**2. Epidemiology**

Recent studies suggest that allergic contact dermatitis remains more common in adults than in children (Kwangsukstith & Maibach, 1995) affecting approximately 10% of the adult population (Marks, 1997) and accounting for just over 4% of all dermatologic consultations (Mendenhall et al., 1973). Though the condition is increasingly being recognized in the pediatric population, most epidemiologic studies have been completed retrospectively and investigate the occurrence of positive patch tests in symptomatic patients only. Generally, standard series are used. For example, the European Standard Series is commonly utilized in European studies. Yet, some variation in tested allergens exists and studies often evaluate specific pediatric populations, making it difficult to compare studies. The exact rates of incidence and prevalence remain less clear, potentially due to only recent interest in studying this condition in children. Furthermore, only a minority of studies report on the relevance of positive patch test results.

#### **2.1 Prevalence in infants and young children**

A common explanation for low rates of allergic contact dermatitis in children was their lack of a robust immune system. Early studies seemed to support this theory. For instance, Straus

Contact Dermatitis in Children 129

416 6-15 yo 40.9% Not addressed Nickel sulfate (15.9%)

670 6mo–12 yo 42% Not addressed Thimerosal (23%)

relevant, Fragrance & Rubber Chemicals relevant

1094 7 mo-12 yo 52.1% Not addressed Neomycin 20% gel (13.2%)

depending on age and allergen

500 <16 yo 27% 61% Nickel (33%)

391 0-18 yo 51.2% Not addressed Nickel (28.3%)

2340 < 21 yo 45.4% 27 – 83%

**Relevance Most Frequent Allergens** 

Thimerosal (11.3%) Benzoyl Peroxide (8.9%) Fragrance Mix (8.2%) Cobalt sulfate (7.5%)

Nickel (7.76%) Kathon CG (5.67%) Fragrance Mix (5.52%) Neomycin sulfate (3.58%)

Nickel (23.7%) Fragrance (9.8%)

Not addressed Thimerosal (18.2%, 14.3%)

(13.1%, 7.1%)

Wool wax alcohols (8.6%) Potassium dichromate (8%) Balsam of peru (4.7%)

Benzoyl Peroxide (16.5%, 8.0%) Phenylmercuric Acetate

Gentamicin sulfate (12.5%, 2.9%)

Ammoniated Mercury (8.9%)

Para-phenylenediamine (8%)

Nickel (10.3%, 16.7%)

Nickel 5% (10.9%) Wool Alcohols (10.1%) Thimerosal (10.1%)

Fragrance Mix (18%)

Balsam of peru (8%)

Cobalt Chloride (17.9%) Thimerosal (15.3%) Neomycin (8.0%)

Gold Sodium Thiosulfate (7.7%)

Cobalt (11%)

Nickel (40%) Thimerosal (15%) Colophony (9%) Lanolin (8%) Cobalt (8%)

**Patch Test** 

337 1-15 yo 66% Nickel not

52.6% 49.7%

6-12 yo 13-18 yo

**Study No. Age Positive** 

Brasch & Geier (1997)

Manzini et al. (1998)

Roul et al. (1999)

Heine et al. (2004)

Seidenari et al.

Clayton et al. (2006)

Goon et al. (2006)

Zug et al. (2008)

(2005)

285 217

found negative patch test results after evaluating 119 infants with poison ivy dermatitis (Straus, 1931). However, in 1960, Uhr and colleagues were able to demonstrate allergic responses to dinitrofluorobenzene in a small series of infants. Of note, premature infants were less likely to have positive reactions compared to infants aged 2-12 months (Uhr et al., 1960). Uhr's study supported that infants could indeed be sensitized, but the younger the infant, the weaker the response. After his work, it would be another twenty years before contact allergy was investigated in children on a broader scale.

The literature now provides numerous studies describing the presence of allergic contact sensitization in very young children. In 1995, Motolese and colleagues reported that up to 60% of symptomatic infants aged 3-24 months elicit positive patch tests (Motolese et al., 1995). Three years later, Manzini and colleagues patch tested a total of 670 children aged 6 months – 12 years old, with suspected disease, and detected positive results in 42% of patients. Furthermore, at least two studies have shown that the highest rate of sensitization occurs in children less than 3 years old (Manzini et al., 1998; Roul et al., 1999). Interestingly, many children (77%) in one such study had concurrent atopic dermatitis, which introduces a much contended issue regarding the relationship between atopic dermatitis and contact dermatitis and whether atopic skin predisposes children to contact allergy (Manzini et al., 1997). In 2003, Wohrl tested 2770 children and adults with suspected disease, finding positive patch tests in 49% of study participants. The highest rate of sensitization was found in children less than 10 years old at a rate of 62% (Wohrl et al., 2003).

There are also many reports that describe the occurrence of allergic contact dermatitis in very young patients, even as young as 1 month of age (Fisher, 1994; Seidenari et al., 1992). This may be related to the fact that infants and children are increasingly exposed to more antigens. This is illustrated by the report of a 5-month-old infant with contact allergy to colophony found in electrocardiogram electrodes used to monitor for sudden infant death syndrome (Oestmann et al., 2007). Or, consider the series of three young children, aged 9 months to 2 years, who developed a diaper dermatitis as a result of disposable diaper dye (Alberta et al., 2005). Such new exposures may, in part, explain the increase in diagnosis of pediatric allergic contact dermatitis.

#### **2.2 Prevalence in symptomatic versus asymptomatic populations**

Studies of various sizes attempt to assess the prevalence of pediatric allergic contact dermatitis. However, because of their retrospective nature, most of these studies are limited in that they evaluate symptomatic patients only (Table 1). In the majority of studies, subjects were either suspected of having allergic contact dermatitis or suffered from additional dermatoses including atopic dermatitis and psoriasis. Prevalence in these groups of patients ranges from 14.5% to 83% (Balato et al., 1989; Zug et al., 2008). Though most often, the prevalence is within the range of 40-60%. The most common allergens detected in this setting are nickel, fragrances, cobalt, thimerosal and neomycin. Unfortunately, many of these studies do not indicate the percentage of positive tests that were considered clinically relevant, and this value may be as high as 92% (Rademaker et al., 1989). The responsibility remains with the clinician to determine whether a dermatitis is likely attributable to a contact allergen in the setting of positive test results.

found negative patch test results after evaluating 119 infants with poison ivy dermatitis (Straus, 1931). However, in 1960, Uhr and colleagues were able to demonstrate allergic responses to dinitrofluorobenzene in a small series of infants. Of note, premature infants were less likely to have positive reactions compared to infants aged 2-12 months (Uhr et al., 1960). Uhr's study supported that infants could indeed be sensitized, but the younger the infant, the weaker the response. After his work, it would be another twenty years before

The literature now provides numerous studies describing the presence of allergic contact sensitization in very young children. In 1995, Motolese and colleagues reported that up to 60% of symptomatic infants aged 3-24 months elicit positive patch tests (Motolese et al., 1995). Three years later, Manzini and colleagues patch tested a total of 670 children aged 6 months – 12 years old, with suspected disease, and detected positive results in 42% of patients. Furthermore, at least two studies have shown that the highest rate of sensitization occurs in children less than 3 years old (Manzini et al., 1998; Roul et al., 1999). Interestingly, many children (77%) in one such study had concurrent atopic dermatitis, which introduces a much contended issue regarding the relationship between atopic dermatitis and contact dermatitis and whether atopic skin predisposes children to contact allergy (Manzini et al., 1997). In 2003, Wohrl tested 2770 children and adults with suspected disease, finding positive patch tests in 49% of study participants. The highest rate of sensitization was found in children less than 10 years old at a rate of 62% (Wohrl et

There are also many reports that describe the occurrence of allergic contact dermatitis in very young patients, even as young as 1 month of age (Fisher, 1994; Seidenari et al., 1992). This may be related to the fact that infants and children are increasingly exposed to more antigens. This is illustrated by the report of a 5-month-old infant with contact allergy to colophony found in electrocardiogram electrodes used to monitor for sudden infant death syndrome (Oestmann et al., 2007). Or, consider the series of three young children, aged 9 months to 2 years, who developed a diaper dermatitis as a result of disposable diaper dye (Alberta et al., 2005). Such new exposures may, in part, explain the increase in diagnosis of

Studies of various sizes attempt to assess the prevalence of pediatric allergic contact dermatitis. However, because of their retrospective nature, most of these studies are limited in that they evaluate symptomatic patients only (Table 1). In the majority of studies, subjects were either suspected of having allergic contact dermatitis or suffered from additional dermatoses including atopic dermatitis and psoriasis. Prevalence in these groups of patients ranges from 14.5% to 83% (Balato et al., 1989; Zug et al., 2008). Though most often, the prevalence is within the range of 40-60%. The most common allergens detected in this setting are nickel, fragrances, cobalt, thimerosal and neomycin. Unfortunately, many of these studies do not indicate the percentage of positive tests that were considered clinically relevant, and this value may be as high as 92% (Rademaker et al., 1989). The responsibility remains with the clinician to determine whether a dermatitis is likely attributable to a

**2.2 Prevalence in symptomatic versus asymptomatic populations** 

contact allergen in the setting of positive test results.

contact allergy was investigated in children on a broader scale.

al., 2003).

pediatric allergic contact dermatitis.


Contact Dermatitis in Children 131

patch test results in 13.3% of 562 schoolchildren. Using this data, investigators suggested that allergic contact dermatitis may be more common than previously suspected (Barros et al., 1991). Weston showed that of 314 healthy children, 20% had at least one positive patch test (Weston et al., 1986). Finally, Bruckner has reported the highest overall prevalence at 24.5% when evaluating 85 healthy patients who presented for routine well-child care visits. In this study, subjects were 6 months to 5 years old, further supporting that young children are not uncommonly sensitized (Bruckner et al., 2000). The most common allergens detected in unselected populations are nickel, thimerosal, neomycin, cobalt, fragrances and Kathon

Studies are not consistent with regard to prevalence of pediatric allergic contact dermatitis varying between the sexes. Many suggest that there is no difference (Barros et al., 1991; Bruckner et al., 2000; Weston et al., 1986). Other researchers report that the disease is more prevalent in females (Clayton et al., 2006). Mortz and colleagues reported positive patch tests in 19.4% of unaffected females and 10.35% of unaffected males (Mortz et al., 2002). Giordano-Labadie et al. remark that males and females have a similar overall prevalence of allergic contact dermatitis but that females more commonly show sensitization to nickel in comparison to males (Giordano-Labadie et al., 1999). This sentiment is echoed in other studies, and Beattie reports that up to 82% of positive patch tests to nickel in symptomatic patients occur in females (Beattie et al., 2007; Brasch & Geier, 1997). One reason for this difference between the sexes is likely allergen exposure. Jewelry that contains nickel is more commonly worn by female rather than male children (Modjtahedi et al., 2004). In fact, Jensen and colleagues demonstrated that young Danish girls who had their ears pierced prior to a Danish law that regulated nickel exposure were 3.3 times more likely to display sensitization to nickel compared to females without pierced ears. After regulation, patients were only 1.2 times more likely to be sensitized to

When evaluating a patient with suspected allergic contact dermatitis, it is important to consider cultural context. Allergen exposure and age of exposure may vary depending on cultural practices. For example, in a study of 70 symptomatic Indian children, the secondmost common allergen was potassium dichromate. Investigators attributed this high prevalence to the frequent use of leather footwear without socks. Another cited cause is the trend towards urbanization in India, which has resulted in exposure to potassium dichromate found in cement and metals. The same article suggests that children may be sensitized to nickel early on due to jewelry that is worn at a young age for religious reasons

Obtaining the appropriate level of suspicion for an allergic contact dermatitis does not depend on a clinician's complete understanding of a patient's lifestyle or culture, but rather, the clinician's ability to ask the proper questions. Social factors such as job-related exposures are still relevant in the pediatric adolescent population. In one German study, higher rates of sensitization were discovered in adolescents aged 13-18 who worked as hair dressers or in the healthcare field (Heine et al., 2004). Another consideration is the child's hobbies and

CG (Table 2).

**2.3 Prevalence in females versus males** 

nickel if their ears were pierced (Jensen et al., 2002).

**2.4 Prevalence as related to culture** 

(Sarma & Ghosh, 2010).


Table 1. Prevalence of Allergic Contact Dermatitis in Selected (Symptomatic) Populations (Studies with > 250 patients)

Fewer studies have been completed that investigate the prevalence of allergic contact dermatitis in the general, asymptomatic population (Table 2). One study reported positive


Table 2. Prevalence of Allergic Contact Dermatitis in Unselected (Asymptomatic) Populations

Not addressed Nickel (16.3%)

Cobalt Chloride (8.6%) Fragrance Mix (7.3%) Potassium Dichromate (4.3%)

Thimerosal (1.7%) Nickel (21.56%) Thimerosal (18.03%) Cobalt Chloride (12.9%) Potassium Dichromate (9.4%) Fragrance Mix (4.7%)

**Most Frequent Allergens** 

Nickel (7.6%) Dichromate (7.6%) Thimerosal (3.5%) Balsam of peru (1.5%) Formaldehyde (1.5%)

Thimerosal PTBPF resin Fragrance Mix

Cobalt (5.7%) Kathon CG (5.2%) Lanolin (1.7%) Neomycin (1.4%)

Thimerosal (9.4%) Kathon CG (2.4%) Neomycin (1.2%) Cobalt (1.2%)

*p-tert*-butylphenol (1.2%)

Fragrance Mix (1.8%) Colophony (1%) Cobalt Chloride (1%) Thimerosal (1%)

< 16 yo 47.8%

60%

Table 1. Prevalence of Allergic Contact Dermatitis in Selected (Symptomatic) Populations

**Test** 

562 Schoolchildren 13.3% Neomycin

424 7-12 yo 23.3% Nickel (14.9%)

85 6 mo–5 yo 24.5% Nickel (12.9%)

1146 13 yo 15.2% Nickel (8.6%)

Table 2. Prevalence of Allergic Contact Dermatitis in Unselected (Asymptomatic)

314 <18 yo 20% Neomycin (8.1%)

Fewer studies have been completed that investigate the prevalence of allergic contact dermatitis in the general, asymptomatic population (Table 2). One study reported positive

Milingou et al.

Weston et al. (1986)

Barros et al. (1991)

Dotterud & Falk (1995)

Bruckner et al. (2000)

Mortz et al. (2002)

Populations

232 (1980-93)

255 (1994-07)

**Study No. Age Positive Patch** 

(Studies with > 250 patients)

(2010)

patch test results in 13.3% of 562 schoolchildren. Using this data, investigators suggested that allergic contact dermatitis may be more common than previously suspected (Barros et al., 1991). Weston showed that of 314 healthy children, 20% had at least one positive patch test (Weston et al., 1986). Finally, Bruckner has reported the highest overall prevalence at 24.5% when evaluating 85 healthy patients who presented for routine well-child care visits. In this study, subjects were 6 months to 5 years old, further supporting that young children are not uncommonly sensitized (Bruckner et al., 2000). The most common allergens detected in unselected populations are nickel, thimerosal, neomycin, cobalt, fragrances and Kathon CG (Table 2).

#### **2.3 Prevalence in females versus males**

Studies are not consistent with regard to prevalence of pediatric allergic contact dermatitis varying between the sexes. Many suggest that there is no difference (Barros et al., 1991; Bruckner et al., 2000; Weston et al., 1986). Other researchers report that the disease is more prevalent in females (Clayton et al., 2006). Mortz and colleagues reported positive patch tests in 19.4% of unaffected females and 10.35% of unaffected males (Mortz et al., 2002). Giordano-Labadie et al. remark that males and females have a similar overall prevalence of allergic contact dermatitis but that females more commonly show sensitization to nickel in comparison to males (Giordano-Labadie et al., 1999). This sentiment is echoed in other studies, and Beattie reports that up to 82% of positive patch tests to nickel in symptomatic patients occur in females (Beattie et al., 2007; Brasch & Geier, 1997). One reason for this difference between the sexes is likely allergen exposure. Jewelry that contains nickel is more commonly worn by female rather than male children (Modjtahedi et al., 2004). In fact, Jensen and colleagues demonstrated that young Danish girls who had their ears pierced prior to a Danish law that regulated nickel exposure were 3.3 times more likely to display sensitization to nickel compared to females without pierced ears. After regulation, patients were only 1.2 times more likely to be sensitized to nickel if their ears were pierced (Jensen et al., 2002).

### **2.4 Prevalence as related to culture**

When evaluating a patient with suspected allergic contact dermatitis, it is important to consider cultural context. Allergen exposure and age of exposure may vary depending on cultural practices. For example, in a study of 70 symptomatic Indian children, the secondmost common allergen was potassium dichromate. Investigators attributed this high prevalence to the frequent use of leather footwear without socks. Another cited cause is the trend towards urbanization in India, which has resulted in exposure to potassium dichromate found in cement and metals. The same article suggests that children may be sensitized to nickel early on due to jewelry that is worn at a young age for religious reasons (Sarma & Ghosh, 2010).

Obtaining the appropriate level of suspicion for an allergic contact dermatitis does not depend on a clinician's complete understanding of a patient's lifestyle or culture, but rather, the clinician's ability to ask the proper questions. Social factors such as job-related exposures are still relevant in the pediatric adolescent population. In one German study, higher rates of sensitization were discovered in adolescents aged 13-18 who worked as hair dressers or in the healthcare field (Heine et al., 2004). Another consideration is the child's hobbies and

Contact Dermatitis in Children 133

and enzymes. An elevated pH results when bacterial ureases split urea in the urine to release ammonia, and this predisposes infant skin to dermatitis. Friction may also play a role, though this is likely a predisposing or exacerbating rather than dominant factor. Fecal enzymes including proteases and lipases have direct irritant action on the skin and their effects are increased by an alkaline environment. Finally, microorganisms, particularly candida, but also staphylococcus, peptostreptococcus, bacteroides, herpes virus, and dermatophytes can worsen irritant diaper dermatitis (Prasad et al., 2003; Wolf et al., 2000). Other causes of dermatitis in the diaper region include seborrheic dermatitis, psoriasis, atopic dermatitis, congenital syphilis, acrodermatitis enteropathica (zinc deficiency), scabies, child abuse and miliaria. Finally, dermatitis of the diaper area may also be allergic contact dermatitis. Allergens to consider in this setting include sorbitansesquioleate, fragrances (mix I and balsam of peru), disperse dye, cyclohexlthiopthalimide, mercaptobenzothiazole, iodopropylcarbamate, bronopol and *p*-*tertiary*-butyl-phenol-

Prevention and management of irritant diaper dermatitis revolves around keeping the occluded skin dry and limiting the amount of time that the skin is exposed to urine and feces. Removing diapers is one of the oldest and most effective measures in preventing and treating this condition. Frequent diaper changes are most helpful if done immediately after urination and bowel movements (every hour in neonates and every 3-4 hours in infants). Some experts recommend washing the area with mild soap, while others suggest that rinsing the area in lukewarm water is sufficient. New technology has allowed diapers to be much more absorbent and effective in keeping skin dry and with a normal pH. In terms of topical treatments, low potency steroids can be effective for inflamed skin. However, even if these are applied for a short time to acute disease, a waterproof emollient should be placed over them as a barrier to protect the skin. Ideally, emollients should be reapplied after every diaper change. Emollients effective in this setting are usually made of a large quantity of fine powder, such as zinc oxide, suspended in a greasy vehicle. For those eruptions which are superinfected with candida, topical antifungals may also be required (Wolf et al., 2000).

An entity that is distinct from diaper dermatitis is perianal dermatitis. Fecal components including fecal lipase and bile acids can cause degradation of the skin barrier perianally, leading to an erythematous irritant dermatitis limited to perianal skin (Ruselet-van Embden et al., 2004). There are several less common diagnoses that are thought to be related to irritant perianal dermatitis and some believe that these exist on a spectrum of one disease. These entities include granuloma gluteale infantum, pseudoverrucous papules and Jacquet's

Granuloma gluteale infantum is thought to be multifactorial and related to occlusion, powder, topical halogenated steroids, *Candida* infection, urine and feces. It classically appears as oval, red-purple granulomatous nodules at sites of occlusion (Robson et al., 2006). This condition will improve with removal of inciting agents (Al-Faraidy & Al-Natour, 2010). Pseudoverrucous papules and nodules is a less common condition and was first reported in association with urostomy sites but may also be seen in children in a perianal distribution. Lesions are shiny, smooth, red, moist, flat-topped and round and may be

formaldehyde (Smith & Jacob, 2009).

**3.1.2 Perianal dermatitis** 

erosive dermatitis.

extracurricular activities. Consider the case of an 11-year-old female cellist with a three year history of an eruption on the right first, second and third digits. She patch tested positive to para-phenylenediamine, which the manufacturer of her bow verified was present in the bow stain (O'Hagan and Bingham, 2001).
