Patch-test results in children and adolescents: systematic review of a 15-year period*
Identifieur interne : 000058 ( Pmc/Corpus ); précédent : 000057; suivant : 000059Patch-test results in children and adolescents: systematic review of a 15-year period*
Auteurs : Dulcilea Ferraz Rodrigues ; Eugênio Marcos Andrade GoulartSource :
- Anais Brasileiros de Dermatologia [ 0365-0596 ] ; 2016.
Abstract
The number of studies on patch-test results in children and adolescents has gradually increased in recent years, thus stimulating reviews. This paper is a systematic review of a 15-year period devoted to studying the issue. Variations pertaining to the number and age groups of tested children and/or adolescents, the number of subjects with atopy/atopic dermatitis history, the quantity, type and concentrations of the tested substances, the test technique and type of data regarding clinical relevance, must all be considered in evaluating these studies, as they make it harder to formulate conclusions. The most common allergens in children were nickel, thimerosal, cobalt, fragrance, lanolin and neomycin. In adolescents, they were nickel, thimerosal, cobalt, fragrance, potassium dichromate, and Myroxylon pereirae. Knowledge of this matter aids health professionals in planning preventive programs aimed at improving children's quality of life and ensuring that their future prospects are not undermined.
Url:
DOI: 10.1590/abd1806-4841.20163927
PubMed: 26982781
PubMed Central: 4782649
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PMC:4782649Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Patch-test results in children and adolescents: systematic review of
a 15-year period<xref ref-type="fn" rid="fn1">*</xref></title><author><name sortKey="Rodrigues, Dulcilea Ferraz" sort="Rodrigues, Dulcilea Ferraz" uniqKey="Rodrigues D" first="Dulcilea Ferraz" last="Rodrigues">Dulcilea Ferraz Rodrigues</name><affiliation><nlm:aff id="aff1">Santa Casa de Misericórdia de Belo Horizonte - Belo Horizonte (MG), Brazil.</nlm:aff></affiliation></author><author><name sortKey="Goulart, Eugenio Marcos Andrade" sort="Goulart, Eugenio Marcos Andrade" uniqKey="Goulart E" first="Eugênio Marcos Andrade" last="Goulart">Eugênio Marcos Andrade Goulart</name><affiliation><nlm:aff id="aff2">Universidade Federal de Minas Gerais (UFMG) - Belo Horizonte (MG), Brazil.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26982781</idno><idno type="pmc">4782649</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782649</idno><idno type="RBID">PMC:4782649</idno><idno type="doi">10.1590/abd1806-4841.20163927</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000058</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000058</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Patch-test results in children and adolescents: systematic review of
a 15-year period<xref ref-type="fn" rid="fn1">*</xref></title><author><name sortKey="Rodrigues, Dulcilea Ferraz" sort="Rodrigues, Dulcilea Ferraz" uniqKey="Rodrigues D" first="Dulcilea Ferraz" last="Rodrigues">Dulcilea Ferraz Rodrigues</name><affiliation><nlm:aff id="aff1">Santa Casa de Misericórdia de Belo Horizonte - Belo Horizonte (MG), Brazil.</nlm:aff></affiliation></author><author><name sortKey="Goulart, Eugenio Marcos Andrade" sort="Goulart, Eugenio Marcos Andrade" uniqKey="Goulart E" first="Eugênio Marcos Andrade" last="Goulart">Eugênio Marcos Andrade Goulart</name><affiliation><nlm:aff id="aff2">Universidade Federal de Minas Gerais (UFMG) - Belo Horizonte (MG), Brazil.</nlm:aff></affiliation></author></analytic><series><title level="j">Anais Brasileiros de Dermatologia</title><idno type="ISSN">0365-0596</idno><idno type="eISSN">1806-4841</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The number of studies on patch-test results in children and adolescents has
gradually increased in recent years, thus stimulating reviews. This paper is a
systematic review of a 15-year period devoted to studying the issue. Variations
pertaining to the number and age groups of tested children and/or adolescents,
the number of subjects with atopy/atopic dermatitis history, the quantity, type
and concentrations of the tested substances, the test technique and type of data
regarding clinical relevance, must all be considered in evaluating these
studies, as they make it harder to formulate conclusions. The most common
allergens in children were nickel, thimerosal, cobalt, fragrance, lanolin and
neomycin. In adolescents, they were nickel, thimerosal, cobalt, fragrance,
potassium dichromate, and Myroxylon pereirae. Knowledge of this matter aids
health professionals in planning preventive programs aimed at improving
children's quality of life and ensuring that their future prospects are not
undermined.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bonitsis, Ng" uniqKey="Bonitsis N">NG Bonitsis</name></author><author><name sortKey="Tatsioni, A" uniqKey="Tatsioni A">A Tatsioni</name></author><author><name sortKey="Bassioukas, K" uniqKey="Bassioukas K">K Bassioukas</name></author><author><name sortKey="Ioannidis, Jp" uniqKey="Ioannidis J">JP ioannidis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mortz, Cg" uniqKey="Mortz C">CG Mortz</name></author><author><name sortKey="Andersen, Ke" uniqKey="Andersen K">KE Andersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spiewak, R" uniqKey="Spiewak R">R Spiewak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sharma, Vk" uniqKey="Sharma V">VK Sharma</name></author><author><name sortKey="Asati, Dp" uniqKey="Asati D">DP 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<front><journal-meta><journal-id journal-id-type="nlm-ta">An Bras Dermatol</journal-id><journal-id journal-id-type="iso-abbrev">An Bras Dermatol</journal-id><journal-id journal-id-type="publisher-id">abd</journal-id><journal-title-group><journal-title>Anais Brasileiros de Dermatologia</journal-title></journal-title-group><issn pub-type="ppub">0365-0596</issn><issn pub-type="epub">1806-4841</issn><publisher><publisher-name>Sociedade Brasileira de Dermatologia</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26982781</article-id><article-id pub-id-type="pmc">4782649</article-id><article-id pub-id-type="doi">10.1590/abd1806-4841.20163927</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Patch-test results in children and adolescents: systematic review of
a 15-year period<xref ref-type="fn" rid="fn1">*</xref></article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Rodrigues</surname><given-names>Dulcilea Ferraz</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="corresp" rid="c1"></xref></contrib><contrib contrib-type="author"><name><surname>Goulart</surname><given-names>Eugênio Marcos Andrade</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Santa Casa de Misericórdia de Belo Horizonte - Belo Horizonte (MG), Brazil.</aff><aff id="aff2"><label>2</label>Universidade Federal de Minas Gerais (UFMG) - Belo Horizonte (MG), Brazil.</aff><author-notes><corresp id="c1">Mailing address: Dulcilea Ferraz Rodrigues, Av. Bernardo Monteiro,
890, sala 603, Bairro Santa Efigênia, 30150-281 - Belo Horizonte - MG,
Brazil.<email>dulcilea.ferraz@gmail.com</email></corresp></author-notes><pub-date pub-type="epub-ppub"><season>Jan-Feb</season><year>2016</year></pub-date><pmc-comment>Fake ppub date generated by PMC from publisher
pub-date/@pub-type='epub-ppub' </pmc-comment>
<pub-date pub-type="ppub"><season>Jan-Feb</season><year>2016</year></pub-date><volume>91</volume><issue>1</issue><fpage>64</fpage><lpage>72</lpage><history><date date-type="received"><day>10</day><month>8</month><year>2014</year></date><date date-type="accepted"><day>01</day><month>9</month><year>2014</year></date></history><permissions><copyright-statement>© 2016 by Anais Brasileiros de
Dermatologia</copyright-statement><copyright-year>2016</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/"><license-p>This is an Open Access article distributed under the terms of the
Creative Commons Attribution Non-Commercial License which permits
unrestricted non-commercial use, distribution, and reproduction in any
medium provided the original work is properly cited.</license-p></license></permissions><abstract><p>The number of studies on patch-test results in children and adolescents has
gradually increased in recent years, thus stimulating reviews. This paper is a
systematic review of a 15-year period devoted to studying the issue. Variations
pertaining to the number and age groups of tested children and/or adolescents,
the number of subjects with atopy/atopic dermatitis history, the quantity, type
and concentrations of the tested substances, the test technique and type of data
regarding clinical relevance, must all be considered in evaluating these
studies, as they make it harder to formulate conclusions. The most common
allergens in children were nickel, thimerosal, cobalt, fragrance, lanolin and
neomycin. In adolescents, they were nickel, thimerosal, cobalt, fragrance,
potassium dichromate, and Myroxylon pereirae. Knowledge of this matter aids
health professionals in planning preventive programs aimed at improving
children's quality of life and ensuring that their future prospects are not
undermined.</p></abstract><kwd-group><kwd>Adolescent</kwd><kwd>Allergens</kwd><kwd>Child</kwd><kwd>Dermatitis</kwd><kwd>Dermatitis, allergic contact</kwd><kwd>Dermatitis, contact</kwd><kwd>Patch-tests</kwd></kwd-group></article-meta></front><body><sec sec-type="intro"><title>INTRODUCTION</title><p>The increase in the number of published studies on patch-test results in children and
adolescents has contributed vast knowledge on the subject and shown that contact
sensitization (or contact allergy) and allergic contact dermatitis (ACD) are not
uncommon in childhood or adolescence, contrary to what was believed.<sup><xref rid="r1" ref-type="bibr">1</xref></sup></p><p>Most of these studies were based on selected populations: children and adolescents
with suspected ACD, many with a diagnosis of atopic dermatitis (AD). There are few
studies that examine the general population.<sup><xref rid="r2" ref-type="bibr">2</xref>,<xref rid="r3" ref-type="bibr">3</xref></sup> Many papers present
contact sensitization frequency data, without data on the positive tests' clinical
relevance or conclusions on ACD frequency.<sup><xref rid="r2" ref-type="bibr">2</xref>,<xref rid="r4" ref-type="bibr">4</xref>,<xref rid="r5" ref-type="bibr">5</xref></sup> The higher frequency of positive patch-tests in
children aged under 3 years has indicated that contact sensitization may occur early
in life. The association between atopy and ACD has been studied and still presents
controversial results.<sup><xref rid="r2" ref-type="bibr">2</xref></sup></p><p>Dermatologists, pediatricians and allergologists pursue a valuable interest in
identifying the substance causing ACD, differentiating it from other dermatoses and
identifying the possible coexistence of AD and ACD in patients.</p><p>Nowadays, children and adolescents frequently use cosmetics (fragrances, makeup, nail
polish, etc.) and adornments (Henna tattoo, jewelry, piercing, etc.) that can be
sources of potential allergens.<sup><xref rid="r6" ref-type="bibr">6</xref>-<xref rid="r10" ref-type="bibr">10</xref></sup> Therefore, it is justifiable to
expect a higher number of positive reactions to patch-tests among these age
groups.</p><p>The objective of this study is to perform a systematic review, gathering and
synthesizing information about patch-test results in children and adolescents
published during a 15-year period, thus enhancing our knowledge.</p></sec><sec sec-type="materials|methods"><title>MATERIALS AND METHODS</title><p>A literature search to find descriptors for this systematic review was undertaken via
six databases: BVS COCHRANE, BVS LILACS, BVS IBECS, BVS MEDLINE, Web of Science and
PUBMED. It used the following terms: patch-test, contact sensitization, contact
allergy, contact hyper sensitization, allergic contact dermatitis, and contact
eczema. Filters were placed for age (children and/or adolescents aged up to 19
years; classification adopted by the World Health Organization), study period
(January 1997 to May 2012) and language (Portuguese, English and Spanish). A study
was selected with patients aged up to 20 years, taking into account the sample size
(n=2340) and lack of Asian studies in this review.</p><p>Seventy articles were picked out. All the data about the subjects' characteristics
and patch-test results from 48 articles were recorded and catalogued in specific
forms, which were divided into three categories:</p><list list-type="order"><list-item><p>Studies with selected samples (34): patients with suspected ACD.</p></list-item><list-item><p>Studies with no selected samples (2): children and/or adolescents with no
suspected ACD.</p></list-item><list-item><p>Studies with selected (9) and non-selected (3) samples with specific
focus.</p></list-item></list><p>Categories 1 and 2 include articles presenting samples of at least 50 children and/or
adolescents, in addition to data on the frequency results of tested substances.
Category 3 includes specific articles, with greater flexibility regarding the
data.</p></sec><sec><title>STUDIES IN SELECTED SAMPLES: PATIENTS WITH SUSPECTED ALLERGIC CONTACT
DERMATITIS</title><sec><title>1.Country, period, number of centers and delineation of studies</title><p>The data were organized according to the study period intending the evaluation of
the tests results temporal evolution (<xref ref-type="table" rid="t01">Table
1</xref>).</p><table-wrap id="t01" orientation="portrait" position="float"><label>Table 1</label><caption><p>Patch-test results in selected groups of children and adolescents with
suspected allergic contact dermatitis (34 selected groups)</p></caption><table frame="hsides" rules="groups"><thead><tr><th rowspan="1" colspan="1">Author Country</th><th rowspan="1" colspan="1">Data Collection, years</th><th rowspan="1" colspan="1">N° of children and adolescents tested</th><th rowspan="1" colspan="1">Age</th><th rowspan="1" colspan="1">Adolescents and children with >1 positive reaction (%)</th><th rowspan="1" colspan="1">Relevance<xref ref-type="table-fn" rid="TFN1">*</xref> of
positive tests (%)</th><th rowspan="1" colspan="1">Two most common allergens Frequency of positive reactions</th></tr></thead><tbody><tr><td rowspan="1" colspan="1">Goon et al.<sup><xref rid="r11" ref-type="bibr">11</xref></sup></td><td rowspan="1" colspan="1">1986-2003</td><td rowspan="1" colspan="1">2340</td><td rowspan="1" colspan="1">< 20 years</td><td rowspan="1" colspan="1">45.4</td><td rowspan="1" colspan="1">Calculated per substance</td><td rowspan="1" colspan="1">Nickel 40.0%</td></tr><tr><td rowspan="1" colspan="1">Singapore</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Thimerosal 15.0%</td></tr><tr><td rowspan="1" colspan="1">Manzini et al.<sup><xref rid="r12" ref-type="bibr">12</xref></sup></td><td rowspan="1" colspan="1">1988-1994</td><td rowspan="1" colspan="1">670</td><td rowspan="1" colspan="1">6 months-12 years</td><td rowspan="1" colspan="1">42.0</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Thimerosal 12.2%</td></tr><tr><td rowspan="1" colspan="1">Italy</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Nickel 7.7%</td></tr><tr><td rowspan="1" colspan="1">Brash et al.<sup><xref rid="r13" ref-type="bibr">13</xref></sup></td><td rowspan="1" colspan="1">1990-1995</td><td rowspan="1" colspan="1">416</td><td rowspan="1" colspan="1">6-15 years</td><td rowspan="1" colspan="1">40.9</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Nickel 15.9%</td></tr><tr><td rowspan="1" colspan="1">Germany</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Thimerosal 11.3%</td></tr><tr><td rowspan="1" colspan="1">Fernandez et al.<sup><xref rid="r14" ref-type="bibr">14</xref></sup></td><td rowspan="1" colspan="1">1990-2000</td><td rowspan="1" colspan="1">96</td><td rowspan="1" colspan="1">< 15 years</td><td rowspan="1" colspan="1">54.2</td><td rowspan="1" colspan="1">57.7</td><td rowspan="1" colspan="1">Thimerosal 21.0%</td></tr><tr><td rowspan="1" colspan="1">Spain</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Mercury 19.0%</td></tr><tr><td rowspan="1" colspan="1">Shah et al.<sup><xref rid="r15" ref-type="bibr">15</xref></sup></td><td rowspan="1" colspan="1">1991-1995</td><td rowspan="1" colspan="1">83</td><td rowspan="1" colspan="1">6-16 years</td><td rowspan="1" colspan="1">49.0</td><td rowspan="1" colspan="1">100.0</td><td rowspan="1" colspan="1">Nickel 14.0%</td></tr><tr><td rowspan="1" colspan="1">UK</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Fragrance mix I 7.2%</td></tr><tr><td rowspan="1" colspan="1">Romaguera et al.<sup><xref rid="r16" ref-type="bibr">16</xref></sup></td><td rowspan="1" colspan="1">1992-1997</td><td rowspan="1" colspan="1">141</td><td rowspan="1" colspan="1">< 14 years</td><td rowspan="1" colspan="1">50.0</td><td rowspan="1" colspan="1">calculated per substance</td><td rowspan="1" colspan="1">Nickel 19.1%</td></tr><tr><td rowspan="1" colspan="1">Spain</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Cobalt 11.3%</td></tr><tr><td rowspan="1" colspan="1">Lewis et al.<sup><xref rid="r17" ref-type="bibr">17</xref></sup></td><td rowspan="1" colspan="1">1993-2003</td><td rowspan="1" colspan="1">191</td><td rowspan="1" colspan="1">< 16 years</td><td rowspan="1" colspan="1">41.0</td><td rowspan="1" colspan="1">51.7</td><td rowspan="1" colspan="1">Nickel 13.0%</td></tr><tr><td rowspan="1" colspan="1">UK</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Fragrance mix I 9.0%</td></tr><tr><td rowspan="1" colspan="1">Onder et al.<sup><xref rid="r18" ref-type="bibr">18</xref></sup></td><td rowspan="1" colspan="1">1993-2005</td><td rowspan="1" colspan="1">360</td><td rowspan="1" colspan="1">2-16 years</td><td rowspan="1" colspan="1">32.0</td><td rowspan="1" colspan="1">30.5%</td><td rowspan="1" colspan="1">Nickel 46.0%</td></tr><tr><td rowspan="1" colspan="1">Turkey</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Cobalt 9.5%</td></tr><tr><td rowspan="1" colspan="1">Milingou et al.<sup><xref rid="r19" ref-type="bibr">19</xref></sup></td><td rowspan="1" colspan="1">1994-2007</td><td rowspan="1" colspan="1">255</td><td rowspan="1" colspan="1"><16 years</td><td rowspan="1" colspan="1">60.0</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Nickel 21.6%</td></tr><tr><td rowspan="1" colspan="1">Greece</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Thimerosal 18.3%</td></tr><tr><td rowspan="1" colspan="1">Kuljanac et al.<sup><xref rid="r20" ref-type="bibr">20</xref></sup></td><td rowspan="1" colspan="1">1994-2009</td><td rowspan="1" colspan="1">412</td><td rowspan="1" colspan="1">4-18 years</td><td rowspan="1" colspan="1">26.0</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Nickel 25.4%</td></tr><tr><td rowspan="1" colspan="1">Croatia</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Thimerosal 17.8%</td></tr><tr><td rowspan="1" colspan="1">Roul et al.<sup><xref rid="r21" ref-type="bibr">21</xref></sup></td><td rowspan="1" colspan="1">1995-1997</td><td rowspan="1" colspan="1">337</td><td rowspan="1" colspan="1">1-15 years</td><td rowspan="1" colspan="1">67.0</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Nickel 23.7%</td></tr><tr><td rowspan="1" colspan="1">France</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Fragrance mix I 9.5%</td></tr><tr><td rowspan="1" colspan="1">Seidenari et al.<sup><xref rid="r22" ref-type="bibr">22</xref></sup></td><td rowspan="1" colspan="1">1995-2001</td><td rowspan="1" colspan="1">1094</td><td rowspan="1" colspan="1">7 months-12 years</td><td rowspan="1" colspan="1">52.1</td><td rowspan="1" colspan="1">70.0</td><td rowspan="1" colspan="1">Neomycin 13.2%</td></tr><tr><td rowspan="1" colspan="1">Italy</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Nickel 10.9%</td></tr><tr><td rowspan="1" colspan="1">Heine et al.<sup><xref rid="r23" ref-type="bibr">23</xref></sup></td><td rowspan="1" colspan="1">1995-2002</td><td rowspan="1" colspan="1">2460</td><td rowspan="1" colspan="1">6-12 years</td><td rowspan="1" colspan="1">52.6</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Thimerosal 18.2%</td></tr><tr><td rowspan="1" colspan="1">Germany</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">13-18 years</td><td rowspan="1" colspan="1">49.7</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Nickel 16.7%</td></tr><tr><td rowspan="1" colspan="1">Clayton et al.<sup><xref rid="r24" ref-type="bibr">24</xref></sup></td><td rowspan="1" colspan="1">1995-2004</td><td rowspan="1" colspan="1">500</td><td rowspan="1" colspan="1">< 16 years</td><td rowspan="1" colspan="1">27.0</td><td rowspan="1" colspan="1">61.0</td><td rowspan="1" colspan="1">Nickel 33.0%</td></tr><tr><td rowspan="1" colspan="1">UK</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Fragrance mix I 18.0%</td></tr><tr><td rowspan="1" colspan="1">Duarte et al.<sup><xref rid="r25" ref-type="bibr">25</xref></sup></td><td rowspan="1" colspan="1">1996-2001</td><td rowspan="1" colspan="1">102</td><td rowspan="1" colspan="1">10-19 years</td><td rowspan="1" colspan="1">56.0</td><td rowspan="1" colspan="1">100.0</td><td rowspan="1" colspan="1">Nickel 31.0%</td></tr><tr><td rowspan="1" colspan="1">Brazil</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Tosylamide 12.0%<xref ref-type="table-fn" rid="TFN2">†</xref></td></tr><tr><td rowspan="1" colspan="1">Hogeling et al.<sup><xref rid="r26" ref-type="bibr">26</xref></sup></td><td rowspan="1" colspan="1">1996-2006</td><td rowspan="1" colspan="1">100</td><td rowspan="1" colspan="1">4-18 years</td><td rowspan="1" colspan="1">70.0</td><td rowspan="1" colspan="1">55.8</td><td rowspan="1" colspan="1">Nickel 26.0%</td></tr><tr><td rowspan="1" colspan="1">Canada</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Cobalt 14.0%</td></tr><tr><td rowspan="1" colspan="1">Wohrl et al.<sup><xref rid="r27" ref-type="bibr">27</xref></sup></td><td rowspan="1" colspan="1">1997-2000</td><td rowspan="1" colspan="1">79</td><td rowspan="1" colspan="1">1-10 years</td><td rowspan="1" colspan="1">62.0</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Nickel 34.2%</td></tr><tr><td rowspan="1" colspan="1">Austria</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Ethylmercury 25.3%<xref ref-type="table-fn" rid="TFN3">‡</xref></td></tr><tr><td rowspan="1" colspan="1">Giordano et al.<sup><xref rid="r28" ref-type="bibr">28</xref></sup></td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">137</td><td rowspan="1" colspan="1">4 months-16 years</td><td rowspan="1" colspan="1">43.0</td><td rowspan="1" colspan="1">100.0</td><td rowspan="1" colspan="1">Nickel 14.9%</td></tr><tr><td rowspan="1" colspan="1">France</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Fragrance mix I 4.4%</td></tr><tr><td rowspan="1" colspan="1">Beattie et al.<sup><xref rid="r29" ref-type="bibr">29</xref></sup></td><td rowspan="1" colspan="1">1999-2002</td><td rowspan="1" colspan="1">114</td><td rowspan="1" colspan="1">3-15 years</td><td rowspan="1" colspan="1">54.0</td><td rowspan="1" colspan="1">54.0</td><td rowspan="1" colspan="1">Nickel 20.0%</td></tr><tr><td rowspan="1" colspan="1">UK</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Fragrance mix I 7.2%</td></tr><tr><td rowspan="1" colspan="1">Hammonds et al.<sup><xref rid="r30" ref-type="bibr">30</xref></sup></td><td rowspan="1" colspan="1">2000-2006</td><td rowspan="1" colspan="1">136</td><td rowspan="1" colspan="1">3-18 years</td><td rowspan="1" colspan="1">61.0</td><td rowspan="1" colspan="1">53.0</td><td rowspan="1" colspan="1">Nickel 22.0%</td></tr><tr><td rowspan="1" colspan="1">USA</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Cobalt 17.0%</td></tr><tr><td rowspan="1" colspan="1">Zug et al.<sup><xref rid="r31" ref-type="bibr">31</xref></sup></td><td rowspan="1" colspan="1">2001-2004</td><td rowspan="1" colspan="1">391</td><td rowspan="1" colspan="1">0-18 years</td><td rowspan="1" colspan="1">65.7</td><td rowspan="1" colspan="1">51.2<xref ref-type="table-fn" rid="TFN4">§</xref></td><td rowspan="1" colspan="1">Nickel 28.3%</td></tr><tr><td rowspan="1" colspan="1">USA, Canada</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Cobalt 17.8%</td></tr><tr><td rowspan="1" colspan="1">Jacob et al.<sup><xref rid="r32" ref-type="bibr">32</xref></sup></td><td rowspan="1" colspan="1">2001-2006</td><td rowspan="1" colspan="1">65</td><td rowspan="1" colspan="1">1-18 years</td><td rowspan="1" colspan="1">83.0</td><td rowspan="1" colspan="1">77.0</td><td rowspan="1" colspan="1">Nickel 17.5%</td></tr><tr><td rowspan="1" colspan="1">USA</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Thimerosal 12.5%</td></tr><tr><td rowspan="1" colspan="1">Fortina et al.<sup><xref rid="r33" ref-type="bibr">33</xref></sup></td><td rowspan="1" colspan="1">2002-2008</td><td rowspan="1" colspan="1">321</td><td rowspan="1" colspan="1">3-36 months </td><td rowspan="1" colspan="1">62.3</td><td rowspan="1" colspan="1">calculated per substance</td><td rowspan="1" colspan="1">Nickel 26.8%</td></tr><tr><td rowspan="1" colspan="1">Italy</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">substance</td><td rowspan="1" colspan="1">Potassium dich.9.0%<xref ref-type="table-fn" rid="TFN5">|</xref></td></tr><tr><td rowspan="1" colspan="1">Moustafa et al.<sup><xref rid="r34" ref-type="bibr">34</xref></sup></td><td rowspan="1" colspan="1">2002-2008</td><td rowspan="1" colspan="1">110</td><td rowspan="1" colspan="1">2-18 years</td><td rowspan="1" colspan="1">44.0</td><td rowspan="1" colspan="1">44.0</td><td rowspan="1" colspan="1">Drugs 15.4%</td></tr><tr><td rowspan="1" colspan="1">UK</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Nickel 10.0%</td></tr><tr><td rowspan="1" colspan="1">de Waard-van der Spek et al.<sup><xref rid="r35" ref-type="bibr">35</xref></sup></td><td rowspan="1" colspan="1">2003-2008</td><td rowspan="1" colspan="1">79</td><td rowspan="1" colspan="1">1-18 years</td><td rowspan="1" colspan="1">51.0</td><td rowspan="1" colspan="1">calculated per substance</td><td rowspan="1" colspan="1">Nickel 21.5%</td></tr><tr><td rowspan="1" colspan="1">Netherlands</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Potassium dich. 6.0%<xref ref-type="table-fn" rid="TFN5">|</xref></td></tr><tr><td rowspan="1" colspan="1">Jacob et al.<sup><xref rid="r36" ref-type="bibr">36</xref></sup></td><td rowspan="1" colspan="1">2004-2006</td><td rowspan="1" colspan="1">69</td><td rowspan="1" colspan="1">6 months-18 years</td><td rowspan="1" colspan="1">95.6</td><td rowspan="1" colspan="1">76.7</td><td rowspan="1" colspan="1">Nickel 23.3%</td></tr><tr><td rowspan="1" colspan="1">USA</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Cocamido 23.3%<xref ref-type="table-fn" rid="TFN6">¶</xref></td></tr><tr><td rowspan="1" colspan="1">Stoskute et al.<sup><xref rid="r37" ref-type="bibr">37</xref></sup></td><td rowspan="1" colspan="1">not reported<xref ref-type="table-fn" rid="TFN7">#</xref></td><td rowspan="1" colspan="1">194</td><td rowspan="1" colspan="1">3-17 years</td><td rowspan="1" colspan="1">55.0</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Nickel 18.0%</td></tr><tr><td rowspan="1" colspan="1">Lithuania</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Cobalt 13.8%</td></tr><tr><td rowspan="1" colspan="1">Belhadjalli et al.<sup><xref rid="r38" ref-type="bibr">38</xref></sup></td><td rowspan="1" colspan="1">2005-2006</td><td rowspan="1" colspan="1">63</td><td rowspan="1" colspan="1">mean: 69 months</td><td rowspan="1" colspan="1">39.7</td><td rowspan="1" colspan="1">38.2<xref ref-type="table-fn" rid="TFN4">§</xref></td><td rowspan="1" colspan="1">Nickel 24.7%</td></tr><tr><td rowspan="1" colspan="1">Tunisia</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Potassium dich. 7.9%<xref ref-type="table-fn" rid="TFN5">|</xref></td></tr><tr><td rowspan="1" colspan="1">Sarma et al.<sup><xref rid="r39" ref-type="bibr">39</xref></sup></td><td rowspan="1" colspan="1">2005-2008</td><td rowspan="1" colspan="1">70</td><td rowspan="1" colspan="1">1-15 years</td><td rowspan="1" colspan="1">80.0</td><td rowspan="1" colspan="1">60.7</td><td rowspan="1" colspan="1">Paraben 43.0%</td></tr><tr><td rowspan="1" colspan="1">India</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Potassium dich. 27.0%<xref ref-type="table-fn" rid="TFN5">|</xref></td></tr><tr><td rowspan="1" colspan="1">Czarnobilska et al.<sup><xref rid="r40" ref-type="bibr">40</xref></sup></td><td rowspan="1" colspan="1">2007</td><td rowspan="1" colspan="1">229</td><td rowspan="1" colspan="1">7 years</td><td rowspan="1" colspan="1">43.8</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Nickel 30.2%</td></tr><tr><td rowspan="1" colspan="1">Poland</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">16 years</td><td rowspan="1" colspan="1">52.6</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Thimerosal 27.8%</td></tr><tr><td rowspan="1" colspan="1">Kobata<sup><xref rid="r41" ref-type="bibr">41</xref></sup></td><td rowspan="1" colspan="1">2007-2009</td><td rowspan="1" colspan="1">62</td><td rowspan="1" colspan="1">2-12 years</td><td rowspan="1" colspan="1">61.0</td><td rowspan="1" colspan="1">70.0</td><td rowspan="1" colspan="1">Nickel 27.4%</td></tr><tr><td rowspan="1" colspan="1">Brazil</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Thimerosal 17.7%</td></tr><tr><td rowspan="1" colspan="1">Czarnobilska et al.<sup><xref rid="r42" ref-type="bibr">42</xref></sup></td><td rowspan="1" colspan="1">2008-2009</td><td rowspan="1" colspan="1">196</td><td rowspan="1" colspan="1">7-8 years</td><td rowspan="1" colspan="1">67.0</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Nickel 35.9%</td></tr><tr><td rowspan="1" colspan="1">Poland</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">16-17 years</td><td rowspan="1" colspan="1">58.1</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Thimerosal 37.6%</td></tr><tr><td rowspan="1" colspan="1">Jacob et al.<sup><xref rid="r43" ref-type="bibr">43</xref></sup></td><td rowspan="1" colspan="1">2008-2009</td><td rowspan="1" colspan="1">102</td><td rowspan="1" colspan="1">6-18 years</td><td rowspan="1" colspan="1">76.2</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Nickel 29.7%</td></tr><tr><td rowspan="1" colspan="1">USA</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">p-tert-Butylphenol 16.8%<xref ref-type="table-fn" rid="TFN8">**</xref></td></tr><tr><td rowspan="1" colspan="1">Herro et al.<sup><xref rid="r44" ref-type="bibr">44</xref></sup></td><td rowspan="1" colspan="1">not reported<xref ref-type="table-fn" rid="TFN9">††</xref></td><td rowspan="1" colspan="1">101</td><td rowspan="1" colspan="1">6-18 years</td><td rowspan="1" colspan="1">78.0</td><td rowspan="1" colspan="1">not reported</td><td rowspan="1" colspan="1">Nickel 31.0%</td></tr><tr><td rowspan="1" colspan="1">USA</td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1"> </td><td rowspan="1" colspan="1">Lanolin 18.0%</td></tr></tbody></table><table-wrap-foot><fn id="TFN1"><label>*</label><p>Relevance: current and/or past;</p></fn><fn id="TFN2"><label>†</label><p>tosylamide formaldehyde resin;</p></fn><fn id="TFN3"><label>‡</label><p>cloreto ethylmercuric chloride;</p></fn><fn id="TFN4"><label>§</label><p>calculated from number of tested patients;</p></fn><fn id="TFN5"><label>|</label><p>potassium dichromate;</p></fn><fn id="TFN6"><label>¶</label><p>cocamidopropyl betaine;</p></fn><fn id="TFN7"><label>#</label><p>published in 2005;</p></fn><fn id="TFN8"><label>**</label><p>p-tert-Butylphenol formaldehyde resin;</p></fn><fn id="TFN9"><label>††</label><p>published in 2011.</p></fn></table-wrap-foot></table-wrap><p>Twenty-two studies were carried out in Europe, five in the USA, one in the USA
and Canada, one in Canada, two in Brazil, two in Asia and one in
Africa.<sup><xref rid="r11" ref-type="bibr">11</xref>-<xref rid="r44" ref-type="bibr">44</xref></sup></p><p>Only three studies were performed in more than three centers; twenty-four were
carried out at only one center.<sup><xref rid="r11" ref-type="bibr">11</xref>-<xref rid="r44" ref-type="bibr">44</xref></sup></p><p>Regarding the delineation, twenty-six studies were based on retrospective data,
while eight were prospective.<sup><xref rid="r11" ref-type="bibr">11</xref>-<xref rid="r44" ref-type="bibr">44</xref></sup></p></sec><sec><title>2.Research subjects: sample size and selection, age, sex, atopy history,
dermatitis location and duration</title><p>The number of patients was below 200 in 20 studies and a maximum of 100 in
10.<sup><xref rid="r11" ref-type="bibr">11</xref>-<xref rid="r44" ref-type="bibr">44</xref></sup></p><p>In the 34 studies, tests were carried out in patients with suspected ACD but half
of these involved a significant percentage of patients (over 30.0%) with AD or
atopy history.<sup><xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r13" ref-type="bibr">13</xref>,<xref rid="r15" ref-type="bibr">15</xref>,<xref rid="r19" ref-type="bibr">19</xref>-<xref rid="r22" ref-type="bibr">22</xref>,<xref rid="r25" ref-type="bibr">25</xref>,<xref rid="r26" ref-type="bibr">26</xref>,<xref rid="r29" ref-type="bibr">29</xref>,<xref rid="r31" ref-type="bibr">31</xref>,<xref rid="r33" ref-type="bibr">33</xref>-<xref rid="r35" ref-type="bibr">35</xref>,<xref rid="r41" ref-type="bibr">41</xref>,<xref rid="r43" ref-type="bibr">43</xref>,<xref rid="r44" ref-type="bibr">44</xref></sup> In 13 studies, there was
monitoring of Hanifin and Rajka criteria for this diagnosis.<sup><xref rid="r45" ref-type="bibr">45</xref></sup> In some studies, all subjects
with suspected ACD presented an AD diagnosis, compared with only a small
percentage in others (below 30.0%).<sup><xref rid="r14" ref-type="bibr">14</xref>,<xref rid="r28" ref-type="bibr">28</xref>,<xref rid="r32" ref-type="bibr">32</xref>,<xref rid="r38" ref-type="bibr">38</xref>,<xref rid="r39" ref-type="bibr">39</xref></sup> In 2 studies,
patients presented chronic recalcitrant eczematous dermatitis or severe
AD.<sup><xref rid="r32" ref-type="bibr">32</xref>,<xref rid="r35" ref-type="bibr">35</xref></sup></p><p>Children and adolescents of varying ages and age groups were examined; one study
included exclusively children aged 3-36 months<sup><xref rid="r33" ref-type="bibr">33</xref></sup>, whereas another included
adolescents.<sup><xref rid="r25" ref-type="bibr">25</xref></sup></p><p>Regarding gender, females were predominant in 25 studies and males were
predominant in 2.<sup><xref rid="r11" ref-type="bibr">11</xref>-<xref rid="r44" ref-type="bibr">44</xref></sup></p><p>As for dermatitis evolution prior to testing, a study revealed that 80.0% of
dermatitis cases had durations of over three months.<sup><xref rid="r25" ref-type="bibr">25</xref></sup></p><p>The body sites most affected by dermatitis were: the face and hands, followed by
the feet, generalized dermatitis, the legs and neck.<sup><xref rid="r14" ref-type="bibr">14</xref>-<xref rid="r16" ref-type="bibr">16</xref>,<xref rid="r18" ref-type="bibr">18</xref>-<xref rid="r20" ref-type="bibr">20</xref>,<xref rid="r23" ref-type="bibr">23</xref>-<xref rid="r26" ref-type="bibr">26</xref>,<xref rid="r29" ref-type="bibr">29</xref>,<xref rid="r39" ref-type="bibr">39</xref></sup></p><p>3.Technique:</p><p>Batteries were used in six pediatric studies: 17 substances for children under 5
years;<sup><xref rid="r21" ref-type="bibr">21</xref></sup> 30 substances
for children under 10 years;<sup><xref rid="r22" ref-type="bibr">22</xref></sup>pediatric series of 30 substances in another three studies<sup><xref rid="r33" ref-type="bibr">33</xref>,<xref rid="r34" ref-type="bibr">34</xref>,<xref rid="r36" ref-type="bibr">36</xref></sup> and a series
of 10 substances.<sup><xref rid="r40" ref-type="bibr">40</xref></sup> Others
used adult standardized batteries.<sup><xref rid="r11" ref-type="bibr">11</xref>,<xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r15" ref-type="bibr">15</xref>-<xref rid="r21" ref-type="bibr">21</xref>,<xref rid="r23" ref-type="bibr">23</xref>-<xref rid="r26" ref-type="bibr">26</xref>,<xref rid="r29" ref-type="bibr">29</xref>-<xref rid="r32" ref-type="bibr">32</xref>,<xref rid="r35" ref-type="bibr">35</xref>,<xref rid="r37" ref-type="bibr">37</xref>,<xref rid="r38" ref-type="bibr">38</xref>,<xref rid="r41" ref-type="bibr">41</xref>,<xref rid="r43" ref-type="bibr">43</xref>,<xref rid="r44" ref-type="bibr">44</xref></sup></p><p>The number of substances tested varied. Approximately 50.0% of these studies
assessed 22-40 substances.<sup><xref rid="r11" ref-type="bibr">11</xref>,<xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r15" ref-type="bibr">15</xref>,<xref rid="r17" ref-type="bibr">17</xref>-<xref rid="r23" ref-type="bibr">23</xref>,<xref rid="r25" ref-type="bibr">25</xref>,<xref rid="r27" ref-type="bibr">27</xref>,<xref rid="r28" ref-type="bibr">28</xref>,<xref rid="r30" ref-type="bibr">30</xref>,<xref rid="r33" ref-type="bibr">33</xref>,<xref rid="r36" ref-type="bibr">36</xref>-<xref rid="r38" ref-type="bibr">38</xref>,<xref rid="r41" ref-type="bibr">41</xref>,<xref rid="r44" ref-type="bibr">44</xref></sup> In one study, 25185 substances
(mean: 92) were evaluated; the number was 48 or 66 in another, and 65 in one
other.<sup><xref rid="r29" ref-type="bibr">29</xref>-<xref rid="r31" ref-type="bibr">31</xref></sup> The smallest number of tested
allergens was 10.<sup><xref rid="r40" ref-type="bibr">40</xref></sup></p><p>Furthemore, the concentrations of some substances were also diverse: nickel (most
studies: 5.0%, some: 2.5%), thimerosal (most: 0.1%, some: 1.0% and 0.05%),
fragrance mix I (most: 8.0%, some: 5.0%, 7.0%, 14.0%), potassium dichromate
(most: 0.5%, some: 0.25%), cobalt (most: 1.0%, one study: 0.5%),<sup><xref rid="r40" ref-type="bibr">40</xref></sup> Kathon CG (2.0% and
0.5%).<sup><xref rid="r13" ref-type="bibr">13</xref>,<xref rid="r22" ref-type="bibr">22</xref>,<xref rid="r23" ref-type="bibr">23</xref>,<xref rid="r25" ref-type="bibr">25</xref>,<xref rid="r27" ref-type="bibr">27</xref>,<xref rid="r31" ref-type="bibr">31</xref>-<xref rid="r33" ref-type="bibr">33</xref>,<xref rid="r40" ref-type="bibr">40</xref>-<xref rid="r42" ref-type="bibr">42</xref></sup></p><p>Most studies followed the ICDRG (International Contact Dermatitis Research Group)
testing criteria.<sup><xref rid="r46" ref-type="bibr">46</xref></sup> One study
reduced the test occlusion time to 24 hours in 11 centers<sup><xref rid="r23" ref-type="bibr">23</xref></sup> and three increased it to 72
hours.<sup><xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r22" ref-type="bibr">22</xref>,<xref rid="r27" ref-type="bibr">27</xref></sup> Another study implemented only a 48-hour
reading.<sup><xref rid="r29" ref-type="bibr">29</xref></sup> There was
no active sensitization and the number of irritant reactions was small in the
Manzini study.<sup><xref rid="r12" ref-type="bibr">12</xref></sup></p><p>Data about the tests' clinical relevance are presented below.</p></sec><sec><title>4.Response to patch-tests</title><sec><title>• Relationship with age</title><p>Seven studies showed no difference in contact sensitization regarding
age<sup><xref rid="r23" ref-type="bibr">23</xref>,<xref rid="r26" ref-type="bibr">26</xref>,<xref rid="r29" ref-type="bibr">29</xref>,<xref rid="r30" ref-type="bibr">30</xref>,<xref rid="r32" ref-type="bibr">32</xref>,<xref rid="r33" ref-type="bibr">33</xref>,<xref rid="r39" ref-type="bibr">39</xref></sup> but three
found a greater frequency of positive tests in older age groups: 11-15
years, 12 years,15-16 years.<sup><xref rid="r11" ref-type="bibr">11</xref>,<xref rid="r19" ref-type="bibr">19</xref>,<xref rid="r24" ref-type="bibr">24</xref></sup> In addition, two studies
showed higher sensitization rates in children aged over 5 and 6.<sup><xref rid="r28" ref-type="bibr">28</xref>,<xref rid="r35" ref-type="bibr">35</xref></sup> Despite the link found between increased contact
sensitization indicators and older ages, three studies revealed higher
sensitization rates among children under 3.<sup><xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r21" ref-type="bibr">21</xref>,<xref rid="r22" ref-type="bibr">22</xref></sup></p></sec><sec><title>• Relationship with gender</title><p>Three studies showed a significant difference regarding the relationship
between contact sensitization frequency and gender: two with a higher
frequency among girls<sup><xref rid="r19" ref-type="bibr">19</xref>,<xref rid="r24" ref-type="bibr">24</xref></sup> and one among
boys.<sup><xref rid="r33" ref-type="bibr">33</xref></sup> However,
there were five studies that revealed no differences in this
respect.<sup><xref rid="r13" ref-type="bibr">13</xref>,<xref rid="r22" ref-type="bibr">22</xref>,<xref rid="r26" ref-type="bibr">26</xref>,<xref rid="r30" ref-type="bibr">30</xref>,<xref rid="r39" ref-type="bibr">39</xref></sup> In addition, five studies
demonstrated differences concerning only certain allergens: nickel (more
frequent among girls), nickel and cobalto and other substances.<sup><xref rid="r14" ref-type="bibr">14</xref>,<xref rid="r16" ref-type="bibr">16</xref>,<xref rid="r28" ref-type="bibr">28</xref>,<xref rid="r29" ref-type="bibr">29</xref>,<xref rid="r42" ref-type="bibr">42</xref></sup></p></sec><sec><title>• Relationship with atopy</title><p>There was no statistically significant difference regarding contact
sensitization among atopic and non-atopic patients in nine
studies.<sup><xref rid="r14" ref-type="bibr">14</xref>,<xref rid="r20" ref-type="bibr">20</xref>-<xref rid="r22" ref-type="bibr">22</xref>,<xref rid="r25" ref-type="bibr">25</xref>,<xref rid="r26" ref-type="bibr">26</xref>,<xref rid="r28" ref-type="bibr">28</xref>,<xref rid="r31" ref-type="bibr">31</xref>,<xref rid="r33" ref-type="bibr">33</xref></sup> In contrast, four studies
did reveal a significant difference.<sup><xref rid="r13" ref-type="bibr">13</xref>,<xref rid="r24" ref-type="bibr">24</xref>,<xref rid="r39" ref-type="bibr">39</xref>,<xref rid="r44" ref-type="bibr">44</xref></sup> In three studies, all the patients under study had
AD, thus making assessment impossible, though one of them showed higher
sensitization rates in severe AD (60.9%) than in the moderate (37.5%) and
mild (30.0%) forms.<sup><xref rid="r28" ref-type="bibr">28</xref>,<xref rid="r32" ref-type="bibr">32</xref>,<xref rid="r38" ref-type="bibr">38</xref></sup> One study compared a group of children and
adolescents with AD to a healthy group of adolescents (asymptomatic),
demonstrating contact sensitization frequencies of 55.0% and 15.0%,
respectively.<sup><xref rid="r37" ref-type="bibr">37</xref></sup>Other studies presented data on atopy, without statistical data on the
association.</p></sec><sec><title>• Relationship with body sites affected by dermatitis</title><p>The body sites most frequently affected by dermatitis in patients with
positive tests were: the trunk, followed by the face, hands, feet and
generalized dermatitis.<sup><xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r14" ref-type="bibr">14</xref>,<xref rid="r22" ref-type="bibr">22</xref>,<xref rid="r24" ref-type="bibr">24</xref>,<xref rid="r33" ref-type="bibr">33</xref></sup></p></sec><sec><title>• Relationship with allergen sources</title><p>There was a significant association between mercapto mix and plantar eczema
in one study.<sup><xref rid="r24" ref-type="bibr">24</xref></sup> Footwear
was considered a source of rubber derivatives, formaldehyde, potassium
dichromate and metallic mercury.<sup><xref rid="r14" ref-type="bibr">14</xref>,<xref rid="r15" ref-type="bibr">15</xref>,<xref rid="r19" ref-type="bibr">19</xref></sup> Sports equipment was
regarded as sources of rubber derivatives, while "natural" cosmetics were
considered sources of propolis.<sup><xref rid="r17" ref-type="bibr">17</xref>,<xref rid="r22" ref-type="bibr">22</xref></sup></p></sec><sec><title>• Relationship with the first site of dermatitis</title><p>One study showed that the initial site of the most common dermatitis in
positive tests was the palm region (33.0%), followed by the plantar region
(29.0%) and legs (29.0%). But there was no statistically significant
difference in the relationship between the first site of dermatitis and the
positive result of contact testing.<sup><xref rid="r24" ref-type="bibr">24</xref></sup></p><p>Two studies reported that the initial dermatitis site did not match any
specific allergen.<sup><xref rid="r24" ref-type="bibr">24</xref>,<xref rid="r26" ref-type="bibr">26</xref></sup> Except for the involvement
of the ears, which is characteristic of sensitization by nickel, no other
body site has been related to a specific allergen.<sup><xref rid="r12" ref-type="bibr">12</xref></sup></p></sec><sec><title>• Relationship with occupation and polysensitization</title><p>The few reports regarding occupation were on: hairdressers, construction
workers, health professionals and metallurgical workers.<sup><xref rid="r14" ref-type="bibr">14</xref>-<xref rid="r16" ref-type="bibr">16</xref>,<xref rid="r19" ref-type="bibr">19</xref>,<xref rid="r23" ref-type="bibr">23</xref></sup></p><p>Six studies presented data on polysensitization, with the following,
respective frequency rates: 42.0%, 29.6%, 19.6%, 17.8% of children
undergoing tests; and 54.0%, 51.0% of positive test cases.<sup><xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r17" ref-type="bibr">17</xref>,<xref rid="r22" ref-type="bibr">22</xref>,<xref rid="r26" ref-type="bibr">26</xref>,<xref rid="r29" ref-type="bibr">29</xref>,<xref rid="r33" ref-type="bibr">33</xref></sup></p></sec><sec><title>• Percentage of patients who had at least one positive
reaction</title><p>Frequency rates ranged from 26.0% to 95.6%.</p><p>Thirteen studies revealed rates of below 50.0%, 17 studies had frequencies
ranging from 50.0% to 70.0%, and 5 reported a frequency of over
70.0%.<sup><xref rid="r11" ref-type="bibr">11</xref>-<xref rid="r44" ref-type="bibr">44</xref></sup> There was the total of 35
studies as one study separated these frequencies: children and
adolescents.</p></sec><sec><title>• Percentage of patients with clinical relevance of positive
tests</title><p>Among the studies containing data on the clinical relevance of positive
tests, fifteen revealed a frequency above 50.0%, of which five had an 100.0%
relevance in cases of positive tests. Frequency relevance varied from 30.5%
to 100.0%. Four studies did not take this frequency from all positive tests;
calculations were made based on the number of positive tests for each
substance assessed. Two studies presented the relevance calculated only from
the total number of patients undergoing tests (not from positive tests),
while twelve studies presented no data on the matter.<sup><xref rid="r11" ref-type="bibr">11</xref>-<xref rid="r44" ref-type="bibr">44</xref></sup></p></sec><sec><title>• Frequency of the most common allergens</title><p>The most common allergens in children were nickel, thimerosal, cobalt,
fragrance mix I, lanolin and neomycin. In adolescents, they were nickel,
thimerosal, cobalt, fragrance mix I, potassium dichromate, and balsam of
Peru (Myroxylon pereirae).<sup><xref rid="r11" ref-type="bibr">11</xref>-<xref rid="r44" ref-type="bibr">44</xref></sup></p><p>Nickel was the most frequent allergen in 29 studies and was placed among the
10 most common allergens in the 34 studies, with frequency varying from
7.76% to 46.0%.<sup><xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r18" ref-type="bibr">18</xref></sup></p><p>There were reports of positive reactions for cobalt as well as nickel in
68.0% and 71.0% of cases.<sup><xref rid="r26" ref-type="bibr">26</xref>,<xref rid="r32" ref-type="bibr">32</xref></sup> Pure
sensitization for cobalt was uncommon.<sup><xref rid="r11" ref-type="bibr">11</xref>,<xref rid="r25" ref-type="bibr">25</xref></sup></p><p>Thimerosal was the most frequent substance in four studies and classed among
the 10 most common allergens in 29 studies. Its frequency varied from 0.9%
to 37.6%.<sup><xref rid="r33" ref-type="bibr">33</xref>,<xref rid="r42" ref-type="bibr">42</xref></sup></p><p>Fragrance mix I was among the 10 most frequent allergens in 28 studies,
cobalt in 27 studies, neomycin in 18, potassium dichromate in 15, lanolin in
12, balsam of Peru in 12, para-Phenylenediamine in 10, formaldehyde and
rubber derivatives in 8, colophony in 7, quaternium-15 and
p-tert-Butylphenol in 6.<sup><xref rid="r11" ref-type="bibr">11</xref>-<xref rid="r44" ref-type="bibr">44</xref></sup></p><p>Neomycin was the most common allergen in 1 study, paraben mix also in 1 and
drug allergens (lanolin, quinoline mix, gentamycin, tixocortol pivalate) in
another. Kathon CG, tosylamide formaldehyde resin, gold thiosulfate,
disperse dyes, cocamidopropylbetaine, tixocortol pivalate, propolis and
paraben mix, were also among the 10 most frequent allergens in some
studies.<sup><xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r17" ref-type="bibr">17</xref>,<xref rid="r22" ref-type="bibr">22</xref>,<xref rid="r25" ref-type="bibr">25</xref>,<xref rid="r26" ref-type="bibr">26</xref>,<xref rid="r30" ref-type="bibr">30</xref>,<xref rid="r32" ref-type="bibr">32</xref>,<xref rid="r33" ref-type="bibr">33</xref>,<xref rid="r34" ref-type="bibr">34</xref>,<xref rid="r36" ref-type="bibr">36</xref>,<xref rid="r38" ref-type="bibr">38</xref>,<xref rid="r39" ref-type="bibr">39</xref>,<xref rid="r43" ref-type="bibr">43</xref></sup></p><p>Amerchol L-101 and plant allergens were ranked among the most common
allergens in 1 study.<sup><xref rid="r34" ref-type="bibr">34</xref></sup>Cocamidopropylbetaine was tested in 3 studies and the allergy contact
frequency varied from 7.2% to 23.3%.<sup><xref rid="r32" ref-type="bibr">32</xref>,<xref rid="r33" ref-type="bibr">33</xref>,<xref rid="r36" ref-type="bibr">36</xref></sup></p><p>In studies that tested tixocortol pivalate, the frequency of positive
reactions (among the most frequent allergens) varied from 5.0% to
7.9%.<sup><xref rid="r17" ref-type="bibr">17</xref>,<xref rid="r43" ref-type="bibr">43</xref>,<xref rid="r44" ref-type="bibr">44</xref></sup></p></sec></sec></sec><sec><title>STUDIES IN NON-SELECTED SAMPLES</title><p>A European study was carried out in 40 schools where most students had a history of
AD and hand eczema. They assessed 1,146 adolescents aged 12-16 years using the TRUE
test and nickel in three concentrations (<xref ref-type="table" rid="t02">Table
2</xref>).<sup><xref rid="r47" ref-type="bibr">47</xref></sup></p><table-wrap id="t02" orientation="portrait" position="float"><label>Table 2</label><caption><p>Patch -test results in children and adolescents without suspected allergic
contact dermatitis (two unselected groups)</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Author </th><th rowspan="3" align="left" colspan="1">Data collection years</th><th rowspan="3" align="left" colspan="1">N° of children and adolescents tested</th><th rowspan="3" align="left" colspan="1">Age</th><th rowspan="3" align="left" colspan="1">Adolescents and Children with >1
positive reaction (%)</th><th rowspan="3" align="left" colspan="1">Relevance<xref ref-type="table-fn" rid="TFN10">*</xref> of positive tests (%)</th><th align="left" rowspan="1" colspan="1">Three most common allergens.</th></tr><tr><th align="left" rowspan="1" colspan="1">Country </th><th rowspan="2" align="left" colspan="1">Frequency of positive reactions</th></tr><tr><th align="left" rowspan="1" colspan="1">N° of centers</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Mortz et al.<sup><xref rid="r45" ref-type="bibr">45</xref></sup></td><td align="left" rowspan="1" colspan="1">1995-1996</td><td align="left" rowspan="1" colspan="1">1146</td><td align="left" rowspan="1" colspan="1">12-16 years</td><td align="left" rowspan="1" colspan="1">15.2</td><td align="left" rowspan="1" colspan="1">47.7</td><td align="left" rowspan="1" colspan="1">Nickel 8.6%</td></tr><tr><td align="left" rowspan="1" colspan="1">Denmark</td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1">Fragrance mix I 1.8%</td></tr><tr><td align="left" rowspan="1" colspan="1">40 centers</td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1">Cobalt 1.0% </td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1">Thimerosal 1.0%</td></tr><tr><td align="left" rowspan="1" colspan="1">Bruckner et al.<sup><xref rid="r46" ref-type="bibr">46</xref></sup></td><td align="left" rowspan="1" colspan="1">not reported<xref ref-type="table-fn" rid="TFN11">†</xref></td><td align="left" rowspan="1" colspan="1">85</td><td align="left" rowspan="1" colspan="1">6 months-5 years</td><td align="left" rowspan="1" colspan="1">24.5</td><td align="left" rowspan="1" colspan="1">not reported</td><td align="left" rowspan="1" colspan="1">Nickel 12.9%</td></tr><tr><td align="left" rowspan="1" colspan="1">USA</td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1">Thimerosal 9.4%</td></tr><tr><td align="left" rowspan="1" colspan="1">1 center</td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1">Kathon CG 2.4%<xref ref-type="table-fn" rid="TFN12">‡</xref></td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1"> </td><td align="left" rowspan="1" colspan="1">Neomycin 1.2%</td></tr></tbody></table><table-wrap-foot><fn id="TFN10"><label>*</label><p>Relevance: current and/or past;</p></fn><fn id="TFN11"><label>†</label><p>published in 2000;</p></fn><fn id="TFN12"><label>‡</label><p>methylchloroisothiazolinone/methylisothiazolinone</p></fn></table-wrap-foot></table-wrap><p>An American study evaluated 95 asymptomatic children of both sexes, aged between 6
months and 5 years, via the TRUE test.<sup><xref rid="r48" ref-type="bibr">48</xref></sup></p><sec><title>Response to patch-tests</title><p>In the European study, there were significantly more female adolescents with
positive tests. No association emerged between contact sensitization and AD,
though there was a significant association between contact sensitization and
hand eczema. Reactions to two or more allergens were reported in 14.9% of the
adolescents. The relevance frequency of positive tests was 47.7%.<sup><xref rid="r47" ref-type="bibr">47</xref></sup></p><p>In the American study, 45.0% of children with positive tests were aged under 18
months.<sup><xref rid="r48" ref-type="bibr">48</xref></sup></p><p>Patients with at least one positive reaction to the patch-test had the following
frequency rates: 15.2% of adolescentes and 24.5% of children undergoing
tests.<sup><xref rid="r47" ref-type="bibr">47</xref>,<xref rid="r48" ref-type="bibr">48</xref></sup></p><p>The most common allergens in these two studies were nickel. Nickel, cobalt,
thimerosal, and p-tert-butylphenol were among the six most frequent
allergens.<sup><xref rid="r47" ref-type="bibr">47</xref>,<xref rid="r48" ref-type="bibr">48</xref></sup></p></sec></sec><sec><title>STUDIES IN SELECTED SAMPLES (9) AND NON-SELECTED SAMPLES (3) WITH SPECIFIC
FOCUS</title><p>Preservatives were tested in 811 children (566 with AD) and 7.27% of the children had
at least one positive reaction to a preservative: imidazolidinylurea,
diazolidinylurea, paraben mix, formaldehyde, quaternium 15, Euxyl K 400, Kathon CG
(methylcloroisothiazolinone/methylizothiazolinone), butylated hydroxyanisole. Kathon
CG was the most frequent and quaternium 15 entailed no positive reactions, thus
emphasizing the importance of patch-tests for preservatives in children with eczema
and/or AD.<sup><xref rid="r49" ref-type="bibr">49</xref></sup></p><p>An investigation of 2,482 children and adolescents (0-19 years) showed a frequency
variation for fragrance mix of 2.5-3.4%, with a lower frequency among those aged 0-9
years.<sup><xref rid="r50" ref-type="bibr">50</xref></sup></p><p>Allergy to cosmetics occurred in 21 (30.0%) children out of 70, aged 1-15 years,
followed by topical medication, metals and rubber derivatives.<sup><xref rid="r51" ref-type="bibr">51</xref></sup></p><p>One study demonstrated a higher proportion of very strong reactions (3+) to the
para-phenylenediamine in patch-tests among children aged up to 14 years, compared
with other age groups and other tested allergens (nickel, fragrance mix I and Kathon
CG). It was suggested that the concentration of para-phenylenediamine for testing
should be reduced for children with a history of allergy to hair dyes and/or Henna
tattoos.<sup><xref rid="r52" ref-type="bibr">52</xref></sup></p><p>In a study of 641 children with AD diagnoses, the contact sensitization frequency to
AD topical treatments was 6.2%. The risk factors associated with contact
sensitization to AD topical treatments were: disease seriousness (more frequent in
moderate to severe AD), early AD onset (before 6 months) and sensitization mediated
by IgE. The most frequent sensitizers were antiseptics (chlorhexidene) and
emollients (particularly vegetal protein extracts and fragrances). The authors
suggested including antiseptics and emollients in the contact test battery for
children with AD and suspected ACD. In addition, they recommended using emollients
devoid of fragrances and vegetal protein extracts.<sup><xref rid="r53" ref-type="bibr">53</xref></sup></p><p>The ISAAC (International Study of Asthma and Allergies in Childhood) undertook a
study of 143 children, concluding that every case of recurrent chronic dermatitis in
children requires differential diagnosis of ACD with other dermatoses (AD, etc.),
even if they are predominantly located in the flexural areas.<sup><xref rid="r54" ref-type="bibr">54</xref></sup></p><p>A multicentric study of 111 children with hand eczema revealed frequencies of 46.8%
(contact allergy) and 36.0% (ACD). Nickel, fragrances and Kathon CG were the most
common allergens. It was recommended that patch-testing be performed on any child
with chronic hand eczema.<sup><xref rid="r55" ref-type="bibr">55</xref></sup></p><p>One study tested 1,255 children with suspected ACD, using propolis at 20.0%. The
frequency for positive reactions was 5.9% of cases. It was suggested that propolis
should not be used as a constituent of topical products for children.<sup><xref rid="r56" ref-type="bibr">56</xref></sup></p><p>In another study, 1,098 children were tested with 30 substances, including dyes: 5
disperse dyes in 964 and 7 disperse dyes in 134 children. Further, 4.6% had positive
tests, involving at least 1 disperse dye, the most common being: disperse yellow 3,
disperse orange 3, disperse blue 124, disperse red 1 and
p-dimethylaminoazobenzene.<sup><xref rid="r57" ref-type="bibr">57</xref></sup></p><p>Two studies of non-selected samples tested only metals, while one tested just nickel
and fragrance mix.<sup><xref rid="r58" ref-type="bibr">58</xref>-<xref rid="r60" ref-type="bibr">60</xref></sup> A study showed that children with
pierced ears were more likely to react to nickel that those without, revealing a
nickel frequency of 20.0%.<sup><xref rid="r60" ref-type="bibr">60</xref></sup> The
frequency of positive tests for fragrance mix I in children aged under 18 months was
low.<sup><xref rid="r59" ref-type="bibr">59</xref></sup> Another study
showed that 18.2-29.6% of positive reactions to patch-tests for nickel would not be
detected with only a 48-hour reading.<sup><xref rid="r58" ref-type="bibr">58</xref></sup></p></sec><sec sec-type="discussion"><title>DISCUSSION</title><p>Contact testing seems to be as important in children (even those aged under 3 years)
as in adolescents, since contact sensitization occurs in every age group, though
sensitization frequencies vary according to the specific age group.<sup><xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r21" ref-type="bibr">21</xref>,<xref rid="r22" ref-type="bibr">22</xref>,<xref rid="r48" ref-type="bibr">48</xref></sup> Importantly, age-related variations occur only in
relation to some allergens.<sup><xref rid="r14" ref-type="bibr">14</xref>,<xref rid="r31" ref-type="bibr">31</xref>,<xref rid="r40" ref-type="bibr">40</xref>,<xref rid="r42" ref-type="bibr">42</xref></sup></p><p>Females were predominant among the tested patients but there was no consensus
regarding contact sensitization and gender.<sup><xref rid="r19" ref-type="bibr">19</xref>,<xref rid="r22" ref-type="bibr">22</xref>,<xref rid="r24" ref-type="bibr">24</xref>,<xref rid="r26" ref-type="bibr">26</xref>,<xref rid="r30" ref-type="bibr">30</xref>,<xref rid="r33" ref-type="bibr">33</xref>,<xref rid="r39" ref-type="bibr">39</xref></sup></p><p>The association between atopy and contact sensitization remains a point of
contention<sup><xref rid="r13" ref-type="bibr">13</xref>'<xref rid="r14" ref-type="bibr">14</xref>'<xref rid="r20" ref-type="bibr">20</xref>-<xref rid="r22" ref-type="bibr">22</xref>'<xref rid="r24" ref-type="bibr">24</xref>-<xref rid="r29" ref-type="bibr">29</xref>'<xref rid="r31" ref-type="bibr">31</xref>-<xref rid="r33" ref-type="bibr">33</xref>'<xref rid="r37" ref-type="bibr">37</xref>-<xref rid="r39" ref-type="bibr">39</xref>'<xref rid="r44" ref-type="bibr">44</xref></sup></p><p>ACD diagnoses depend on correct technique procedures and reading and interpretation
of patch-tests. In some studies, there was variation in the occlusion period and
reading, which may have influenced patch-test results (false-positives and
false-negatives).<sup><xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r13" ref-type="bibr">13</xref>,<xref rid="r22" ref-type="bibr">22</xref>,<xref rid="r23" ref-type="bibr">23</xref>,<xref rid="r27" ref-type="bibr">27</xref>,<xref rid="r29" ref-type="bibr">29</xref></sup></p><p>In the thirty-four studies on selected samples, contact sensitization frequency
varied from 26.0% to 95.6% and in the two studies on non-selected samples, the range
was 15.2-24.5%, showing that the rate changed according to the type of sample
assessed.<sup><xref rid="r11" ref-type="bibr">11</xref>-<xref rid="r44" ref-type="bibr">44</xref>,<xref rid="r47" ref-type="bibr">47</xref>,<xref rid="r48" ref-type="bibr">48</xref></sup> Studies with
frequencies of over 70.0% used more extensive batteries; one was composed of 65
allergens.<sup><xref rid="r32" ref-type="bibr">32</xref>,<xref rid="r36" ref-type="bibr">36</xref>,<xref rid="r39" ref-type="bibr">39</xref>,<xref rid="r43" ref-type="bibr">43</xref>,<xref rid="r44" ref-type="bibr">44</xref></sup> In two studies, samples were composed 70.0% and
50.0% respectively of children with a history of AD.<sup><xref rid="r32" ref-type="bibr">32</xref>,<xref rid="r36" ref-type="bibr">36</xref>,<xref rid="r44" ref-type="bibr">44</xref></sup> In the three studies with lower
frequencies for positive tests, the batteries used were less extensive.<sup><xref rid="r20" ref-type="bibr">20</xref>,<xref rid="r24" ref-type="bibr">24</xref>,<xref rid="r38" ref-type="bibr">38</xref></sup> In two of these,
43.0% and 100.0% of the patients had AD.<sup><xref rid="r20" ref-type="bibr">20</xref>,<xref rid="r38" ref-type="bibr">38</xref></sup></p><p>Some substance concentrations varied, which may have affected the frequency of
contact sensitization.</p><p>Nickel revealed significant frequency variation: 7.76-46.0% in thirty-four studies
across selected samples; and 8.6-20.0% in three studies of nonselected
samples.<sup><xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r18" ref-type="bibr">18</xref>,<xref rid="r58" ref-type="bibr">58</xref>-<xref rid="r60" ref-type="bibr">60</xref></sup> Most tested nickel at 5.0% but
three assessed it at 2.5%.<sup><xref rid="r31" ref-type="bibr">31</xref>,<xref rid="r40" ref-type="bibr">40</xref>,<xref rid="r42" ref-type="bibr">42</xref></sup> The sensitization frequency for thimerosal varied from 0.9%
to 37.6%. Its lowest frequency occurred in a study where the concentration was 0.1%
whereas its highest frequency occurred when tested at 1.0%.<sup><xref rid="r13" ref-type="bibr">13</xref>,<xref rid="r33" ref-type="bibr">33</xref>,<xref rid="r42" ref-type="bibr">42</xref></sup> In four studies,
the concentration was 0.05%.<sup><xref rid="r13" ref-type="bibr">13</xref>,<xref rid="r25" ref-type="bibr">25</xref>,<xref rid="r27" ref-type="bibr">27</xref>,<xref rid="r41" ref-type="bibr">41</xref></sup> Most studies
deemed that thimerosal had no clinical relevance.</p><p>Regarding studies with propolis, sensitization frequency varied from 0.74% to 16.5%
in selected samples but the substance was tested at 10.0% in one study and at 20.0%
in two.<sup><xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r22" ref-type="bibr">22</xref>,<xref rid="r42" ref-type="bibr">42</xref>,<xref rid="r56" ref-type="bibr">56</xref></sup></p><p>Drawing on studies involving disperse dyes in children, the frequency of positive
reactions varied as follows: disperse blue 106 (2.98-16.3%); disperse blue 124
(1.27-3.1%); disperse red 1 (0.72-2.8%) and disperse yellow 3 (0.54-1.9%).<sup><xref rid="r32" ref-type="bibr">32</xref>,<xref rid="r33" ref-type="bibr">33</xref>,<xref rid="r36" ref-type="bibr">36</xref>,<xref rid="r57" ref-type="bibr">57</xref></sup></p><p>Some authors have recommended using pediatric batteries including emollients,
antisseptics, preservatives, propolis and fragrance mix II, as well as smaller
chambers in the adhesives of childrens' tests.<sup><xref rid="r12" ref-type="bibr">12</xref>,<xref rid="r21" ref-type="bibr">21</xref>,<xref rid="r28" ref-type="bibr">28</xref>,<xref rid="r42" ref-type="bibr">42</xref>,<xref rid="r49" ref-type="bibr">49</xref>,<xref rid="r53" ref-type="bibr">53</xref>,<xref rid="r61" ref-type="bibr">61</xref></sup></p><p>Nickel was the most frequent allergen in children and adolescents, followed by
thimerosal, fragrance mix I, cobalt, neomycin, potassium dichromate, lanolin,
para-phenylenediamine, formaldehyde and rubber derivatives.<sup><xref rid="r11" ref-type="bibr">11</xref>-<xref rid="r44" ref-type="bibr">44</xref></sup></p><p>The clinical relevance of positive tests is important in interpreting patch-test
results, as this enables the differentiation of ACD and contact
sensitization.<sup><xref rid="r10" ref-type="bibr">10</xref>,<xref rid="r46" ref-type="bibr">46</xref></sup> Important data on clinical
relevance include: type (current, past), frequency calculated for positive tests and
frequency calculated for each substance.</p><p>It is important the physician, the parents and the patient interests in relating a
substance identified in the test to the patient's current dermatitis and to the
allergen source, not limited only to the identification of contact sensitization,
thus making possible the ACD treatment and the recurrence prevention.<sup>(62)</sup>Furthermore, monitoring patients after patch-testing is important as regards
clinical relevance and treatment evaluation.<sup><xref rid="r15" ref-type="bibr">15</xref>,<xref rid="r28" ref-type="bibr">28</xref>,<xref rid="r34" ref-type="bibr">34</xref>,<xref rid="r36" ref-type="bibr">36</xref></sup></p><p>Patch-tests are an effective method for identifying the causative agent of ACD,
inducing the type IV immune reaction in children and adolescents, as it comes about
in adults.<sup><xref rid="r63" ref-type="bibr">63</xref>,<xref rid="r64" ref-type="bibr">64</xref>,<xref rid="r65" ref-type="bibr">65</xref></sup>Experience is necessary to undertake selection of patients and substances relevant
to these patients' problems.<sup><xref rid="r66" ref-type="bibr">66</xref></sup> The
conclusion was that a clinic specialized in patch-testing can detect more ACD cases
than a non-specialized one.<sup><xref rid="r67" ref-type="bibr">67</xref></sup></p><p>Preventive measures can be taken, as has occurred in many countries.<sup><xref rid="r68" ref-type="bibr">68</xref>,<xref rid="r69" ref-type="bibr">69</xref></sup> Furthermore, educational programs can be implemented and
directed towards physicians, pregnant women, children and their families, in order
to provide guidance on the importance of avoiding contact with allergens in
childhood, especially metals and fragrances in atopic children.<sup><xref rid="r37" ref-type="bibr">37</xref>,<xref rid="r44" ref-type="bibr">44</xref>,<xref rid="r70" ref-type="bibr">70</xref></sup></p></sec><sec sec-type="conclusions"><title>CONCLUSION</title><p>The most common allergens in children were nickel, thimerosal, cobalt, fragrance mix,
lanolin and neomycin. In adolescents, they were nickel, thimerosal, cobalt,
fragrance mix, potassium dichromate, and Myroxylon pereirae. The following also
featured among the 10 most frequent allergens in some studies, representing emerging
allergens: Kathon CG, tosylamide formaldehyde resin, gold thiosulfate, disperse
dyes, cocamidopropylbetaine, tixocortol pivalate and propolis. This knowledge is
important when considering preventive measures.</p><p>Since they make it difficult to draw conclusions, variations in the following factors
must be taken into account when evaluating the studies: the number and age groups of
children and/or adolescents tested, the number of subjects with a history of
atopy/atopic dermatitis, the quantity, type and concentration of tested substances,
the test techniques and type of data with clinical relevance.</p><p>Given the difficulty in comparing the results of the study on patch-tests due to
regional differences regarding exposure to allergens, as well as the aforementioned
factors, an evidence-based, standardized database is needed.</p></sec></body><back><fn-group><fn fn-type="conflict"><p>Conflict of Interest: None.</p></fn><fn fn-type="supported-by"><p>Financial Support: None.</p></fn><fn fn-type="other" id="fn1"><label>*</label><p>Work performed at the Universidade Federal de Minas Gerais (UFMG) and Santa Casa
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