is a particular type

Table 23.4  Some Plants Known to Cause Irritant Dermatitis Plant

Characteristics

Contact reactions

Anthemis cotula (mayweed, dog fennel, camomile) Member of Compositae family

A species of weed introduced to the United States from Europe. It can be found sporadically throughout the United States. It is found on roadsides, orchards, pastures, and agricultural lands. Irritant found in the plant’s volatile oil

Rowe (1934) applied dry samples of the plant to the normal skin of 21 adults for 24 hours. Sixteen subjects showed definite areas of irritant dermatitis. Several workers pulling weeds manually in a field of winter sugar beets in California developed vesicular or blistering dermatitis due to contact with A. cotula (O’Malley et al., 2001). This was attributed to an irritant reaction May also cause allergic contact dermatitis (Menz and Winkelmann, 1987) and contact urticaria (Shelmire, 1940)

Cocklebur (Xanthium strumarium, Xanthium pennsylvanicum) Member of Compositae family

Common weed in the United States

Mechanical irritant; spines on fruit (Lovell, 1993). O’Malley et al. (2001) reported suspected irritant dermatitis in workers pulling weeds. The most prevalent weed was the cocklebur Cocklebur extract is known to cause irritant reactions (Mitchell et al., 1980) May also cause an allergic contact dermatitis (Menz and Winkelmann, 1987)

Velvet leaf (Abutilon theophrasti)

Common weed in the United States/Canada, particularly in the Midwest

O’Malley et al. (2001) reported cases of irritant dermatitis of hands and forearms in workers pulling weeds and encountering velvet leaf

Borage

Mass cultivated for oil

Physical irritant by penetration of skin by coarse “hairs” results in a papular irritant eruption (Lovell, 1993)

Euphorbia family (spurge)

Some in this family – E. pepulus (petty spurge), E. helioscopia (sun spurge), and E. lathyrus (caper spurge) – are weeds Contain irritant milky latex

Contact with latex may produce erythema and blistering on skin. May also cause irritant keratoconjunctivitis (Calnan, 1975; Lovell, 1993; Webster, 1986)

Ranunculaceae family (buttercup family)

The irritant protoanemonin is formed after injury to the plant. It is only found in freshly injured plants Can be found in field buttercups

May cause severe vesiculation mimicking a phototoxic reaction (Lovell, 1993; Oztas et al., 2006)

Brassicaciae family (radish, horseradish, and mustard)

Irritant is thiocyanate

Can cause irritation (Cleenwerke and Martin, 1995). May also cause allergic contact dermatitis (Mitchell and Jordan, 1974)

Peppers

Irritant is capsaicin

“Hunan hand” Workers who pick or otherwise handle hot peppers may be subject to burning, irritation, and erythema, without vesiculation (Williams et al., 1995)

Chapter | 23  Irritant Dermatitis

of chemical-induced irritant contact dermatitis that occurs after exposure to the offending plant and solar radiation. This entity is discussed in Chapter 24. Lastly, chemical toxins within the plant can be injected via physical means, as seen with members of the plant family Urticaceae (stinging nettle). These plants have small spines that contain histamine and produce wheals (urticaria) upon contact with the skin (Lovell, 1993). When evaluating a patient with suspected plant dermatitis, it should be noted that some plants may have the ability to cause irritant as well as allergic (immune-mediated) dermatitis.

Conclusion It would be ideal if agricultural workers knew the irritating potential of each chemical product encountered in their work. Unfortunately, most of the animal-based registration data remain unavailable to workers, and if available, few would be prepared to interpret the data. Few human studies exist, and new studies are currently inhibited by the U.S. Environmental Protection Agency’s ethics system. Lastly, epidemiologic data that are so helpful for many contact allergens remain scarce for agricultural irritants. The authors welcome any initiative that will help the worker. The techniques and assays are efficient; however, a regulatory system that promotes developing and registering relevant data in this arena is lacking.

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Chapter | 23  Irritant Dermatitis

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