**7. The common allergens in children**

Nickel is always the most common allergen in children, followed by cobalt, mercurials (thimerosal and metallic mercury), rubber chemicals (thiuram mix, carba mix, mercapto mix and mercaptobenzothiazole, PPD) and fragrance mix. The most frequent sources are costume jewellery (nickel in earrings), medications, footwear, cosmetics and plants (Rademaker & Forsyth, 1989; Barros et al., 1991; Stables et al., 1996; Militello et al., 2006; Goossens & Morren, 2006).

#### **7.1 Nickel**

Nickel is by far the most common allergen in patients of all ages, including children. Nickel was the top allergen in children in 14 of the 17 studies of patch testing summarized by Mortz and Andersen (Mortz & Andersen, 1999). Even in younger children nickel allergy is not uncommon (Jøhnke et al., 2004). Published rates of nickel sensitization in children range between 10% and 24% (Wöhrl et al., 2003; Heine et al., 2004; Lewis et al., 2004; Seidenari et al., 2005; Vozmediano & Hita, 2005; Clayton et al., 2006; Militello et al., 2006; Goossens & Morren, 2006; Milingou et al., 2010). Ear piercing along with atopy is regarded as a major risk factor for the development of nickel sensitization, especially in girls (Militello et al., 2006; Goossens & Morren, 2006). Nickel sensitization sources in children are numerous: jewellery (earrings), jean studs, belt buckles, zippers or buttons (Clayton et al., 2006). Sensitization to nickel is not necessarily followed by ACD, but infants with a reproducible positive reaction to nickel sulfate could represent a group at risk of developing clinically manifest nickel dermatitis later in life (Magnusson & Moller, 1979). In agreement with earlier studies in older children and adults (Dotterund & Falk, 1995; Mortz et al., 2001; Uter et al., 2004; Jøhnke et al., 2004), a female predominance of positive reactions to nickel sulfate was found in infants (girls 13.1% and boys 4.0%). Despite a marked decrease in nickel allergy and nickel dermatitis in young women after nickel regulation came into force (Schnuch & Uter, 2003; Thyssen et al., 2009; 2011), the prevalence of nickel allergy remains very high, and seems to have stabilized at a high level (Schnuch et al., 2011). However, women who were ear-pierced after regulatory intervention in Denmark had a significantly lower prevalence of nickel allergy and dermatitis than women who were ear-pierced before (Thyssen et al., 2009; 2011). It is important to emphasize that nickel allergy remains very prevalent in some European countries. The proportion of positive patch test reactions to nickel sulfate has remained stable at 10%-20% among young female German dermatitis patients (< 18 years) since the beginning of the new millennium (Schnuch et al., 2011). The 2005-2006 clinical patch test data registered in 10 European countries and reported to the European Surveillance System on Contact Allergies revealed high prevalence of nickel allergy in western, southern, central and north-eastern Europe, being, respectively, 20.8%, 24.5%, 19.7% and 22.4% (Uter et al., 2009). There may be several explanations for this finding (Thyssen et al., 2011), but it is generally accepted that excessive nickel release from consumer items is one of the most important single factors (Schnuch & Uter, 2003).

#### **7.2 Thiomersal and metallic mercury**

Sensitization to thiomersal (an organic mercurial compound) is frequently observed in infants and children. The widespread use as a preservative in a variety of compounds, including vaccine and antitoxin preparations, ophthalmic drops and contact lens solutions,

Nickel is always the most common allergen in children, followed by cobalt, mercurials (thimerosal and metallic mercury), rubber chemicals (thiuram mix, carba mix, mercapto mix and mercaptobenzothiazole, PPD) and fragrance mix. The most frequent sources are costume jewellery (nickel in earrings), medications, footwear, cosmetics and plants (Rademaker & Forsyth, 1989; Barros et al., 1991; Stables et al., 1996; Militello et al., 2006;

Nickel is by far the most common allergen in patients of all ages, including children. Nickel was the top allergen in children in 14 of the 17 studies of patch testing summarized by Mortz and Andersen (Mortz & Andersen, 1999). Even in younger children nickel allergy is not uncommon (Jøhnke et al., 2004). Published rates of nickel sensitization in children range between 10% and 24% (Wöhrl et al., 2003; Heine et al., 2004; Lewis et al., 2004; Seidenari et al., 2005; Vozmediano & Hita, 2005; Clayton et al., 2006; Militello et al., 2006; Goossens & Morren, 2006; Milingou et al., 2010). Ear piercing along with atopy is regarded as a major risk factor for the development of nickel sensitization, especially in girls (Militello et al., 2006; Goossens & Morren, 2006). Nickel sensitization sources in children are numerous: jewellery (earrings), jean studs, belt buckles, zippers or buttons (Clayton et al., 2006). Sensitization to nickel is not necessarily followed by ACD, but infants with a reproducible positive reaction to nickel sulfate could represent a group at risk of developing clinically manifest nickel dermatitis later in life (Magnusson & Moller, 1979). In agreement with earlier studies in older children and adults (Dotterund & Falk, 1995; Mortz et al., 2001; Uter et al., 2004; Jøhnke et al., 2004), a female predominance of positive reactions to nickel sulfate was found in infants (girls 13.1% and boys 4.0%). Despite a marked decrease in nickel allergy and nickel dermatitis in young women after nickel regulation came into force (Schnuch & Uter, 2003; Thyssen et al., 2009; 2011), the prevalence of nickel allergy remains very high, and seems to have stabilized at a high level (Schnuch et al., 2011). However, women who were ear-pierced after regulatory intervention in Denmark had a significantly lower prevalence of nickel allergy and dermatitis than women who were ear-pierced before (Thyssen et al., 2009; 2011). It is important to emphasize that nickel allergy remains very prevalent in some European countries. The proportion of positive patch test reactions to nickel sulfate has remained stable at 10%-20% among young female German dermatitis patients (< 18 years) since the beginning of the new millennium (Schnuch et al., 2011). The 2005-2006 clinical patch test data registered in 10 European countries and reported to the European Surveillance System on Contact Allergies revealed high prevalence of nickel allergy in western, southern, central and north-eastern Europe, being, respectively, 20.8%, 24.5%, 19.7% and 22.4% (Uter et al., 2009). There may be several explanations for this finding (Thyssen et al., 2011), but it is generally accepted that excessive nickel release from

consumer items is one of the most important single factors (Schnuch & Uter, 2003).

Sensitization to thiomersal (an organic mercurial compound) is frequently observed in infants and children. The widespread use as a preservative in a variety of compounds, including vaccine and antitoxin preparations, ophthalmic drops and contact lens solutions,

**7.2 Thiomersal and metallic mercury** 

**7. The common allergens in children** 

Goossens & Morren, 2006).

**7.1 Nickel** 

may explain the high rate of positive patch test reactions (Katsarou et al., 1996; Militello et al., 2006; Goossens & Morren, 2006; Milingou et al., 2010). Low clinical relevance along with sensitization rates is probably related to its presence in vaccines (Novák et al., 1986; Osawa et al., 1991; Lee et al., 2009). Recently, percentages of sensitization in children have increased from 2.3% (Barros et al., 1991) to 10% (Möller, 1997) due to iatrogenic sources (antiseptics, topical medications, thermometers and vaccines) and footwear (Novák et al., 1986; Osawa et al., 1991; Militello et al., 2006; Goossens & Morren, 2006; Lee et al., 2009).

#### **7.3 Topical antibiotics**

Neomycin, bacitracin and gentamycin are topical antibiotics with high rates of allergic contact sensitization in children (Heine et al., 2004; Seidenari et al., 2005; Jacob et al. 2008). Neomycin sulfate has remained second place in the most common culprits in ACD for close to 25 years (Spann et al., 2003; Lee et al., 2009). It is a topical antibiotic with multiple clinical indications, including use for superficial wounds or burns and can be found in many overthe-counter products in the US or Europe. It is also formulated in combinations with other antibiotics, antifungals or corticosteroids (Lee et al., 2009). Menezes de Pádua et al. (Menezes de Pádua et al., 2005) found 2.5% positive reactions to neomycin, while in 1.1%, ACD was additionally diagnosed.

#### **7.4 Cosmetics allergens**

The market for cosmetic products specially formulated for children is expanding and usage of cosmetics being seen to increase in children. Consequently, one can expect cosmetics to become more important causes of ACD in children (Goossens et al., 2002). At least one cosmetic or cosmetic ingredient gave a positive reaction in 30% of the children investigated (Goossens et al., 2002; Goossens & Morren, 2006). Almost every ingredient may be responsible for cosmetic dermatitis (Goossens et al., 2002; Goossens & Morren, 2006). Fisher (Fisher, 1995) further stated that children often become allergic to cosmetics used by the mother or the person taking care of them. The localizations often involved seem to be the forehead and the cheeks, with perfume, lipstick, hairspray or nail lacquer as the responsible agents (Fisher 1995; Goossens et al., 2002; Buckley et al., 2003; Goossens & Morren, 2006). However, children often use cosmetic products themselves and this may not always be revealed immediately (Goossens et al., 2002; Goossens & Morren, 2006).

#### **7.4.1 Fragrances**

The use of cosmetic products in babies and young children can cause perfume allergy (Fisher 1995; Goossens et al., 2002; Buckley et al., 2003; Goossens & Morren, 2006). A large numbers of perfumed products are marketed especially for children (Rastogi et al., 1999; Kohl et al., 2002). Fragrance allergy is increasingly common and even young children are exposed (Rastogi et al., 1999). Exposure is usually due to perfumes or to other aromatic topical products such as moisturizers or deodorants. Typical sites of involvement include face, neck and axillae, in addition to full systemic contact dermatitis (Tomar et al., 2005; Garg et al., 2009; Lee et al., 2009). Fragrance allergy is usually detected by patch testing to three mixtures of scented compounds: Fragrance Mix I, Fragrance Mix II and *Myroxylon pereirae* tree extract *(*Balsam of Peru). The rate of sensitization to fragrance appears to increase with age (Buckley et al., 2003; Lee et al., 2009). The *Myroxylon pereirae* tree extract

Allergic Contact Dermatitis in Children 119

(scaring and sensitization) can be permanent. PPD is a very potent contact sensitizer included in the European baseline series for patch testing. PPD is also contained in permanent hair dyes and related compounds (Lee et al., 2009). The content of PPD in semipermanent tattoo ink has been reported to vary between 0.4 and 15.7%, far exceeding the limit permissible for hair dyes (<6%) (Brancaccio et al., 2002; Avnstorp et al., 2002; Sosted et al., 2006; Lee et al., 2009). The long duration of skin contact, the high concentrations of sensitizing materials (diaminobenzenes or diaminotoluenes) and the lack of a neutralizing agent increase the risk of skin sensitization. Because of the worldwide vogue for skin painting, a greater number of patients sensitized to PPD and diaminobenzenes or diaminotoluenes can be expected (Le Coz et al., 2000; Onder et al., 2001; Neri et al., 2002; Jovanovic & Slavkovic-Jovanovic, 2009). The unusually severe reactions to PPD in young 12 to 15 year old adolescents have occurred after dyeing their hair having been previously sensitized to PPD in black henna tattoo at a younger age. In some cases, the children developed severe angioedema-like reactions necessitating admission to hospital and intensive care treatment (Sosted et al., 2006). Severe allergic reactions were reported in 1.4% of women and 1.3% of men after dying their hair (Sosted et al., 2005). Sensitization to PPD is potential for lifelong sensitization and systemic contact dermatitis can be evoked with exposure to cross-reactors such as benzocaine, diuretics (hydrochlorothiazide) and sulfonamide medications (Sosted et al., 2006; Lee et al., 2009). Notably, 25% of those allergic to PPD can also be reactive to semi-permanent dyes found in synthetic clothing. PPD base, being a part of the European baseline series, is regarded as a screening agent for contact allergy to *para* and azo compounds in hair dyes, but not for textile and leather dye allergy

Rubber additives are typically present in many rubber products (e.g. elastic waistbands, socks, swimwear, shoes, toys, cosmetic applicators and adhesives) and could be main allergens from them. Thiurams, mercapto chemicals and less commonly carbamates are the responsible allergens in rubber allergy in children; thiourea derivates in neoprene may also be the cause of dermatitis (Goossens & Morren, 2006; Lee et al., 2009). Roul et al. (Roul et al., 1998) reported a particular type of diaper dermatitis called ʻLucky Luke' dermatitis. The rubber parts used for a new anti-leaking system in these diapers provoked the reaction. Mercaptobenzothiazole and thiuram derivates are also present in certain types of glues (Roul et al., 1996; Cockayne et al., 1998). Type I allergic reactions may also occur (contact urticaria syndrome), sometimes associated with a type IV reaction. It is typical for children who had undergone multiple surgical operations (for example children suffering from spina bifida). Moreover, these children are particularly susceptible to natural rubber latex proteins

*Toxicodendron* (Poison Ivy) dermatitis can occur at any age, although infants are apparently not as easily sensitized as adults. After the age of 3, children become highly susceptible and by 12 years of age nearly all have become sensitized to poison ivy (Kligman 1974). Plants belonging to the Rhus family are the ones most often involved in ACD among children living in the United States (Goossens & Morren, 2006). The oleoresin (urushiol) of the sap of the *Toxicodendron* plants contains catechols, which are very strong sensitizing chemicals. The

**7.7 Toxicodendron dermatitis (Poison Ivy, Poison Oak, Poison Sumac)** 

(Koopmans & Bruynzeel, 2003).

in this regard (Goossens & Morren, 2006).

**7.6 Rubber compounds** 

(Balsam of Peru) is used as a screen for fragrance allergy, due to its wide usage and natural cross-reactivity with other frequently encountered fragrances (Tomar et al., 2005; Garg et al., 2009; Lee et al., 2009). These allergens (or chemically similar ones) are also used in soft drinks and flavouring such as cinnamon, cloves, curry and vanilla. Although dietary intervention remains controversial, there is evidence that it may help those with significant disease that is not resolving with more typical fragrance avoidance (Magnusson & Wilkinson, 1975; Salam & Fowler Jr., 2001; Tomar et al., 2005). Although guidelines for the maximum concentration of preservatives and fragrances in cosmetics have been provided (Goossens et al., 2004), it has been demonstrated that toys may contain much higher concentrations of fragrance (Rastogi et al., 1999). No extra safety requirements for toys intended for children are required (White, 2000).
