**2.2 Prevalence of contact allergy in an unselected population**

In the general pediatric population, the prevalence of ACD may be underestimated, which can be attributed to the low frequency of patch tests performed on children (compared to adults) and by the fact that in clinical practice, manifestations of ACD are often attributed to morphological look-alikes, such as atopic dermatitis (AD) or irritant dermatitis (Militello et al., 2006). The results from patch testing in children and adolescents in the general population revealed that 13-24.5% had positive patch tests to standard allergens. The prevalence of past or current relevant reactions was found to be 7%, with a higher risk seen in females (Dotterund & Falk, 1995; Bruckner et al., 2000; Mortz et al., 2001; Jacob et al., 2008). Few population-based studies have examined contact sensitization in asymptomatic healthy children. Barros et al. (Barros et al., 1991) patch tested 562 Portuguese school children (5-14 years old) with 25 allergens. Positive reactions were seen in 13.3%. Multiple sensitivities were seen in 2% of the children. Dotterud et Falk (Dotterund & Falk, 1995) patch tested 424 Norwegian school children (7-12 years old) with 20 allergens. One or more positive reactions were seen in 23.3%. Multiple sensitivities were seen in 8.5% of the children. Weston et al. (Weston et al., 1986) patch tested 314 otherwise healthy American children and adolescents under the age of 18 years with 20 allergens. He found at least one positive patch reaction in 20%. In Bruckner et al. (Bruckner et al., 2000) population-based study of 95 healthy asymptomatic children aged 6 to 67.5 months was showed that the prevalence of sensitization was 24.5% (≥ 1 positive reaction to an allergen). In our group of Czech schoolchildren, positive reactions were detected in 30.7%. Multiple sensitivities were seen in 8.7%. The relevance of reactions was 61% (Machovcová, 2006).

#### **2.3 Prevalence related to sex**

Sex may also play a role on the different prevalence in children. While some authors (Weston et al., 1986; Barros et al., 1991; Stables et al., 1996) detected similar prevalence in both boys and girls, other (Dotterund & Falk, 1995; Wantke et al., 1996; Goossens & Morren, 2006) reported a higher prevalence in girls. This is especially the case for nickel (Brasch & Geier, 1997; Wöhrl et al., 2003) and after the age of 12 (Rademaker & Forsyth, 1989; Rudzki & Rebandel, 1996; Katsarou et al., 1996; Goossens & Morren, 2006). Brasch & Geier (Brasch & Geier, 1997) found significantly more girls than boys reacted to nickel (25.0% vs. 4.5%). Hormonal factors may be a contributory factor here (Brasch & Geier, 1997; Goossens & Morren, 2006).

#### **2.4 Prevalence related to age**

112 Contact Dermatitis

Patch test studies in series of selected children with suspected ACD have reported frequencies of positive reactions varying from 14% to 71% of patients. Of these, about 56- 93% was of current relevance (Weston & Weston, 1984; Pevny et al., 1984b; Fisher, 1994a; Rudzki & Rebandel, 1996; Stables et al., 1996; Manzini et al., 1998; Bruckner et al., 2000; Machovcová et al., 2001; Wöhrl et al., 2003; Heine et al., 2004; Lewis et al., 2004; Jøhnke et al., 2004; Vozmediano & Hita, 2005; Wahlberg & Lindberg, 2006; Goossens & Morren, 2006; Jacob et al., 2008). Among the children with a positive patch test 3.2% to 54.4% had multiple

In the general pediatric population, the prevalence of ACD may be underestimated, which can be attributed to the low frequency of patch tests performed on children (compared to adults) and by the fact that in clinical practice, manifestations of ACD are often attributed to morphological look-alikes, such as atopic dermatitis (AD) or irritant dermatitis (Militello et al., 2006). The results from patch testing in children and adolescents in the general population revealed that 13-24.5% had positive patch tests to standard allergens. The prevalence of past or current relevant reactions was found to be 7%, with a higher risk seen in females (Dotterund & Falk, 1995; Bruckner et al., 2000; Mortz et al., 2001; Jacob et al., 2008). Few population-based studies have examined contact sensitization in asymptomatic healthy children. Barros et al. (Barros et al., 1991) patch tested 562 Portuguese school children (5-14 years old) with 25 allergens. Positive reactions were seen in 13.3%. Multiple sensitivities were seen in 2% of the children. Dotterud et Falk (Dotterund & Falk, 1995) patch tested 424 Norwegian school children (7-12 years old) with 20 allergens. One or more positive reactions were seen in 23.3%. Multiple sensitivities were seen in 8.5% of the children. Weston et al. (Weston et al., 1986) patch tested 314 otherwise healthy American children and adolescents under the age of 18 years with 20 allergens. He found at least one positive patch reaction in 20%. In Bruckner et al. (Bruckner et al., 2000) population-based study of 95 healthy asymptomatic children aged 6 to 67.5 months was showed that the prevalence of sensitization was 24.5% (≥ 1 positive reaction to an allergen). In our group of Czech schoolchildren, positive reactions were detected in 30.7%. Multiple sensitivities were

**2.1 Prevalence of contact allergy in a selected population** 

**2.2 Prevalence of contact allergy in an unselected population** 

seen in 8.7%. The relevance of reactions was 61% (Machovcová, 2006).

Sex may also play a role on the different prevalence in children. While some authors (Weston et al., 1986; Barros et al., 1991; Stables et al., 1996) detected similar prevalence in both boys and girls, other (Dotterund & Falk, 1995; Wantke et al., 1996; Goossens & Morren, 2006) reported a higher prevalence in girls. This is especially the case for nickel (Brasch & Geier, 1997; Wöhrl et al., 2003) and after the age of 12 (Rademaker & Forsyth, 1989; Rudzki & Rebandel, 1996; Katsarou et al., 1996; Goossens & Morren, 2006). Brasch & Geier (Brasch & Geier, 1997) found significantly more girls than boys reacted to nickel (25.0% vs. 4.5%). Hormonal factors may be a contributory factor here (Brasch & Geier, 1997; Goossens &

**2.3 Prevalence related to sex** 

Morren, 2006).

contact allergies (Mortz & Andersen, 1999).

Sensitization to contact allergens begins in infancy and continues to be more common in toddlers and young children (Seidenari et al., 1992; Giordano-Labadie et al., 1999; Vozmediano & Hita, 2005; Militello et al., 2006; Clayton et al., 2006; Garg et al., 2009; De Waard-van der Spek & Oranje, 2009), the age of sensitization can occur very early. In study of Bruckner et al. (Bruckner et al., 2000), 45% of patients with positive reactions were younger than 18 months. Even neonates may be sensitized (Fisher, 1994a; Bruckner et al., 2000). Fisher (Fisher, 1994a) reported a 1-week-old infant with strongly positive patch test reaction to epoxy resin, manifesting as band-like dermatitis above the wrist because of vinyl band that was made of an epoxy resin. A 7-month-old child has revealed ACD from nickel– plated snaps on the back (Fisher, 1994a). Motolese et al. (Motolese et al., 1995) studied 53 infants (3 months to 2 years) with dermatitis and patch tested them. Positive patch tests were seen in 32 (60%) and 20 out of the 32 sensitized infants had clinically relevant contact allergies. Hjorth (Hjorth, 1981) thought that patch test reactions in infants were predominantly irritant reactions, especially when testing with nickel sulfate. In a study of Jøhnke et al. (Jøhnke et al., 2004) it was confirmed that increasing numbers of infants positively patch tested to nickel sulfate but most reactions were transient and probably irritant or non-specific nature. Experimental CA to plants of the *Rhus* genus has also been induced in infants, showing that sensitization is possible (Epstein, 1961). Manzini et al. (Manzini et al., 1998) reported that the highest sensitization rate was noted in children aged up to 3 years. It is still unclear why some sensitivities, for example nickel, are prevalent in the young but less common in the old. Possible explanations include changing trends in exposure to nickel (i.e. increased use of imitation jewellery and different frequencies of ear piercing in different generations) or loss of clinical allergy because of avoidance, induction of tolerance, or inability to mount an immune response despite continuing exposure (Garg et al., 2009). Recall studies showed persistence of CA to nickel after 8 years in 79% and 60% to other allergens (Nielsen et al., 2001; Garg et al., 2009). Others found that lanolin, only 41% had persistent allergy at 5 years (Carmichael et al., 1991). The increase in fragrance allergy with age may be because of cumulative exposure to toiletries and increased use of medicaments (Garg et al., 2009).

#### **3. Contact sensitisation and atopic dermatitis**

The relationship between CA and atopy is frequently discussed and still not settled (Rystedt, 1985; Schnuch et al., 2006). Several studies have been performed in children with suspected CA or suffering from AD or chronic dermatitis. Patch testing in symptomatic children with dermatitis has revealed positive reactions in 15% to 52% of subjects (Rademaker & Forsyth, 1989; De Groot, 1990; Katsarou et al., 1996; Rudzki & Rebandel, 1996; Stables et al., 1996; Shah et al., 1997; Vozmediano & Hita, 2005; Goossens & Morren, 2006; Wahlberg & Lindgerg, 2006). Some authors have indicated that ACD is less prevalent in patients with AD (Uhr, 1960; Rystedt, 1985; De Groot, 1990; Katsarou et al., 1996; Stables et al., 1996; Brasch & Geier, 1997). Several authors were unable to detect differences between atopic and nonatopic subjects in this regard (Marghescu, 1985; Pambor et al., 1991; Goossens et al., 1995; Akhavan & Cohen, 2003; Beattie et al., 2007; Milingou et al., 2010). Against this others have even found a greater prevalence of ACD in patients with AD (De la Cuadra et al., 1990; Lammintausta et al., 1992; Dotterund & Falk, 1995; Lugovic & Lipozencic, 1997; Giordano-Labadie et al., 1999; Clayton et al., 2006). A higher prevalence of CA in AD could

Allergic Contact Dermatitis in Children 115

activities, use of topical pharmaceutical products and cosmetics and contact with plants (Goossens, 2001). The children and their parents can themselves provide many indications but often need to be convinced that the allergenic product may not have been introduced only recently into their environment. Indeed, it can take several days before the clinical symptoms and signs appear after the contact. The delay in reaction by 24-48 hours after allergen exposure can make difficulties to establish (Goossens, 2001). Children and their parents are not typically aware of this delay in reaction and often search for immediate associations. A detailed history of events during the week preceding the onset of symptoms

The gold standard for definitive diagnosis of ACD is epicutaneous patch testing (Militello et al., 2006; Goossens & Morren, 2006). Most authors agree that the patch testing in children is safe (Weston et al., 1989; Rademaker & Forsyth, 1989; Fisher, 1994b; Goossens & Morren, 2006), the only problems being mainly technical due to small patch test surface (Rademaker & Forsyth, 1989; Goossens & Morren, 2006), hypermobility, particularly in smaller children (Shah et al., 1997; Goossens & Morren, 2006). Patch testing involves the placement of a small amount of potential allergens under occlusion on the patient's back. These patches are typically removed after 48 hours and an initial reading is performed. A delayed reading at 72 and/or at 96 hours is recommended. Positive reactions are evaluated according to the criteria of the International Contact Dermatitis Research Group as – (negative), +- (doubtful) and +, ++, +++ (weak, moderate and strong reaction, respectively) depending on the grade of erythema, induration or blistering that occurs at the site of allergen placement (Wahlberg & Lindgerg, 2006). The patch test concentrations have been discussed in detail in the literature (Goossens & Morren, 2006). Some authors have recommended lower concentrations (Hjorth, 1981; Pambor et al., 1991), particularly with regard to specific allergens such as nickel and formaldehyde (Fisher, 1991), mercurials (Fisher, 1994b), potassium dichromate and thiuram mix (Fisher, 1994b). The others use the same test concentrations as those used in adults (Pevny et al., 1984a; Pevny et al., 1984b; Stables et al.,

Children should be tested strictly based on the indication using a standard protocol. A negative patch test result does not exclude contact dermatitis. False-negative reactions have various causes, often ′missed′ allergen, which may be picked up by detailed questioning (Goossens, 2001; Goossens & Morren, 2006). For the skin tests, the possible risks of overlooking a CA are thus centred on the allergen itself, the test method, the test concentration and vehicle

Contact sensitization, however, does not necessarily equate with clinical diseases. Clinical relevance of allergic reactions on patch testing was determined according to the clinical history, type of dermatitis and the allergen concerned. Relevance of allergens should be determined for all patients with one or more positive reactions. Clinical relevance was confirmed if the allergen was found to be present in the patient's environment, the dermatitis corresponded to point(s) of contact with the allergen and the dermatitis significantly improved upon isolation of the allergen, or recurred with re-challenge (positive use test) (Jacob et al., 2008). Reported clinical relevance in children has been varied between 20% and 93% (Pevny et al., 1984b; Rademaker & Forsyth, 1989; Pambor et al., 1991; Stables,

1996; Seidenari et al., 1992; Motolese et al., 1995; Worm et al., 2007).

used, the time of reading and, finally, the relevance (Goossens, 2001).

is vital (Militello et al., 2006).

**6. Clinical relevance** 

1996; Mortz & Andersen, 1999).

be explained by the alterations of the epidermal barrier and the greater permeability of irritated skin in AD that favours sensitization to ACD (Dotterund & Falk, 1995; Vozmediano & Hita, 2005). Moreover, patients with AD are chronically exposed to potentially more sensitizers because of the topical medications used for their skin (Giordano-Labadie et al., 1999; Vozmediano & Hita, 2005; Clayton et al., 2006). Also there exists a higher probability of false positive results in the patch tests conducted in patients with AD (Lammintausta et al., 1992; Mortz et al., 2001). Seguraro Rodriguez et al. (Segurado Rodriguez et al., 2004) found that a family history of AD (85%), female sex (74%) and age 11-16 (63%) were predisposing risk factors to sensitization. On the other hand, Giordano-Labadie et al. (Giordano-Labadie et al., 1999) systematically evaluated contact sensitization in a series of atopic pediatric patients. It was observed that 43% of the 114 children who patch tested had positive reactions without association with AD. From Vozmediano's (Vozmediano & Hita, 2005) point of view, AD did not affect the sensitization to the different allergens, although a higher number of irritative responses or false positives were frequently observed. Onder and Adisen reported only 0.3% of the patients having AD and positive patch test reactions in their study in a pediatric population in Turkey (Onder & Adisen, 2008).

### **4. Clinical presentation**

The clinical characteristics of ACD are the same in children as in adults (Militello et al., 2006; Goossens & Morren, 2006). The classical clinical presentation of ACD is pruritic eczematous dermatitis. The location can be important for identification of the causal allergen since contact dermatitis is generally restricted to the contact site. Textile allergens usually cause dermatitis in areas in which the garment continually rubs against the skin, such as subaxillary and/or flexural areas of the extremities. Cosmetic allergens tend to produce facial, neck or periorbital dermatitis. Shoe allergens often present on the dorsum of the feet (Goossens, 2001; Militello et al., 2006; Goossens & Morren, 2006). Spreading of the dermatitis, often in the form of small papules, may occur far from the original contact site and may be generalized. This can be explained by hematogenous dissemination of the allergens (Goossens, 2001) or by contact with allergenic or allergen-contaminated surfaces, transfer of an allergen via the hands to the face or other sites, which gives rise to an 'ectopic' contact dermatitis. CA can be caused also by products that have come in contact with the parents or other persons in the environment of the children ('connubial' or 'consort' dermatitis). The 'ectopic' or 'connubial' reactions are commonly involved the skin of the eyelids or neck. Additionally, distant or widespread eruptions (commonly referred to as 'Id' reactions) can often be triggered by localized ACD to such chemicals as nickel and poison ivy (Goossens, 2001; Militello et al., 2006; Goossens & Morren, 2006). Untreated reactions from highly potent allergens, such a poison ivy, can be severe and last for several weeks (Militello et al., 2006). Continued exposure even to low levels of allergen can perpetuate these skin eruptions indefinitely. Recognizing potential pediatric patients with ACD either as the primary diagnosis or the confounding factor is crucial. Often the findings are difficult to distinguish, clinically and histopathologically, from AD or irritant dermatitis (Goossens, 2001; Militello et al., 2006; Goossens & Morren, 2006).

### **5. Diagnosis and patch testing in children**

Diagnosis rests on taking a substantial clinical history. Essential is an extensive and standardized anamnesis that covers all possible etiological factors like hobbies, leisure time

be explained by the alterations of the epidermal barrier and the greater permeability of irritated skin in AD that favours sensitization to ACD (Dotterund & Falk, 1995; Vozmediano & Hita, 2005). Moreover, patients with AD are chronically exposed to potentially more sensitizers because of the topical medications used for their skin (Giordano-Labadie et al., 1999; Vozmediano & Hita, 2005; Clayton et al., 2006). Also there exists a higher probability of false positive results in the patch tests conducted in patients with AD (Lammintausta et al., 1992; Mortz et al., 2001). Seguraro Rodriguez et al. (Segurado Rodriguez et al., 2004) found that a family history of AD (85%), female sex (74%) and age 11-16 (63%) were predisposing risk factors to sensitization. On the other hand, Giordano-Labadie et al. (Giordano-Labadie et al., 1999) systematically evaluated contact sensitization in a series of atopic pediatric patients. It was observed that 43% of the 114 children who patch tested had positive reactions without association with AD. From Vozmediano's (Vozmediano & Hita, 2005) point of view, AD did not affect the sensitization to the different allergens, although a higher number of irritative responses or false positives were frequently observed. Onder and Adisen reported only 0.3% of the patients having AD and positive patch test reactions in their

The clinical characteristics of ACD are the same in children as in adults (Militello et al., 2006; Goossens & Morren, 2006). The classical clinical presentation of ACD is pruritic eczematous dermatitis. The location can be important for identification of the causal allergen since contact dermatitis is generally restricted to the contact site. Textile allergens usually cause dermatitis in areas in which the garment continually rubs against the skin, such as subaxillary and/or flexural areas of the extremities. Cosmetic allergens tend to produce facial, neck or periorbital dermatitis. Shoe allergens often present on the dorsum of the feet (Goossens, 2001; Militello et al., 2006; Goossens & Morren, 2006). Spreading of the dermatitis, often in the form of small papules, may occur far from the original contact site and may be generalized. This can be explained by hematogenous dissemination of the allergens (Goossens, 2001) or by contact with allergenic or allergen-contaminated surfaces, transfer of an allergen via the hands to the face or other sites, which gives rise to an 'ectopic' contact dermatitis. CA can be caused also by products that have come in contact with the parents or other persons in the environment of the children ('connubial' or 'consort' dermatitis). The 'ectopic' or 'connubial' reactions are commonly involved the skin of the eyelids or neck. Additionally, distant or widespread eruptions (commonly referred to as 'Id' reactions) can often be triggered by localized ACD to such chemicals as nickel and poison ivy (Goossens, 2001; Militello et al., 2006; Goossens & Morren, 2006). Untreated reactions from highly potent allergens, such a poison ivy, can be severe and last for several weeks (Militello et al., 2006). Continued exposure even to low levels of allergen can perpetuate these skin eruptions indefinitely. Recognizing potential pediatric patients with ACD either as the primary diagnosis or the confounding factor is crucial. Often the findings are difficult to distinguish, clinically and histopathologically, from AD or irritant dermatitis (Goossens,

Diagnosis rests on taking a substantial clinical history. Essential is an extensive and standardized anamnesis that covers all possible etiological factors like hobbies, leisure time

study in a pediatric population in Turkey (Onder & Adisen, 2008).

2001; Militello et al., 2006; Goossens & Morren, 2006).

**5. Diagnosis and patch testing in children** 

**4. Clinical presentation** 

activities, use of topical pharmaceutical products and cosmetics and contact with plants (Goossens, 2001). The children and their parents can themselves provide many indications but often need to be convinced that the allergenic product may not have been introduced only recently into their environment. Indeed, it can take several days before the clinical symptoms and signs appear after the contact. The delay in reaction by 24-48 hours after allergen exposure can make difficulties to establish (Goossens, 2001). Children and their parents are not typically aware of this delay in reaction and often search for immediate associations. A detailed history of events during the week preceding the onset of symptoms is vital (Militello et al., 2006).

The gold standard for definitive diagnosis of ACD is epicutaneous patch testing (Militello et al., 2006; Goossens & Morren, 2006). Most authors agree that the patch testing in children is safe (Weston et al., 1989; Rademaker & Forsyth, 1989; Fisher, 1994b; Goossens & Morren, 2006), the only problems being mainly technical due to small patch test surface (Rademaker & Forsyth, 1989; Goossens & Morren, 2006), hypermobility, particularly in smaller children (Shah et al., 1997; Goossens & Morren, 2006). Patch testing involves the placement of a small amount of potential allergens under occlusion on the patient's back. These patches are typically removed after 48 hours and an initial reading is performed. A delayed reading at 72 and/or at 96 hours is recommended. Positive reactions are evaluated according to the criteria of the International Contact Dermatitis Research Group as – (negative), +- (doubtful) and +, ++, +++ (weak, moderate and strong reaction, respectively) depending on the grade of erythema, induration or blistering that occurs at the site of allergen placement (Wahlberg & Lindgerg, 2006). The patch test concentrations have been discussed in detail in the literature (Goossens & Morren, 2006). Some authors have recommended lower concentrations (Hjorth, 1981; Pambor et al., 1991), particularly with regard to specific allergens such as nickel and formaldehyde (Fisher, 1991), mercurials (Fisher, 1994b), potassium dichromate and thiuram mix (Fisher, 1994b). The others use the same test concentrations as those used in adults (Pevny et al., 1984a; Pevny et al., 1984b; Stables et al., 1996; Seidenari et al., 1992; Motolese et al., 1995; Worm et al., 2007).

Children should be tested strictly based on the indication using a standard protocol. A negative patch test result does not exclude contact dermatitis. False-negative reactions have various causes, often ′missed′ allergen, which may be picked up by detailed questioning (Goossens, 2001; Goossens & Morren, 2006). For the skin tests, the possible risks of overlooking a CA are thus centred on the allergen itself, the test method, the test concentration and vehicle used, the time of reading and, finally, the relevance (Goossens, 2001).
