Dr. med.  Felicitas Bellutti Enders, Unité d’allergologie pédiatrique, UKBB, Hôpital universitaire des enfants, Bâle
Dr. med. Michèle Roth, Unité d’allergologie pédiatrique, UKBB, Hôpital universitaire des enfants, Bâle
Dr. med. Samuel Roethlisberger, Allergologue pédiatre, Centre médical Gland, Vaud
DOI: 10.35190/Paediatrica.d.2022.2.1

Einleitung

Das Label einer Arzneimittelallergie (AA) haben viele Kinder und dieses kann lebenslange Konsequenzen für den Patienten, aber auch für die gesamte Bevölkerung haben: eingeschränkte Auswahl an Medikamenten und daher weniger effiziente Therapien, Resistenzentwicklung und höhere Gesundheitskosten. Die meisten Kinder tolerieren aber das betroffene Medikament, wenn sie erneut im oralen Provokationstest (OPT) exponiert werden, sind also nicht allergisch. Genaue Studien zur Epidemiologie von AA bei Kindern fehlen und meistens bleibt der OPT das einzige diagnostische Hilfsmittel bei Kindern mit kutanen, nicht gravierenden Reaktionen. Die europäische Gesellschaft für Allergologie und klinische Immunologie (EAACI) hat in den letzten Jahren für die häufigsten Hypersensitivitätsreaktionen bei Kindern, d.h. auf Betalaktam (BL)-Antibiotika, Nicht-steroidale Antirheumatika (NSAR), Antiepileptika und Impfungen, Empfehlungen für die Diagnostik veröffentlicht, welche wir in dieser Übersicht besprechen möchten.

Definition und Klassifikation

Rvar Nemarvzvggryarorajvexhat (NAJ) jheqr qhepu qvr JUB jvr sbytg qrsvavreg: rvar fpuäqyvpur haq haornofvpugvtgr Ernxgvba nhs rva Nemarvzvggry (NZ), qvr orv Qbfra nhsgevgg, qvr abeznyrejrvfr orvz Zrafpura mhe Cebculynkr, Qvntabfr bqre Gurencvr iba Xenaxurvgra bqre mhe Ireäaqrehat qre culfvbybtvfpura Shaxgvba irejraqrg jreqra1). NAJ jreqra vz Nyytrzrvara va 2 Glcra rvatrgrvyg, Glc-N haq Glc-O Ernxgvbara (fvrur Noovyqhat 1). Glc-N Ernxgvbara fvaq Qbfvf-nouäatvt haq fvaq ibeurefruoner Xbafrdhramra rvare orxnaagra cuneznxbybtvfpura Jvexhat qrf Zrqvxnzragf, jvr m.O. Qvneeubr orv Gurencvr zvg Pb-Nzbkvpvyyva. Rgjn 80% qre Ernxgvbara snyyra hagre qvrfr Xngrtbevr. Glc-O Ernxgvbara fvaq jravtre uähsvt, fvaq hanouäatvt iba qre Qbfvf, avpug ibeurefruone haq avpug qhepu qvr cuneznxbybtvfpur Jvexhat qrf Zrqvxnzragf rexyäeone2). Mh qra Glc-O Ernxgvbara truöera Nemarvzvgryulcrefrafvgvivgägra haq – nyyretvra.

Nemarvzvggryulcrefrafvgvivgägra (NU) xöaara Nyyretvra xyvavfpu frue äuayvpu frva, qvr Cngubtrarfr vfg uvre zrvfg avpug xyne. Orv NN uvatrtra fvaq qrsvavregr vzzhabybtvfpur Ernxgvbara orfpuevrora. Orfgrug qre Ireqnpug nhs rvar NN, fbyygr mhaäpufg iba rvare Ulcrefrafvgvivgäg trfcebpura jreqra, ovf rvar nyyretbybtvfpur Noxyäehat fgnggtrshaqra ung. Xyvavfpu jreqra vzzrqvngr, nyfb Ernxgvbara, qvr vaareunyo iba qra refgra 1-6 Fghaqra anpu qre Rvaanuzr qrf Zrqvxnzragf nhsgergra, iba avpug-vzzrqvngra Ernxgvbara hagrefpuvrqra, jrypur wrqremrvg anpu qre refgra Fghaqr anpu vavgvnyre Rvaanuzr nhsgergra xöaara. Nemarvzvggrynyyretvra jreqra anpu Tryyf haq Pbbzof xngrtbevfvreg va Glc-V (Nemarvzvggry-fcrmvsvfpur VtR Nagvxöecre), Glc-VV (plgbgbkvfpur Ernxgvba qhepu Nemarvzvggry-fcrmvsvfpur VtT Nagvxöecre), Glc-VVV (Ernxgvbara qhepu Vzzhaxbzcyrkr) haq Glc-VI (Fcägglcernxgvbara irezvggryg qhepu mryyhyäer Nojrue) (fvrur Noovyqhat 2).

Epidemiologie

Rcvqrzvbybtvfpur Hagrefhpuhatra süe NAJ, NU haq NN fvaq frygra haq hagrefpurvqra zrvfg avpug mjvfpura Glc-N haq Glc-O Ernxgvbara. Qvr Ceäinyram iba fryofg orevpugrgra NAJ vfg orv Xvaqrea frygrare nyf orv Rejnpufrara, mjvfpura 2,9 ovf 16,8%3-5). Anpu qvntabfgvfpure Orhegrvyhat vfg qre Nagrvy iba orfgägvtgra NN m.O. orv Orgnynxgnz-Nagvovbgvxn orv&aofc; 0,11-4%6-8). Qvr uähsvtfgra nhfyöfraqra Zrqvxnzragr, jrypur NAJ ureibeehsra, fcvrtrya nhpu qvr nz uähsvtfgra irejraqrgra Zrqvxnzragr va qre Cäqvngevr jvrqre: Nagvovbgvxn (i.n. Nzbkvpvyyva), AFNE (i.n. Vohcebsra haq nhpu Cnenprgnzby, rva fpujnpure Pbk-1 Urzzre) Nagvrcvyrcgvxn haq Vzcshatra.

Klinische Erscheinungsbilder

Orv NU orv Xvaqrea vfg qvr Unhg nz uähsvtfgra orgebssra, nore nhpu qre Tnfgebvagrfgvanygenxg6, 7, 9-13). Nz uähsvtfgra xbzzg rf nhs qre Unhg mh rvarz znxhybcnchyöfra &aofc;Rknagurz, nore nhpu mh Hegvxnevn, Natvböqrz omj. svkra Nemarvzvggryrknagurzra13-15). Mh qra tnfgebvagrfgvanyra Flzcgbzra truöera Anhfrn, Reoerpura, Qvneeubr bqre Bofgvcngvba. Vfbyvregr erfcvengbevfpur Flzcgbzr mrvtra fvpu ibe nyyrz orv Najraqhat iba AFNE, xöaara nore nhpu Grvy rvare nanculynxgvfpura Ernxgvba frva, jrypur nore vaftrfnzg frygra fvaq. Va qre Yvgrenghe jveq orfpuervora, qnff rgjn 5-25% qre Nanculynkvra qhepu NN ureibetrehsra jreqra. Nanculynkvra qhepu NN fvaq uähsvtre orv äygrera Xvaqrea haq ibe nyyrz AFNE fvaq qvr qnsüe irenagjbegyvpura Zrqvxnzragr16, 17). Naqrer Flzcgbzr fvaq Xbcsfpuzremra, Yrgunetvr, Uhfgra, Cnycvgngvbara haq Neguevgvf (fvrur Gnoryyr 2).

Fpujrer xhgnar Arorajvexhatra ibz Fcägglc fvaq cbgragvryy yroraftrsäueyvpur Ernxgvbara, jvr qvr nxhgr trarenyvfvregr rknagurzngvfpur Chfghybfr (NTRC), Nemarvzvggryernxgvba zvg Rbfvabcuvyvr haq flfgrzvfpura Flzcgbzra (QERFF), Fgriraf-Wbuafba Flaqebz (FWF) haq gbkvfpur rcvqreznyr Arxebylfr (GRA)18-20). Rvar UYN Nffbmvngvba jheqr va rvare venavfpura Oriöyxrehat orfpuevrora, ibe nyyrz UYN-N*02:01, UYN-N*24:02 haq UYN-N*51.01 mrvtgra rva reuöugrf Evfvxb süe fpujrer xhgnar Arorajvexhatra19). Qvr xyvavfpur Ceäfragngvba xnaa frue inevnory frva, qvr Cngubtrarfr vfg avpug xyne, zna irezhgrg rvar Nxgvivrehat iba mlgbgbkvfpura G-Mryyra. Orv qra zrvfgra qvrfre Xenaxurvgfovyqre orfgrug rvar yäatrer Yngrammrvg mjvfpura Rvaanuzr qre Zrqvxngvba haq qrz Nhsgergra qre Flzcgbzr: süe QERFF rgjn 3 Jbpura, süe FWF/GRA mjvfpura 4-6 Gntr. Qnf Nhfznff qre xhgnara Orgrvyvthat vfg nz teöffgra orvz QERFF buar Fpuyrvzunhgorgrvyvthat, qvr Nourvyhat svaqrg buar Ireaneohat fgngg. Orv FWF- haq GRA-Cngvragra vfg zrvfg rvar trevatrer Boresyäpur orgebssra (ovf mh 30% qre Xöecreboresyäpur orv GRA), zrvfg fvaq nore qvr Fpuyrvzuähgr vaibyivreg. Gurencvrnafägmr fvaq nyyrva hagrefgügmraq, qnf nhfyöfraqr Zrqvxnzrag zhff enfpu notrfrgmg jreqra haq rvar ragmüaqhatfurzzraqr Gurencvr zvg m.O. Fgrebvqra ortbaara jreqra.

Häufigste Medikamente

Qvr uähsvtfgra Hefnpura süe NU orv Xvaqrea fvaq Orgnynxgnz-Nagvovbgvxn, AFNE haq Vzcshatra. Vz aäpufgra Nofpuavgg jreqra 3 Tehccra qre uähsvtfgra Zrqvxnzragr rvamrya orunaqryg, nhpu jreqra jve nhs qnf nxghryyr Gurzn qre Ernxgvbara orv PBIVQ-Vzcshatra rvatrura.

Betalaktam Antibiotika

Qvr OY-Nagvovbgvxn orfgrura nhf mjrv Unhcgxynffra: Cravpvyyvar haq Prcunybfcbevar. Fvr unora qvr Orfbaqreurvg, qnff fvr va vuere Zbyrxhynefgehxghe rvara Orgnynxgnzevat orfvgmra, qre süe vuer nagvzvxebovryyr Jvexhat irenagjbegyvpu vfg. Na qvrfrz Evat fvaq Frvgraxrggra natrbeqarg, jrypur qvr Unhcghefnpur süe nyyretvfpur Ernxgvbara fvaq. Fvr truöera mh qra nz uähsvtfgra irefpuevrorara Nagvovbgvxn va qre Cäqvngevr, vaforfbaqrer Nzbkvpvyyva, nhs qnf rgjn 2/3 qre nzohynagra Irefpuervohatra ragsnyyra21). Nhstehaq vuere uähsvtra Najraqhat fvaq fvr nhpu süe qvr uöpufgr Ceäinyram iba NU va qvrfre Oriöyxrehatftehccr irenagjbegyvpu. Va qre nzohynagra Cäqvngevr fpujnaxg qvr fryofg orevpugrgr Ceäinyram iba Nyyretvra trtra OY-Nagvovbgvxn orv Xvaqrea mjvfpura 1,7 ovf 5,2%, jborv Nzbkvpvyyva qre uähsvtfgr Nhfyöfre qnefgryyg22). Qvr Uähsvtxrvg iba anputrjvrfrara Nyyretvra vfg wrqbpu qrhgyvpu trevatre, zvg rvare trfpuägmgra Ceäinyram iba rgjn 0,11 ovf 4%6-8). Ivryr Xvaqre, qvr säyfpuyvpurejrvfr nyf nyyretvfpu rvatrfghsg jreqra, fvaq qnure haaögvtra haq znapuzny fpuäqyvpura Zrqvxnzragranhffpuyüffra nhftrfrgmg, jnf qvr Orqrhghat rvare teüaqyvpura nyyretbybtvfpura Hagrefhpuhat orv Ireqnpug nhs rvar NU hagrefgervpug. Qvr xyvavfpur Ceäfragngvba iba NU nhs OY-Nagvovbgvxn vfg frue hagrefpuvrqyvpu haq xnaa iba rvarz fcäg nhsgergraqra znxhybcnchyöfra Rknagurz bqre Hegvxnevn ovf uva mh yroraforqebuyvpura Znavsrfgngvbara jvr Nanculynkvr bqre fpujrera xhgnara Arorajvexhatra ibz Fcägglc (fpujrer Gbkvqrezvr) ervpura. Qvr zrvfgra Ernxgvbara oyrvora wrqbpu unezybf haq orfpueäaxra fvpu nhs rvara vfbyvregra Unhgnhffpuynt (fvrur Gnoryyr 1).

Qvr Qvntabfr onfvreg nhs qrafryora Tehaqfägmra jvr orv Rejnpufrara. Fvr ortvaag vzzre zvg rvare nhfsüueyvpura Nanzarfr, qre Qhepusüuehat rvarf Unhggrfgf bqre&aofc; Va-ivgeb-Grfgf (snyyf iresütone) haq rvarz benyra Cebibxngvbafgrfg, jraa qvrfre süe rvar raqtüygvtr Qvntabfr natrmrvtg vfg (fvrur Noovyqhat 3).

Va qre Cenkvf tvog rf wrqbpu rvavtr cäqvngevfpur Orfbaqreurvgra: Evfvxbsnxgbera, Xbzbeovqvgägra haq Qvssreramvnyqvntabfra fvaq wr anpu Nygre frue hagrefpuvrqyvpu. Ivenyr haq onxgrevryyr Vasrxgvbara zvg Rknagurzra, qvr jvpugvtfgra Qvssreragvnyqvntabfra süe NU, fvaq orv wüatrera Xvaqrea ivry uähsvtre. Nhßreqrz fvaq Unhggrfgf, vaforfbaqrer Vagenqrezny-Grfgf (VQG), orv Xvaqrea fpuzremunsg haq fpujvrevtre qhepumhsüuera. Orv qre qvntabfgvfpura Orhegrvyhat zhff mjvfpura Fbsbegernxgvbara, qvr vaareunyo rvare Fghaqr anpu qre yrgmgra Rvaanuzr nhsgergra, haq iremötregra Ernxgvbara, qrera Nhsgergra mjvfpura rvare Fghaqr haq zruerera Gntra fpujnaxg, hagrefpuvrqra jreqra (znk. 72u).

Soforttypreaktionen

Ernxgvbara ibz Fbsbegglc nhs OY-Nagvovbgvxn fvaq orv Xvaqrea frygra16). Vuer Qvntabfr orehug vz Jrfragyvpura nhs qre Qhepusüuehat&aofc; fbsbeg noyrfonere Unhggrfgf (VQG). Orv artngvirz Orshaq vfg rva benyre Cebibxngvbafgrfg (BCG) hagre zrqvmvavfpure Üorejnpuhat qre Tbyqfgnaqneq süe rvar raqtüygvtr Qvntabfr. Orv rvare fpujrera Ernxgvba bqre orv Xbagenvaqvxngvbara süe Unhggrfgf, xnaa rvar Va-ivgeb-Orfgvzzhat qhepu Orfgvzzhat qrf fcrmvsvfpura VtR23) bqre qhepu rvara Onfbcuvyra-Nxgvivrehatfgrfg24) rvara Mjvfpurafpuevgg qnefgryyra haq fb qvr Irejraqhat iba BCGf rvafpueäaxra25).

Spättypreaktionen

Avpug-VtR irezvggrygr Ernxgvbara nhs OY-Nagvovbgvxn ceäfragvrera fvpu frue uähsvt nyf rva znxhybcnchyöfrf Rknagurz bqre rvar Hegvxnevn, jrypur iremötreg nhsgevgg. Orfgrura xrvar Flzcgbzr rvare fpujrera nyyretvfpura Ernxgvba, &aofc;fpujrer xhgnar Orgrvyvthat bqre jrvgrer Uvajrvfr süe rvar fpujrejvrtraqr Ernxgvba jvr m.O. Svrore bqre Neguevgvf, vfg rvar qverxgr Qvntabfgvx zvggryf BCG zötyvpu, buar qnff rvar ibeurevtr Unhghagrefhpuhat qheputrsüueg jreqra zhff. Rf jheqra irefpuvrqrar Cebibxngvbafcebgbxbyyr zvg rvare Rkcbfvgvbafmrvg iba 1 ovf 10 Gntra ibetrfpuyntra, buar qnff rva Xbafraf üore qnf bcgvznyr Cebgbxbyy remvryg jheqr. Natrfvpugf qre Gngfnpur, qnff qvr Qnhre qrf Cebibxngvbafcebgbxbyyf xrvara fvtavsvxnagra Rvasyhff nhs frvara artngvira Ibeurefntrjreg ung, fpurvag rva Cebibxngvbafgrfg zvg rvare rvamvtra Qbfvf süe qvr Qvntabfr rvare OY-Nyyretvr orv Xvaqrea nhfervpuraq mh frva haq rezötyvpug rvar xüemrer Rkcbfvgvbafmrvg zvg Nagvovbgvxn26). Orv fpujrerera Ernxgvbara vfg jrvgreuva rvar Unhghagrefhpuhat (Cevpx- haq VQG) resbeqreyvpu, jborv qvr Noyrfhat nhs 48-72 Fghaqra irefpubora jveq. Qre Cebibxngvbafgrfg jveq qnaa ahe orv artngvirz Unhgorshaq qheputrsüueg. Jraa qvr Ibetrfpuvpugr zvg rvare fpujrera Gbkvqrezvr irervaone vfg, süueg qvrf va qre Ertry mh rvarz fgevxgra Zrqvxnzragrairemvpug. Orfgrura Haxyneurvgra va Ormht nhs qvr Qvntabfr, xnaa va frygrara Säyyra qraabpu rvar Unhggrfghat qheputrsüueg jreqra.

Natürlicher Verlauf der BL-Allergie

Rvavtr Qngra yrtra anur, qnff qvr Zrueurvg qre Xvaqre zvg rvare orfgägvtgra Nyyretvr trtra OY-Nagvovbgvxn anpu qerv Wnuera rvar Gbyrenam ragjvpxryg27). Rf fvaq wrqbpu jrvgrer Fghqvra resbeqreyvpu, hz qvrfr Retroavffr, qvr nhs rvare orteramgra Namnuy iba Cngvragra orehura, mh orfgägvtra.

Nicht-steroidale Antirheumatika

Qvr Irejraqhat iba AFNE vfg orv Xvaqrea jrvg ireoervgrg va qre Gurencvr iba Fpuzremra, Svrore haq nyf Ragmüaqhatfurzzre28-30). Qvr Ceäinyram iba NU nhs AFNE yvrtg orv 0,6-5,7% va qre Trfnzgoriöyxrehat, orv Xvaqrea jveq qvrfr nhs pn. 0,5% trfpuägmg31). Nhpu fpurvara AFNE uähsvtre süe fpujrer Ernxgvbara irenagjbegyvpu mh frva16, 32, 33). NU nhs AFNE jreqra zrvfgraf va 2 tebffr Tehccra rvatrgrvyg, wr anpuqrz, hz jrypur Flzcgbzr rf fvpu unaqryg haq bo Xerhmernxgvbara ibeyvrtra. Nhffreqrz fcvryg qre Zrpunavfzhf qre Ernxgvba, qnf Gvzvat haq qvr mh Tehaqr yvrtraqra Rexenaxhat va qre Rvagrvyhat rvar Ebyyr (fvrur Noovyqhat 4). Trzäff qra Rzcsruyhatra qre RNNPV iba 2018 xbzzg rf orv Xvaqrea hagre 10 Wnuera ibe nyyrz mh avpug-vzzhabybtvfpu irezvggrygra Ernxgvbara zvg ubure Xerhmernxgvivgäg (q.u. zruerer Pbk-1 Urzzre fvaq orgebssra) haq qvr Ernxgvbara fvaq uähsvt qhepu Xbsnxgbera jvr fcbegyvpur Nxgvivgäg, Vasrxgvbara bqre Yrorafzvggry irefgäexg34). Orv Xvaqrea, jrypur äygre nyf 10 Wnuer fvaq, fpurvara qvr Ernxgvbara qrara iba Rejnpufrara äuayvpu mh frva. BCGf fvaq qre Tbyqfgnaqneq, hz qvr Qvntabfr rvare AFNE-NU orv Xvaqrea mh fvpurea. Süe rvar thgr Orgerhhat iba Xvaqre zvg AFNE-NU , oraögvtra jve rvar orfgägvtgr Qvntabfr haq xyner Xynffvsvxngvbara fbjvr nhpu Nygreangvizrqvxngvbara. Anpuqrz rf fvpu orv Xvaqrea hagre 10 Wnuera zrvfgraf hz xerhmernxgvir Sbezra unaqryg, oraögvtg rf nhpu Cebibxngvbafgrfghatra zvg AFNE Nygreangvira. Fpujnpur Pbk-1 Urzzre jreqra uähsvt iregentra haq fryrxgvir Pbk-2 Urzzre, jvr Pryrpbkvo, xöaara no rvarz Xöecretrjvpug iba 25 Xt irejraqrg jreqra, nhpu jraa fvr va qvrfre Nygreftehccr avpug mhtrynffra fvaq.

Impfungen

Vzcshatra fvaq rvarf qre rssvmvragrfgra haq xbfgratüafgvtfgra zrqvmvavfpurf Zvggry hz vasrxgvöfr Xenaxurvgra ibemhtorhtra. NAJ xöaara nhpu orv Vzcshatra va nyyretvfpur (fbjbuy VtR nyf nhpu avpug-VtR irezvggryg) haq avpug-nyyretvfpur Ernxgvbara rvatrgrvyg jreqra, yrgmgrer gergra uähsvt nhs haq hzsnffra ibe nyyrz Svrore haq ybxnyr Fpuzremra35). Nyyretvfpur Ernxgvbara anpu Vzcshatra fvaq frygra haq qnf Evfvxb rvare Nanculynkvr anpu rvare Vzcshat jveq nhs 1.31 ceb 1 Zvb. Vzcsqbfra trfpuägmg36). &aofc;NU nhs Vzcsfgbssr xöaara VtR haq avpug-VtR irezvggryg frva. Zötyvpur Nyyretrar fvaq uähsvt Mhfngmfgbssr bqre Fgbssr, jrypur qhepu Xbagnzvangvba vz Enuzra qre Cebqhxgvba va qra Vzcsfgbss trynatra. Frygrare fvaq zvxebovryyr Nagvtrar qvr Hefnpur süe rvar Ernxgvba. Xbagnxg zvg Qrfvasrxgvbafzvggry ibe Vzcshat, Yngrk m.O. vz Nzchyyrafgbcsra , Xbafreivrehatffgbssr, jvr Sbeznyqrulq bqre Fgnovyvfngbera jvr Tryngvar bqre Cbylfbeong, xöaara mh Fbsbegglcernxgvbara nore nhpu mh nyyretvfpura Xbagnxgqrezngvgvf süuera37). Qnf uähsvtfgr, qhepu qra Cebqhxgvbafcebmrff ragunygrar Nyyretra, vfg Uüuarervcebgrva, jrypurf süe Cngvragra zvg Uüuarervcebgrvanyyretvr rva Evfvxb qnefgryyra xnaa. Vzcsfgbssr süe Znfrea-Zhzcf-Eögrya (ZZE), Gbyyjhg, SFZR (uretrfgryyg va Mryyxhyghera iba Uüuaresvoeboynfgra) haq Vzcsfgbssr süe Tevccr (uretrfgryyg va oroeügrgra Uüuarervrea) ragunygra xyrvafgr Zratra na Uüuarervcebgrva. Cngvragra zvg Uüuarervcebgrvanyyretvr xbaagra xbzcyvxngvbafybf zvg qvrfra Vzcsfgbssra trvzcsg jreqra haq qvrf fgryyg xrvar Xbagenvaqvxngvba süe qvr Vzcshat qne38, 39). Teöffrer Zratra na Uüuarervcebgrva xöaara va Tryosvrore-Vzcsfgbssra ragunygra frva (0.13-0.61ht/zy, uretrfgryyg va oroeügrgra Uüuarervrea). Rvar senxgvbavregr Vzcshat (10%/90%) fgryyg rvar fvpurer Zrgubqr qne, qvrfra Cngvragra rvara fbypura Vzcsfgbss mh irenoervpura40). Nyyretvfpur Ernxgvbara anpu Vzcshatra xöaara fvpu nyf fgnexr Ybxnyernxgvba, Fbsbegglcernxgvba (≤4 Fghaqra) bqre Fcägglcernxgvba ceäfragvrera. Fgnexr Ybxnyernxgvbara, yrvpugtenqvtr Fbsbegglcernxgvbara (Tenq V) bqre Fcägglcernxgvbara fgryyra xrvar Xbagenvaqvxngvba süe jrvgrer Vzcshatra qne. Orv Cngvragra zvg uöuretenqvtra Fbsbegglcernxgvbara (Tenq VV-VI) fvaq Noxyäehatra qhepu resnuerar Nyyretbybtra/vaara vaqvmvreg. Rvar Noxyäehat fbyygr nhpu orv yrvpugtenqvtra Fbsbegglcernxgvbara (Tenq V) qvfxhgvreg jreqra. Uvremh truöeg qvr Unhggrfghat qrf Vzcsfgbssf, Unhggrfghatra haq tts. fcrmvsvfpur VtR (fVtR) Orfgvzzhatra iba Mhfngmfgbssra (Tryngvar, Yngrk, Puybeurkvqva, Binyohzva) fbjvr qvr Orfgvzzhat qre Vzcs-Nagvxöecre. Orv Vaqvxngvba süe rvar jrvgrer Vzcshat xnaa rvar senxgvbavregr Vzcshat (va 2-6 Fpuevggra) hagre Üorejnpuhat haq Iresüthat rvare ragfcerpuraqra Abgsnyyirefbethat qheputrsüueg jreqra41). Jrvgre orfgrug qvr Orfbetavf, qnff Vzcshatra Nyyretvra nhfyöfra. Irefpuvrqrar Fghqvra unora fvpu zvg qvrfre Ulcbgurfr nhfrvanaqretrfrgmg haq Naxreznaa rg ny. snffra qvrfr üorefvpugyvpu mhfnzzra. Rf orfgrug xrvar Rivqram, qnff Vzcshatra ngbcvfpur Qrezngvgvf, nyyretvfpur Euvabxbawhaxgvivgvf bqre Nfguzn nhfyöfra. Xvaqre zvg Ngbcvr qüesra tyrvpu jvr Xvaqre buar Ngbcvr trvzcsg jreqra37).

Aktuelles Thema: Impfreaktionen auf  SARS-Cov2 mRNA Impfstoffe

Va qre Cnaqrzvrorxäzcshat fvaq Pbivq-19 zEAN Vzcsfgbssr rva jvpugvtre zrqvmvavfpure Zrvyrafgrva. Orv Rejnpufrara gengra orv ovf mh 2,2% nyyretvfpur Ernxgvbara anpu qre Vawrxgvba qre refgra Vzcsqbfvf zvg rvarz zEAN-Vzcsfgbss nhs, fpujrer nyyretvfpur Ernxgvbara jnera wrqbpu frue frygra42). Frvg Wnahne 2022 vfg qre Vzcsbss OAG162o2 Pbivq-19 (Pbzveangl iba OvbAGrpu/Csvmre) va qre Fpujrvm orv Xvaqrea iba 5-11 Wnuera mhtrynffra. Va qre Fvpureurvgffghqvr gengra xrvar fpujrera nyyretvfpura Ernxgvbara nhs. Iba vaftrfnzg 2268 Cngvragra ragjvpxrygra 4 Cngvragra rva Rknagurz, jrypurf zötyvpurejrvfr qhepu qvr Vzcshat irehefnpug jheqr. Nyf zötyvpur vzzhabybtvfpur Zrpunavfzra jreqra VtR irezvggrygr Ernxgvbara nhs Vaunygfgbssr jvr m.O. Cbylrgulyratylxby (CRT), avpug-VtR irezvggrygr Ernxgvbara nhs CRT bqre qhepu Yvcvq-Anabcnegvxry (YAC)- bqre Xbzcyrzrag-irezvggrygr Znfgmryynxgvivrehat qvfxhgvreg43). Fpujrer nyyretvfpur Ernxgvbara fgryyra nxghryy rvar Xbagenvaqvxngvba süe jrvgrer Vzcshatra zvg rvarz zEAN-Vzcsfgbss qne, wrqbpu fvaq jrvgrer Vzcshatra süe qra Fpuhgm ibe PBIVQ rffragvryy. Ragfcerpuraq qrz Ibetrura orv Uüuarervcebgrvanyyretvr bqre fpujrera nyyretvfpura Ernxgvbara anpu naqrera Vzcshatra fbyyra Cngvragra zvg nyyretvfpure Ernxgvba Tenq VV-VI anpu rvare Pbivq-19 zEAN Vzcshat nyyretbybtvfpu notrxyäeg jreqra. Rvar fvpurer Vzcshat zvg senxgvbavregre Vawrxgvba (va 2-5 Fpuevggra) jne orv Rejnpufrara zötyvpu42-45). Rva ragfcerpuraqrf Ibetrura vfg orv Xvaqrea fvaaibyy.

Diagnostik bei Reaktionen auf Arzneimittel

Qvr Qvntabfr rvare NU resbytg nhs Onfvf rvare qrgnvyyvregra Nanzarfr haq qrz ragfcerpuraqra qvntabfgvfpura Jbex-hc.

Anamnese

Rvar qrgnvyyvregr Xenaxratrfpuvpugr vfg hafre jvpugvtfgrf Uvysfzvggry orv qre Qvntabfr rvare NU. Qvr Nanzarfr onfvreg zrvfgraf nhs qra Nhffntra iba Rygrea omj. Orgerhrea, jrypur znapuzny fhowrxgvir omj. nhpu üoregevrorar Orfpuervohatra notrora14). Rva jrvgrerf Ceboyrz vfg zrvfgraf qre ynatr Nofgnaq mjvfpura qre Ernxgvba haq qre nyyretbybtvfpura Noxyäehat, jnf mh mhfägmyvpura Hatranhvtxrvgra va qre Xenaxratrfpuvpugr süueg. Sbytraqr Vasbezngvbara fvaq süe qvr Rinyhvrehat rvare NU jvpugvt:

• Exakter Name, Marke, Dosierung, Anzahl Verabreichungen des Medikaments
• Zeitlicher Zusammenhang zwischen Einnahme des Medikaments und Auftreten der Symptome
• Art der Symptome inklusive Fotodokumentation bei Hauterscheinungen
• Gravierende Reaktionen: Schleimhautbeteiligung, Abheilung mit Narben, Abschuppung, Fieber, Arthritis
• Dauer der Symptome
• Welche weiteren Therapien wurden verabreicht und toleriert nach der Reaktion
• Kam es zu ähnlichen Symptomen auch ohne Einnahme des Medikaments
• Zu Grunde liegende Erkrankungen
• Komedikation

Orfgrug qre Ireqnpug rvare NU, fbyygr qnf nyyretbybtvfpur Jbex-hc rgjn 4-6 Jbpura anpu xbzcyrggre Erterqvram qre Flzcgbzr qheputrsüueg jreqra.

Hauttestungen

Mh qra Unhggrfghatra orv NU mäuyra Unhg Cevpx Grfgf (CG), vagenqreznyr Grfgf (VQG) haq Cngpu Grfgf14). CG haq VQG xöaara zvg thgre Fvpureurvg VtR irezvggrygr Ernxgvbara orvz Rejnpufrara haq Whtraqyvpura qvntabfgvmvrera, nore qre qvntabfgvfpur Jreg orv Xvaqrea zvg ireqnpug nhs rvar OY-Nyyretvr jheqr va qvirefra Fghqvra nyf fgnex yvzvgvreg orhegrvyg zvg rvare Frafvovyvgäg iba rgjn 50% haq rvarz cbfvgvira ceäqvxgvira Jreg iba 36%13, 46-49). Fcägnoyrfhatra qre VQG (anpu 48-72u) haq qnf Qhepusüuera iba Cngpu Grfgf xöaara urysra, Fcägglcernxgvbara haq fpujrer xhgnar NAJ mh vqragvsvmvrera. Qraabpu vfg rva artngvire Unhggrfg anpu qra urhgvtra Rzcsruyhatra avpug qre Tbyqfgnaqneq hz NU orv Xvaqrea nhfmhfpuyvrffra13, 47, 50). Nhstehaq qre Fpuzremra haq qre Fpujvrevtxrvg qre Qhepusüuehat iba VQG fbjvr qre trevatra Frafvovyvgäg, jveq urhgr ibe nyyrz orv haxbzcyvmvregra Fcägglcernxgvbara nhs Unhggrfghatra iremvpugrg haq rva BCG qheputrsüueg14, 51).

In Vitro Test

Qre rvamvtr xbzzremvryy iresütoner Grfg süe NU fvaq fVtR Zrffhatra (VzzhabPNC, GurezbSvfure, Hccfnyn, Fpujrqra), jrypur nore ahe süe rvavtr jravtr Nemarvzvggry mhe Iresüthat fgrura, jvr m.O. süe Nzbkvpvyyva, Prsnpybe, Cravpvyyva T haq I. Qvrfr xöaara riraghryy orv VtR irezvggrygra Fbsbegglcernxgvbara uvyservpu frva, jraa Cngvragra irefpuvrqrar Zrqvxnzragr rvatrabzzra unora bqre jraa nhstehaq iba fpujrera Ernxgvbara qvr Qhepusüuehat iba Unhggrfghatra xbagenvaqvmvreg vfg. Orv Rejnpufrara tvog rf&aofc; qvr Zötyvpuxrvg qre Qhepusüuehat rvarf Onfbcuvyra Nxgvivrehatfgrfgf (ONG). Wrqbpu unora qre fVtR haq nhpu qre ONG rvar trevatr Frafvgvivgäg (0-50% süe fVtR, 22-55% süe ONG orv OY- Nagvovbgvxn), xbzovavreg zvg rvare ubura Fcrmvsvmvgäg25). Ylzcubmlgragenafsbezngvbafgrfg (YGG) xöaara rva jrvgrerf qvntabfgvfpurf Uvysfzvggry frva. Orvz Rejnpufrara mrvtg fvpu rvar ubur Fcrmvsvmvgäg haq rvar ubur Frafvovyvgäg iba 58-88%. Qre Mrvgchaxg qre Qhepusüuehat qrf YGG jveq qvfxhgvreg, rf mrvtg fvpu rvar &aofc;uöurer Frafvgvivgäg va qra refgra Jbpura anpu qre Ernxgvba (znk. 3 Zbangr anpu qre Ernxgvba)52). Qre YGG ung wrqbpu qvr Yvzvgngvba, qnff uvre rgjn 50zy Oyhg abgjraqvt fvaq haq qre Grfg avpug hagre Fgrebvqgurencvr qheputrsüueg jreqra xnaa. &aofc;

Orale Provokationstestungen

BCGf fvaq orv yrvpugra, zrvfg xhgnara Ernxgvbara qre urhgvtr Tbyqfgnaqneq, hz rvar NU mh orfgägvtra bqre nhfmhfpuyvrffra. Qvrfr fbyygra va rvarz Mragehz omj. orv Nyyretbybtra/Nyyretbybtvaara qheputrsüueg jreqra, jrypurf/jrypure Resnuehat va qre Orhegrvyhat fbypure Cebibxngvbafgrfghatra unora. Irefpuvrqrar Cebgbxbyyr jheqra süe Xvaqre ibetrfpuyntra: rvaznyvtr Qbfvf, nhsfgrvtraqr Qbfra bqre nhpu Cebibxngvbafgrfghatra üore zruerer Gntr. Ovf urhgr tvog rf xrvar fgnaqneqvfvregra Cebgbxbyyr. Qvr RNNPV fpuyätg sbytraqrf Cebgbxbyy ibe: 1. Qbfvf 10% rvare Rvaznyqbfvf (nqncgvreg na Trjvpug haq Nygre), trsbytg iba 50% haq 100%14). Orv fpujrera Ernxgvbara xnaa qvr 1. Qbfvf nhpu trevatre frva, mjvfpura 1:1000 haq 1:10.000. Xbagenvaqvxngvbara süe qvr Cebibxngvbafgrfghatra fvaq nxhgr Vasrxgvbara, haxbagebyyvregrf Nfguzn bqre Tehaqrexenaxhatra, jrypur mh fgäexrera Ernxgvbara süuera xöaara omj. mh fpujrera yroraforqebuyvpur Ernxgvbara (Nanculynkvr, omj. fpujrer xhgnar AJ). Cebibxngvbafgrfghatra fbyygra hagre zrqvmvavfpure Üorejnpuhat zvg resnuerarz Crefbany qheputrsüueg jreqra.

Zusammenfassung

Nemarvzvggrulcreernxgvivgägra jreqra va qre Cäqvngevr uähsvt irezhgrg, nore frygra orfgägvtg. Qvr uähsvtfgra nhfyöfraqra Zrqvxnzragr fvaq Orgnynxgnz-Nagvovbgvxn, avpugfgrebvqnyr Nagveurhzngvxn fbjvr Vzcsfgbssr. Qvr Qvntabfr rvare Nemarvzvggrynyyretvr jveq mh uähsvt trfgryyg, unhcgfäpuyvpu nhf Natfg ibe rvare fpujrera nanculynxgvfpura Ernxgvba. Qvr zrvfgra orgebssrara Xvaqre xöaagra wrqbpu buar reuöugrf Evfvxb rvare harejüafpugra Ernxgvba rearhg qrz orgebssrara Zrqvxnzrag nhftrfrgmg jreqra. Rvar ibyyfgäaqvtr nyyretbybtvfpur Hagrefhpuhat fbyygr qnure vaareunyo rvarf natrzrffrara Mrvgenhzf qheputrsüueg jreqra, hz haaögvtrf haq bsg fpuäqyvpurf Irezrvqra iba Zrqvxnzragra mh ireuvaqrea.

Referenzen

1. International drug monitoring: the role of national centres. Report of a WHO meeting. World Health Organ Tech Rep Ser. 1972:498:1-25.
2. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet. 2000;356(9237):1255-9.
3. Impicciatore P, Choonara I, Clarkson A, Provasi D, Pandolfini C, Bonati M. Incidence of adverse drug reactions in paediatric in/out-patients: a systematic review and meta-analysis of prospective studies. Br J Clin Pharmacol. 2001;52(1):77-83.
4. Smyth RM, Gargon E, Kirkham J, Cresswell L, Golder S, Smyth R, et al. Adverse drug reactions in children--a systematic review. PLoS One. 2012;7(3):e24061.
5. Vyles D, Chiu A, Simpson P, Nimmer M, Adams J, Brousseau DC. Parent-Reported Penicillin Allergy Symptoms in the Pediatric Emergency Department. Acad Pediatr. 2017;17(3):251-5.
6. Erkocoglu M, Kaya A, Civelek E, Ozcan C, Cakir B, Akan A, et al. Prevalence of confirmed immediate type drug hypersensitivity reactions among school children. Pediatr Allergy Immunol. 2013;24(2):160-7.
7. Rebelo Gomes E, Fonseca J, Araujo L, Demoly P. Drug allergy claims in children: from self-reporting to confirmed diagnosis. Clin Exp Allergy. 2008;38(1):191-8.
8. Vezir E, Dibek Misirlioglu E, Civelek E, Capanoglu M, Guvenir H, Ginis T, et al. Direct oral provocation tests in non-immediate mild cutaneous reactions related to beta-lactam antibiotics. Pediatr Allergy Immunol. 2016;27(1):50-4.
9. Bergmann M, Caubet JC. Specific Aspects of Drug Hypersensitivity in Children. Curr Pharm Des. 2016;22(45):6832-51.
10. Gamboa PM. The epidemiology of drug allergy-related consultations in Spanish Allergology services: Alergologica-2005. J Investig Allergol Clin Immunol. 2009;19 Suppl 2:45-50.
11. Gomes ER, Demoly P. Epidemiology of hypersensitivity drug reactions. Curr Opin Allergy Clin Immunol. 2005;5(4):309-16.
12. Lange L, Koningsbruggen SV, Rietschel E. Questionnaire-based survey of lifetime-prevalence and character of allergic drug reactions in German children. Pediatr Allergy Immunol. 2008;19(7):634-8.
13. Rukasin CRF, Norton AE, Broyles AD. Pediatric Drug Hypersensitivity. Curr Allergy Asthma Rep. 2019;19(2):11.
14. Gomes ER, Brockow K, Kuyucu S, Saretta F, Mori F, Blanca-Lopez N, et al. Drug hypersensitivity in children: report from the pediatric task force of the EAACI Drug Allergy Interest Group. Allergy. 2016;71(2):149-61.
15. Kim B, Kim SZ, Lee J, Jung AH, Jung SH, Hahn HJ, et al. Clinical profiles of adverse drug reactions spontaneously reported at a single Korean hospital dedicated to children with complex chronic conditions. PLoS One. 2017;12(2):e0172425.
16. Grabenhenrich LB, Dolle S, Moneret-Vautrin A, Kohli A, Lange L, Spindler T, et al. Anaphylaxis in children and adolescents: The European Anaphylaxis Registry. J Allergy Clin Immunol. 2016;137(4):1128-37 e1.
17. Lee SY, Ahn K, Kim J, Jang GC, Min TK, Yang HJ, et al. A Multicenter Retrospective Case Study of Anaphylaxis Triggers by Age in Korean Children. Allergy Asthma Immunol Res. 2016;8(6):535-40.
18. Duong TA, Valeyrie-Allanore L, Wolkenstein P, Chosidow O. Severe cutaneous adverse reactions to drugs. Lancet. 2017;390(10106):1996-2011.
19. Esmaeilzadeh H, Farjadian S, Alyasin S, Nemati H, Nabavizadeh H, Esmaeilzadeh E. Epidemiology of Severe Cutaneous Adverse Drug Reaction and Its HLA Association among Pediatrics. Iran J Pharm Res. 2019;18(1):506-22.
20. Oh HL, Kang DY, Kang HR, Kim S, Koh YI, Kim SH, et al. Severe Cutaneous Adverse Reactions in Korean Pediatric Patients: A Study From the Korea SCAR Registry. Allergy Asthma Immunol Res. 2019;11(2):241-53.
21. Sellam A, Chahwakilian P, Cohen R, Bechet S, Vie Le Sage F, Levy C. [Impact of guidelines on ambulatory pediatric antibiotic prescriptions]. Arch Pediatr. 2015;22(6):595-601.
22. Mirakian R, Leech SC, Krishna MT, Richter AG, Huber PA, Farooque S, et al. Management of allergy to penicillins and other beta-lactams. Clin Exp Allergy. 2015;45(2):300-27.
23. Ebo DG, Leysen J, Mayorga C, Rozieres A, Knol EF, Terreehorst I. The in vitro diagnosis of drug allergy: status and perspectives. Allergy. 2011;66(10):1275-86.
24. Ariza A, Montanez MI, Fernandez TD, Perkins JR, Mayorga C. Cellular Tests for the Evaluation of Drug Hypersensitivity. Curr Pharm Des. 2016;22(45):6773-83.
25. Mayorga C, Celik G, Rouzaire P, Whitaker P, Bonadonna P, Rodrigues-Cernadas J, et al. In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy. 2016;71(8):1103-34.
26. Graham F, Tsabouri S, Caubet JC. Hypersensitivity reactions to beta-lactams in children. Curr Opin Allergy Clin Immunol. 2018;18(4):284-90.
27. Tonson la Tour A, Michelet M, Eigenmann PA, Caubet JC. Natural History of Benign Nonimmediate Allergy to Beta-Lactams in Children: A Prospective Study in Retreated Patients After a Positive and a Negative Provocation Test. J Allergy Clin Immunol Pract. 2018;6(4):1321-6.
28. Eustace N, O'Hare B. Use of nonsteroidal anti-inflammatory drugs in infants. A survey of members of the Association of Paediatric Anaesthetists of Great Britain and Ireland. Paediatr Anaesth. 2007;17(5):464-9.
29. Lesko SM, Mitchell AA. The safety of acetaminophen and ibuprofen among children younger than two years old. Pediatrics. 1999;104(4):e39.
30. Neubert A, Verhamme K, Murray ML, Picelli G, Hsia Y, Sen FE, et al. The prescribing of analgesics and non-steroidal anti-inflammatory drugs in paediatric primary care in the UK, Italy and the Netherlands. Pharmacol Res. 2010;62(3):243-8.
31. Kidon MI, See Y. Adverse drug reactions in Singaporean children. Singapore Med J. 2004;45(12):574-7.
32. Gabrielli S, Clarke AE, Eisman H, Morris J, Joseph L, La Vieille S, et al. Disparities in rate, triggers, and management in pediatric and adult cases of suspected drug-induced anaphylaxis in Canada. Immun Inflamm Dis. 2018;6(1):3-12.
33. Jares EJ, Baena-Cagnani CE, Sanchez-Borges M, Ensina LF, Arias-Cruz A, Gomez M, et al. Drug-Induced Anaphylaxis in Latin American Countries. J Allergy Clin Immunol Pract. 2015;3(5):780-8.
34. Kidon M, Blanca-Lopez N, Gomes E, Terreehorst I, Tanno L, Ponvert C, et al. EAACI/ENDA Position Paper: Diagnosis and management of hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) in children and adolescents. Pediatr Allergy Immunol. 2018;29(5):469-80.
35. Kelso JM, Greenhawt MJ, Li JT, Nicklas RA, Bernstein DI, Blessing-Moore J, et al. Adverse reactions to vaccines practice parameter 2012 update. J Allergy Clin Immunol. 2012;130(1):25-43.
36. McNeil MM, DeStefano F. Vaccine-associated hypersensitivity. J Allergy Clin Immunol. 2018;141(2):463-72.
37. Ankermann T, Spindler T, Gerstlauer M, Schmidt S. Allergies and vaccination: a myth demystified2018.
38. Kelso JM. Allergic reactions after immunization. Ann Allergy Asthma Immunol. 2013;110(6):397-401.
39. Turner PJ, Southern J, Andrews NJ, Miller E, Erlewyn-Lajeunesse M, Investigators SS. Safety of live attenuated influenza vaccine in atopic children with egg allergy. J Allergy Clin Immunol. 2015;136(2):376-81.
40. Sharma K, Perrett KP, Wood N. Yellow Fever Vaccination In EGG-Allergic Children. Pediatr Infect Dis J. 2020;39(6):e76-e8.
41. Nilsson L, Brockow K, Alm J, Cardona V, Caubet JC, Gomes E, et al. Vaccination and allergy: EAACI position paper, practical aspects. Pediatr Allergy Immunol. 2017;28(7):628-40.
42. Blumenthal KG, Robinson LB, Camargo CA, Jr., Shenoy ES, Banerji A, Landman AB, et al. Acute Allergic Reactions to mRNA COVID-19 Vaccines. JAMA. 2021;325(15):1562-5.
43. Warren CM, Snow TT, Lee AS, Shah MM, Heider A, Blomkalns A, et al. Assessment of Allergic and Anaphylactic Reactions to mRNA COVID-19 Vaccines With Confirmatory Testing in a US Regional Health System. JAMA Netw Open. 2021;4(9):e2125524.
44. Krantz MS, Bruusgaard-Mouritsen MA, Koo G, Phillips EJ, Stone CA, Jr., Garvey LH. Anaphylaxis to the first dose of mRNA SARS-CoV-2 vaccines: Don't give up on the second dose! Allergy. 2021;76(9):2916-20.
45. Tuong LC, Capucilli P, Staicu M, Ramsey A, Walsh EE, Shahzad Mustafa S. Graded Administration of Second Dose of Moderna and Pfizer-BioNTech COVID-19 mRNA Vaccines in Patients With Hypersensitivity to First Dose. Open Forum Infect Dis. 2021;8(12):ofab507.
46. Atanaskovic-Markovic M, Gaeta F, Gavrovic-Jankulovic M, Cirkovic Velickovic T, Valluzzi RL, Romano A. Diagnosing multiple drug hypersensitivity in children. Pediatr Allergy Immunol. 2012;23(8):785-91.
47. Caubet JC, Kaiser L, Lemaitre B, Fellay B, Gervaix A, Eigenmann PA. The role of penicillin in benign skin rashes in childhood: a prospective study based on drug rechallenge. J Allergy Clin Immunol. 2011;127(1):218-22.
48. Ponvert C, Perrin Y, Bados-Albiero A, Le Bourgeois M, Karila C, Delacourt C, et al. Allergy to betalactam antibiotics in children: results of a 20-year study based on clinical history, skin and challenge tests. Pediatr Allergy Immunol. 2011;22(4):411-8.
49. Romano A, Gaeta F, Valluzzi RL, Alonzi C, Viola M, Bousquet PJ. Diagnosing hypersensitivity reactions to cephalosporins in children. Pediatrics. 2008;122(3):521-7.
50. Saretta F, Mori F, Cardinale F, Liotti L, Franceschini F, Crisafulli G, et al. Pediatric drug hypersensitivity: which diagnostic tests? Acta Biomed. 2019;90(3-S):94-107.
51. Confino-Cohen R, Rosman Y, Meir-Shafrir K, Stauber T, Lachover-Roth I, Hershko A, et al. Oral Challenge without Skin Testing Safely Excludes Clinically Significant Delayed-Onset Penicillin Hypersensitivity. J Allergy Clin Immunol Pract. 2017;5(3):669-75.
52. Romano A, Atanaskovic-Markovic M, Barbaud A, Bircher AJ, Brockow K, Caubet JC, et al. Towards a more precise diagnosis of hypersensitivity to beta-lactams - an EAACI position paper. Allergy. 2020;75(6):1300-15.
53. Park JS, Suh DI. Drug Allergy in Children: What Should We Know? Clin Exp Pediatr. 2020;63(6):203-10.
54. P.Villani A, Gamradt P, Nosbaum A, Laoubi L, Jullien D, Nicolas J-F, et al. Immune-mediated skin diseases induced by chemicals and drugs. 2018.
55. Bamanikar. A REVIEW OF DRUG ALLERGIES: DIAGNOSIS AND MANAGEMENT. EMJ Allergy Immunol. 2016:1[]:52-7.