Contact Allergy in Children 43 A

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Chapter 43 Contact Allergy in Children 43 A. Goossens, M. Morren

Contents 43.7 Proposal for a Shortened Standard Series for Children ...... 825 43.1 Introduction ...... 811 43.8 Conclusions ...... 825 43.2 Prevalence and Incidence ...... 811 43.2.1 Prevalence of Contact Allergy Suggested Reading ...... 826 in an Unselected Population ...... 811 References ...... 826 43.2.2 Prevalence of Contact Allergy in a Selected Population ...... 812 43.2.3 Prevalence in Relation to Genetic Factors . . 814 43.2.4 Prevalence Related to Sex ...... 814 43.1 Introduction 43.2.5 Prevalence Related to Age ...... 814 43.2.6 Prevalence Related to Origin ...... 815 43.2.7 Prevalence in Relation Contact allergy has not been studied as extensively in to the Sensitization Source ...... 815 children as in adults. Although there are many simi- larities between these two patient populations, the 43.3 The Clinical Picture ...... 815 results obtained in adults cannot always be applied to 43.4 Allergic Contact Dermatitis and Atopy . . . . 816 children. A child is not simply a small version of an 43.5 Patch Testing in Children ...... 817 adult. 43.6 The Most Frequent Allergens in Children . . 817 43.6.1 Metals ...... 817 43.6.1.1 Nickel ...... 817 43.2 Prevalence and Incidence 43.6.1.2 Cobalt ...... 818 43.6.1.3 Potassium Dichromate ...... 818 Allergic contact dermatitis in children has always 43.6.1.4 Mercury ...... 818 been considered rare, and their eczematous condi- 43.6.1.5 Aluminum ...... 818 tions have mostly been attributed to endogenous fac- 43.6.1.6 Palladium ...... 818 tors such as atopic or seborrheic dermatitis, some- 43.6.1.7 Iron ...... 819 times in association with irritancy induced by soap, 43.6.1.8 Copper ...... 819 clothing, and so on [1–3]. One of the reasons for this 43.6.2 Pharmaceutical Products ...... 819 would be their reduced exposure to environmental 43.6.3 Cosmetics ...... 820 allergens (professional,cosmetic,pharmaceutical) [3, 43.6.4 Tattoos ...... 821 4]. Some authors also cite a lower reactivity and sen- 43.6.5 Toys ...... 821 43.6.6 Rubber Items ...... 821 sitization capacity for children’s skin [5, 6]. 43.6.7 Shoes and Clothes ...... 822 Until fairly recently, allergic contact dermatitis 43.6.8 Plastic Materials and Resins ...... 823 was not usually suspected in children, so little patch 43.6.9 Plants ...... 823 testing was performed [7]. Since the 1980s, however, 43.6.9.1 Poison Ivy, Poison Oak, Poison Sumac . . . . 823 this diagnosis has been considered more frequently 43.6.9.2 Toxicodendron succedaneum (Rhus Tree) . . 823 [8]. Photoallergic contact dermatitis does seem to be 43.6.9.3 Urtica urens ...... 824 rare [1, 7], although it may too be under-diagnosed. 43.6.9.4 Asteraceae or Compositae ...... 824 43.6.9.5 Lichens ...... 824 43.6.9.6 Gingko Fruit ...... 824 43.2.1 Prevalence of Contact Allergy 43.6.9.7 Dioscorea batatas Decaisne ...... 824 in an Unselected Population 43.6.9.8 Protein Contact Dermatitis ...... 824 43.6.9.9 Various Plant Materials ...... 824 Data on the prevalence of contact allergy in healthy 43.6.10 Occupational Allergens ...... 824 children are scarce: in a population of 314 healthy 43_811_830 05.11.2005 11:37 Uhr Seite 812

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children younger than 18 years old, Weston and co- relevance of which was estimated to be 50%, for the workers [9] found positive patch test results in 20%; present or the past (7.2%). Girls reacted more fre- Barros and coworkers [10] reported a 13% prevalence quently [14]. in 562 children aged between 5 and 14; while Dotte- rud and Falk [11] observed that 23% of 424 healthy children from 7 to 12 years old had a contact allergy. 43.2.2 Prevalence of Contact Allergy More recently, Bruckner and coworkers [12] found in a Selected Population that 24.5% of 85 children between 6 months and 5 - years of age, attending well-child visits and tested Several studies have been performed in children sus- with a TRUE Test panel, presented one (16 infants) or pected of contact allergy or suffering from atopic or two (4 infants) positive tests. Nickel and thimerosal juvenile plantar dermatitis,orofacial granulomatosis, were the most frequent allergens identified.However, dyshidrosis, psoriasis, photosensitivity, urticaria, or Johnke and coworkers [13] warn for false-positive other dermatoses. The studies ([15–37], see Table 1) tests, especially with nickel sulfate in such young differ in the numbers and ages of the patients in- children: they found many (111/543 infants) weak volved, the clinical symptoms, as well as the relevan- transient reactions with the highest (200 µg/cm2) cy and the prevalence of the positive reactions ob- nickel concentration tested,of which only 8.6% could served. In a study by Pambor and co-workers in 1991 be reproduced. Hence, single positive nickel patch [38], only 3.6% of the children tested showed clinical- tests in small children should be assessed with cau- ly relevant positive patch tests, whereas Pevny and tion! In a Danish study on adolescents between 12 co-workers observed relevancy rates of up to 71% and 16 years old, a prevalence of 15.2% was found, the [16], with the majority around 40%.

Table 1. Incidence of allergic contact dermatitis in selected populations Author, Number Age Categories % Relevancy Most frequent allergens (% of Reference (%) children with positive test)

Veien et al [15] 168 <14 years Suspicion of ACD 46 80 Nickel > dichromate > rubber Pevny et al [16] 147 3–16 years Suspicion of ACD 71 93 Nickel > cobalt > para-dyes > dichromate Romaguera 1023 <14 years ACD and others 31 69.5 Nickel/cobalt > pharmaceutical et al [17] (45% atopics) ingredients > cosmetics > shoes > clothes > professional Rademaker and 129 <12 years Atopic eczema, eczema, 48 92 Metals > perfume > rubber Forsyth [18] atypical JPD, contact dermatitis, orofacial granulomatosis, other Kuiters et al [19] 67 <16 years Dermatitis 28 84 Nickel > balsam of Peru > fragrance mix > colophony > carba mix Balato et al [20] 585 <14 years Eczema 14 ? Nickel > cobalt > ethylenediamine > dichromate > mercury ammonium chloride > mercaptobenzothiazole > neomycin > mercapto mix Pambor et al [21] 366 2–14 years Atopic dermatitis 25 5 Nickel > chloramphenicol > (n=214) parabens > turpentine Other dermatosis 18 7 (n=142) Ayala et al [22] 323 <14 years Atopic dermatitis 35.2 61.7 Metals > pharmaceutical Contact dermatitis ingredients > preservatives > Dyshidrotic eczema fragrance > shoes 43 Foot, diaper or perioral eczema (palmar/plantar psoriasis) Gonçalo 329 <14 years ACD 51.7 65.3 Nickel, thimerosal, cobalt, et al [23] mercury ammonium chloride, fragrance mix, dichromate 43_811_830 05.11.2005 11:37 Uhr Seite 813

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Table 1. Continued Author, Number Age Categories % Relevancy Most frequent allergens (% of Reference (%) children with positive test)

Sevilla et al [24] 272 2–14 years ACD 37.1 54.4 Nickel, rubber, mercury chloride, cobalt, thimerosal, benzoyl peroxide, fragrance mix Motolese 53 <3 years Dermatitis 50 62.5 Thimerosal, nickel, ammoniated et al [25] mercury Stables et al. [26] 92 3–14 years Atopic dermatitis 32.6 87 Nickel, fragrance mix, balsam Localized dermatitis of Peru, thimerosal, neomycin, JPD cobalt, lanolin, dichromate, Orofacial granulomatosis mercapto mix Reactions to vaccines Atypical psoriasis Rudzki et al [27] 626 3–16 years ? 42.7 ? Nickel, dichromate, cobalt, mercury chloride, fragrance mix, para-phenylenediamine, neomycin, balsam of Peru Wilkowska 100 5–15 years Atopic dermatitis 49 ? Dichromate, cobalt, neomycin et al [28] Eczema Nonallergic dermatoses Katsarou 232 <16 years ACD ? 43.5 ? Nickel, cobalt, fragrance mix, et al [29] dichromate, para-phenylenediamine, para-tertiary-butylphenol-formaldehyde resin, mercapto mix, mercury ammonium chloride, balsam of Peru Wantke et al [30] 234 <15 years ACD ? Ethylmercuric chloride, 72 0–7 years 44.65a thimerosal and nickel (girls) 162 7–14 years 40.51a Brasch et al [31] 416 6–15 years ACD 41 ? Nickel, thimerosal, benzoyl peroxide, fragrance mix, cobalt, amalgam, mercury ammonium chloride, phenyl- mercury acetate, Amerchol L-101, cobalt chloride, dichromate, colophony Shah et al [32] 83 6–16 years Atopic dermatitis 49 ? Nickel, fragrance mix, cobalt, Hand/feet dermatitis neomycin, para-phenylene- (Peri)oral dermatitis diamine, colophony, para- Reactions to local tertiary-butylphenol- anesthetics formaldehyde resin Dermatoses with unusual localizations Perianal dermatitis Urticaria Photoreactions Manzini 670 6 months Dermatitis 42 ? Thimerosal, nickel, et al [33] to 12 years methyl(chloro)isothiazolinone, fragrance mix, neomycin, wool alcohols, ammoniated mercury Romaguera 141 <15 years ACD 50 80 Nickel, cobalt, mercurials, et al [34] fragrance, rubber Giordani-Labadie 137 <16 years Atopic dermatitis 43 ? Metals (mainly nickel), et al [35] fragrance, balsam of Peru, lanolin, neomycin Roul et al [36] 337 <16 years ACD 66 ? Nickel, fragrance, rubber Duarte et al [37] 102 10–19 years ACD 56 100 Nickel, tosylamide/ formaldehyde resin

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Other factors that render comparison of those transdermal clonidine being more frequently ob- studies difficult [26] include the different test popu- served in women than in men; and finally, a greater lations involved (for example the presence or not of susceptibility of feminine skin to irritation and atopy, differences in origin and habits), the variabil- hence to sensitization. ity of the test conditions (materials, allergens, concentrations, vehicles, reading times), and the inter- pretation of the test results (allergic or irritant). 43.2.5 Prevalence Related to Age The question arises as to whether contact allergy in children has become more frequent in recent Unlike some authors [10, 26, 36, 44], most report an years. According to Björksten [39], its prevalence in increasing prevalence of allergic contact dermatitis 18-year-old Swedish males increased from 0.9% in with age, and attribute it to the increasing exposure 1978 to 1.5% in 1993. to environmental allergens [8, 20, 24, 27, 28, 46]. This also applies to the development of multiple sensitiv- Core Message ities [23].A reduced sensitization potential in younger children has also been suggested [5, 6]. This has been experimentally demonstrated by Uhr and co- í Contact allergy in children is more workers [47], who showed that sensitization to dini- frequent than previously suspected, trofluorobenzene does occur among premature in- the prevalence in an unselected population fants but less frequently than among infants carried being about 20%. to term, and in both of these groups less frequently than in children aged 2–12 months. Epstein [48] obtained sensitization to pentadecylcatechol in 44% of children below 1 year of age, in about 58% between 1 and 3 years old,and in 87% of children between 4 and 43.2.3 Prevalence in Relation 8 years old. In contrast to this, Moltolese and cowork- to Genetic Factors ers [25] found a contact allergy in 32/53 infants (3 months to 2 years) with dermatitis. At least 20 out According to Walton and coworkers [40], occupa- of the 32 were considered relevant. tional and environmental factors are essential but the Fisher reported several cases of allergic contact hereditary background can also be important, as dermatitis in neonates and infants [49–52]: epoxy could be demonstrated, for example, by the higher resin in a vinyl identification band in a 1-week-old prevalence of HLA-B35 and BW22 antigens and their neonate, three cases of ethylenediamine contact al- correlation with an increased risk of nickel sensitiza- lergy (induced by Mycolog) in children aged 6 weeks tion in a female population. The importance of ge- to 1 year, one case of nickel allergy due to earrings in netic factors has also been studied in children a 4-week-old girl, neomycin as a cause of an allergic [41–43]: these authors conclude that there is a specif- contact dermatitis on the penis of a 5-week-old boy ic genetic selection at the level of the peripheral T- who was circumcised, balsam of Peru in an ointment lymphocyte system. to treat diaper rash in an 8-week-old girl (who had received this treatment for only 1 week), and finally nickel in underwear causing a row of contact derma- 43.2.4 Prevalence Related to Sex titis lesions on the back of a 7-month-old boy. Seide- nari [53] also described three remarkable contact al- While some authors [9, 10, 26] detected similar prev- lergy cases (two of them connubial) in babies: nickel alence in both boys and girls, others [11, 30] reported present in the bars of a crib caused dyshidrosis of the a higher prevalence in girls.This is especially the case hands and feet in a 12-month-old atopic boy; nickel for nickel [15,40,44] and after the age of 12 [18,27,29]. in his mother’s jewelry (she wore rings on all her fin- Hormonal factors may be a contributory factor here gers) exacerbated the atopic eczema of a 6-month- [23,31].Kwangsukstith and Maibach [45] have formu- old boy; and para-phenylenediamine in her mother’s lated several arguments for the existence of sex-relat- dyed hair caused hand dermatitis in a 12-month-old ed differences in the prevalence of allergic contact girl.Aihara and Ikezawa [54] have reported a neonate 43 dermatitis: varying test results obtained depending who was allergic to a mydriatic agent used for fun- upon the menstrual cycle; increased sensitization li- doscopy (the responsible allergen was not detected). ability in females, in general, and enhanced reactivity Moreover, several cases of contact allergy in in- to dinitrochlorobenzene (DNCB) in females taking fants have been reported due to the rubber anti-leak- contraceptives; allergic contact dermatitis due to ing system in their diapers [55–57]. 43_811_830 05.11.2005 11:37 Uhr Seite 815

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Recently, we diagnosed a contact allergy to the Table 2. Correlation between the localization of the lesions and electrodes used to monitor an infant for sudden the nature of the allergens para death. An allergy to -tertiary-butylphenol-for- Face: Ingredients of topical pharmaceuti- maldehyde (PTBPF) resin was found, but we were not cal products (e.g., benzoyl peroxide), able to confirm the presence of this allergen in the cosmetics [e.g., methyl(chloro)iso- electrode. thiazolinone], and perfume components; plants Periorbital area: Ophthalmic preparations; nickel, 43.2.6 Prevalence Related to Origin cobalt Perioral area: Stuck-on objects (rubber additives); nickel, cobalt, and palladium; flavor- The exposure of children to certain contact allergens ing agents (cinnamic aldehyde) varies throughout the world [8]. For example, in con- Ears: Nickel and cobalt, eardrops trast to Europe, poison ivy (and other members of Neck: Nickel the Rhus family) is particularly apt at inducing sensi- Trunk: Clothing dyes, rubber additives, tization in certain parts of North and South America nickel (periumbilically), PTBP-resin [1, 8]. In Scandinavian countries, plant dermatitis in (electrode), PPD and essential oils children is rare except for reactions to Heracleum in temporary tattoos spp. [3]. Exposure and subsequent sensitivity to neo- Arms: Cosmetics (e.g., sunscreens), alumi- mycin also seems to vary geographically; for exam- num (vaccines), plants, PPD and ple, there is a high prevalence in Portugal [10], Italy essential oils (temporary tattoos) [22], and certain areas in the USA such as Denver [9], Wrists: Nickel and cobalt, dichromate as opposed to Philadelphia [58]. In contrast to Scan- (leather watch-strap) dinavian countries [3], shoe dermatitis seems to be Hands and fingers: Preservatives (cosmetics, play gels, Plasticine), nickel and cobalt, plants, particularly common in the USA [59], mainly due to rubber and resin components rubber [58]. In developing countries occupational al- Buttocks and thighs: Aluminum (vaccines), plastic lergy is more common in older children than in (toilet seat) Western countries [37]. Diaper area: Topical pharmaceutical (e.g., ethy- Regional variations in the type of clothing and liv- lenediamine, neomycin) and cos- ing conditions clearly influence the allergen spec- metic products, rubber (or glue) in trum [15]. anti-leaking system from diapers Legs: Plants, orthopedic appliances (resins, such as PTBPF and epoxy) 43.2.7 Prevalence in Relation Feet: Shoe allergens (rubber additives, to the Sensitization Source glues) (PTBP), dichromate, plants, topical pharmaceutical products Objects or materials common to the child’s environment may give rise to some unusual allergen sources. Diapers [55–57], and, for example, wirh regard to al- It is of the utmost importance to take a detailed his- lergic cheilitis and perioral dermatitis, sucked-on tory, in order to specify the environment of the child objects are not at all rare causes (also due to rubber and of those taking care of it, and to examine allergens), particularly in the younger age group thoroughly the topography of the lesions. The local- [60]. This also applies to mercurials [31, 59] present ization is often an indication of the allergen or aller- in vaccines and topical pharmaceuticals used to treat gens involved [8]. Based on data published in the lit- abrasions and infections of the skin. However, nickel erature, we compiled a list of allergens in relation to [22, 31], cosmetic ingredients [8], and occupational specific body sites (see Table 2). allergens [5, 16, 37] are causes of allergy more in old- Sometimes the clinical picture is unusual: er children. The prevalence of the allergens found mainly depends on the exposure, which itself varies í A hypertrophic verrucous cheilitis due to the with the age of the population [30]. topical application of thimerosal used to treat fissures [61] 43.3 The Clinical Picture í A bullous dermatitis induced by a neomycin- containing finger bandage; patch tests were positive to neomycin, colophony, and thiuram The clinical characteristics of allergic contact derma- mix [16] titis are, in general, the same in children as in adults. 43_811_830 05.11.2005 11:37 Uhr Seite 816

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í A “baboon syndrome” [62, 63] from mercury, 43.4 Allergic Contact Dermatitis and Atopy due to the intake of erythromycin to treat an infection of the throat [64] The association between atopy and contact allergy in í An EEM-like eruption on the thighs spreading children is a controversial subject [78].The conclu- to the trunk after an initial contact eczema- sions drawn differ largely according to the allergens tous reaction induced by a plant extract con- investigated and whether the prevalence of contact taining St John’s wort [65], to a temporary allergy in atopic children or the prevalence of atopy henna tattoo [66], to disperse dyes in a 2 year in children suffering from allergic contact dermatitis old boy [67], to tea tree oil [68] as well as to children is being investigated [79]. mephenesin (own observation) Several authors were unable to detect differences í A lichenoid contact dermatitis on the feet, between atopic and nonatopic subjects in this regard hands, and buttocks lasting 6 years, due to [22, 80, 81], but others have. Some authors were able topical aminoglycosides in which lichenoid to find a higher prevalence in atopic than in nonatop- positive patch tests were also obtained [69] (a ic children [11, 28, 82] and this was sometimes attrib- papular pattern of allergic contact dermatitis uted to the greater permeability of irritated skin [11]. does not seem to be rare, such as occurs with Others report the opposite [26, 29, 31, 47]. nickel [70]); this lichenoid pattern of reaction Nickel reactions are more often seen in atopics is also frequently seen in reactions to p-phen- [70, 81, 83], and then mainly in girls [84], which re- ylene-diamine (PPD) in temporary tattoos flects the greater importance of sex and ear piercing [71]. Healing may be with depigmentation [72] than atopy as such. The latter authors (in agreement í Itching nodules and granulomas that may per- with, for example, Pambor and coworkers [80]), sist for months or even years at the injection stress the irritant properties of metals and particu- site of vaccines due to a delayed reaction to larly nickel on atopic skin, and, indeed, papulopustu- aluminum in vaccines [73] lar patch test reactions are a frequent finding [79]. í A generalized nummular dermatitis in both a Dotterud and Falk [84] doubt that metal sensitivity is boy and a girl induced by application of an associated with atopy. First, there is the reduced cel- ethylenediamine-containing preparation to lular immunity of atopics: positive reactions are the groins and the feet, respectively [74]; a found more often in atopic children with moderate positive reaction to thimerosal was found in dermatitis than in those with severe atopic eczema five atopic children (7–28 months old) with [85, 86]; second, there is the greater permeability of nummular eczema on the trunk, limbs and diseased skin, particularly on the hands, which facil- face [75] itates the penetration of allergens [85, 87]. í A generalized eczema occurred twice in an 18- Besides nickel, Oranje and co-workers [88] also month-old boy caused by sensitivity to phe- found cobalt and balsam of Peru (Myroxylon perei- noxyethanol used as a preservative in a DTP rae) to be important allergens in an atopic child pop- vaccine [76]; the third booster vaccine con- ulation; furthermore, they observed few reactions on taining thimerosal as the preservative did not patch testing with food. produce a reaction Contact allergy to ingredients of topical medica- í A systemic contact dermatitis in a 14-year-old tions are also common in atopic dermatitis patients boy caused by an orthodontic appliance that [35, 78]. contained nickel [77] As with nonatopics, the prevalence of contact allergy was found to increase with age [86, 87].

Core Message Core Message

í Certain contactants are characteristic of í Positive reactions in atopics must be children (Table 2), and may be responsible interpreted carefully, as atopic skin is for unusual clinical presentations. readily irritated; this is especially the 43 case for metals. 43_811_830 05.11.2005 11:37 Uhr Seite 817

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43.5 Patch Testing in Children ing in general, false-positive as well as false-negative reactions may occur [1, 49]. It is therefore important Patch testing is indicated not only when contact al- that the relevance of the tests are further investigat- lergy is suspected,but also in cases of persistent ecze- ed, if necessary, with a serial dilution test, repeated ma [20] on specific localizations, such as on the open application test (ROAT) or a usage test [95]. For hands and the feet and around the mouth [32] and al- marginal irritants such as dichromate, fragrance so in the umbilical region, particularly in atopics mix, formaldehyde, mercury compounds and carba [79].The latter group should certainly be tested when mix in particular [94], repeated patch testing with multiple exacerbations occur, even when they are standardized tests (such as TRUE Test) should be treated, or when the dermatitis is asymmetrical [32]. performed in order to demonstrate reproducibility Most authors agree that patch testing in children and, if necessary, the concentration should be adapt- is safe [9, 18, 61, 89], the only problems being mainly ed. Johnke and coworkers [13] have already demon- µ 2 technical due to the small patch test surface [18], hy- strated that in infants 200 g/cm nickel sulfate pro- permobility (which may result in loss of patch test duces many transient reactions (111/543), whereas re- materials), particularly in younger children [32], and producible tests were obtained only in 8.6% of the the reluctance of some parents to allow patch testing cases. They therefore favor a lower patch concentra- [4, 32]. Mallory [90] gives the following instructions tion for nickel in children. when testing children: Core Message í Test in different sessions if the test area is very small í Patch testing in children is safe, but false- í Should the patches come off, ask the parents positive reactions are possible. Particularly to report it and instruct them not to reapply for children under the age of five, patch them testing should only be performed if there í It may be necessary to use a stronger adhesive is high suspicion by history and clinical than usual, though this could be irritating [9] picture. í The application has to be performed as quick- ly as possible while the child is distracted í Make a diagram of the tested allergens (this applies for adults, too) í Inform the parents about the test procedure 43.6 The Most Frequent Allergens and the measures that may be taken to opti- in Children mize the patch test conditions 43.6.1 Metals

The patch test concentrations have been discussed in 43.6.1.1 Nickel detail in the literature. Some authors have recommended lower concentrations [3, 80, 91, 92], particularly with regard to specific allergens such as nickel Nickel is the most common allergen both in children and formaldehyde [6, 83], mercurials [61], potassium and adults in Europe, as it is in many other parts of dichromate, MBT, and thiuram mix [52]. Irritancy the world. In the general population, about 10% of fe- problems have been reported with patch testing, es- males react to it, the prevalence being influenced by pecially in the younger age group [6, 9, 11, 21], while the increasing popularity of ear and other piercings others use the same test concentrations as in adults [84].Indeed,ear piercing along with atopy – the latter [5, 15, 16, 26, 53, 81, 93]. Wahlberg and Goossens [94] even in children between 4 and 17 months old [70,96] critically reviewed studies on the prevalence of con- – have been regarded as major risk factors for the de- tact allergy, and found that very high prevalences are velopment of nickel sensitization, especially in girls found in “healthy” children as compared with those [84, 97]. Boys may also be affected though [98]. Ra- found in adults. They suspect that a lot of those reac- demaker and Forsyth [18] could not determine sig- tions might be irritant and therefore conclude that all nificant differences between boys and girls below the patch test concentrations used in adults are not nec- age of 12. Subumbilical and periumbilical, mostly essarily suitable for use in children, as was already papular reactions are also common and are frequent- suggested for metals by Roul and coworkers [36]. In ly accompanied by an id-like spread [96, 99, 100]. dubious cases one might have to retest with a lower Veien [101] attributes the high prevalence of nick- test concentration [79]. Moreover, as with patch test- el allergy in young females to the common habit of 43_811_830 05.11.2005 11:37 Uhr Seite 818

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wearing cheap jewelry, to reduced suppressor activ- 43.6.1.3 Potassium Dichromate ity correlated with their higher estrogen levels,and to higher skin permeability to nickel. Permeability Leather seems to be the most important cause of could be increased by decreased iron levels associat- chromium allergy; the examples published concern ed with menarche, as iron is a competitive inhibitor shoes (see below), a body splint [110], and a prayer in the skin and on the surface of Langerhans cells. strap in a 13-year-old Jewish boy [61]. Concomitant Nickel sensitization sources in children are nu- reactions to nickel have been observed [31]. merous: jewelry, even when worn by the mother [53] and particularly earrings [49,51] (stainless steel,even though silver- or gold-plated is not always “safe” in 43.6.1.4 Mercury this regard [102]), metal buttons and snaps in underwear, identification bracelets, safety pins, zippers, Contact allergy to mercurials is very common in chil- jeans and belt buckles [90,96,99,100],metal accesso- dren, particularly in countries where they are still ries on shoes, coins, metal toys, magnets, medallions, widely used as antiseptics (for example mercuroch- keys, door handles, and so on [51, 83]. Even bed rails rome), such as Spain [97, 111] and Italy [112]. Other have caused nickel contact allergy [53, 103]. Due to re- sensitization sources for mercurials are other topi- strictions on the concentration of nickel allowed in cally applied medicaments, such as eye-drops, depig- jewelry, advised by the authorities in Europe in the menting creams [111], pediculosis preparations [113], beginning of the 1990s, a decline in the prevalence of vaccines [114], as well as broken thermometers [63], nickel allergy has been registered in Denmark [104] amalgam fillings, contact lens solutions, and pesti- and Germany [105]. In the USA, Byer et al [100] could cides. Levy and coworkers [59] warn against the use only detect nickel in 10% of 74 pairs of jeans buckles, of mercurials in medications because of their poten- whereas the dimethylglyoxime test was positive in 25 tial systemic toxicity, which may cause kidney dam- of the 47 belts, indicating that this nickel source is age, particularly when large skin surfaces are treated. more important for sensitization induction. Orthodontic appliances may occasionally be at the origin of a nickel allergy, causing cheilitis, perioral 43.6.1.5 Aluminum eczema [77, 106, 107] and also stomatitis, sometimes associated with systemically induced dermatitis on For aluminum, vaccines and occasionally also hypo- the eyelids, fingers, ears, periorbital area [107], or sensitization therapy in pollen allergy are reported more generalized reactions [77], even a severe deteri- as being the most important sensitization sources oration of atopic dermatitis [108]. Van Hoogstraten [73, 115–118]. Clinically, the reactions often present as et al [98] were able to show that wearing a dental ap- long-lasting, pruritic, excoriated, subcutaneous nod- paratus before nickel skin contact has occurred may ules, occasionally accompanied by hypertrichosis actually induce tolerance to this metal. [73, 119]. In many cases, the contact eczema is re- A low nickel diet might be useful in resistant nick- vealed by positive reactions to Finn chambers used el allergy cases [15]. in patch testing or to deodorants [115],eardrops [118], or even toothpaste [116] containing aluminum salts. 43.6.1.2 Cobalt Flare-ups of previous injection sites may be ex- plained by the persistence of this metal in the skin [115]. The aluminum sensitivity is probably lost with Cobalt allergies are often found in association with time as this sensitivity is extremely rare in adults nickel allergies in both adults and children [31]. Not [120]. only metallic objects but also certain plastic materials may release cobalt or cobalt salts and induce contact sensitivity. For example, Grimm [109] described 43.6.1.6 Palladium the case of an 11-year-old boy who had suffered for 4 - years from eczematous lesions at the site of his spec- This metal, shown to be an allergen in animals, is tacle frames, on his wrist, and around his mouth. The mainly present in orthodontic appliances and jewel- dermatitis was attributed to cobalt present in the me- ry [121]. As with adults, most palladium-allergic chil- 43 tallic part of his wristwatch, in the polyester resin- dren also react to nickel [31,122],for which cross-sen- type plastics of the spectacle frames, and the ball- sitization seems to be the most plausible explanation. point pen which he habitually chewed on. 43_811_830 05.11.2005 11:37 Uhr Seite 819

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43.6.1.7 Iron tain quinine [131]).Plant extracts may also be responsible for allergic reactions [65]. There seems to be only one case report of iron con- Certain topical medicaments are specifically used tact allergy, which was caused by an orthopedic pros- in older children, namely those used to treat acne thesis in a 7-year-old boy [123], so this metal seems to such as benzoyl peroxide [1, 16]. be an extremely rare allergen. An allergic dermatitis from the parenteral admin- istration of vitamin K has been reported by Pigatto and coworkers [132]. 43.6.1.8 Copper Not only active principles but also other ingredients may be responsible for allergic reactions in According to a Viennese report, copper, present in children: emulsifiers and vehicle components, such dental amalgam, caused problems in children [44]. as wool wax alcohols and derivatives, propylenegly- col and cetostearyl alcohol, as well as a specific ingredient of eardrops – triethanolamine oleyl polypep- 43.6.2 Pharmaceutical Products tide – are typical examples of this [133]. Sometimes, rarer allergens are involved such as laureth-4 [134], Many topical pharmaceutical ingredients have been ethyl sebacate [128] and Tween 80 [135]. described as allergens in children and should cer- Ethylenediamine, used in Mycolog cream, has tainly not be overlooked [124]. They include antibio- been widely used to treat various skin conditions, in- tics, mainly neomycin [16, 49], which is often used in cluding diaper dermatitis [50, 74], and may cross- the treatment of otitis [58]. Leyden and Kligman [58], react with some antihistamines and aminophylline in contrast to Weston and coworkers [9], suggest that to induce severe systemic reactions [50]. This chemi- neomycin allergy is less frequently seen in children cal is also used in ophthalmic solutions, insecticides, than in adults. Cross-reactivity with other aminogly- fungicides, epoxy hardeners, and rubber stabilizers cosides does occur [69]; antivirals such as tromanta- [90]. dine (own observations) and Zovirax, of which the Preservatives are not at all rare causes of allergic responsible allergen could not be identified [125]; reactions in children [136]. Goulden and Goodfield antihistamines such as dexchlorpheniramine ma- [137] reported the case of a 12-year-old boy who even leate [126]; nonsteroidal anti-inflammatory agents reacted to a methylprednisolone injection due to his such as fepradinol [127]; local anesthetics, particular- sensitivity to the preservative myristyl picolinium ly benzocaine [16],which often cross-reacts with oth- chloride. er ester-type anesthetics [90] and also with perma- Thimerosal has attracted much attention in the lit- nent hair dyes and textile dyes, which may later cause erature, since it is frequently observed as an allergen problems due to their chemical relationship [49]. in young children [138–140], and its inclusion in the Even corticosteroid preparations may cause contact standard series has been discussed [141, 142]. It is allergy in children [128], and not infrequently in used as an antiseptic, disinfectant, and preservative atopics [129]. Tixocortol pivalate and budesonide agent for contact lens solutions, eyedrops, and vac- may be used as markers in the standard series, but all cines, the last being regarded as the main sensitiza- topical preparations used by the child should be test- tion source through contamination of the tip of the ed as well. Contact allergy to the new class of topical needle [138, 139, 143, 144]. According to Möller [141] immunomodulatory drugs, especially for tacrolimus, and Aberer [144, 145], the many positive patch test re- has been reported recently. A provocation test was actions found are in most cases not relevant to the positive after 1 week for lesions in the face but only patient’s skin condition. after 7 weeks when applied to the antecubital region. A positive reaction to thimerosal should be taken Patch tests were only positive after 5 days with tacrol- into account with hyposensitization solutions, eye- imus 5% and 2.5% in ethanol, but not with Protopic drops, eye cosmetics, or contact-lens solutions [144], ointment as is, nor with lower concentrations of ta- but does not seem to preclude future vaccinations, crolimus. The authors suggest that the low percut- provided that they are administered intramuscularly. aneous absorption through intact extrafacial skin is Furthermore, as this molecule contains two allergen- the reason for this delay in positive results and the ic parts – mercury and thiosalicylic acid – one must need for high concentrations [130]. consider cross-reactions with other mercurials and Other agents which have been reported include with the photoproduct of piroxicam, which is chemi- quinine present in a balsam used in the treatment of cally related to the thiosalicylic acid part [114, 138, respiratory infections (the adult formulation was 146]. Efforts are now being made to omit thimerosal used and not the one for children which did not con- from commonly used vaccines [68]. 43_811_830 05.11.2005 11:37 Uhr Seite 820

820 A. Goossens, M. Morren

Phenoxyethanol contact allergy has also been de- Almost every ingredient may be responsible for scribed in relation to a DTP vaccine [76]. cosmetic dermatitis. Conti [136] reviewed preserva- Last but not least,adhesive tape can also be a cause tives and found that 44% of the children reacting to of allergy due to colophony and thiuram derivatives chemicals such as formaldehyde and its releasers, [16]. Children may also be exposed to colophony in parabens, methyl(chloro)isothiazolinone, Euxyl K400 preparations to treat verrucae [120]. (methyldibromoglutaronitrile and phenoxyethanol), and the antioxidant butylhydroxyanisole (BHA), were atopic (Fig. 1). 43.6.3 Cosmetics The use of cosmetic products in babies and small children, and particularly those containing balsam of The market for cosmetic products specially formu- Peru (Myroxylon pereirae), has been described as be- lated for children is expanding and habits common ing the cause of a subsequent perfume allergy. Fisher for adults such as going to “beauty farms” are being [49, 50] has reported two such cases: one of a 4- adapted for this young age group. Consequently, one month-old baby and another of an 11-year-old girl, can expect cosmetics to become more important both of whom became sensitized by the application causes of contact allergy and they may become the of a balsam ointment in the diaper area. One later de- most frequent cause of contact allergy in children veloped contact eczema from the mother’s perfume [147]. At least one cosmetic or cosmetic ingredient and the other from a deodorant. gave a positive reaction in 30% of the children inves- Fisher [60] further stated that children often be- tigated. come allergic to cosmetics used by the mother (or the

43 Fig. 1. Allergic contact dermatitis from a play gel containing parabens 43_811_830 05.11.2005 11:37 Uhr Seite 821

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person taking care of them). In a 7-year-old girl with in the case of PPD allergy, and potential problems allergy to cinnamic aldehyde (cinnamal), cheilitis with dark tanned clothing or hair dyes may follow. and perioral dermatitis were caused by the mother’s Eczematous reactions are mostly seen at the site of lipstick that was left after she kissed her. The local- the tattoo and they may be long-lasting. EEM-like izations often involved seem to be the forehead and [66] or lichenoid reactions [71] are also described. the cheeks, with perfume, lipstick, hairspray, or nail Moreover, some patients may develop depigmenta- lacquer as the responsible agents. A PPD allergy in- tion [71, 72] following the acute reaction, and this duced by the mother’s dyed hair was observed in a 12- may persist for a period of several months up to over month-old girl [53]. a year. However, children often use cosmetic products themselves, even though this may not always be revealed immediately! An example of “ectopic” derma- 43.6.5 Toys titis, localized unilaterally on the face and neck, due to surreptitious use of the mother’s nail lacquer illus- Preservatives in play gels have been described as trates this [61]. causes of acute eczema on the hands; in the two cas- Although guidelines for the maximum concentra- es, parabens were found to be the responsible aller- tion of preservatives and fragrances in cosmetics gens [154, 155]. Tosti [156], too, has described two girls have been provided [68], it has been demonstrated who were sensitized by the preservatives meth- that cosmetic toys may contain much higher concen- yl(chloro)isothiazolinone and 2-chloro-N-methyl- trations of fragrance [148]. No extra safety require- chloroacetamide in Plasticine. ments for those products intended for children are Pevny and coworkers [16] observed a 14-year-old required [120]. boy with hand eczema from a model kit, glue, and Contact allergy to the sunscreen agents 4-methyl- firearm accessories: positive patch tests were found benzylidene camphor, isopropyl dibenzoylmethane, with the plastic materials he had come into contact and 2-ethylhexyl methoxycinnamate has been de- with and with benzoyl peroxide, p-tert-butyl cate- scribed in an 18-month-old boy [149]. Shah and co- chol, and p-tert-butyl phenol (present in the glues), workers [32] reported two sunscreen agents as being as well as to potassium dichromate in the gun oil. the cause of photoallergic contact dermatitis. But in- Facial allergy due to contact with a cuddly toy [90] gredients other than the sunscreen may also be re- and from balloons (see below) has been described. sponsible, such as triethanolamine used as an emul- An allergy to rubber from his basketball was also the sifier [150], or recently, polymers added to make for- cause of persistent hand eczema in a 9-year old boy mulations more water resistant, such as polyvinyl- [157]. pyrrolidone-1-triacontene copolymer [151]. Music playing may also provoke eczema: PPD used to stain the bow used to play the cello provoked eczematous lesions of the first three fingers of the 43.6.4 Tattoos right hand in an 11-year-old girl [158]. Colophony used as rosin for the bow or in the gripping powder The practice of temporary henna tattooing has used by gymnasts is also a possible allergen [120]. gained popularity in Western youngsters, especially when on holiday. Whereas contact allergy to henna itself seems to be rare, in tourist areas additives are 43.6.6 Rubber Items added to make the process proceed more rapidly and to obtain a darker pigment. PPD, coffee, oil of euca- Additives in the rubber of balloons may occasionally lyptus, mustard, clove, lemon juice, turpentine, tea cause a facial dermatitis [2, 159], but they may also be and even fresh urine from camels or yaks are exam- responsible for dermatitis in elastic underwear, par- ples of such components [66, 71, 72, 152]. It has been ticularly when bleached [160, 161], in a ball causing demonstrated that the concentration of PPD in some persistent hand eczema [157], in rubber sponges used of these tattoos is higher than that allowed for hair to apply cosmetics [161], and in gloves [159] (al- dyes [153], even although the use of diaminobenzene though a preservative in the glove, cetyl pyridinium derivatives is forbidden in skin dyes [68]. chloride, may be an exceptional allergen as well Contact allergies to PPD, and less frequently to es- [162]). As with balloons, for example, type I allergic sential oils in temporary tattoos are increasingly re- reactions may also occur, sometimes associated with ported in children [66, 71, 72, 152]. These allergies a type IV reaction, as was the case in a 6-year-old boy may have consequences for their future, as certain who had undergone multiple surgical operations and professions become risky (for instance hairdressing) who reacted to both gloves and a rubber dam used in 43_811_830 05.11.2005 11:37 Uhr Seite 822

822 A. Goossens, M. Morren

dentistry [163]. Moreover, contact urticaria syn- Lucky Luke”) was reported by Roul et al [55, 56] drome induced by natural rubber latex proteins is a (Fig. 2). The reaction was provoked by the rubber frequent finding in such children, those suffering parts used for the new anti-leaking system in these from spina bifida being particularly susceptible in diapers. The rubber parts were positive in all children this regard. and in some MBT, cyclohexyl thiophthalimide [57], A particular type of diaper dermatitis reminiscent and PTBP resin were probably present in the glue. of a cowboy’s gunbelt holsters (hence the term “- Rubber additives are also the main allergens responsible for shoe dermatitis (see below). Thiurams, mercapto chemicals and less commonly carbamates are the responsible allergens in rubber allergy in children; thiourea derivatives in neoprene may also be the cause in for example goggles [172], trainers [120] and diving suits (own case). Polyure- thane is usually tolerated and IPPD used in industri- al rubbers is unlikely to be the cause [120].

43.6.7 Shoes and Clothes

Shoe dermatitis generally affects the back of the feet (Fig. 3). Mercaptobenzothiazole and thiuram derivatives, which are present not only in rubber shoes but

Fig. 3. Shoe dermatitis due to thiuram derivatives in an atopic Fig. 2. “Lucky Luke” dermatitis from rubber derivatives in dia- child, complicated by a corticosteroid (triamcinolone-aceto- pers nide) contact allergy 43_811_830 05.11.2005 11:37 Uhr Seite 823

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also in certain glues [15, 124, 164], are important shoe allergens. Other potential culprits are PPD, which is also a possible dye allergen in socks [165], PPD derivatives such as diaminodiphenylmethane [164], and chromates [140, 166]. Trevistan and Kokelj [140] also consider dodecylmercaptane and thimerosal, used as a preservative in leather or leather cream, to be relevant shoe allergens. Topical medication was the most frequent cause of foot dermatitis in a retrospective study by Shackelford and Belsito [167], the allergens of which persist in shoe material for a long time. On the other hand, shoe allergens may persist in cotton socks even when they are washed. When only the soles of the feet are affected, especially the first toe and forefoot, particularly in atopics, juvenile plantar dermatosis is more likely. In Italy, 51 (4.6%) out of 1098 children tested positive to one or more disperse dyes used in synthetic clothes and especially to disperse yellow 3 and disperse orange 3. As only 17% of these children also Fig. 4. Allergic contact dermatitis from plastic toilet seat (presence of para-tertiary-butylphenol-formaldehyde (PTBPF) res- were positive to PPD in the standard series, the au- in to which the child reacted upon patch testing, however, not thors suggest adding disperse dyes to the standard confirmed) series [168].

43.6.8 Plastic Materials and Resins 43.6.9 Plants

Plastic toys as well as glues have been described as Children often come into contact with plants while typical allergen sources for children [16] (see above). playing and do not know about their potential irri- para-Tertiary-butylphenol-formaldehyde (PTBPF) tant, phototoxic (such as in giant hogweed) or aller- resin is the most frequently used phenol-formalde- genic effects. In a review on plant dermatitis in Aus- hyde (PF) resin and is mainly used in neoprene-type tralia [174], children as well as gardeners were con- adhesives and all-purpose glues. sidered at risk. Vincenzi and coworkers [169] reported the case of an adolescent with a linear vesicular dermatitis on the left leg caused by a glue in a knee-guard. There 43.6.9.1 Poison Ivy, Poison Oak, were positive patch tests to PTBPF and PF resins. Poison Sumac Shono and coworkers [170] observed four adolescents who reacted to these resins in an adhesive tape Plants belonging to the Rhus family are the ones used for ankle support. One of them also reacted to most often involved in allergic contact dermatitis sports shoes. It was also reported to be the cause of among children living in northern California. Expo- contact dermatitis to a limb prosthesis in a 5-year old sure can be direct or indirect (such as transfer of the boy [171], and is possibly used as a glue for electrodes allergen via pets), the latter being more difficult to to monitor sudden death in infants (personal obser- diagnose [1]. Mallory [90] reports the possible pres- vation). Phenol-formaldehyde resin and benzoyl per- ence of black spots on the skin caused by the oleore- oxide were reported as the cause of contact allergy to sin in poison ivy as a clue to its diagnosis. swimming goggles in a 12-year old girl; dibutylthiou- rea in black neoprene rubber may also be the cause [172]. 43.6.9.2 Toxicodendron succedaneum Epoxy resin was the cause of a dermatitis due to (Rhus Tree) the glue used to fix kneepads in trousers [90] as well as an allergy to an identification band [51]. Ten cases of phytophotodermatitis from Toxicoden- Not just the resins themselves, but also preserva- dron succedaneum in children under the age of 15 tives, such as benzalkonium chloride in plaster of were reported in New Zealand. Generally, the face Paris, may cause contact allergy [173]. was involved [175]. 43_811_830 05.11.2005 11:37 Uhr Seite 824

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43.6.9.3 Urtica urens 43.6.9.8 Protein Contact Dermatitis

A combined contact urticarial and contact eczema- Oat-containing moisturizers are used for mainte- tous reaction on the hands and arms has been de- nance therapy in atopic dermatitis.Although allergic scribed by Edwards [176]. reactions to these products are rare, a protein contact dermatitis to avena extract has been reported by Paz- zaglia and co-workers [182]. 43.6.9.4 Asteraceae or Compositae

Wakelin and coworkers [177] reported the case of an 43.6.9.9 Various Plant Materials atopic boy with exacerbations of his chronic eczema on the palmar side of his right, dominant hand. Patch Fisher [60] has reported the occurrence of allergic tests revealed positivity to sesquiterpene lactones reactions due to the presence of various plant com- and to chrysanthemums, daisies, and dandelions, ponents or extracts in topically applied products. some of which he fed his rabbits. Moreover, as the use of herbal preparations is dra- Commens and coworkers [178] discussed the matically increasing, contact allergy to “natural” in- problem of Bindii (Soliva pterosperma) dermatitis, gredients such as tea tree oil, especially when photo- which is most often located on the palms,soles,knees aged (sun degraded), Calendula officinalis,and so and elbows, and tends to occur in Australian children on, is becoming more frequent [68]. (mainly boys who play sports) in the spring and early summer. The persistence for several months of er- ythematous papules, and sometimes also squamous 43.6.10 Occupational Allergens and pustular lesions, has been ascribed to a residue of the allergenic seed in the skin. The differential di- Among adolescents, certain occupational activities agnoses include dermatitis herpetiformis. are likely to induce sensitization [23], particularly in hairdressers and construction workers [17,29] and to a lesser extent in metal workers [17]. 43.6.9.5 Lichens Pre-employment patch testing is not recommended, although some authors advocate it, particularly Wood and Rademaker [179] reported a facial derma- with regard to metal allergy [183]. titis in an 8-year old atopic girl, which occurred However, children like to help adults and this may whenever she climbed trees. Patch testing was posi- also produce problems, as in the case reported by Co- tive to lichens and usnic acid, thus indicating Parme- razza and coworkers [184], who reacted to methyl- lia spp. as the sensitization source. chloroisothiazolinone in a beeswax used to polish old wooden furniture. 43.6.9.6 Gingko Fruit Core Message Squashing the fruit of Gingko biloba or using it as marbles has been reported as a cause of allergic con- í Metals, ingredients of pharmaceutical tact dermatitis in children in France [180]. products or cosmetics, rubber additives (in shoes, toys, diapers, sports equipment, and so on), plastics, resins (including those 43.6.9.7 Dioscorea batatas Decaisne used in glues, orthopedic devices), and plants are allergens in children. In adoles- Kubo and coworkers [181] described the case of a 9- cents, sensitization via temporary tattoos year-old girl who had accidentally touched her cheek or occupational allergens are also possible. with the rasped root of this plant, which resulted in the development of both an irritant and an allergic 43 contact dermatitis. 43_811_830 05.11.2005 11:37 Uhr Seite 825

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43.7 Proposal for a Shortened Standard Table 3. Suggested abbreviated standard patch test series for children Series for Children 1. Potassium dichromate 0.5% pet. In view of the lack of chemical exposure of children 2. Neomycin 20% pet. compared to that of adults and the smaller patch test 3. Thiuram mix 1% pet. area, especially with younger children, Vigan [185] 4. PPD-free base 1% pet. and Brasch and Geier [31] proposed testing with an 5. Cobalt chloride 1% pet. abbreviated standard patch test series of 16 allergens. 6. Formaldehyde 1% aq. This was based on the results of four studies [17, 18, 7. Colophony (colophonium) 20% pet. 23, 140]. Roul and coworkers [36] also suggest reduc- 8. Balsam of Peru (Myroxylon pereirae) 25% pet. ing the number of tests: in children up to 6 years old 9. Woolwax alcohols (lanolin alcohol) 30% pet. a series of 17 allergens, and in older children a re- 10. Mercapto mix 2% pet. stricted European standard series of 29 allergens. 11. Paraben mix 16% pet. These tests have to be completed with allergens de- 12. PTBP-FR 1% pet. pending on the symptoms and localization of the dermatitis. 13. Fragrance mix 8% pet. A multicenter retrospective study performed by 14. Nickel sulfate 5% pet. the Réseau de Vigilance en Dermato-Allergologie 15. Chloromethyl- and methyl- 0.01% aq. (Revidal) created by the Groupe d’Etudes et de Re- isothiazolinone cherche en Dermato-Allergologie (GERDA, France) 16. Mercaptobenzothiazole 2% pet. examined the patch test results of 959 children below the age of 15 tested at 11 different centers from 1995 to 1997. The purpose of this study was mainly to determine the usefulness of standard allergens in chil- 0.1% pet. (besides the corticosteroids used by the pa- dren. tient) is indicated. Of course, according to the specif- The following ten allergens were tested in all cen- ic history and chemical environment of the patient, ters: potassium dichromate, neomycin, thiuram mix, other substances should also be tested. formaldehyde, colophony, balsam of Peru, paraben mix, woolwax alcohols, fragrance mix, and nickel sul- Core Message fate. Other standard allergens were often tested too: PPD, cobalt chloride, benzocaine, chinoform, IPPD, mercapto mix, mercaptobenzothiazole, PTBP-FR, í In children, an abbreviated standard series, epoxy resin, methyl(chloro)isothiazolinone, quater- supplemented with allergens suggested by nium-15, sesquiterpene lactone mix, and even pri- the history, should be tested. min. The results [186] were as follows:

í Primine: no reactions 43.8 Conclusions í Benzocaine, chinoform, IPPD, epoxy resin, quaternium-15, sesquiterpene lactone mix: Contact allergy in children is more frequent than <1% previously recognized. In an unselected population, í All other allergens: >1% of the patients tested. for instance one consisting of schoolchildren, the prevalence is about 20%, while in a selected popula- This argues for the inclusion of PPD, cobalt chloride, tion (children suspected of contact allergy or suffer- mercapto mix, mercaptobenzothiazole, PTBP resin, ing from atopic or other types of dermatitis) the and methyl(chloro)isothiazolinone in the standard prevalence is found to be variable, for example relat- series, because reactions to them occurred in more ed to geographical origin, with a mean of 40%. than 1% of patients tested. Immunological differences between children (es- IPPD and sesquiterpene lactone mix can be ex- pecially neonates) and adults do exist, but their im- cluded, which reduces the series to 16 standard aller- pact on the clinical development of contact allergy is gens (Table 3). In cases where corticosteroids have still unknown. Although allergic contact dermatitis been used, testing with corticosteroid allergy mark- has occasionally been observed in neonates, it is gen- ers, tixocortol pivalate 0.1% pet. and budesonide erally agreed that susceptibility to contact sensitiza- 43_811_830 05.11.2005 11:37 Uhr Seite 826

826 A. Goossens, M. Morren

tion and certainly also exposure to environmental al- Suggested Reading lergens increase with the child’s age. Whether allergic contact dermatitis is more or less Brasch J, Geier J (1997) Patch test results in schoolchildren. frequently associated with atopy is still a matter of Contact Dermatitis 37 : 286–293 discussion. On the one hand, there is the reduced Th1 In a retrospective study in 22 German centers of the Ger- response in acute atopic eczema, so atopics are less man Contact Dermatitis Research Group, the results from patch tests in children 6–15 years of age were analyzed. The likely to develop contact allergy; on the other hand, allergens were related to sex and age. Nickel sulfate was the the damaged skin barrier facilitates allergen penetra- most important allergen (positive in 15.9% of all children), tion. The possibility of allergic contact dermatitis in especially in older girls. Mercury components were the sec- atopic children must be considered, particularly if ond most important group (thimerosal positive in 11.3% of the distribution of the lesions is asymmetrical, when all children tested), and especially important in the younger age group (6–13 years); this was followed by fragrance al- the dermatitis is located umbilically (nickel!), and lergens (fragrance mix positive in 8.2% of all children test- when the dermatitis persists when being treated. ed). For screening purposes a shortened standard series As with adults, the history and localization of the comprising nickel, cobalt, dichromate, thimerosal, fra- dermatitis are crucial for the diagnosis of allergic grance-allergens, wool wax alcohols, amerchol and methyl- contact dermatitis, though certain contactants chloro- and methylisothiazolinone, all of which produced positive tests in at least 1% of the tested children, was sug- and/or habits that are characteristic of the child or gested. the adolescent may be responsible for unusual clini- Wahlberg JE, Goossens A (2001) Use of patch test concentra- cal presentations. tions for adults in children and their influence on test reac- Patch testing in children is safe; most authors tivity. Occup Environ Dermatol 49 : 97–101 A comparison between positive patch test results obtained think that irritant reactions are not frequently ob- in healthy children with non-eczematous dermatoses and served (except in atopics, particularly with metals) those obtained in adults gave much higher percentages in and that the same patch test concentrations as used children than in adults, which indicates that contact aller- in adults can be applied. However, the possibility of gy was over-diagnosed in children. The authors favored the false-positive and false-negative reactions has to be use of reduced test concentrations in children for allergens, such as potassium dichromate, nickel sulfate, formalde- considered and, if there is doubt, lower patch test hyde, and possibly also for rubber chemicals. A “wish list” concentrations should be tested later on. for improving patch testing in children includes: more Due to reduced test surface area, diminished envi- studies in healthy children, comparison with in vitro tests, ronmental exposure to certain allergens and particu- defined dosage and dilution series studies, as well as re- larly hypermobility of young children, testing with peated patch testing in order to demonstrate reproducibility. For individual children, serial dilution tests, repeated an abbreviated standard series is recommended. testing, use tests (though difficult in children), but above The most important allergens observed in this all a clinical follow-up are useful if doubt exists about the population are metals such as nickel (sometimes as- patch test results. sociated with cobalt), particularly in girls, which is attributed to the popularity of cheap jewelry. The extent to which hormonal factors play a role is still a References matter of discussion. Mercury and its derivatives are still used as antiseptic agents in some countries, but 1. Epstein E (1971) Contact dermatitis in children. Pediatr the allergic reactions observed to them, even in Clin North Am 18 : 839–852 2. Cronin E (1980) Contact dermatitis. Churchill Living- young children, are often not clinically relevant. This stone, Edinburgh, pp 20–21 is particularly true for thimerosal, for which vaccines 3. Hjorth N (1981) Contact dermatitis in children. Acta have been regarded as the main sensitization source. Derm Venerol (Stockh) 95 : 36–39 However, such an allergy does not seem to preclude 4. Tennstedt D, Lachapelle JM (1987) Eczéma de contact al- lergique chez l´enfant. Bull Actual Thérap 32 : 3223–3228 future vaccinations, provided the tip of the needle is 5. Pevny I,Brennenstuhl M,Razinskas G (1984) Patch testing not contaminated and the injection is administered in children (1). Contact Dermatitis 11 : 201–206 intramuscularly. 6. Marcussen PV (1963) Primary irritant patch-test reac- Other allergens identified in children mainly con- tions in children. Arch Dermatol 87 : 378–382 cern ingredients of pharmaceutical products and 7. Mortz CG, Andersen KE (1999) Allergic contact dermatitis in children and adolescents. Contact Dermatitis 41 : cosmetics (sometimes via another member of the 121–130 household), rubber derivatives, which are often re- 8. Weston WL, Weston JA (1984) Allergic contact dermatitis 43 sponsible for shoe or diaper dermatitis, resins, and in children. Am J Dis Child 138 : 932–936 plants. Certain occupational allergens (such as those 9. Weston WL,Weston JA,Kinoshita J,Kloepfer S,Carreon L, associated with hairdressing, construction, metal- Toth S, Bullard D, Harper K, Martinez S (1986) Prevalence of positive epicutaneous tests among infants, children, working) are found in adolescents. and adolescents. Pediatrics 78 : 1070–1074 43_811_830 05.11.2005 11:37 Uhr Seite 827

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