Course of Skin Symptoms and Quality of Life in Children Referred for Patch Testing A Long-term Follow-up Study

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1 Act Derm Venereol 2015; 95: CLINICAL REPORT Course of Skin Symptoms nd Qulity of Life in Children Referred for Ptch Testing A Long-term Follow-up Study Anne B. SIMONSEN 1, Mette SOMMERLUND 1, Mette DELEURAN 1, Chrlotte G. MORTZ 2 nd Jenne D. JOHANSEN 3 1 Deprtment of Dermtology nd Venereology, Arhus University Hospitl, Arhus, 2 Deprtment of Dermtology nd Allergy Centre, Odense University Hospitl, Odense, nd 3 Ntionl Allergy Reserch Centre, Gentofte Hospitl, Hellerup, Denmrk Children re ptch-tested in the sme mnner s dults, but little hs been done to estblish whether positive or negtive findings influence the course of skin symptoms. To uncover the course of skin symptoms nd the impct of persistent eczem on life qulity in peditric ptients referred for ptch testing, retrospective questionnire ws sent to children nd dolescents referred for ptch testing during 9-yer period. Persistent eczem t follow-up ws strongly ssocited to topic dermtitis, but ws not explined by gender, ge, contct llergy or time spn from ptch testing to follow-up. Among ptients without topic dermtitis, 23.5% reported to suffer from chronic eczem. Persistent eczem incresed the risk of severe impirment of life qulity. Our findings indicte significnt risk of childhood eczem becoming chronic nd ffecting life qulity considerbly. Ptch testing did not ffect the course of eczem, highlighting the difficulties of voidnce behviour. Key words: ptch testing; children; dolescents; llergic contct dermtitis; contct llergy; topic dermtitis. Accepted Jun 9, 2014; Epub hed of print Jun 10, 2014 Act Derm Venereol 2015; 95: Anne Birgitte Simonsen, Ntionl Allergy Reserch Centre, Gentofte Hospitl, Niels Andersens Vej 65, DK 2900 Hellerup, Denmrk. E-mil: nbsim@rm.dk Allergic contct dermtitis (CD is common dermtologicl disorder nd often results in ongoing disese nd disbility (1, 2. Even young children my become sensitised nd suffer from llergic CD (3. Erly identifiction nd subsequent voidnce of the contct llergen by the ptient should reduce the durtion nd disbility of the disese nd its progression. However, studies on the outcome of ptch testing in children with suspected llergic CD re limited (4 nd little hs been done to estblish whether positive or negtive findings influence the course of skin symptoms (5. It is well known tht mny skin diseses hve significnt impct on qulity of life (QoL (6. This hs been demonstrted in children with topic dermtitis (7 s well s in dult ptients with llergic CD (1, but little ttention hs been pid to children nd dolescents suffering from the ltter. The im of this study ws to uncover the course of skin symptoms in peditric ptients referred for ptch testing, nd to evlute the impct of skin symptoms on QoL. METHODS Ptient selection From 1 Jnury 2003 to 31 December 2011 totl of 2,594 ptients ged 1 17 yers were ptch-tested in 12 dermtologicl clinics throughout Denmrk (The Dnish Group for Contct Dermtitis, which is estimted to cover bout 1/5 of ptients ptch-tested in Denmrk. All ptients either suffered from reclcitrnt eczem or hd suspected dignosis of llergic CD. Chrcteristics ccording to the MOAHLFA index (Mle, Occuptionl dermtitis,, Hnd dermtitis, Leg dermtitis, Fce dermtitis were registered by the dermtologist prior to ptch testing. The dignosis of topic dermtitis ws estblished ccording to the Hnifin nd Rjk criteri (8. Ptch testing The children were tested with either the Europen Bseline Series (llergens retrieved from either Chemotechnique Dignostics, Mlmö, Sweden, or from Almirll Herml, Reinbek, Germny or with TRUE test (SmrtPrctice Denmrk, Hilleroed, Denmrk supplemented with the llergens from the Europen Bseline Series tht re not included in the TRUE test. Ptch tests were removed on dy 2. Redings were performed ccording to The Interntionl Contct Dermtitis Reserch Group Guideline on minimum dy 2 or dy 4, nd often lso dy 2 nd dy 7. Rections designted either 1+, 2+, or 3+ were regrded s positive. Follow-up Of the 2,594 ptients in the dtbse, 2,591 were registered in the Dnish Civil Registrtion System, nd 2,567 hd vlid ddress in Denmrk. Since 307 did not wish to be contcted for reserch purposes, the questionnire-bsed follow-up ws conducted on the remining 2,260 ptients in the spring of Questionnire The questionnire designed for this follow-up study imed to describe the skin sttus of the cohort nd to uncover persisting skin symptoms. Since some of the ptients were younger children, we mde it optionl for them to either nswer the questionnire themselves or with help from their prents. To investigte how well the outcome of the ptch test ws remembered by the ptients nd/or their prents, they were sked if they hd contct llergy to metls, frgrnces, preservtives, plnts or rubber. To study the current skin sttus of the ptients, they were sked how often do you/your child hve eczem? with the response options never, 2015 The Authors. doi: / Journl Compiltion 2015 Act Dermto-Venereologic. ISSN

2 Course of skin symptoms nd qulity of life in children referred for ptch testing 207 ll the time/every dy, every week, 1 3 times every month, 4 6 times every yer, nd 1 3 times every yer. To investigte the QoL of those with persisting skin symptoms, the Children s Dermtology Life Qulity Index (CLDQI questionnire (9 ws used for ptients ged 16 or younger. For ptients ged 17 nd bove, the Dermtology Life Qulity Index (DLQI (10 questionnire ws used. The CDLQI nd DLQI ech consists of 10 questions tht focus on the effects of skin disese on ctivities of dily life during the preceding week. Since this ws follow-up study, the temporl prmeter ws expnded to the preceding yer. Definitions To clssify the severity of skin symptoms t follow-up nd identify the ptients tht were severely ffected, we defined the vribles persistent eczem s eczem ll the time/every dy or t lest once every week, frequent eczem s eczem 1 3 times ech month, nd rrely eczem s episodes of eczem less thn 6 times ech yer. The CDLQI/DLQI is clculted by summing the score for ech question, which results in mximum score of 30 nd minimum score of 0. The scoring nd interprettion ws done ccording to the uthors instructions (9, 11. Severely ffected life qulity ws defined s CDLQI score 13 or DLQI score 11 ( very lrge or extremely lrge effect on ptient s life. Sttistics Chrcteristics of prticipnts were compred using the χ 2 test. A binry logistic regression nlysis ws performed with persistent eczem s the dependent vrible, nd topic dermtitis, contct llergy, gender, ge t ptch testing (1 5 yers, 6 12 yers, nd yers nd follow-up time (2 4 yers, 5 7 yers, 8 10 yers s independent, explntory vribles. Since topic dermtitis ws mjor confounder, the logistic regression model ws repeted, including only the ptients without topic dermtitis. The χ 2 -test ws used to compre groups nd ssess explntory prmeters of severely ffected life qulity. All results were expressed s odds rtios with 95% confidence intervls nd employing 5% significnce level. The dt nlysis ws done using sttisticl softwre (Sttisticl Product nd Service Solution pckge for Windows, Relese 19, SPSS Inc., Chicgo, IL, USA. RESULTS In totl, 1,039 questionnires were returned fter one reminder, giving response rte of 46%. The demogrphic chrcteristics of the cohort nd differences between the responders nd non-responders re summrised in Tble I. Respondents were more likely to be femle, younger thn 20 yers t follow-up, ptchtested less thn 5 yers go, nd hving dignosis of topic dermtitis t the time of ptch testing. The respondents were 3 17 yers (men 12.8 yers t the time of ptch testing. Time to follow-up ws between 2 nd 10 yers (men 5.2 yers, nd the current ge of the respondents ws 4 28 yers (men 17.7 yers. More thn two thirds of the respondents were girls (68.1% vs. 32.9%, 48.6% (n = 505 hd dignosis of topic dermtitis (AD when ptch-tested, nd 25% (n = 260 hd t lest one positive ptch test rection. Among respondents, there were no sex difference in the likelihood of Tble I. Demogrphic chrcteristics of responders versus nonresponders All ptients 2,260 (100 n (% Responders 1,039 (46 n (% hving t lest one positive ptch test rection, nd the shre tht suffered from AD ws the sme in the 2 groups. Skin symptoms t follow-up Non-responders 1,221 (54 n (% OR < ( ( ( ( *** ( ( ( ( ** ( ( ( ( * > ( ( ( ( * Mle 776 ( ( ( ( * Femle 1,484 ( ( (63.6 Yes 1,011 ( ( ( ( ** No 1,249 ( ( (58.6 Contct llergy Yes 556 ( ( ( ( No 1,694 ( ( (74.9 Follow-up, yers ( ( ( ( *** ( ( ( ( ( ( ( ( *** *p < 0.05, **p < 0.005, ***p < Odds rtio (OR found by χ 2 testing cross subgroups. CI: confidence intervl. Of ll respondents, 90.8% (n = 943 nswered the question regrding their current skin sttus. In this group, 51.5% (n = 486 hd dignosis of AD nd 80.3% (n = 757 reported tht they still suffer from eczem t lest once every yer. Persistent eczem t follow-up ws reported by 31.1% (n = 293 nd ws not surprisingly ssocited with hving AD t the time of ptch testing (OR 2.10, CI , p < 0.01, but not with hving contct llergy (OR 0.91, CI , p = 0.55 or hving 2 or more llergies (OR 0.65, CI , p = No difference between genders or cross ge groups ws observed, nd the risk of hving persistent eczem t follow-up ws the sme regrdless of the time from ptch testing to follow-up (Tble II. The sme pplied when the nlyses were strtified by AD (Tble SI 1. Among respondents without AD, 70.4% (n = 342 reported to suffer from eczem t lest once every yer nd 23.5% (n = 114 suffered from persistent eczem. Metls, frgrnce nd rubber chemicls were the most frequent sensitisers, but no specific group of llergens ws ssocited with hving continuous eczem t follow-up. Of the 260 ptients who were sensitized to t lest one llergen, 66.5% (n = 173 nswered the question regr- 1

3 208 A.B. Simonsen et l. Tble II. Logistic regression nlysis with the outcome persistent eczem nd different explntory vribles vribles ding the outcome of the ptch test nd 55.5% (n = 96 of these were ble to correctly identify the group of llergens to which the specific llergen belonged. The bility to correctly recll the llergen group decresed with time. There ws no ssocition between hving persistent eczem t follow-up nd being unble to identify the correct group of llergens (OR 0.91, CI , p = Life qulity Persistent eczem Crude OR b Adjusted OR b Mle 30.9 (94/304 1 (ref 1 (ref Femle 31.1 (199/ ( ( < (27/78 1 (ref 1 (ref (51/ ( ( (138/ ( ( > (77/ ( ( No 23.5 (114/486 1 (ref 1 (ref Yes 39.2 (179/ ( ( * Contct llergy c No 31.6 (220/696 1 (ref 1 (ref Yes 29.6 (73/ ( ( Follow-up, yers (152/450 1 (ref 1 (ref (78/ ( ( (63/ ( ( *p < n = 293. b Adjusted for ll explntory vribles. c Positive ptch test rection to t lest one llergen. OR: odds rtio; CI: confidence intervl. Among those who suffered from eczem t lest once yer, 76.1% (n = 576 nswered the CDLQI or DLQI depending on ge. The men CDLQI score ws 6.38 (rnge 0 23 vs. men DLQI score of 6.81 (rnge The CDLQI/DLQI score ws correlted to the severity of the eczem nd ptients with AD were more ffected thn ptients without this dignosis in both groups (Fig. S1 1. Persistent eczem ws strong nd significnt risk fctor for hving severely impired life qulity in both ptients 16 yers nd in ptients 17 yers. However, the mjority of ptients hd CDLQI/DLQI scores corresponding to smll or moderte impct on life qulity. In the group of respondents 16 yers, young children were more likely to hve severely ffected life qulity t follow-up (Tble III. This ws ssocited to AD wheres no gender difference ws observed. The ssocition to AD did not rech sttisticl significnce t 5% level, which is likely due to smll smple sizes. Becuse of the strong link between hving AD nd persistent eczem t follow-up, nlyses were strtified by AD. Persistent eczem ws still the strongest predictor of severely ffected life qulity. The pttern ws similr in ptients 17 yers. In this ge group, the role of AD ws less pronounced. As in the youngest ge group, the risk of hving severely ffected life qulity incresed with the severity of eczem, nd this pttern persisted when strtified by AD. There ws no ge difference within this group but we did observe significnt gender difference, with the life qulity of femles being more ffected thn tht of mles (Tble IV. DISCUSSION Tble III. Predictors of hving severely ffected life qulity. Ptients 16 yers vribles All ptients CDLQI severely ffected (n = 124 Crude OR Without topic dermtitis CDLQI severely ffected (n = 54 Crude OR Mle 15.8 (9/57 1 (ref 12.0 (3/25 1 (ref Femle 16.4 (11/ ( (2/ ( (12/49 1 (ref 12.5 (2/16 1 (ref (8/ ( * 7.9 (3/ ( No 9.3 (5/54 1 (ref Yes 21.4 (15/ ( ** Contct llergy b No 16.0 (15/94 1 (ref 9.8 (4/41 1 (ref Yes 16.7 (5/ ( (1/ ( Persistent eczem No 7.1 (6/84 1 (ref 4.8 (2/42 1 (ref Yes 35.0 (14/ ( * 25.0 (3/ ( * Odds rtios (OR clculted by χ 2 testing cross subgroups. b At lest one positive ptch test rection. *p < 0.05, **p = To our knowledge, this is the first long-term followup study exploring the course of skin symptoms in children referred for ptch testing. A significnt shre of the respondents still suffered from flre-ups of eczem t follow-up nd mny suffered from persistent eczem. AD ws the single most importnt risk fctor for hving persistent eczem t follow-up, but even mong the children nd dolescents without dignosed AD the shre of ptients who suffered from persistent eczem ws substntil. At bseline, ll ptients were suspected of hving llergic CD either s complicting fctor or s the min cuse of disese. However, positive ptch test result ws not found to ffect the prognosis of eczem. There re severl possible explntions for this. First of ll, the ccurcy of ptch testing is multifctoril nd depends on the competence of the tester (12. A stisfctory result requires creful considertion of exposures nd selection of pproprite llergens for the ptch testing. Further, the benefits of ptch testing

4 Course of skin symptoms nd qulity of life in children referred for ptch testing 209 Tble IV. Predictors of hving severely ffected life qulity. Ptients 17 yers vribles All ptients DLQI severely ffected (n = 452 Crude OR Without topic dermtitis DLQI severely ffected (n = 198 Crude OR Mle 9.5 (11/116 1 (ref 6.0 (3/50 1 (ref Femle 25.3 (85/ ( ** 22.3 (33/ ( * (69/315 1 (ref 19.1 (26/136 1 (ref (27/ ( (10/ ( No 18.2 (36/198 1 (ref Yes 23.6 (60/ ( Contct llergy b No 21.3 (72/338 1 (ref 18.4 (4/41 1 (ref Yes 21.1 (24/ ( (11/ ( Persistent eczem No 11.8 (32/271 1 (ref 7.2 (9/125 1 (ref Yes 35.4 (64/ ( ** 37.0 (27/ ( ** Odds rtios (OR clculted by χ 2 testing cross subgroups. b At lest one positive ptch test rection. *p < 0.05, **p < depends on the informtion given regrding voidnce of llergens (13, 14, nd most importntly the ptient s bility to recll the results of the ptch testing (12 nd subsequently void the contct llergen. Avoidnce of llergens cn be mjor chllenge, s demonstrted by Lewis et l. (15. Among 43 ptients with llergic CD, only hlf were ble to void the llergens concerned. Accordingly, our results suggest tht the ptients who were dignosed with llergic CD my hve hd difficulties in dopting suitble voidnce behviour. Another spect of voidnce behviour is the ptient s bility to recll the results of the ptch test. Jmil et l. (12 showed tht ptients bility to recll the dignosed llergen decresed over time nd t 10-yer follow-up only 17% percent were ble to recll the correct llergen. In our study only 55.5% were ble to correctly identify the group of llergens. We hypothesised tht being unble to remember the outcome of the ptch test ws correlted to hving persistent skin symptoms t follow-up. However, we were not ble to show tht this ws the cse. It could be rgued tht our question regrding the outcome of the ptch test ws too vgue, i.e. sking the respondents to nme the llergen to which they hd positive rection would hve been more ccurte. It is lso possible tht the chllenge of voidnce behviour bised the result, i.e. those who correctly reclled the outcome, were unble to void the specific llergen. In ny event, our results indicte tht there is need of reminding ptients of ny positive results, nd this is likely to be even more pronounced if the ptch testing is crried out t n erly ge, where informtion is primrily given to the prents. We cnnot reject the possibility tht AD in some cses were misclssified, which would help explin the lrge shre with persistent skin symptoms. However, it is well known tht CD often results in ongoing disese (2, nd it could lso be tht shre of the children nd dolescents with skin symptoms not explined by AD or contct llergy, represent group suffering from irritnt CD, indicting tht this is significnt problem mong children. Other differentil dignoses re nummulr eczem, seborroheic dermtitis, nd solr dermtitis. Finlly, it is possible tht some of the ptients developed new contct llergies in the time from primry ptch testing to follow up. Mortz et l. (16 recently showed tht the incidence rte of contct llergy incresed from dolescence to dulthood. As expected, life qulity nd disese severity were correlted. Life qulity ws severely ffected in significnt shre of ptients with persistent eczem. However, in n even lrger proportion of ptients, persistent eczem only hd smll to moderte effect on life qulity. This finding my help to explin why so mny suffered from persistent eczem, i.e. the impct on life qulity is not perceived s significnt enough to offset the efforts of implementing voidnce strtegies in dily life. Children ged 3 10 yers were more likely to hve severely ffected life qulity thn children ged 11 16, which ws explined by the interction effect of AD nd persistent eczem. Becuse of the smll size of the subgroups mong respondents of the CDLQI, we were unble to mke strong conclusions for children 16. Sttisticl nlyses with djustment for gender, ge, AD, nd ny interction effects between explntory vribles would hve been idel. Unfortuntely our smple size did not llow this. Severl studies hve explored the impct of different skin disorders on life qulity in children nd dolescents nd most concern AD. Like Gånemo et l. (17 we were unble to show ny gender difference in children 16 yer. We demonstrted convincing gender difference in our popultion of ptients 17 yers with ongoing eczem regrdless of the nturl history. Similr to our results, Bllrdini et l. (18 found pre-dolescent girls with mild eczem to hve greter impirment of selfperceived helth compred to boys. Our finding my well reflect tht dolescent girls nd young women re more concerned bout ppernce thn mles of the sme ge. Despite the reltively low response rte of 46%, we did chieve lrge smple size of 1039 subjects. The low response rte my to some extent be explined by the lrge spn in follow-up time, i.e. ptients my be less likely to respond to questionnires regrding events tht hppened severl yers go.

5 210 A.B. Simonsen et l. There ws n overrepresenttion of femle respondents. The unequl gender distribution ws, however, to some degree expected, s two thirds of the ptients in our originl dt set ws femle nd ccordingly, severl studies hve shown tht there is femle predominnce mong ptients referred for ptch testing (12. In ddition, it hs previously been demonstrted tht young men re more likely to be non-responders thn responders (19, nd tht women re more likely to return miled questionnire (1. Strtified dt nlyses should eliminte ny confounding. Another possible limittion is the fct tht ptients who suffer from eczem my be more likely to prticipte in questionnire surveys concerning skin disese nd further, retrospective questionnire studies imply the inevitble limittion of recll bis. As regrds to the ssessment of continuous eczem, this ws bsed on the ptient s informtion, nd one could rgue tht clinicl ssessment would hve been more ccurte. Our findings indicte significnt risk of childhood eczem becoming chronic nd ffecting life qulity considerbly. As expected persistent eczem ws strongly ssocited to AD, but ws not explined by gender, ge, contct llergy or time spn from ptch testing to follow-up. Persistent eczem t follow-up incresed the risk of severe impirment of life qulity nd this ws especilly pronounced in femles 17 yers. Ptch testing did not ffect the course of eczem, indicting tht it cn be extremely difficult to void the responsible llergens nd further, ptients my forget the ptch test outcome. Children with skin symptoms should be crefully treted nd guided, in order to minimise the disese burden nd void chronicity nd future socioeconomic consequences. We recommend providing ech ptient with personl llergy informtion crd. The subject of this study is lrgely unexplored nd there is need of further elucidtion of the re. Future studies should include clinicl follow-up. It would lso be of interest to repet the ptch test in order to determine if ny new llergies hve evolved. ACKNOWLEDGEMENTS Members of the Dnish Group for Contct Dermtitis: Drs Niels Kren Veien, Anne Toftegrd Funding, Hns Lomholt nd Henrik Sølvsten (Alborg, Christin Avnstorp, Anne Hjorther nd Bent Stberg (Rødovre, Morten Østerblle, Kristin Otkjær nd Aksel Otkjær (Herning, Bo Lsthein (Svendborg, Niels Henrik Nielsen (Bgsværd, Henrik Thormnn (Vejle, Nthlie Dfour (Klundborg, Anne Dnielsen, Gitte Struss, Mds Nielsen nd Rune Lindskov (Copenhgen, Susnne Vissing (Hørsholm re grtefully cknowledged for prticipting in the primry dt collection. Funding. The Lundbeck Foundtion, Age Bngs Foundtion, nd Ase nd Ejnr Dnielsens Foundtion provided funding for the preprtion nd printing of the questionnires, postge nd hndling fee, nd expenses relted to dt collection. The uthors declre no conflict of interest. REFERENCES 1. Kdyk DL, McCrter K, Achen F, Belsito DV. 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