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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">LV</journal-id>
<journal-id journal-id-type="nlm-ta">Lijec Vjesn</journal-id>
<journal-title-group>
<journal-title>Lijecnicki Vjesnik</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Lijec. Vjesn.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="ppub">0024-3477</issn>
<issn pub-type="epub">1849-2177</issn>
<publisher><publisher-name>Croatian Medical Association</publisher-name></publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">LV-144-279</article-id>
<article-id pub-id-type="doi">10.26800/LV-144-9-10-1</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Guidelines</subject></subj-group>
</article-categories>
<title-group>
<article-title>Smjernice za lije&#x010D;enje atopijskog dermatitisa</article-title>
<trans-title-group xml:lang="en">
<trans-title>Guidelines for treatment of atopic dermatitis</trans-title>
</trans-title-group>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3640-9567</contrib-id><name><surname>Ljubojevi&#x0107; Had&#x017E;avdi&#x0107;</surname><given-names>Suzana</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pusti&#x0161;ek</surname><given-names>Nives</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lugovi&#x0107; Mihi&#x0107;</surname><given-names>Liborija</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>O&#x017E;ani&#x0107;-Buli&#x0107;</surname><given-names>Suzana</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Puizina-Ivi&#x0107;</surname><given-names>Neira</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Peternel</surname><given-names>Sandra</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vuk&#x0161;i&#x0107; Poli&#x0107;</surname><given-names>Melita</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref><xref ref-type="aff" rid="aff7"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Marinovi&#x0107; Kuli&#x0161;i&#x0107;</surname><given-names>Sandra</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Juraki&#x0107; Ton&#x010D;i&#x0107;</surname><given-names>Ru&#x017E;ica</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Murat Su&#x0161;i&#x0107;</surname><given-names>Slobodna</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Husar</surname><given-names>Karmela</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Skerlev</surname><given-names>Mihael</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Martinac Ciglar</surname><given-names>Ivana</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Duvan&#x010D;i&#x0107;</surname><given-names>Tomislav</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bulat</surname><given-names>Vedrana</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dediol</surname><given-names>Iva</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ivani&#x0161;evi&#x0107;</surname><given-names>Ranka</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Boj&#x010D;i&#x0107;</surname><given-names>Iva</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Brajac</surname><given-names>Ines</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kuric</surname><given-names>Igor</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kotrulja</surname><given-names>Lena</given-names></name><xref ref-type="aff" rid="aff8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tomi&#x0107; Babi&#x0107;</surname><given-names>Lucija</given-names></name><xref ref-type="aff" rid="aff9"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Krnjevi&#x0107;-Pezi&#x0107;</surname><given-names>Gordana</given-names></name><xref ref-type="aff" rid="aff9"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>&#x010C;avka</surname><given-names>Vlatka</given-names></name><xref ref-type="aff" rid="aff10"><sup>10</sup></xref></contrib><contrib contrib-type="author"><name><surname>Stanimirovi&#x0107;</surname><given-names>Andrija</given-names></name><xref ref-type="aff" rid="aff11"><sup>11</sup></xref><xref ref-type="aff" rid="aff12"><sup>12</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bukvi&#x0107; Mokos</surname><given-names>Zrinka</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>&#x0160;itum</surname><given-names>Mirna</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Marinovi&#x0107;</surname><given-names>Branka</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib>
<aff id="aff1"><label>1</label>Klinika za dermatovenerologiju, Medicinski fakultet Sveu&#x010D;ili&#x0161;ta u Zagrebu, Klini&#x010D;ki bolni&#x010D;ki centar Zagreb</aff>
<aff id="aff2"><label>2</label>Klinika za pedijatriju, Klinika za dje&#x010D;je bolesti Zagreb</aff>
<aff id="aff3"><label>3</label>Klinika za ko&#x017E;ne i spolne bolesti, Stomatolo&#x0161;ki fakultet Sveu&#x010D;ili&#x0161;ta u Zagrebu, Klini&#x010D;ki bolni&#x010D;ki centar &#x201E;Sestre milosrdnice&#x201C;</aff>
<aff id="aff4"><label>4</label>Klinika za ko&#x017E;ne i spolne bolesti, Medicinski fakultet Sveu&#x010D;ili&#x0161;ta u Splitu, Klini&#x010D;ki bolni&#x010D;ki centar Split</aff>
<aff id="aff5"><label>5</label>Klinika za dermatovenerologiju, Medicinski fakultet Sveu&#x010D;ili&#x0161;ta u Rijeci, Klini&#x010D;ki bolni&#x010D;ki centar Rijeka</aff>
<aff id="aff6"><label>6</label>Zavod za dermatologiju i venerologiju, Klini&#x010D;ki bolni&#x010D;ki centar Osijek</aff>
<aff id="aff7"><label>7</label>Medicinski fakultet Sveu&#x010D;ili&#x0161;ta J. J. Strossmayera u Osijeku</aff>
<aff id="aff8"><label>8</label>Poliklinika za dermatologiju i venerologiju &#x201E;DermaPlus&#x201C;, <addr-line>Zagreb</addr-line></aff>
<aff id="aff9"><label>9</label>Odjel za dermatologiju, Specijalna bolnica za medicinsku rehabilitaciju Naftalan, Ivani&#x0107; Grad</aff>
<aff id="aff10"><label>10</label>Poliklinika &#x201E;Vlatka &#x010C;avka&#x201C;, <addr-line>Zagreb</addr-line></aff>
<aff id="aff11"><label>11</label><institution>Zdravstveno veleu&#x010D;ili&#x0161;te</institution>, <addr-line>Zagreb</addr-line></aff>
<aff id="aff12"><label>12</label>School of Medicine, European University Cyprus, Nikozija, Cipar</aff>
</contrib-group>
<author-notes>
<corresp id="cor1">Adresa za dopisivanje: Prof. dr. sc. Suzana Ljubojevi&#x0107; Had&#x017E;avdi&#x0107;, <ext-link ext-link-type="uri" xlink:href="https://orcid.org/0000-0002-3640-9567">https://orcid.org/0000-0002-3640-9567</ext-link> Klinika za dermatovenerologiju, Medicinski fakultet Sveu&#x010D;ili&#x0161;ta u Zagrebu, KBC Zagreb, Ki&#x0161;pati&#x0107;eva 12, 10000 Zagreb, e-po&#x0161;ta: <email xlink:href="suzana.ljubojevic@gmail.com">suzana.ljubojevic@gmail.com</email></corresp></author-notes>
<pub-date pub-type="epub-ppub"><month>10</month><year>2022</year></pub-date>
<volume>144</volume>
<issue>9-10</issue>
<fpage>279</fpage>
<lpage>294</lpage>
<permissions>
<copyright-year>2022</copyright-year>
<copyright-holder>Croatian Medical Association</copyright-holder>
<license xlink:href="https://creativecommons.org/licenses/by-nc-nd/4.0/" specific-use="CC BY-NC-ND 4.0"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND) 4.0 License.</license-p></license>
</permissions>
<abstract>
<title>SA&#x017D;ETAK</title>
<p>Atopijski dermatitis &#x010D;esta je, kroni&#x010D;no recidiviraju&#x0107;a upalna bolest ko&#x017E;e karakterizirana slo&#x017E;enom etiopatogenezom i raznolikim klini&#x010D;kim fenotipom. Klini&#x010D;ka slika mo&#x017E;e biti razli&#x010D;ita, a bolest je obilje&#x017E;ena ponavljaju&#x0107;im dermatitisom, izra&#x017E;enim svrbe&#x017E;om i zna&#x010D;ajnim utjecajem na kvalitetu &#x017E;ivota oboljele osobe i cijele obitelji. Dijagnoza se postavlja na temelju klini&#x010D;ke slike prema standardiziranim dijagnosti&#x010D;kim kriterijima, a procjena te&#x017E;ine bolesti prema standardiziranim instrumentima za procjenu te&#x017E;ine bolesti. Lije&#x010D;enje treba prilagoditi svakom bolesniku, a cilj lije&#x010D;enja je smanjiti simptome svrbe&#x017E;a, obnoviti o&#x0161;te&#x0107;enu ko&#x017E;nu barijeru, sprije&#x010D;iti egzacerbaciju bolesti, sprije&#x010D;iti odnosno lije&#x010D;iti komplikacije i komorbiditete te smanjiti negativni utjecaj bolesti na kvalitetu &#x017E;ivota. Zahvaljuju&#x0107;i napretku u razumijevanju etiopatogeneze, terapijske mogu&#x0107;nosti su zadnjih godina zna&#x010D;ajno napredovale. Hrvatsko dermatovenerolo&#x0161;ko dru&#x0161;tvo Hrvatskoga lije&#x010D;ni&#x010D;kog zbora predstavlja smjernice za dijagnostiku i lije&#x010D;enje atopijskog dermatitisa. Smjernice su rezultat konsenzusa hrvatskih stru&#x010D;njaka za atopijski dermatitis koji su kriti&#x010D;ki prou&#x010D;ili mjerodavnu znanstvenu literaturu, koja se temelji na najboljim dokazima.</p>
</abstract>
<trans-abstract xml:lang="en">
<title>SUMMARY</title>
<p>Atopic dermatitis is a common, chronically recurrent inflammatory skin disease characterized by a complex etiopathogenesis and a variable clinical phenotype. The clinical presentation is heterogeneous, and the disease is characterized by a recurrent dermatitis, intense itching and a significant impact on the quality of life of patients and their family. The diagnosis is based on the clinical presentation according to the standardized diagnostic criteria, while the assessment of disease severity of the disease is based on the standardized tools for disease severity assessment. Treatment should be tailored to each patient profile, and the goal of the treatment is focused on decreasing symptoms and renewing damaged skin barrier, preventing the exacerbation of the disease and preventing or treating the complications and comorbidities, and decreasing the negative influence of the disease on the patient&#x2019;s quality of life. Due to progress in understanding the etiopathogenesis, treatment options have significantly expanded in the past years. The Croatian Society of Dermatovenerology of the Croatian Medical Association is presenting guidelines for diagnosis and treatment of atopic dermatitis. These guidelines are the result of consensus of Croatian experts based on critical analysis of relevant, evidence-based scientific literature.</p>
</trans-abstract>
<kwd-group kwd-group-type="author"><kwd>Deskriptori ATOPIJSKI DERMATITIS &#x2013; dijagnoza, lije&#x010D;enje</kwd><kwd>DERMATOLO&#x0160;KI LIJEKOVI &#x2013; terapijska uporaba</kwd><kwd>PROCJENA TE&#x017D;INE BOLESTI</kwd><kwd>KVALITETA &#x017D;IVOTA</kwd><kwd>SMJERNICE</kwd><kwd>HRVATSKA</kwd></kwd-group>
<kwd-group kwd-group-type="translator" xml:lang="en"><title>Descriptors </title><kwd>DERMATITIS, ATOPIC &#x2013; diagnosis, therapy</kwd><kwd>DERMATOLOGIC AGENTS &#x2013; therapeutic use</kwd><kwd>SEVERITY OF ILLNESS INDEX</kwd><kwd>QUALITY OF LIFE</kwd><kwd>PRACTICE GUIDELINES AS TOPIC</kwd><kwd>CROATIA</kwd></kwd-group>
</article-meta>
</front>
<body>
<p>Atopijski dermatitis (AD) &#x010D;esta je, kroni&#x010D;no recidiviraju&#x0107;a upalna bolest, popra&#x0107;ena simptomima svrbe&#x017E;a i bolnosti ko&#x017E;e, a pojavljuje se u osoba s atopijskom konstitucijom. (<xref ref-type="bibr" rid="r1"><italic>1</italic></xref>) AD je poznat i pod sinonimima egzem, neurodermitis, prurigo-egzem, fleksuralni egzem, prurigo Besnier, atopijski egzem, endogeni egzem, astmatski egzem, atopijski egzem / dermatitis sindrom, <italic>pruridermatitis allegica chronica constitutionalis</italic> (Kogoj), <italic>lichen agrius</italic>, infantilni egzem i atopiformni dermatitis. (<xref ref-type="bibr" rid="r2"><italic>2</italic></xref>, <xref ref-type="bibr" rid="r3"><italic>3</italic></xref>) U literaturi postoji najvi&#x0161;e dvojbi i nejasno&#x0107;a oko upotrebe termina egzem, atopijski egzem i atopijski dermatitis. Godine 2017. grupa klini&#x010D;ara i istra&#x017E;iva&#x010D;a, eksperata za AD, preporu&#x010D;ila je uporabu naziva atopijski dermatitis umjesto atopijski egzem. (<xref ref-type="bibr" rid="r3"><italic>3</italic></xref>)</p>
<p>Prevalencija AD-a je od 2% do 10% u odraslih osoba, odnosno do 20% u djece. (<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>, <xref ref-type="bibr" rid="r5"><italic>5</italic></xref>) To je ujedno i jedna od naj&#x010D;e&#x0161;&#x0107;ih bolesti ko&#x017E;e. (<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>) Tipi&#x010D;an po&#x010D;etak bolesti je izme&#x0111;u drugog i &#x0161;estog mjeseca &#x017E;ivota; u 45% djece bolest po&#x010D;inje tijekom prvih &#x0161;est mjeseci, u 60% tijekom prve godine, a u 85% do pete godine &#x017E;ivota. (<xref ref-type="bibr" rid="r5"><italic>5</italic></xref>) AD ima tendenciju povla&#x010D;enja s dobi tako da se u oko 50% djece ko&#x017E;ni simptomi povuku do sedme godine &#x017E;ivota, a u 70% prije adolescentne dobi, no ipak &#x0107;e do &#x010D;ak 30% djece imati AD u odrasloj dobi. (<xref ref-type="bibr" rid="r5"><italic>5</italic></xref>) AD je &#x010D;esto udru&#x017E;en s alergijskom astmom, alergijskim rinokonjunktivitisom, alergijom na hranu te eozinofilnim ezofagitisom. (<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>) Va&#x017E;no je istaknuti i psihosocijalne komorbiditete poput anksioznosti, depresije, suicidalnosti i drugih. (<xref ref-type="bibr" rid="r6"><italic>6</italic></xref>, <xref ref-type="bibr" rid="r7"><italic>7</italic></xref>)</p>
<p>Hrvatsko dermatovenerolo&#x0161;ko dru&#x0161;tvo Hrvatskoga lije&#x010D;ni&#x010D;kog zbora (HDVD HLZ) predstavlja smjernice za dijagnostiku i lije&#x010D;enje AD-a. Smjernice su rezultat konsenzusa hrvatskih stru&#x010D;njaka za AD koji su kriti&#x010D;ki prou&#x010D;ili mjerodavnu znanstvenu literaturu, koja se temelji na najboljim dokazima. Smjernice su raspravljene na sastanku radne skupine hrvatskih stru&#x010D;njaka za AD. Izrada smjernica nije financijski potpomognuta.</p>
<p>Navodima u Smjernicama pridru&#x017E;eni su dokazi odgovaraju&#x0107;e ja&#x010D;ine.</p>
<p>Razine preporuka (A; B; C; D) ocijenjene su na temelju razine dokaza (1&#x2013;4): A. Metaanaliza randomiziranih kontroliranih ispitivanja (RCT, od engl. <italic>randomised controlled trial</italic>; 1a) ili pojedina&#x010D;no RCT (1b). B. Sustavni pregled kohortnih studija (2a) ili pojedina&#x010D;ne kohortne studije ili RCT ograni&#x010D;ene kvalitete (2b) ili sustavni pregled prikaza serije kontroliranih slu&#x010D;ajeva (engl. <italic>case control studies</italic>) (3a) ili pojedina&#x010D;ni prikaz serije kontroliranih slu&#x010D;ajeva (3b). C. Serija slu&#x010D;ajeva ili studija kontrole slu&#x010D;aja ili kohortna studija ograni&#x010D;ene kvalitete (4). D. Mi&#x0161;ljenje stru&#x010D;njaka (&#x2013;). (<xref ref-type="bibr" rid="r8"><italic>8</italic></xref>&#x2013;<xref ref-type="bibr" rid="r11"><italic>11</italic></xref>)</p>
<sec sec-type="other1">
<title>Dijagnoza</title>
<p>Dijagnoza AD-a se postavlja na temelju klini&#x010D;ke slike, a procjena te&#x017E;ine bolesti odre&#x0111;uje se prema standardiziranim kriterijima i indeksima za procjenu te&#x017E;ine bolesti. Postoji nekoliko kriterija za postavljanje dijagnoze: naj&#x010D;e&#x0161;&#x0107;e su kori&#x0161;teni kriteriji Hanifin i Rajka, kriteriji <italic>&#x201E;Millenium&#x201C;</italic> i kriteriji Ameri&#x010D;ke akademije za dermatologiju. (<xref ref-type="bibr" rid="r12"><italic>12</italic></xref>&#x2013;<xref ref-type="bibr" rid="r15"><italic>15</italic></xref>) Hanifin i Rajka odredili su 1980. godine kriterije za postavljanje dijagnoze AD-a tako da su definirali osnovne (velike) i sporedne (male) kriterije (<xref ref-type="table" rid="t1">Table 1</xref>). (<xref ref-type="bibr" rid="r12"><italic>12</italic></xref>) Za postavljanje dijagnoze AD-a potrebna su tri od &#x010D;etiri osnovna kriterija i tri od 23 sporedna kriterija. Osnovni kriteriji su svrbe&#x017E;, promjene ko&#x017E;e na predilekcijskim mjestima, kroni&#x010D;no-recidiviraju&#x0107;i tijek, osobna ili obiteljska sklonost atopiji. (<xref ref-type="bibr" rid="r12"><italic>12</italic></xref>) U sporedne kriterije ubrajaju se hiperlinearnost dlanova i tabana, ihtioza, dermatitis mamila, heilitis, infraorbitalna brazda (Dennie-Morganov infraorbitalni nabor), bijeli dermografizam, bljedilo lica, tamnija ko&#x017E;a oko o&#x010D;iju, Hertogheov znak (postrani&#x010D;no prorije&#x0111;ene ili potpuno odsutne obrve), niski rast kose u frontalnoj i temporalnoj regiji, folikularna keratoza i druge (<xref ref-type="table" rid="t1">Table 1</xref>). (<xref ref-type="bibr" rid="r12"><italic>12</italic></xref>) Kriteriji <italic>&#x201E;Millenium&#x201C;</italic> su nastali pregledom literature; razlikuje se atopijski od atopiformnog dermatitisa. Za postavljanje dijagnoze tim kriterijima, uz nalaz povi&#x0161;enoga specifi&#x010D;nog IgE-protutijela i/ili pozitivnog nalaza <italic>prick</italic> testa, potrebno je zadovoljiti i tri glavna kriterija (svrbe&#x017E;, tipi&#x010D;an izgled i distribucija promjena, kroni&#x010D;ni ili kroni&#x010D;no-recidiviraju&#x0107;i tijek bolesti). (<xref ref-type="bibr" rid="r13"><italic>13</italic></xref>) Dijagnosti&#x010D;ki kriteriji Ameri&#x010D;ke akademije za dermatologiju uklju&#x010D;uju: osnovne kriterije (koji moraju biti prisutni): svrbe&#x017E;, dermatitis (akutni, subakutni, kroni&#x010D;ni), karakteristi&#x010D;ne ko&#x017E;ne promjene s tipi&#x010D;nom distribucijom, kroni&#x010D;ni ili kroni&#x010D;no-recidiviraju&#x0107;i tijek dermatitisa; va&#x017E;ne kriterije (nalaze se u ve&#x0107;ine oboljelih, govore u prilog dijagnozi): rani po&#x010D;etak bolesti, atopija (pozitivna osobna ili obiteljska anamneza, povi&#x0161;ena razina ukupnog IgE-a), suho&#x0107;a ko&#x017E;e; udru&#x017E;ene kriterije (koji poma&#x017E;u u postavljanju dijagnoze, ali nisu specifi&#x010D;ni za postavljanje dijagnoze): atipi&#x010D;ni vaskularni odgovor (npr. bljedilo lica, bijeli dermografizam, odgo&#x0111;eno bljedilo), <italic>keratosis pilaris</italic>, <italic>pityriasis alba</italic>, hiperlinearnost dlanova, ihtioza, okularne i periokularne promjene, perioralne/periaurikularne lezije, te lihenifikacija/prurigo promjene. (<xref ref-type="bibr" rid="r14"><italic>14</italic></xref>, <xref ref-type="bibr" rid="r15"><italic>15</italic></xref>) Dijagnosti&#x010D;ki kriteriji navode i bolesti koje je potrebno isklju&#x010D;iti poput svraba, seboreji&#x010D;nog dermatitisa, kontaktnoga alergijskog i/ili iritativnog dermatitisa, ihtioze, T-stani&#x010D;nog limfoma, psorijaze, fotosenzitivne dermatoze, imunodeficijencije s promjenama ko&#x017E;e, eritodermije drugih uzroka. (<xref ref-type="bibr" rid="r14"><italic>14</italic></xref>, <xref ref-type="bibr" rid="r15"><italic>15</italic></xref>) Ukoliko AD ne odgovara na primijenjenu terapiju, treba isklju&#x010D;iti razli&#x010D;ite nutritivne, metaboli&#x010D;ke i imunosne poreme&#x0107;aje u djece i kutani T-stani&#x010D;ni limfom u odraslih. (<xref ref-type="bibr" rid="r14"><italic>14</italic></xref>, <xref ref-type="bibr" rid="r15"><italic>15</italic></xref>) U slu&#x010D;aju pogor&#x0161;anja dermatitisa ili ukoliko dermatitis slabo reagira na terapiju i/ili se pogor&#x0161;ava, posebice na ko&#x017E;i lica i &#x0161;aka, potrebno je u&#x010D;initi alergolo&#x0161;ko testiranje zbog potvrde odnosno isklju&#x010D;enja alergijskog kontaktnog dermatitisa. (<xref ref-type="bibr" rid="r14"><italic>14</italic></xref>, <xref ref-type="bibr" rid="r15"><italic>15</italic></xref>) Ne postoje dobro definirani biomarkeri za AD. Naj&#x010D;e&#x0161;&#x0107;e kori&#x0161;ten laboratorijski parametar jest povi&#x0161;en ukupni, odnosno specifi&#x010D;ni IgE koji je prisutan u oko 80% oboljelih. (<xref ref-type="bibr" rid="r16"><italic>16</italic></xref>) Ovisno o vrijednosti ukupnog IgE razlikujemo dva tipa AD-a: &#x201E;intrinzi&#x010D;ni&#x201C; (bolest nije udru&#x017E;ena s IgE-om) i &#x201E;ekstrinzi&#x010D;ni&#x201C; (oblik bolesti udru&#x017E;en s povi&#x0161;enim IgE-om). (<xref ref-type="bibr" rid="r17"><italic>17</italic></xref>)</p>
<table-wrap id="t1" position="float">
<label>Table 1</label><caption><title>Hanifin and Rajka criteria for atopic dermatitis</title>
</caption>
<table frame="hsides" rules="groups">
<col width="100%"/>
<thead>
<tr>
<th valign="middle" align="left" scope="col" style="border-left: solid 0.75pt; border-top: solid 0.75pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Veliki kriteriji (moraju biti prisutna 3)<break/>/ Major criteria (must have 3)</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="middle" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">1. Svrbe&#x017E; / Pruritus<break/>2. Dermatitis koji zahva&#x0107;a pregibe u odraslih ili lica i ekstenzorne povr&#x0161;ine u dojen&#x010D;adi / Dermatitis affecting flexural surfaces in adults or face and extensor surfaces in infants<break/>3. Kroni&#x010D;an ili kroni&#x010D;no-recidiviraju&#x0107;i dermatitis / Chronic or relapsing dermatitis<break/>4. Osobna ili obiteljska anamneza za ko&#x017E;ne i respiratorne alergije / Personal or family history of cutaneous or respiratory allergy</td>
</tr>
<tr>
<td valign="middle" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Mali kriteriji (moraju biti prisutna 3)<break/>/ Minor criteria (must have 3)</td>
</tr>
<tr>
<td valign="middle" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.75pt">1. Promjene na licu &#x2013; bljedo&#x0107;a lica, eritem lica, hipopigmentirani areali, Dennie-Morganova infraorbitalna brazda, infraorbitalne hiperpigmentacije, helitis, recidiviraju&#x0107;i konjunktivitis, nabori prednjeg dijela vrata, Hertogheov znak / Facial features &#x2013; facial pallor, erythema, hypopigmented patches, Dennie-Morgan infraorbital folds, infraorbital darkening, cheilitis, recurrent conjunctivitis, anterior neck folds, Hertogh sign<break/>2. Trigeri &#x2013; emocionalni faktori, faktori okoli&#x0161;a, hrana, ko&#x017E;ni iritansi / Triggers &#x2013; emotional factors, enviromental factors, food, skin irritants<break/>3. Komplikacije &#x2013; sklonost ko&#x017E;nim infekcijama ko&#x017E;e, oslabljen stani&#x010D;no posredovan imunitet, predispozicija za keratokonus i kataraktu, reakcije ranog tipa preosjetljivosti / Complications &#x2013; susceptibility to skin infections, impaired cell-mediated immunity, predisposition to keratoconus or cataracts, immediate skin reactivity<break/>4. Ostalo &#x2013; po&#x010D;etak u ranoj &#x017E;ivotnoj dobi, suho&#x0107;a ko&#x017E;e, ihtioza, hiperlinearnost dlanova, folikularna keratoza, dermatitis &#x0161;aka i stopala, egzem bradavica dojki, bijeli dermografizam, <italic>Pityriasis alba,</italic> svrbe&#x017E; pri znojenju, nepodno&#x0161;enje vune i lipidnih otapala / Other &#x2013; early age of onset, dry skin, ichthyosis, hyperlinear palms, keratosis pilaris, hand and foot dermatitis, nipple eczema, white dermographism, pityriasis alba, itching on sweating, intolerance to wool and lipid solvents</td>
</tr>
</tbody>
</table><table-wrap-foot>
<p>* Modificirano prema / Modified according to: Hanifin JM, Rajka G (<xref ref-type="bibr" rid="r12"><italic>12</italic></xref>)</p>
</table-wrap-foot></table-wrap>
</sec>
<sec sec-type="other2">
<title>Odre&#x0111;ivanje te&#x017E;ine bolesti</title>
<p>Postoje brojni instrumenti za procjenu te&#x017E;ine AD-a. (<xref ref-type="bibr" rid="r14"><italic>14</italic></xref>, <xref ref-type="bibr" rid="r18"><italic>18</italic></xref>&#x2013;<xref ref-type="bibr" rid="r20"><italic>20</italic></xref>) Naj&#x010D;e&#x0161;&#x0107;e kori&#x0161;teni indeksi jesu <italic>SCORing Atopic Dermatitis</italic> (SCORAD), <italic>Eczema Area and Severity Index</italic> (EASI), <italic>Investigator&#x2019;s Global Assessment</italic> (IGA) i <italic>Six Area, Six Sign Atopic Dermatitis Severity Score</italic> (SASSAD). (<xref ref-type="bibr" rid="r18"><italic>18</italic></xref>, <xref ref-type="bibr" rid="r19"><italic>19</italic></xref>) Najbolje validirani instrumenti za procjenu te&#x017E;ine AD-a su indeks SCORAD i EASI. (<xref ref-type="bibr" rid="r18"><italic>18</italic></xref>, <xref ref-type="bibr" rid="r19"><italic>19</italic></xref>) Ve&#x0107;ina se ovih instrumenata rabi u klini&#x010D;kim istra&#x017E;ivanjima, rijetko u praksi.</p>
<p>Indeks SCORAD uklju&#x010D;uje objektivni i subjektivni SCORAD. (<xref ref-type="bibr" rid="r18"><italic>18</italic></xref>, <xref ref-type="bibr" rid="r19"><italic>19</italic></xref>) Objektivni SCORAD procjenjuje pro&#x0161;irenost bolesti i klini&#x010D;ke parametre kao &#x0161;to su: eritem, edem/papule, u&#x010D;inak grebanja &#x2013; ekskorijacije, vla&#x017E;enje/stvaranje krasta, lihenifikaciju i suho&#x0107;u ko&#x017E;e. Svaki klini&#x010D;ki parametar ocjenjuje se s 0, 1, 2, 3, ovisno o intenzitetu promjena. Uvijek se preporu&#x010D;uje ocjenjivati najizra&#x017E;enije promjene. Pro&#x0161;irenost bolesti ocjenjuje se prema postotku povr&#x0161;ine ko&#x017E;e zahva&#x0107;ene promjenama ko&#x017E;e. Postupak je sljede&#x0107;i: prvo se na praznoj shemi tijela ozna&#x010D;i povr&#x0161;ina tijela zahva&#x0107;ena promjenama ko&#x017E;e, a zatim se prema tzv. pravilu devetke izra&#x010D;una postotak zahva&#x0107;ene ko&#x017E;e. Za osobe starije od dvije godine postotak povr&#x0161;ine tijela prema pravilu devetke jest: za prednji dio tijela &#x2013; glava 4,5%; svaka ruka 4,5%; &#x0161;ake 1%; trup 18%; spolovilo 1%; svaka noga 9%. (<xref ref-type="bibr" rid="r19"><italic>19</italic></xref>) Za stra&#x017E;nji dio tijela postotci su jednaki i posebno se obra&#x010D;unavaju. Za djecu mla&#x0111;u od dvije godine primjenjuje se modificirano pravilo devetke: za glavu 8,5% (posebno prednji, posebno stra&#x017E;nji dio), za noge 6%, ne zbrajaju se odvojeno &#x0161;ake, odnosno spolovilo, ve&#x0107; su dio obra&#x010D;una za ruke, odnosno trup. (<xref ref-type="bibr" rid="r19"><italic>19</italic></xref>) Subjektivni simptomi kao svrbe&#x017E; i nesanica ocjenjuju se analognom ljestvicom od 0 do 10 (0 &#x2013; nema svrbe&#x017E;a, 10 &#x2013; najintenzivniji svrbe&#x017E;). Procjenjuju se svrbe&#x017E; odnosno nesanica u protekla tri dana. SCORAD indeks se kre&#x0107;e u rasponu do 103, manji od 25 ozna&#x010D;ava blagi AD, 25 do 50 srednje te&#x0161;ki AD, a ve&#x0107;i od 50 te&#x0161;ki AD. (<xref ref-type="bibr" rid="r19"><italic>19</italic></xref>)</p>
<p>EASI ocjenjuje zahva&#x0107;enu povr&#x0161;inu tijela i klini&#x010D;ke parametre. (<xref ref-type="bibr" rid="r20"><italic>20</italic></xref>) Pri odre&#x0111;ivanju EASI-ja prvo je potrebno odabrati dio tijela (glava i vrat, trup i genitalije, gornji ekstremiteti, donji ekstremiteti uklju&#x010D;uju&#x0107;i glutealnu regiju), potom je potrebno ozna&#x010D;iti postotak zahva&#x0107;ene povr&#x0161;ine tijela zasebno za svaki klini&#x010D;ki parametar (eritem/induraciju, papule, oticanje/ekskorijacije/lihenifikaciju). (<xref ref-type="bibr" rid="r20"><italic>20</italic></xref>) Zahva&#x0107;enost ko&#x017E;e se ozna&#x010D;ava od 0 do 6 (0 = nema promjena ko&#x017E;e; 1 = 1&#x2013;9%; 2 = 10&#x2013;29%; 3 = 30&#x2013;49%; 4 = 50&#x2013;69%; 5 = 70&#x2013;89%; 6 = 90&#x2013;100%). EASI ne ocjenjuje suho&#x0107;u ko&#x017E;e i lju&#x0161;tenje, a ni subjektivne parametre. EASI indeks se kre&#x0107;e u rasponu do 72. (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>) Za blagi oblik AD-a se smatra EASI 1,1 &#x2013; 7,0, srednje te&#x0161;ki AD 7,1 &#x2013; 21,0, a te&#x0161;ki AD &gt; 21,1. (<xref ref-type="bibr" rid="r20"><italic>20</italic></xref>) Osim apsolutnog EASI-ja u klini&#x010D;kim ispitivanjima &#x010D;esto se koriste EASI 50, EASI 75 ili EASI 90, a ozna&#x010D;avaju 50%, 75% ili 90-postotno pobolj&#x0161;anje AD-a u odnosu na po&#x010D;etak lije&#x010D;enja.</p>
<p>Za mjerenje utjecaja AD-a na kvalitetu &#x017E;ivota oboljelih i &#x010D;lanova obitelji na raspolaganju su razli&#x010D;iti dermatolo&#x0161;ki instrumenti. Naj&#x010D;e&#x0161;&#x0107;e kori&#x0161;teni upitnik za ispitivanje kvalitete &#x017E;ivota u odrasloj dobi jest Indeks kvalitete &#x017E;ivota dermatolo&#x0161;kih bolesnika (DLQI, od engl. <italic>Dermatology Life Quality Index</italic>), a u djece i adolescenata Dje&#x010D;ji dermatolo&#x0161;ki indeks kvalitete &#x017E;ivota (CDLQI, od engl. <italic>Children&#x2019;s Dermatology Life Quality Index</italic>). (<xref ref-type="bibr" rid="r21"><italic>21</italic></xref>, <xref ref-type="bibr" rid="r22"><italic>22</italic></xref>) Prema bodovima ispunjenog upitnika, kvaliteta &#x017E;ivota se mo&#x017E;e podijeliti na: bez utjecaja (0&#x2013;1), mali utjecaj (2&#x2013;5), srednji utjecaj (6&#x2013;10), velik utjecaj (11&#x2013;20) i izuzetno velik utjecaj (21&#x2013;30) na &#x017E;ivot bolesnika. (<xref ref-type="bibr" rid="r23"><italic>23</italic></xref>) Naj&#x010D;e&#x0161;&#x0107;e kori&#x0161;ten upitnik za procjenu utjecaja bolesti na obiteljsku kvalitetu &#x017E;ivota jest Obiteljski indeks kvalitete &#x017E;ivota (FDLQI, od engl. <italic>Family Dermatology Life Quality Index</italic>). (<xref ref-type="bibr" rid="r22"><italic>22</italic></xref>, <xref ref-type="bibr" rid="r24"><italic>24</italic></xref>) Sva tri upitnika slu&#x017E;beno su prevedena na hrvatski jezik uz odobrenje autora i nalaze se na slu&#x017E;benoj stranici Cardiff University. (<xref ref-type="bibr" rid="r22"><italic>22</italic></xref>)</p>
<p>Danas postoje brojne internetske stranice i mobilne aplikacije pomo&#x0107;u kojih se (bez naknade) mo&#x017E;e pristupiti izra&#x010D;unu procjene te&#x017E;ine bolesti. (<xref ref-type="bibr" rid="r25"><italic>25</italic></xref>)</p>
</sec>
<sec sec-type="other3">
<title>Klini&#x010D;ka slika</title>
<p>Klini&#x010D;ka slika, ovisno o dobi bolesnika, obilje&#x017E;ena je suhom ko&#x017E;om, crvenilom i svrbe&#x017E;om. Atopijski dermatitis je &#x010D;esto udru&#x017E;en s drugim atopijskim bolestima kao &#x0161;to su nutritivna alergija, astma i/ili alergijski rinokonjunktivitis. Klini&#x010D;ka slika bitno se razlikuje u dojen&#x010D;adi, starije djece te odraslih bolesnika, stoga prema dobi razlikujemo razli&#x010D;ite faze AD-a: infantilnu fazu, fazu djetinjstva, adolescentnu fazu i pojavu AD-a u odrasloj dobi. Infantilna faza obuhva&#x0107;a dojena&#x010D;ku dob i djecu do druge godine &#x017E;ivota, karakterizirana je znatnim vla&#x017E;enjem promjena (eksudativan, akutni oblik bolesti) te zahva&#x0107;anjem obraza, vlasi&#x0161;ta, vrata, trupa i ekstenzornih strana ekstremiteta te dorzuma &#x0161;aka i stopala. Pelenska regija je tipi&#x010D;no po&#x0161;te&#x0111;ena kao i perioralna regija. Na zahva&#x0107;enim podru&#x010D;jima razvijaju se eritematozne makule uz papulovezikule ili kruste, odnosno infiltrirani plakovi uz vla&#x017E;enje i stvaranje krusta. U fazi djetinjstva, tijekom druge i tre&#x0107;e godine &#x017E;ivota, klini&#x010D;ka slika se mijenja te je &#x010D;esto prisutan polimorfizam sa zahva&#x0107;anjem ekstenzornih i fleksornih strana ekstremiteta. S dobi se postupno razvijaju karakteristi&#x010D;ne papule i &#x017E;ari&#x0161;ta ponajprije na pregibima velikih zglobova, osobito na vratu, laktovima, zape&#x0161;&#x0107;ima, koljenima i sko&#x010D;nim zglobovima, &#x0161;to je i karakteristika AD-a u kasnijem djetinjstvu. Na mjestima kroni&#x010D;nih lezija intenzivan svrbe&#x017E; dovodi do stalnog &#x010D;e&#x0161;anja i trljanja, &#x0161;to posljedi&#x010D;no dovodi do zadebljanja ko&#x017E;e, odnosno lihenifikacije. U adolescentnoj fazi (12&#x2013;18 godina) i odrasloj dobi perzistiraju promjene u pregibima uz promjene na vje&#x0111;ama, &#x0161;akama, stopalima pra&#x0107;ene jakim svrbe&#x017E;om, ekskorijacijama, lihenifikacijom i razvojem hiperpigmentacija i hipopigmentacija.</p>
<p>Komplikacije AD-a uklju&#x010D;uju pove&#x0107;anu u&#x010D;estalost i intenzitet razli&#x010D;itih virusnih (<italic>Herpes simplex virus</italic> i <italic>Varicella zoster virus</italic>), gljivi&#x010D;nih (<italic>Malassezia furfur</italic>) i bakterijskih (diseminirana impetiginizacija ko&#x017E;e sa <italic>Staphylococcus aureus</italic>) infekcija ko&#x017E;e, najvjerojatnije kao posljedica o&#x0161;te&#x0107;ene epidermalne barijere, promjena uro&#x0111;ene i ste&#x010D;ene imunosti te o&#x0161;te&#x0107;enja ko&#x017E;e zbog grebanja uzrokovanog svrbe&#x017E;om. (<xref ref-type="bibr" rid="r1"><italic>1</italic></xref>) Rje&#x0111;e komplikacije su bolesti oka (keratokonus, odvajanje retine, sljepo&#x0107;a), ka&#x0161;njenje u rastu ili usporen rast (zbog hipoproteinemije koja nastaje kao posljedica upale, lo&#x0161;e prehrane ili pothranjenosti).</p>
</sec>
<sec sec-type="other4">
<title>Lije&#x010D;enje</title>
<p>Lije&#x010D;enje AD-a obuhva&#x0107;a op&#x0107;e mjere (edukacija, odgovaraju&#x0107;a njega ko&#x017E;e i izbjegavanje &#x010D;imbenika koji dovode do pogor&#x0161;anja dermatitisa), lokalno farmakolo&#x0161;ko lije&#x010D;enje, fototerapiju, sustavno farmakolo&#x0161;ko lije&#x010D;enje te ostale oblike lije&#x010D;enja poput psihosocijalne podr&#x0161;ke, imunoterapije i sli&#x010D;no (<xref ref-type="fig" rid="f1">Figure 1</xref>). Ciljevi lije&#x010D;enja su smanjiti svrbe&#x017E;, obnoviti epidermalnu barijeru, smanjiti upalu, sprije&#x010D;iti infekciju, lije&#x010D;iti komorbiditete i komplikacije, prevenirati recidive te pobolj&#x0161;ati kvalitetu &#x017E;ivota.</p>
<fig id="f1" position="float" fig-type="figure"><label>Figure 1</label><caption><p>Treatment of atopic dermatitis according to clinical picture</p></caption><graphic xlink:href="LV-144-279-f1"></graphic></fig>
<p>Na <xref ref-type="fig" rid="f2">Figure 2</xref> prikazani su algoritmi lije&#x010D;enja AD-a ovisno o te&#x017E;ini klini&#x010D;ke slike.</p>
<fig id="f2" position="float" fig-type="figure"><label>Figure 2</label><caption><p>Treatment algorithm for atopic dermatitis</p></caption><graphic xlink:href="LV-144-279-f2"></graphic></fig>
<sec>
<title>1) Op&#x0107;e mjere</title>
<p>Bolesnicima je va&#x017E;no objasniti prirodu same bolesti (o&#x0161;te&#x0107;enje ko&#x017E;ne barijere, promijenjen imunosni odgovor, zna&#x010D;aj mikrobioma ko&#x017E;e i utjecaj stresa). Edukacijski program uklju&#x010D;uje i preporuke o izbjegavanju odre&#x0111;enih iritansa i alergena koji dovode do egzacerbacija bolesti, upute o pravilnoj prehrani te psihoterapijsku potporu.</p>
<p>Za pranje (kupanje/tu&#x0161;iranje) preporu&#x010D;uje se primjena sredstava koja ne sadr&#x017E;avaju sapune, primjerice, sinteti&#x010D;ki deterd&#x017E;enti (sindeti) koji su blago kiselog pH (pH 4&#x2013;6), hipoalergeni i bez mirisa, &#x0161;to ih &#x010D;ini tolerantnijima za ko&#x017E;u bolesnika s AD-om. (<xref ref-type="bibr" rid="r8"><italic>8</italic></xref>, <xref ref-type="bibr" rid="r9"><italic>9</italic></xref>) Dovoljno je kupanje jednom dnevno, kroz kra&#x0107;e vrijeme (pet do deset minuta uz temperaturu vode od 27&#x2013;30&#x00B0;C za djecu i odrasle te ne&#x0161;to ispod 37&#x00B0;C za novoro&#x0111;en&#x010D;ad). (<xref ref-type="bibr" rid="r26"><italic>26</italic></xref>) Kako bi se odr&#x017E;ala dobra hidracija ko&#x017E;e nakon kupanja ili tu&#x0161;iranja izuzetno je va&#x017E;no &#x0161;to prije, po mogu&#x0107;nosti dok je ko&#x017E;a jo&#x0161; vla&#x017E;na, nanijeti emolijens. (<xref ref-type="bibr" rid="r27"><italic>27</italic></xref>)</p>
<p>Kod bolesnika u akutnom pogor&#x0161;anju ili u onih sa znakovima impetiginizacije savjetuje se dodavanje antiseptika, poput 0,005% otopine 6% natrij-hipoklorita (izbjeljiva&#x010D;a) u vodu za kupanje (na 1,5 l vode stavi se 0,6 do 1,2 ml 6-postotnog Na-hipoklorita), &#x010D;ime se smanjuje broj bakterija na ko&#x017E;i bolesnika s AD-om i u&#x010D;estalost potrebe za uporabom lokalnih glukokortikoida i antibiotika (A, 1b). (<xref ref-type="bibr" rid="r28"><italic>28</italic></xref>, <xref ref-type="bibr" rid="r31"><italic>31</italic></xref>) Kao antiseptik mo&#x017E;e se upotrebljavati i kalijev hipermangan u koncentraciji 0,01% (100 mg na 1 litru vode). (<xref ref-type="bibr" rid="r32"><italic>32</italic></xref>)</p>
<p>Osnova terapije AD-a je redovito kori&#x0161;tenje emolijensa. Emolijensi su lokalni pripravci koji pove&#x0107;avaju hidrataciju ro&#x017E;natog sloja, smanjuju suho&#x0107;u ko&#x017E;e te pretjerani gubitak vode iz ko&#x017E;e. Redovita primjena emolijensa smanjuje u&#x010D;estalost recidiva bolesti te smanjuje u&#x010D;estalost kori&#x0161;tenja lokalnih glukokortikoida (B, 2a). Minimalna koli&#x010D;ina emolijensa koja se preporu&#x010D;uje jest 100 do 200 grama tjedno za dijete odnosno 200 do 300 grama tjedno za odraslu osobu (C, 3b). (<xref ref-type="bibr" rid="r8"><italic>8</italic></xref>, <xref ref-type="bibr" rid="r9"><italic>9</italic></xref>, <xref ref-type="bibr" rid="r33"><italic>33</italic></xref>) Emolijensi se sastoje od omek&#x0161;avaju&#x0107;ih, okluzivnih i ovla&#x017E;uju&#x0107;ih sastojaka u kombinaciji s vodom, a mogu biti u obliku kreme, masti, ulja, gela ili losiona. Emolijensi koji sadr&#x017E;e lipidnu komponentu preporu&#x010D;uju se tijekom zimskih mjeseci (C, 3b). Razlikujemo dvije generacije emolijensa. Tradicionalni emolijensi su lokalni pripravci koji ne sadr&#x017E;avaju aktivne sastojke. Oni obi&#x010D;no sadr&#x017E;avaju humektante koji pobolj&#x0161;avaju hidrataciju ro&#x017E;natog sloja (urea i glicerol) i okludente (vazelin) koji smanjuju evaporaciju. (<xref ref-type="bibr" rid="r32"><italic>32</italic></xref>) Emolijensi &#x201E;plus&#x201C; su lokalni preparati koji sadr&#x017E;e aktivnu, nemedicinsku tvar poput saponina, flavonoida i riboflavina iz ekstrakta zobi koji ne sadr&#x017E;avaju proteine, bakterijske lizate i sli&#x010D;no. (<xref ref-type="bibr" rid="r1"><italic>1</italic></xref>) Odabir emolijensa ovisan je o individualnom izboru, a bitno je da bude siguran, djelotvoran, financijski prihvatljiv te hipoalergen, odnosno bez aditiva, mirisa i parfema. Kako bi se postigla i odr&#x017E;ala zadovoljavaju&#x0107;a hidracija ko&#x017E;e potrebno je emolijense nanositi barem dva puta dnevno, obvezno odmah nakon kupanja/tu&#x0161;iranja i laganog brisanja ru&#x010D;nikom.</p>
<p>Za sada nema &#x010D;vrstih dokaza da dnevna primjena emolijensa u visokorizi&#x010D;ne djece tijekom prve godine &#x017E;ivota mo&#x017E;e odgoditi ili sprije&#x010D;iti AD. (<xref ref-type="bibr" rid="r34"><italic>34</italic></xref>)</p>
<p>Savjetuje se izbjegavanje relevantnih kontaktnih alergena pozitivnih u epikutanom testu (koji je indicirano napraviti kod bolesnika s perzistentnim dermatitisom, posebice na &#x0161;akama, stopalima i licu), peludi tijekom doba cvatnje, grinja (D,&#x2013;). Ukoliko se kontaktni dermatitis na &#x0161;akama pojavi tijekom adolescentne dobi savjetuje se izbjegavati zanimanja s radom u vla&#x017E;nim uvjetima (npr. frizeri, kozmeti&#x010D;ari, itd.).</p>
<p>Svi bolesnici s AD-om trebaju biti cijepljeni u skladu s nacionalnim planom cijepljenja (B, 2a); me&#x0111;utim, ne savjetuje se cijepljenje tijekom akutnih pogor&#x0161;anja.</p>
<p>U dojena&#x010D;koj dobi svakako se savjetuje isklju&#x010D;ivo dojenje barem &#x010D;etiri mjeseca (C, 2&#x2013;3). Izme&#x0111;u 4. i 6. mjeseca savjetuje se uvo&#x0111;enje dohrane u visokorizi&#x010D;ne i u djece s niskim rizikom od nastanka AD-a (B,1). Nema znanstvenih dokaza da se odgodom uvo&#x0111;enja namirnica s vi&#x0161;im potencijalom za izazivanje alergija u prehranu djeteta mo&#x017E;e prevenirati razvoj alergije na hranu odnosno AD-a i druge atopijske bolesti.</p>
<p>Eliminacijske dijete se ne preporu&#x010D;uju rutinski, osim ukoliko je dokazana preosjetljivost na hranu alergolo&#x0161;kim testom i potvr&#x0111;ena testom ekspozicije (B, 2b).</p>
<p>Edukativni program u sklopu &#x201E;&#x0160;kole atopije&#x201C; za pacijente i roditelje djece s AD-om predstavlja &#x201E;zlatni standard&#x201C; u pristupu i lije&#x010D;enju djece s ovom kroni&#x010D;nom bolesti ko&#x017E;e. (<xref ref-type="bibr" rid="r32"><italic>32</italic></xref>, <xref ref-type="bibr" rid="r35"><italic>35</italic></xref>, <xref ref-type="bibr" rid="r36"><italic>36</italic></xref>) Edukacija utje&#x010D;e na pobolj&#x0161;anje kontrole bolesti i pobolj&#x0161;anje kvalitete &#x017E;ivota za roditelje i oboljelu djecu. (<xref ref-type="bibr" rid="r37"><italic>37</italic></xref>)</p>
</sec>
<sec>
<title>2) Lokalno farmakolo&#x0161;ko lije&#x010D;enje</title>
<p>Lokalno farmakolo&#x0161;ko lije&#x010D;enje uklju&#x010D;uje lokalnu protuupalnu terapiju (lokalni glukokortikoidi, lokalni imunomodulatori). Primjena lokalnih glukokortikoida i inhibitora kalcineurina smanjuje kolonizaciju bakterijom <italic>Staphylococcus aureus.</italic> (<xref ref-type="bibr" rid="r8"><italic>8</italic></xref>) Za srednje te&#x0161;ke oblike bolesti i kao adjuvantna terapija za te&#x0161;ke oblike AD-a dostupni su krisaborol (inhibitor fosfodiesteraze 4), delgocitinib (inhibitor Janus kinaze [JAK]) i ruksolitinib (JAK-inhibitor) koji za sada nisu registrirani u Hrvatskoj. Krisaborol je odobren za djecu od dvije godine s klini&#x010D;kom slikom blagog do srednje te&#x0161;kog AD-a s upalom zahva&#x0107;enom povr&#x0161;inom ko&#x017E;e manjom od 40%. (<xref ref-type="bibr" rid="r32"><italic>32</italic></xref>) Ruksolitinib je indiciran za blagi do srednje te&#x0161;ki AD od 12 godina. (<xref ref-type="bibr" rid="r38"><italic>38</italic></xref>)</p>
<sec id="seca">
<label>a)</label><title>Lokalni glukokortikoidi</title>
<p>Lokalni glukokortikoidi su prva linija lokalnoga protuupalnog lije&#x010D;enja AD-a, a preporu&#x010D;uju se posebice u akutnoj fazi bolesti (D, &#x2013;). Dijele se prema ja&#x010D;ini djelovanja, a razlikujemo europsku i ameri&#x010D;ku klasifikaciju. U Europi su razvrstani u &#x010D;etiri grupe po Niedneru, i to blage (grupa I), srednje (grupa II), jake (grupa III) te vrlo jake djelotvornosti (grupa IV) (<xref ref-type="bibr" rid="r39"><italic>39</italic></xref>), dok ameri&#x010D;ka literatura navodi sedam grupa od vrlo niske (najni&#x017E;e, grupa VII) do vrlo visoke (najvi&#x0161;e, grupa I) jakosti (<xref ref-type="bibr" rid="r26"><italic>26</italic></xref>). U lije&#x010D;enju blagih i srednje te&#x0161;kih oblika bolesti primjenjuju se slabije potentni lokalni glukokortikoidi, a za srednje te&#x0161;ke oblike bolesti i za posebno osjetljive lokacije (lice, genitalna regija, ko&#x017E;ni pregibi) mogu&#x0107;e je kratkotrajno lije&#x010D;enje najpotentnijim dostupnim pripravkom, nakon &#x010D;ega slijedi postupna zamjena sve slabijim preparatima, ali mogu&#x0107;e je zapo&#x010D;injanje lije&#x010D;enja slabijim pripravkom te uporaba ja&#x010D;e potentnih samo u slu&#x010D;aju neuspjeha. (<xref ref-type="bibr" rid="r26"><italic>26</italic></xref>) Potentni glukokortikoidi ne bi se smjeli primjenjivati na osjetljivim podru&#x010D;jima poput lica, vrata, ko&#x017E;nih pregiba i genitalne regije, gdje je apsorpcija ve&#x0107;a i postoji ve&#x0107;i rizik od sustavnih nuspojava. Mogu&#x0107;e nuspojave lokalnih glukokortikoida jesu: atrofija ko&#x017E;e, purpura, teleangiektazije, strije, hipertrihoza, akneiformne lezije i promjene nalik rozaceji (<italic>dermatitis steroidica</italic>, perioralni dermatitis), depigmentacija, usporeno zacjeljivanje rana, egzacerbacija raznih infekcija ko&#x017E;e, razvoj kontaktnog dermatitisa te brojne druge. (<xref ref-type="bibr" rid="r32"><italic>32</italic></xref>)</p>
<p>Lije&#x010D;enje lokalnim glukokortikoidima preporu&#x010D;uje se jednom dnevno (a prema potrebi tijekom nekoliko dana i dva puta dnevno), a s primjenom lokalnog glukokortikoida va&#x017E;no je zapo&#x010D;eti pri prvoj pojavi simptoma upale. (<xref ref-type="bibr" rid="r32"><italic>32</italic></xref>)</p>
<p>Propisivanje glukokortikoida odgovaraju&#x0107;e ja&#x010D;ine odre&#x0111;uje se prema lokalizaciji, izra&#x017E;enosti upale te dobi bolesnika. Prosje&#x010D;ne mjese&#x010D;ne koli&#x010D;ine lokalnih glukokortikoida koje se smatraju sigurnim za dob jesu 15 grama za dojen&#x010D;ad, 30 grama za djecu i 60 do 90 grama za adolescente i odrasle osobe. (<xref ref-type="bibr" rid="r8"><italic>8</italic></xref>, <xref ref-type="bibr" rid="r9"><italic>9</italic></xref>, <xref ref-type="bibr" rid="r32"><italic>32</italic></xref>, <xref ref-type="bibr" rid="r33"><italic>33</italic></xref>) Najjednostavnija metoda kao mjeru za koli&#x010D;inu glukokortikoida primjenjuje jagodicu ka&#x017E;iprsta odrasle osobe (engl. <italic>adult fingertip unit</italic>). Lokalni glukokortikoid istisnut iz tube promjera 5 mm na jagodicu ka&#x017E;iprsta (od distalnoga interfalangealnog zgloba do vrha prsta) odrasle osobe odgovara koli&#x010D;ini od oko 0,5 g, a to je koli&#x010D;ina koja je dovoljna za povr&#x0161;inu veli&#x010D;ine dva dlana odrasle osobe. (<xref ref-type="bibr" rid="r40"><italic>40</italic></xref>)</p>
<p>Vla&#x017E;ni povoji (engl. <italic>wet-wrap therapy</italic>) mogu se primijeniti kod te&#x017E;ih oblika akutnih egzacerbacija bolesti, posebno kod djece, s ciljem postizanja brzoga terapijskog u&#x010D;inka (A, 1b). Rije&#x010D; je o okluzivnoj tehnici u kojoj se ko&#x017E;a na koju je nanesen lokalni pripravak (obi&#x010D;no slabije do umjereno potentni lokalni glukokortikoid, ali u fazi regresije bolesti mo&#x017E;e i emolijens) omota s dva sloja zavoja ili gaze, prvo vla&#x017E;nim, a potom suhim povojem. Uloga vla&#x017E;nih povoja jest pove&#x0107;anje prodiranja lokalnog pripravka u ko&#x017E;u, smanjenje gubitka vode i sprje&#x010D;avanje grebanja ko&#x017E;e. (<xref ref-type="bibr" rid="r26"><italic>26</italic></xref>)</p>
<p>U&#x010D;inak lokalnih glukokortikoida je poja&#x010D;an ako se primijene tehnikom vla&#x017E;nih povoja (1b).</p>
</sec>
<sec id="secb">
<label>b)</label><title>Lokalni imunomodulatori</title>
<p>Lokalni imunomodulatori ili lokalni inhibitori kalcineurina su takrolimus mast (0,03% i 0,1%) i pimekrolimus krema (1%) i predstavljaju drugu liniju lokalnoga protuupalnog lije&#x010D;enja AD-a. Prednost im dajemo na regijama kao &#x0161;to su lice, vrat, pregibi i anogenitalna regija (A, 1b). Neki bolesnici, posebice oni koji apliciraju takrolimus, mogu imati blago prolazno pogor&#x0161;anje promjena ko&#x017E;e. Stoga se kod akutizacije promjena ko&#x017E;e savjetuje prvo tijekom nekoliko dana aplicirati lokalne glukokortikoide, a potom nastaviti s inhibitorima kalcineurina (D, &#x2013;). (<xref ref-type="bibr" rid="r8"><italic>8</italic></xref>, <xref ref-type="bibr" rid="r11"><italic>11</italic></xref>, <xref ref-type="bibr" rid="r32"><italic>32</italic></xref>) Primjena lokalnih inhibitora kalcineurina nije povezana s pove&#x0107;anim rizikom nastanka nemelanomskih zlo&#x0107;udnih tumora ko&#x017E;e, limfoma, kao niti s fotokarcinogenezom. (<xref ref-type="bibr" rid="r8"><italic>8</italic></xref>, <xref ref-type="bibr" rid="r9"><italic>9</italic></xref>, <xref ref-type="bibr" rid="r11"><italic>11</italic></xref>, <xref ref-type="bibr" rid="r32"><italic>32</italic></xref>)</p>
<p>Lokalni inhibitori kalcineurina mogu se (engl. &#x201E;<italic>off-label&#x201C;)</italic> koristiti u dojen&#x010D;adi i male djece, kod kroni&#x010D;nih dermatitisa lica i pregiba.</p>
<p>Uz aplikaciju inhibitora kalcineurina savjetuje se aplikacija krema za za&#x0161;titu od sunca tijekom izlaganja suncu. Ne savjetuje se istovremeno kori&#x0161;tenje inhibitora kalcineurina i provo&#x0111;enje fototerapije.</p>
<p>Ukoliko na lije&#x010D;enom mjestu nastane sekundarna virusna infekcija, terapiju inhibitorima kalcineurina potrebno je privremeno prekinuti.</p>
<p>Inhibitore kalcineurina ne preporu&#x010D;uje se upotrebljavati tehnikom okluzije niti tehnikom vla&#x017E;nih povoja.</p>
<p>Dva su mogu&#x0107;a na&#x010D;ina primjene lokalne protuupalne terapije: reaktivni i proaktivni. Reaktivni oblik terapije uklju&#x010D;uje primjenu lokalne protuupalne terapije (lokalni glukokortikoidi ili lokalni inhibitori kalcineurina) samo na promjene ko&#x017E;e i to toliko dugo koliko je potrebno da do&#x0111;e do regresije promjena (A, 1b). Ako se lokalna protuupalna terapija primjenjuje dva puta tjedno na prethodno dermatitisom zahva&#x0107;ena podru&#x010D;ja u kombinaciji s aplikacijom emolijensa, takva terapija se naziva proaktivna terapija. U proaktivnoj terapiji prednost treba dati lokalnim inhibitorima kalcineurina. Proaktivnu terapiju savjetuje se koristiti najmanje tri mjeseca, a sigurnost inhibitora kalcineurina potvr&#x0111;ena je i kod proaktivne primjene tijekom razdoblja do pet godina. (<xref ref-type="bibr" rid="r41"><italic>41</italic></xref>, <xref ref-type="bibr" rid="r42"><italic>42</italic></xref>) Proaktivni oblik lije&#x010D;enja mo&#x017E;e sprije&#x010D;iti u&#x010D;estale egzacerbacije AD-a (A, 1b).</p>
<p>Proaktivna terapija s lokalnim glukokortikoidima mo&#x017E;e se upotrebljavati do 20 tjedana (A, 1b). (<xref ref-type="bibr" rid="r8"><italic>8</italic></xref>, <xref ref-type="bibr" rid="r9"><italic>9</italic></xref>)</p>
<p>Proaktivna terapija takrolimusom mo&#x017E;e se upotrebljavati do godine dana. (<xref ref-type="bibr" rid="r32"><italic>32</italic></xref>)</p>
</sec>
<sec id="secc">
<label>c)</label><title>Lokalni antibiotici</title>
<p>Ko&#x017E;a je u oboljelih od AD-a kolonizirana bakterijom <italic>Staphylococcus aureus</italic> u vi&#x0161;e od 90% bolesnika. Ako nema posebnih indikacija poput o&#x010D;ite sekundarne infekcije, prisutnosti beta-hemoliti&#x010D;kog streptokoka ili vidljive superinfekcije ko&#x017E;e bakterijom <italic>Staphylococcus aureus,</italic> lokalna primjena antibiotika ne preporu&#x010D;uje se u lije&#x010D;enju AD-a jer ne dovodi do klini&#x010D;kog pobolj&#x0161;anja niti smanjene potrebe za upotrebom glukokortikoida (D, 2). (<xref ref-type="bibr" rid="r8"><italic>8</italic></xref>, <xref ref-type="bibr" rid="r9"><italic>9</italic></xref>, <xref ref-type="bibr" rid="r32"><italic>32</italic></xref>) Primjena lokalnih antibiotika mo&#x017E;e biti povezana s razvojem kontaktnog dermatitisa, a dovode i do ne&#x017E;eljenog pove&#x0107;anja bakterijske rezistencije. (<xref ref-type="bibr" rid="r8"><italic>8</italic></xref>, <xref ref-type="bibr" rid="r9"><italic>9</italic></xref>)</p>
</sec>
<sec id="secd">
<label>d)</label><title>Lokalni antihistaminici</title>
<p>Lokalni antihistaminici nemaju zna&#x010D;ajnog u&#x010D;inka na svrbe&#x017E;, a pove&#x0107;avaju rizik nastanka kontaktne senzibilizacije i fotosenzibilizacije, stoga se njihova primjena ne preporu&#x010D;uje (C, 4).</p>
</sec>
<sec id="sece">
<label>e)</label><title>Lokalni antimikotici</title>
<p>Lokalni antimikotici (rje&#x0111;e sustavni) savjetuju se u bolesnika s AD-om koji imaju dominantno promjene na ko&#x017E;i lica i vrata (engl. <italic>head and neck dermatitis</italic>) zbog kolonizacije <italic>Malassezia furfur</italic> (<xref ref-type="bibr" rid="r43"><italic>43</italic></xref>) (B, 2b).</p>
</sec>
<sec id="secf">
<label>f)</label><title>Ostala lokalna terapija</title>
<p>Lokalni anestetici, terapija cinkom, taninima, katranima ne preporu&#x010D;uju se u lije&#x010D;enju bolesnika s AD-om.</p>
</sec>
</sec>
<sec>
<title>3) Fototerapija</title>
<p>Ako lokalna terapija nije dostatna i/ili po prestanku njene aplikacije brzo nastaju recidivi, savjetuje se provo&#x0111;enje fototerapije (uskospektralna UVB 311 nm terapija, iznimno srednje doze UVA1 terapije) (A, 1b). (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>, <xref ref-type="bibr" rid="r44"><italic>44</italic></xref>) Na po&#x010D;etku provo&#x0111;enja fototerapije preporu&#x010D;uje se istovremena primjena lokalnih glukokortikoida i emolijensa (C). (<xref ref-type="bibr" rid="r9"><italic>9</italic></xref>) Fototerapija na ko&#x017E;u djeluje imunosupresivno, imunomodulatorno, antiinflamatorno i antipruriti&#x010D;ki. Nedostatak fototerapije je potreba za u&#x010D;estalim dolascima lije&#x010D;niku (3&#x2013;5 puta tjedno tijekom 6&#x2013;12 tjedana). (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>, <xref ref-type="bibr" rid="r44"><italic>44</italic></xref>) Prije po&#x010D;etka fototerapije neophodno je bolesnika pitati o dotada&#x0161;njoj reakciji ko&#x017E;e na Sun&#x010D;evo svjetlo te prima li bolesnik neke lijekove koji mogu uzrokovati fototoksi&#x010D;ne i/ili fotoalergijske reakcije na ko&#x017E;i (npr. antibiotici, antidijabetici, psihofarmaci, diuretici i dr.). Fototerapija se ne preporu&#x010D;uje za bolesnike &#x010D;iji se AD pogor&#x0161;ava pri izlaganju UV svjetlu. Fototerapija je apsolutno kontraindicirana u bolesnika lije&#x010D;enih zbog melanoma, u sindroma displasti&#x010D;nog nevusa, u bolesnika koji boluju od autoimunih bolesti, u bolesnika s <italic>Xeroderma pigmentosum</italic> te u Bloomova sindroma. (<xref ref-type="bibr" rid="r45"><italic>45</italic></xref>) Fototerapija se mo&#x017E;e kombinirati s lokalnim glukokortikoidima i s MTX-om, ali se ne smije kombinirati s ciklosporinom. (<xref ref-type="bibr" rid="r46"><italic>46</italic></xref>, <xref ref-type="bibr" rid="r47"><italic>47</italic></xref>) Fototerapija (uskospektralna UVB terapija) nije kontraindicirana u djece, ali je treba koristiti s oprezom (D, &#x2013;). Kod svakog bolesnika koji je imao vi&#x0161;e od pet stotina 311 nm UVB ekspozicija obvezatan je pregled cjelokupne ko&#x017E;e jedanput godi&#x0161;nje. (<xref ref-type="bibr" rid="r48"><italic>48</italic></xref>, <xref ref-type="bibr" rid="r49"><italic>49</italic></xref>)</p>
</sec>
<sec>
<title>4) Sustavno farmakolo&#x0161;ko lije&#x010D;enje</title>
<sec id="secf.a">
<label>a)</label><title>Sustavni antibiotici</title>
<p>Komplikacije AD-a poput bakterijskih i virusnih infekcija lije&#x010D;e se sustavnom antimikrobnom terapijom. Kratkotrajna sustavna primjena antibiotika savjetuje se u slu&#x010D;aju klini&#x010D;ki uo&#x010D;ljivih znakova generalizirane sekundarne bakterijske superinfekcije (prisutnost pustula) (B, 2b). (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>) U tom se slu&#x010D;aju uz postoje&#x0107;u lokalnu terapiju uvodi i sustavna antibiotska terapija (obi&#x010D;no cefaleksin, no mo&#x017E;e i flukloksacilin, amoksicilin te amoksicilin i klavulanska kiselina ako ne postoji preosjetljivost). (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>, <xref ref-type="bibr" rid="r11"><italic>11</italic></xref>) Ako nema sekundarne infekcije peroralni antibiotici nisu u&#x010D;inkoviti u lije&#x010D;enju AD-a (1b).</p>
</sec>
<sec id="secf.b">
<label>b)</label><title>Sustavna antivirusna terapija</title>
<p>Sustavna antivirusna terapija indicirana je u slu&#x010D;aju pojave herpeti&#x010D;kog egzema <italic>(eczema herpeticatum)</italic> (D, 4). (<xref ref-type="bibr" rid="r1"><italic>1</italic></xref>, <xref ref-type="bibr" rid="r8"><italic>8</italic></xref>, <xref ref-type="bibr" rid="r10"><italic>10</italic></xref>)</p>
</sec>
<sec id="secf.c">
<label>c)</label><title>Sustavni antihistaminici</title>
<p>Sustavni antihistaminici blokiraju H1 receptore te se desetlje&#x0107;ima upotrebljavaju u lije&#x010D;enju svrbe&#x017E;a u bolesnika s AD-om, no studije su pokazale njihov slab ili gotovo nikakav u&#x010D;inak na smanjivanje svrbe&#x017E;a u bolesnika s AD-om. (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>) Smatra se da je svrbe&#x017E; u AD-u potaknut s IL-31. (<xref ref-type="bibr" rid="r50"><italic>50</italic></xref>)</p>
<p>Nema dovoljno dokaza za preporuku sedativnih i nesedativnih peroralnih antihistaminika za lije&#x010D;enje svrbe&#x017E;a u bolesnika s AD-om (A, 1b).</p>
<p>Njihovo kori&#x0161;tenje se savjetuje kod udru&#x017E;enosti s ostalim atopijskim bolestima poput alergijskog rinokonjunktivitisa, alergijske astme, alergije na hranu i sli&#x010D;no.</p>
</sec>
<sec id="secf.d">
<label>d)</label><title>Sustavna konvencionalna imunosupresivna terapija</title>
<p>U bolesnika kod kojih se ne uspijeva kontrolirati znakove i simptome bolesti optimalnom primjenom lokalnih protuupalnih lijekova i/ili fototerapijom, a jasno je vidljiv utjecaj bolesti na kvalitetu &#x017E;ivota oboljele osobe indicirano je lije&#x010D;enje sustavnim imunosupresivima (ciklosporin, metotreksat, azatioprin, mikofenolat mofetil). Trenutno dostupni sustavni imunosupresivi koriste se <italic>off-label</italic> (osim ciklosporina). Budu&#x0107;i da se ciklosporin ne nalazi na osnovnoj listi HZZO-a (HZZO ne odobrava propisivanje ciklosporina jer se prema smjernicama liste HZZO-a ne radi o terapijskoj indikaciji), bolesnici mogu dobiti ciklosporin isklju&#x010D;ivo putem dnevnih bolnica klinika, klini&#x010D;kih bolnica ili klini&#x010D;kih zavoda.</p>
</sec>
</sec>
<sec id="secI">
<label>I.</label><title>Ciklosporin (A; 1a)</title>
<p>Ciklosporin je brzo djeluju&#x0107;i sustavni cikli&#x010D;ki polipeptid koji smanjuje aktivnosti bolesti 2 do 4 tjedna nakon po&#x010D;etka primjene te smanjuje povr&#x0161;inu zahva&#x0107;ene ko&#x017E;e kao i stupanj upale preostalih promjena ko&#x017E;e nakon &#x0161;est tjedana kori&#x0161;tenja. (<xref ref-type="bibr" rid="r32"><italic>32</italic></xref>) Preporu&#x010D;ena duljina lije&#x010D;enja ciklosporinom jest od 3 do 6 mjeseci (D, &#x2013;). Nikako se ne savjetuje kontinuirana primjena dulje od dvije godine kontinuirano (A, 1a). (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>, <xref ref-type="bibr" rid="r51"><italic>51</italic></xref>) Trajanje lije&#x010D;enja ciklosporinom ovisi o klini&#x010D;koj u&#x010D;inkovitosti i podno&#x0161;ljivosti lijeka (D, &#x2013;).</p>
<p>Lije&#x010D;enje AD-a ciklosporinom u Hrvatskoj odobrava bolni&#x010D;ko Povjerenstvo za lijekove (nije na osnovnoj listi HZZO-a).</p>
<p>Ako se kre&#x0107;e s ni&#x017E;om dozom (2,5 mg/kg dnevno podijeljeno u dvije doze), a unutar 2 do 4 tjedna nema pobolj&#x0161;anja, doza ciklosporina se postupno podi&#x017E;e (0,5 &#x2013; 1 mg/kg dnevno u intervalu 1&#x2013;2 tjedna) do maksimalno 5 mg/kg dnevno podijeljeno u dvije doze. (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>, <xref ref-type="bibr" rid="r30"><italic>30</italic></xref>, <xref ref-type="bibr" rid="r51"><italic>51</italic></xref>)</p>
<p>Kod te&#x017E;ih oblika AD-a savjetuje se zapo&#x010D;eti s vi&#x0161;om dozom (5 mg/kg dnevno podijeljeno u dvije doze), te se nakon &#x0161;to nastupi pobolj&#x0161;anje klini&#x010D;ke slike (interval od 4 do 6, maksimalno 8 tjedana) savjetuje postupno (svaka dva tjedna) sni&#x017E;avati dozu za 0,5 &#x2013; 1 mg/kg dnevno, do najni&#x017E;e u&#x010D;inkovite doze (obi&#x010D;no 2,5 &#x2013; 3 mg/kg dnevno) koju se savjetuje nastaviti tijekom najmanje nekoliko tjedana te potom ukoliko ne nastupi pogor&#x0161;anje ciklosporin ukinuti, odnosno podi&#x0107;i dozu ako nastupi pogor&#x0161;anje (D, &#x2013;). (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>, <xref ref-type="bibr" rid="r32"><italic>32</italic></xref>, <xref ref-type="bibr" rid="r51"><italic>51</italic></xref>, <xref ref-type="bibr" rid="r52"><italic>52</italic></xref>)</p>
<p>Prije uvo&#x0111;enja ciklosporina (i ukoliko lije&#x010D;enje traje dulje od godinu dana) potrebno je u&#x010D;initi: kompletnu krvnu sliku (KKS), C-reaktivni protein (CRP), ureju, kreatinin, klirens kreatinina, aspartat-aminotransferazu (AST), alanin-aminotransferazu (ALT), gama-glutamil transferazu (GGT), alkalnu fosfatazu (AP), kreatin kinazu (CPK), laktat dehidrogenazu (LDH), kolesterol, trigliceride, elektrolite kalij (K), magnezij (Mg), urate, urin, mjerenje krvnog tlaka (RR), markere na hepatitis B i C, HIV test, Quantiferonski test, a u osoba koje nisu preboljele ili se ne sje&#x0107;aju da su preboljele vari&#x010D;ele potrebno je u&#x010D;initi IgM i IgG na virus <italic>Varicella zoster</italic> (VZV) te najmanje &#x010D;etiri tjedna prije uvo&#x0111;enja sustavne terapije provesti profilaksu VZV cjepivom.</p>
<p>Ukoliko bolesnik ima pozitivan Quantiferonski test, potrebno je prije uvo&#x0111;enja sustavne terapije provesti profilakti&#x010D;nu terapiju za tuberkulozu (u dogovoru s pulmologom).</p>
<p>Savjetuje se ponoviti nakon drugog i &#x010D;etvrtog tjedna te potom svaka dva mjeseca: KKS, CRP, ureju, kreatinin, klirens kreatinina, AST, ALT, GGT, AP, CPK, LDH, kolesterol, trigliceride, elektrolite (K, Mg), urate, RR, a svaka tri mjeseca potrebno je ponoviti kolesterol i trigliceride.</p>
<p>Tijekom terapije nije potrebno mjerenje razine ciklosporina u krvi (D, &#x2013;).</p>
<p>Kombinirana terapija s UV ne preporu&#x010D;uje se zbog mogu&#x0107;e fotosenzibilizacije i karcinogeneze (D, &#x2013;).</p>
<p>Ne preporu&#x010D;uje se istovremena aplikacija inhibitora kalcineurina i uzimanje ciklosporina.</p>
<p>Tijekom lije&#x010D;enja ciklosporinom ne preporu&#x010D;uje se cijepljenje &#x017E;ivim cjepivom zbog mogu&#x0107;ih komplikacija i izostanka u&#x010D;inkovitosti cjepiva. (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>, <xref ref-type="bibr" rid="r52"><italic>52</italic></xref>) Kod cijepljenja &#x017E;ivim cjepivom potrebno je napraviti prekid kori&#x0161;tenja ciklosporina dva tjedna prije i 4&#x2013;6 tjedana nakon cijepljenja. (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>)</p>
<p>Nuspojave ciklosporina su pove&#x0107;ana sklonost infekcijama, nefrotoksi&#x010D;nost, hipertenzija, tremor, hipertrihoza, glavobolja, hiperplazija gingive te pove&#x0107;ani rizik od razvoja karcinoma ko&#x017E;e i limfoma. (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>, <xref ref-type="bibr" rid="r11"><italic>11</italic></xref>, <xref ref-type="bibr" rid="r32"><italic>32</italic></xref>)</p>
<p>Za sada nema dokaza o teratogenim niti mutagenim svojstvima ciklosporina u trudnica.</p>
<p>O&#x010D;ekivani po&#x010D;etak djelovanja ciklosporina jest nakon dva tjedna primjene.</p>
</sec>
<sec id="secII">
<label>II.</label><title>Azatioprin (A, 1b)</title>
<p>Azatioprin je imunosupresiv sporog po&#x010D;etka djelovanja pa se maksimalni u&#x010D;inak posti&#x017E;e tek za 8 do 12 tjedana.</p>
<p>Za odrasle bolesnike savjetuje se po&#x010D;eti s dozom od 50 mg dnevno (D, &#x2013;), potom postupno, ukoliko nema nuspojava, podizati dozu do 2 do 3 mg/kg dnevno. U djece se preporu&#x010D;uje po&#x010D;eti s dozom od 0,5 mg/kg dnevno, potom postupno podizati dozu svakih 7 dana za 0,5 mg/kg dnevno do 1 do 3 mg/kg dnevno (C, 4). (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>)</p>
<p>Doza azatioprina ovisi o individualnoj podno&#x0161;ljivosti i aktivnosti enzima tiopurin metil-transferaze (TPMT) izmjerenoj prije uvo&#x0111;enja terapije. (<xref ref-type="bibr" rid="r8"><italic>8</italic></xref>)</p>
<p>Ako je razina TPMT niska (&lt;6,3 U/mL) kontraindicirana je primjena azatioprina; ukoliko je razina TPMT srednje vrijednosti (6,3 do 15 U/mL), savjetuje se zapo&#x010D;eti s azatioprinom u dozi od 1 mg/kg dnevno, a ukoliko je doza TPMT visoka (&gt;15,1 &#x2013; 26,4 U/mL) savjetuje se doza do 2&#x2013;3 mg/kg dnevno. (<xref ref-type="bibr" rid="r53"><italic>53</italic></xref>)</p>
<p>Prije uvo&#x0111;enja terapije u&#x010D;initi: KKS, CRP, ALT, AST, ALP, amilaze u serumu, TPMT, markere na B i C hepatitis, HIV test, Quantiferonski test, a u osoba koje nisu preboljele ili se ne sje&#x0107;aju da su preboljele vari&#x010D;ele potrebno je u&#x010D;initi IgM i IgG na VZV te najmanje &#x010D;etiri tjedna prije uvo&#x0111;enja sustavne terapije provesti profilaksu VZV cjepivom.</p>
<p>Ukoliko bolesnik ima pozitivni Quantiferonski test potrebno je prije uvo&#x0111;enja sustavne terapije provesti profilakti&#x010D;nu terapiju (u dogovoru s pulmologom).</p>
<p>Potrebno je svakih 1&#x2013;2 mjeseca ili prije podizanja doze u&#x010D;initi: KKS, AST, ALT, GGT, AP i amilaze u serumu.</p>
<p>Fototerapija se ne preporu&#x010D;uje tijekom uzimanja azatioprina. Uz uzimanje azatioprina savjetuje se fotoprotekcija (D, &#x2013;).</p>
<p>Nuspojave azatioprina su mijelotoksi&#x010D;nost, mu&#x010D;nina, povra&#x0107;anje, nadutost, gubitak teka, gr&#x010D;evi u trbuhu, glavobolja, povi&#x0161;enje jetrenih enzima, pove&#x0107;ani rizik od infekcije (A; 1b). (<xref ref-type="bibr" rid="r44"><italic>44</italic></xref>)</p>
<p>O&#x010D;ekivani po&#x010D;etak djelovanja azatioprina je 8 do 12 tjedana nakon po&#x010D;etka uzimanja lijeka.</p>
<p>Azatioprin se mo&#x017E;e nastaviti uzimati u trudno&#x0107;i uz postavljenu strogu indikaciju i uz prepolovljenu dozu lijeka. (<xref ref-type="bibr" rid="r54"><italic>54</italic></xref>)</p>
</sec>
<sec id="secIII">
<label>III.</label><title>Metotreksat (C, 4)</title>
<p>Metotreksat je antagonist folne kiseline. Mo&#x017E;e se primijeniti oralno, supkutano i intravenozno.</p>
<p>Primjenjuje se jednom tjedno u po&#x010D;etnoj dozi od 5&#x2013;15 mg tjedno u odraslih bolesnika te izme&#x0111;u 0,2 i 0,3 mg/kg tjedno za djecu do maksimalne dozvoljene doze od 0,5 mg/kg tjedno za djecu. (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>)</p>
<p>Uzimanje metotreksata mo&#x017E;e smanjiti razinu folata u tijelu. Nedostatak folata mo&#x017E;e dovesti do simptoma kao &#x0161;to su mu&#x010D;nina i abdominalni bolovi, promjena u krvnoj slici, poreme&#x0107;aj jetrenih enzima, stvaranje afti na sluznici usne &#x0161;upljine, stoga se 24 sata nakon uzimanja metotreksata savjetuje uzimanje 5 mg folne kiseline.</p>
<p>Prije uvo&#x0111;enja metotreksata (i ukoliko lije&#x010D;enje traje dulje od godinu dana) potrebno je u&#x010D;initi: KKS, CRP, ureju, kreatinin, AST, ALT, GGT, AP, markere na B i C hepatitis, HIV test, Quaniferonski test, u &#x017E;ena generativne dobi &#x03B2;HCG (humani korionski gonadotropin), a u osoba koje nisu preboljele ili se ne sje&#x0107;aju da su preboljele vari&#x010D;ele potrebno je u&#x010D;initi IgM i IgG na VZV te najmanje &#x010D;etiri tjedna prije uvo&#x0111;enja sustavne terapije provesti profilaksu VZV cjepivom.</p>
<p>Ako bolesnik ima pozitivni Quantiferonski test potrebno je prije uvo&#x0111;enja sustavne terapije provesti profilakti&#x010D;nu terapiju (u dogovoru s pulmologom).</p>
<p>U prvom, drugom i &#x010D;etvrtom tjednu te potom svaka dva mjeseca savjetuje se ponoviti KKS, CRP, ureju, kreatinin, AST, ALT, GGT, AP.</p>
<p>Nije opisan sindrom sustezanja (engl. <italic>rebound fenomen</italic>) nakon naglog ukidanja metotreksata te je pogodan za dugotrajnu primjenu.</p>
<p>Obavezatno nakon dvije godine terapije ili ukoliko se poka&#x017E;u znakovi hepatotoksi&#x010D;nosti (perzistentni trostruki porast jetrenih enzima), savjetuje se u&#x010D;initi aminopeptid prokolagen tip III N-terminalni peptid (P3NP) u serumu ili fibrosken jetre. (<xref ref-type="bibr" rid="r55"><italic>55</italic></xref>)</p>
<p>U &#x017E;ena generativne dobi potrebno je provo&#x0111;enje kontracepcije (jedan mjesec prije uvo&#x0111;enja, tijekom terapije i tri mjeseca nakon prestanka uzimanja metotreksata) (B, 3a).</p>
<p>Mu&#x0161;karcima se ne savjetuje planiranje obitelji tijekom lije&#x010D;enja i tri mjeseca nakon zavr&#x0161;etka lije&#x010D;enja metotreksatom (B, 3a).</p>
<p>Lijek se uglavnom dobro podnosi, ali mogu&#x0107;e su manje gastrointestinalne smetnje poput mu&#x010D;nine, dok su rje&#x0111;e i te&#x017E;e nuspojave mijelotoksi&#x010D;nost, plu&#x0107;na fibroza, hepatotoki&#x010D;nost. U slu&#x010D;ajevima ja&#x010D;ih gastrointestinalnih tegoba dolazi u obzir terapija supkutanim oblikom metotreksata. (<xref ref-type="bibr" rid="r56"><italic>56</italic></xref>)</p>
<p>O&#x010D;ekivani po&#x010D;etak djelovanja metotreksata je 8 do 12 tjedana nakon po&#x010D;etka uzimanja lijeka.</p>
</sec>
<sec id="secIV">
<label>IV.</label><title>Mikofenolat-mofetil (C; 4)</title>
<p>Mikofenolat-mofetil ostvaruje svoj imunosupresivni u&#x010D;inak inhibicijom enzima inozin-monofosfat dehidrogenaze, &#x0161;to dovodi do blokade sinteze purina selektivno u limfocitima B i T. (<xref ref-type="bibr" rid="r1"><italic>1</italic></xref>) Prije uvo&#x0111;enja mikofenolat-mofetila rade se iste pretrage kao prije uvo&#x0111;enja metotreksata.</p>
<p>Doza mikofenolat-mofetila nije to&#x010D;no odre&#x0111;ena pa se primjenjuje u &#x0161;irokom rasponu od 0,5 do 3 g/dan (uobi&#x010D;ajeno 1&#x2013;2 g/dan) podijeljeno u dvije dnevne doze, i to oralno, u obliku suspenzije, kapsula ili tableta. (<xref ref-type="bibr" rid="r32"><italic>32</italic></xref>) Za djecu se savjetuje u dozi od 20 i do 50 mg/kg dnevno (C, 4). (<xref ref-type="bibr" rid="r33"><italic>33</italic></xref>)</p>
<p>Od nuspojava naj&#x010D;e&#x0161;&#x0107;e nastaju blaga mu&#x010D;nina, povra&#x0107;anje, gr&#x010D;evi u trbuhu, glavobolja i umor. (<xref ref-type="bibr" rid="r44"><italic>44</italic></xref>)</p>
<p>U &#x017E;ena generativne dobi potrebno je uvo&#x0111;enje kontracepcije.</p>
<p>O&#x010D;ekivani po&#x010D;etak djelovanja mikofenolat-mofetila jest 8 do 12 tjedana nakon po&#x010D;etka uzimanja lijeka.</p>
</sec>
<sec id="secV">
<label>V.</label><title>Sustavni glukokortikoidi (D;&#x2013;)</title>
<p>Sustavni glukokortikoidi su indicirani samo za kratkotrajnu uporabu (do tjedan dana) kod akutnog pogor&#x0161;anja srednje te&#x0161;kih i te&#x0161;kih oblika AD-a (prednizolon ili metilprednizolon u dozi maksimalno 0,5 mg/kg; jedan do maksimalno dva tjedna) (D, &#x2013;). (<xref ref-type="bibr" rid="r28"><italic>28</italic></xref>, <xref ref-type="bibr" rid="r57"><italic>57</italic></xref>) Ako se glukokortikoidi daju dulje od preporu&#x010D;enoga, iznimno je va&#x017E;no dozu postupno smanjivati kako bi se izbjegao tzv. u&#x010D;inak ustezanja (engl. <italic>rebound effect</italic>) obilje&#x017E;en recidivom bolesti s jo&#x0161; te&#x017E;om klini&#x010D;kom slikom.</p>
<p>Sustavni glukokortikoidi se ne preporu&#x010D;uju kao kontinuirana sustavna terapija. Njihova uporaba savjetuje se kratkotrajno kod akutnih i diseminiranih oblika bolesti ili kako bi se premostio period do po&#x010D;etka djelovanja ostale sustavne imunosupresivne terapije (D;&#x2013;).</p>
<p>O&#x010D;ekivani po&#x010D;etak djelovanja sistemskih glukokortikoida jest jedan do dva tjedna nakon po&#x010D;etka uzimanja lijeka.</p>
<p>Ako bolesnik nema odgovaraju&#x0107;eg odgovora i/ili postoje nuspojave na jedan sustavni konvencionalni imunosupresivni lijek, indicirano je lije&#x010D;enje biolo&#x0161;kom terapijom ili terapijom JAK inhibitorima. Ukoliko po ukidanju sustavnoga konvencionalnog imunosupresiva nastupi pogor&#x0161;anje, kod bolesnika je indicirano lije&#x010D;enje biolo&#x0161;kom terapijom ili terapija JAK inhibitorima.</p>
<sec id="secVe">
<label>e)</label><title>Biolo&#x0161;ka terapija</title>
<p>Biolo&#x0161;ka terapija (biologici) relativno je nova grupa lijekova koja djeluje specifi&#x010D;no na ciljne upalne stanice i/ili medijatore (smanjuje upalu moduliranjem broja, aktivacijom i funkcijom imunolo&#x0161;kih stanica ili djelovanjem citokina ili antitijela koja su specifi&#x010D;na za AD). (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>) Kod &#x017E;ena generativne dobi uz biolo&#x0161;ku terapiju savjetuje se uzimanje oralnih kontraceptiva. Biolo&#x0161;ku terapiju potrebno je ukinuti prije za&#x010D;e&#x0107;a. Lije&#x010D;enje biolo&#x0161;kom terapijom odobrava Bolni&#x010D;ko povjerenstvo za lijekove (u Hrvatskoj trenutno nije odobrena niti jedna biolo&#x0161;ka terapija za lije&#x010D;enje AD-a).</p>
</sec>
</sec>
<sec id="secI___1">
<label>I.</label><title>Dupilumab (A; 1a)</title>
<p>U o&#x017E;ujku 2017. u SAD-u je odobren dupilumab kao prva linija terapije za srednje te&#x0161;ki i te&#x0161;ki oblik AD-a kod odraslih, potom za djecu i adolescente od 12 do 18 godina, a u studenom 2020. godine za lije&#x010D;enje te&#x0161;kog AD-a u djece u dobi od 6 do 11 godina koja su kandidati za sistemsku terapiju. (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>, <xref ref-type="bibr" rid="r32"><italic>32</italic></xref>) Radi se o humanom monoklonskom protutijelu koje inhibira djelovanje interleukina (IL) 4 i IL-13.</p>
<p>Preporu&#x010D;ena po&#x010D;etna doza za odrasle i adolescente tjelesne mase &gt;60 kg jest 600 mg supkutano, nakon &#x010D;ega se primjenjuje doza od 300 mg supkutano svaki drugi tjedan (A; 1a). (<xref ref-type="bibr" rid="r32"><italic>32</italic></xref>, <xref ref-type="bibr" rid="r58"><italic>58</italic></xref>&#x2013;<xref ref-type="bibr" rid="r61"><italic>61</italic></xref>)</p>
<p>Nije potrebno provoditi laboratorijsku obradu prije niti tijekom terapije dupilumabom.</p>
<p>Nuspojave dupilumaba su lokalne reakcije ko&#x017E;e na mjestu primjene lijeka, konjunktivitis koji regredira nakon standardnoga oftalmolo&#x0161;kog lije&#x010D;enja (antihistaminske kapi, ciklosporinske kapi i aplikacija takrolimusa na rub vje&#x0111;a), blefaritis, glavobolje i infekcije uzrokovane virusom <italic>Herpes simplex</italic>. (<xref ref-type="bibr" rid="r32"><italic>32</italic></xref>, <xref ref-type="bibr" rid="r58"><italic>58</italic></xref>&#x2013;<xref ref-type="bibr" rid="r60"><italic>60</italic></xref>)</p>
<p>O&#x010D;ekivani po&#x010D;etak djelovanja dupilumaba je 4 do 6 tjedana nakon primjene prve doze lijeka.</p>
<p>Procjena u&#x010D;inka terapije i aktivnost bolesti treba biti evaluirana u 16. tjednu izra&#x010D;unavanjem vrijednosti EASI i/ili SCORAD i/ili DLQI.</p>
<p>Nastavak lije&#x010D;enja mogu&#x0107; je ako je nakon 16 tjedana postignuto najmanje 50-postotno pobolj&#x0161;anje EASI ili SCORAD vrijednosti ili pobolj&#x0161;anje DLQI vrijednosti vi&#x0161;e od &#x010D;etiri boda, prema procjeni nadle&#x017E;nog lije&#x010D;nika, te je potom potrebno procijeniti u&#x010D;inak svakih &#x0161;est mjeseci.</p>
<p>Lije&#x010D;enje odobrava Bolni&#x010D;ko povjerenstvo za lijekove.</p>
<p>Prije uvo&#x0111;enja lijeka potrebno je odrediti EASI i/ili SCORAD i DLQI.</p>
<p>Za dupilumab se u Hrvatskoj &#x010D;eka odobrenje od HZZO-a.</p>
</sec>
<sec id="secII___1">
<label>II.</label><title>Tralokinumab</title>
<p>Tralokinumab je humano monoklonsko protutijelo koje specifi&#x010D;no neutralizira IL-13, klju&#x010D;ni citokin koji izaziva perifernu upalu u AD-u. (<xref ref-type="bibr" rid="r62"><italic>62</italic></xref>) Tralokinumab u kombinaciji s lokalnim glukokortikoidima pokazao je rano i odr&#x017E;ano pobolj&#x0161;anje znakova i simptoma AD-a.</p>
<p>EMA (engl. <italic>European Medicines Agency</italic>) odobrila ga je u lipnju 2021., u dozi od 150 mg u obliku supkutanih injekcija, za primjenu svaka dva tjedna u lije&#x010D;enju umjerenog do te&#x0161;kog AD-a u odraslih bolesnika koji su kandidati za sustavnu terapiju. (<xref ref-type="bibr" rid="r61"><italic>61</italic></xref>)</p>
<p>Naj&#x010D;e&#x0161;&#x0107;e su nuspojave lijeka crvenilo na mjestu aplikacije, infekcije gornjih di&#x0161;nih putova i konjunktivitis. (<xref ref-type="bibr" rid="r61"><italic>61</italic></xref>, <xref ref-type="bibr" rid="r62"><italic>62</italic></xref>)</p>
<p>Tralokinumab nije odobren od HZZO-a u Hrvatskoj za lije&#x010D;enje AD-a.</p>
<sec id="secIIf">
<label>f)</label><title>Inhibitori Janus kinaza</title>
<p>Inhibitori Janus kinaza (JAK) su male molekule koje imaju zna&#x010D;ajan utjecaj na patofiziologiju upalnih bolesti, uklju&#x010D;uju&#x0107;i i AD. Ciljano inhibiraju nekoliko putova upalnih procesa odjednom i na taj na&#x010D;in pobolj&#x0161;avaju znakove i simptome bolesti. JAK-ovi su unutarstani&#x010D;ni enzimi koji prenose signale koji proizlaze iz interakcija citokina ili &#x010D;imbenika rasta i receptora na stani&#x010D;noj membrani kako bi utjecali na stani&#x010D;ne procese hematopoeze i funkciju imunosnih stanica. JAK-ovi fosforiliraju i aktiviraju prijenosnike signala i aktivatore transkripcije (engl. <italic>Signal Transducers and Activators of Transcription</italic>, STAT) koji moduliraju unutarstani&#x010D;nu aktivnost uklju&#x010D;uju&#x0107;i gensku ekspresiju.</p>
<p>U&#x010D;inak JAK-inhibitora nastupa vrlo brzo, unutar nekoliko dana, ali nakon prestanka uzimanja simptomi se vrlo brzo vra&#x0107;aju.</p>
<p>Zapo&#x010D;injanje terapije JAK-inhibitorima ne savjetuje se kod osoba koje u anamnezi imaju podatak o dubokoj venskoj trombozi.</p>
<p>Kod &#x017E;ena generativne dobi uz terapiju JAK-inhibitorima savjetuje se uzimanje oralnih kontraceptiva.</p>
<p>Lije&#x010D;enje JAK-inhibitorima odobrava Bolni&#x010D;ko povjerenstvo za lijekove.</p>
<p>Prije uvo&#x0111;enja lijeka potrebno je odrediti EASI i/ili SCORAD i DLQI.</p>
<p>Mogu se koristiti u kombinaciji s lokalnim glukokortikoidima ili s lokalnim inhibitorima kalcineurina.</p>
<p>Prije uvo&#x0111;enja JAK-a (i ukoliko lije&#x010D;enje traje du&#x017E;e od godinu dana) potrebno je u&#x010D;initi: KKS, CRP, ureju, kreatinin, AST, ALT, GGT, AP, CPK, kolesterol, trigliceride, markere na hepatitis B i C, HIV test, Quantiferonski test, te kod uvo&#x0111;enja baricitiniba i klirens kreatinina.</p>
<p>Nakon &#x010D;etiri tjedna te potom svaka dva mjeseca potrebno je u&#x010D;initi: KKS, CRP, ureju, kreatinin, AST, ALT, GGT, AP, CPK, a nakon tri mjeseca kolesterol i trigliceride.</p>
<p>Procjena u&#x010D;inka terapije i aktivnost bolesti treba biti evaluirana u 8. tjednu (baricitinib), u 12. tjednu (upadacitinib) odnosno 24. tjednu (abrocitinib) izra&#x010D;unavanjem vrijednosti EASI i/ili SCORAD i/ili DLQI.</p>
<p>Nastavak lije&#x010D;enja mogu&#x0107; je ako je nakon 8 tjedana (baricitinib), 12 tjedana (upadacitinib), 24 tjedna (abrocitinib) postignuto najmanje 50-postotno pobolj&#x0161;anje EASI ili SCORAD vrijednosti ili pobolj&#x0161;anje DLQI vrijednosti vi&#x0161;e od 4 boda, prema procjeni nadle&#x017E;nog dermatologa. Lijek se nakon toga procjenjuje najmanje jedanput tijekom godine izra&#x010D;unavanjem vrijednosti EASI i/Ili SCORAD i DLQI.</p>
<p>Lije&#x010D;enje odobrava bolni&#x010D;ko Povjerenstvo za lijekove.</p>
<p>Procjena u&#x010D;inka terapije i aktivnost bolesti treba biti evaluirana nakon osam tjedana od po&#x010D;etka lije&#x010D;enja, odre&#x0111;ivanjem vrijednosti EASI i/ili SCORAD te DLQI. Nastavak lije&#x010D;enja mogu&#x0107; je ako je nakon osam tjedana postignuto najmanje 50-postotno pobolj&#x0161;anje EASI i/ili SCORAD vrijednosti i pobolj&#x0161;anje DLQI vrijednosti vi&#x0161;e od &#x010D;etiri boda. Procjena u&#x010D;inka terapije se potom evaluira najmanje jedanput godi&#x0161;nje izra&#x010D;unavanjem vrijednosti EASI i/ili SCORAD i DLQI.</p>
<p>Bolesnici se ne smiju cijepiti &#x017E;ivim, atenuiranim cjepivima neposredno prije ili tijekom lije&#x010D;enja.</p>
<p>U slu&#x010D;aju pojave te&#x017E;ih infekcija (npr. herpes zoster, eczema herpeticatum i sl.) terapija JAK-inhibitorima se prekida sve dok se infekcija ne izlije&#x010D;i.</p>
<p>U Hrvatskoj su trenutno odobreni baricitinib i upadacitinib, a &#x010D;eka se odobrenje abracitiniba.</p>
</sec>
</sec>
<sec id="secI___2">
<label>I.</label><title>Baricitinib</title>
<p>U listopadu 2020. godine u Europi je EMA odobrila baricitinib za lije&#x010D;enje srednje te&#x0161;kih i te&#x0161;kih oblika AD-a u odraslih. Baricitinib je selektivan i reverzibilan inhibitor JAK1 i JAK2 te na taj na&#x010D;in inhibira upalni proces djelovanjem unutar stanice. (<xref ref-type="bibr" rid="r63"><italic>63</italic></xref>)</p>
<p>Preporu&#x010D;ena doza baricitiniba je 4 mg peroralno jednom dnevno, uz hranu ili bez nje, u bilo koje doba dana, a uzima se peroralno.</p>
<p>Doza od 2 mg indicirana je za bolesnike u dobi od &#x2265; 75 godina ili za bolesnike koji u anamnezi imaju kroni&#x010D;ne ili rekurentne infekcije ili u bolesnika koji su kandidati za postupno smanjivanje doze nakon &#x0161;to su dozom od 4 mg jedanput na dan postigli odr&#x017E;anu kontrolu aktivnosti bolesti.</p>
<p>Nuspojave su infekcije gornjih di&#x0161;nih putova i hiperkolesterolemija, a rje&#x0111;e druge infekcije poput herpesa zostera, herpesa simpleksa, infekcije mokra&#x0107;nog sustava, gastroenteritisa i tromboembolije. (<xref ref-type="bibr" rid="r63"><italic>63</italic></xref>)</p>
</sec>
<sec id="secII___2">
<label>II.</label><title>Upadacitinib</title>
<p>Upadacitinib je oralni selektivni JAK1-inhibitor koji je EMA odobrila u kolovozu 2021. za lije&#x010D;enje umjerenog do te&#x0161;kog AD-a u djece starije od 12 godina, adolescenata i odraslih bolesnika koji su kandidati za sustavnu terapiju. (<xref ref-type="bibr" rid="r64"><italic>64</italic></xref>)</p>
<p>Odobren je u dvije doze od 15 mg i 30 mg i u obliku je peroralnog pripravka.</p>
<p>Preporu&#x010D;ena doza za lije&#x010D;enje AD-a je 30 mg dnevno. Doza od 15 mg dnevno preporu&#x010D;uje se za bolesnike u dobi od &#x2265;65 godina i adolescente tjelesne te&#x017E;ine najmanje 30 kg.</p>
<p>Upadacitinib zna&#x010D;ajno i brzo (ve&#x0107; od prvog tjedna) dovodi do pobolj&#x0161;anja znakova i simptoma AD-a. (<xref ref-type="bibr" rid="r64"><italic>64</italic></xref>)</p>
<p>&#x010C;e&#x0161;&#x0107;e nuspojave su infekcija gornjih di&#x0161;nih putova, infekcije herpes zoster, akne, pove&#x0107;anje kreatin kinaze u krvi, dok su rje&#x0111;i mu&#x010D;nina i trombocitopenija pa je stoga potrebno laboratorijsko pra&#x0107;enje prije uvo&#x0111;enja i tijekom terapije.</p>
</sec>
<sec id="secIII___1">
<label>III.</label><title>Abrocitinib</title>
<p>Abrocitinib je mala molekula koja selektivno inhibira JAK1. Inhibicija JAK1 modulira multiple citokine (IL-4, IL-13, IL-31, IL-22 i stromalni timusni limfopoietin) koji su uklju&#x010D;eni u patogenezu AD-a i svrbe&#x017E;. (<xref ref-type="bibr" rid="r65"><italic>65</italic></xref>, <xref ref-type="bibr" rid="r66"><italic>66</italic></xref>) Abrocitinib je odobren u Velikoj Britaniji u rujnu 2021., a u prosincu 2021. u Europi kao peroralni pripravak u dozi od 100 mg i 200 mg dnevno.</p>
<p>Indiciran je za lije&#x010D;enje srednje te&#x0161;kih i te&#x0161;kih oblika AD-a u bolesnika starijih od 12 godina. (<xref ref-type="bibr" rid="r66"><italic>66</italic></xref>)</p>
<p>Naj&#x010D;e&#x0161;&#x0107;e nuspojave su mu&#x010D;nina i respiratorne infekcije gornjeg di&#x0161;nog trakta.</p>
<p>U&#x010D;inak abrocitiniba na promjene ko&#x017E;e kod bolesnika s AD-om o&#x010D;ekuje se unutar dva tjedna od po&#x010D;etka primjene, a u&#x010D;inak na svrbe&#x017E; unutar 24 sata. (<xref ref-type="bibr" rid="r65"><italic>65</italic></xref>, <xref ref-type="bibr" rid="r66"><italic>66</italic></xref>)</p>
<sec id="secIIIg">
<label>g)</label><title>Ostalo</title>
<p>U klini&#x010D;koj fazi II i/ili III ispitivanja brojni su drugi lokalni, peroralni i supkutani biolo&#x0161;ki lijekovi (lebrikizumab, nemolizumab, risankizumab, itd.) i JAK inhibitori.</p>
<p>Ostali oblici lije&#x010D;enja uklju&#x010D;uju imunoterapiju, psihoterapijsku podr&#x0161;ku te dodatne i alternativne metode lije&#x010D;enja.</p>
<p>Specifi&#x010D;na imunoterapija se savjetuje u bolesnika s AD-om koji imaju udru&#x017E;enu alergijsku astmu ili alergijski rinitis te u onih kojima se ko&#x017E;ne promjene pogor&#x0161;avaju u kontaktu s ku&#x0107;nom pra&#x0161;inom. Ona se provodi jedino ukoliko se poka&#x017E;e klini&#x010D;ka relevantnost sa specifi&#x010D;nim IgE-om na odre&#x0111;eni alergen (B, 2a).</p>
<p>Budu&#x0107;i da je jasno da psiholo&#x0161;ki i emocionalni &#x010D;imbenici utje&#x010D;u na tijek AD-a i &#x010D;esto uzrokuju pogor&#x0161;anja dermatitisa, a s druge strane s&#x00E2;m AD izrazito podi&#x017E;e razinu stresa i anksioznosti u oboljelih, savjetuje se psihoterapijska podr&#x0161;ka (A, 1a). Naj&#x010D;e&#x0161;&#x0107;e su kori&#x0161;tene terapije bihevioralno-kognitivna terapija, <italic>&#x201E;mindfulness&#x201C;</italic> tehnike, razli&#x010D;ite tehnike opu&#x0161;tanja i autogeni trening. (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>, <xref ref-type="bibr" rid="r67"><italic>67</italic></xref>)</p>
</sec>
</sec>
</sec>
<sec sec-type="other5">
<title>Zaklju&#x010D;ak</title>
<p>Atopijski dermatitis je bolest ko&#x017E;e visoke incidencije, kompleksne etiopatogeneze, klini&#x010D;ke slike i terapije. Srednje te&#x0161;ki i te&#x0161;ki oblici bolesti imaju zna&#x010D;ajan utjecaj na kvalitetu &#x017E;ivota samih bolesnika i njihovih obitelji. Posljednjih godina do&#x0161;lo je do napretka u lije&#x010D;enju bolesnika s AD-om i uvo&#x0111;enja novih lijekova u terapiju. Ovim smjernicama osigurat &#x0107;e se plansko i sistematsko lije&#x010D;enje oboljelih u skladu s europskim i svjetskim smjernicama s ciljem postizanja optimalne u&#x010D;inkovitosti i sigurnosti lije&#x010D;enja.</p>
</sec>
<sec sec-type="other6">
<title>Postupnik za lije&#x010D;enje atopijskog dermatitisa (<xref ref-type="fig" rid="f1">slika 1</xref>, <xref ref-type="table" rid="t2">tablica 2</xref>)</title>
<table-wrap id="t2" position="float">
<label>Table 2</label><caption><title>Recommendation for systemic therapy of atopic dermatitis</title>
</caption>
<table frame="hsides" rules="groups">
<col width="15.35%"/>
<col width="18.29%"/>
<col width="17.01%"/>
<col width="17.02%"/>
<col width="19.14%"/>
<col width="13.19%"/>
<thead>
<tr>
<th valign="middle" align="left" scope="col" style="border-left: solid 0.75pt; border-top: solid 0.75pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt"></th>
<th valign="middle" align="left" scope="col" style="border-left: solid 0.50pt; border-top: solid 0.75pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt"><bold>Ciklosporin / Cyclosporine</bold></th>
<th valign="middle" align="left" scope="col" style="border-left: solid 0.50pt; border-top: solid 0.75pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt"><bold>Metotreksat / Methotrexate</bold></th>
<th valign="middle" align="left" scope="col" style="border-left: solid 0.50pt; border-top: solid 0.75pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt"><bold>Azatioprin / Azathioprine</bold></th>
<th valign="middle" align="left" scope="col" style="border-left: solid 0.50pt; border-top: solid 0.75pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt"><bold>Mikofenolat mofetil</bold><break/><bold>/ Mycophenolate mofetil</bold></th>
<th valign="middle" align="left" scope="col" style="border-left: solid 0.50pt; border-top: solid 0.75pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt"><bold>Glukokortikoidi</bold><break/><bold>/ Glucocorticoids</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Po&#x010D;etna doza (odrasli)<break/>/ Starting dose (adults)</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">2,5&#x2013;5 mg/kg/dnevno<break/>/ 2.5&#x2013;5 mg/kg/daily</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">5&#x2013;15 mg/tjedno<break/>/ 5&#x2013;15 mg/weekly</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">50 mg/dnevno<break/>/ 50 mg/daily</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">1&#x2013;2 g/dnevno<break/>/ 1&#x2013;2 g/daily</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">0,2&#x2013;0,5 mg/kg/dnevno<break/>/ 0.2&#x2013;0.5 mg/kg/daily</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Doza odr&#x017E;avanja (odrasli)<break/>/ Maintenance dose (adults)</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">2,5&#x2013;3 mg/kg/dnevno<break/>/ 2.5&#x2013;3 mg/kg/daily</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">15 mg/tjedno, mogu&#x0107;e podi&#x0107;i i do maksimalno 25 mg/tjedno<break/>/ Can increase to maximum 25 mg/week</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">1&#x2013;3 mg/kg/dnevno<break/>/ 1&#x2013;3 mg/kg/daily</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">1&#x2013;2 g/dnevno<break/>/ 1&#x2013;2 g/daily</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Ne savjetuje se<break/>/ Not recommended</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Po&#x010D;etna doza (djeca)<break/>/ Starting dose (children)</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">2&#x2013;3 mg/kg/dnevno<break/>/ 2&#x2013;3 mg/kg/daily</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">0,2&#x2013;0,3 mg/kg/tjedno<break/>/ 0.2&#x2013;0.3 mg/kg/weekly</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">25&#x2013;50 mg/dnevno<break/>/ 25&#x2013;50 mg/daily</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">20&#x2013;50 mg/dnevno<break/>/ 20&#x2013;50 mg/daily</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">0,2&#x2013;0,5 mg/kg/dan<break/>/ 0.2&#x2013;0.5 mg/kg/daily</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Doza odr&#x017E;avanja (djeca)<break/>/ Maintenance dose (children)</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">U slu&#x010D;aju nedjelotvornosti postupno podizati dozu do ukupno 5 mg/kg/dnevno<break/>/ Gradually increase daily total dose in case of inefficiency up to 5 mg/kg/daily</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Postupno podizati dozu do 0,5 mg/kg/tjedno<break/>/ Gradually increase daily total dose up to<break/>0.5 mg/kg/weekly</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Postupno podizati dozu svakih 7 dana za 0,5 mg/kg/dnevno do ukupno 1 do 3 mg/kg/dnevno<break/>/ Gradually increase daily total dose by 0.5 mg/kg/daily every 7 days up to 1&#x2013;3 mg/kg/daily</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Postupno podizati dozu za 500 mg svakih 2&#x2013;4 tjedna do ukupne doze 30&#x2013;50 mg/kg/dnevno<break/>/ Gradually increase daily total dose by 500 mg every 2&#x2013;4 weeks up to 30&#x2013;50 mg/kg/daily</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Ne savjetuje se<break/>/ Not recommended</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Trudno&#x0107;a<break/>/ Pregnancy</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Dozvoljeno<break/>/ Allowed</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Teratogen; apsolutno kontraindiciran<break/>/ Teratogenic; absolutely contraindicated</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Proturje&#x010D;ni dokazi; mogu&#x0107;e u strogim indikacijama<break/>/ Conflicting data, allowed with strict indication</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Teratogen; apsolutno kontraindiciran<break/>/ Teratogenic; absolutely contraindicated</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Dozvoljeno<break/>/ Allowed</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">O&#x010D;instvo<break/>/ Fathering</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Dozvoljeno<break/>/ Allowed</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Premalo podataka, proturje&#x010D;ni podatci, kontraindicirano<break/>/ Not enough information, conflicting data, contraindicated</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Premalo podataka, mogu&#x0107;e u strogim indikacijama<break/>/ Not enough information allowed with strict indication</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Proturje&#x010D;ni podatci<break/>/ Conflicting data,</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Dozvoljeno<break/>/ Allowed</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Vrijeme potrebno za pobolj&#x0161;anja (tjedni)<break/>/ Time to respond (weeks)</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">2&#x2013;4</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">8&#x2013;12</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">8&#x2013;12</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">8&#x2013;12</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">1&#x2013;2</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Vrijeme recidiva (tjedni)<break/>/ Time to relapse (weeks)</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">&lt;2</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">&gt;12</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">&gt;12</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">&gt;12</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">&lt;2</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.75pt" scope="row">Naj&#x010D;e&#x0161;&#x0107;e nuspojave<break/>/ Most frequent side effects</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.75pt">&#x2191; Kreatinin u serumu<break/>/ &#x2191; Serum creatinine<break/>&#x2191; Krvni tlak<break/>/ &#x2191; Blood pressure</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.75pt">Hematolo&#x0161;ke<break/>/ Hematological<break/>&#x2191; Jetreni enzimi<break/>/ &#x2191; Liver enzymes<break/>Gastrointestinalne<break/>/ Gastrointestinal</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.75pt">Hematolo&#x0161;ke<break/>/ Hematological<break/>&#x2191; Jetreni enzimi<break/>/ &#x2191; Liver enzymes<break/>Gastrointestinalne<break/>/ Gastrointestinal</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.75pt">Hematolo&#x0161;ke<break/>/ Hematological<break/>Infekcije ko&#x017E;e<break/>/ Skin infection<break/>Gastrointestinalne<break/>/ Gastrointestinal</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.75pt">Cushingov sindrom<break/>/ Cushing syndrome<break/>Osteoporoza<break/>/ Osteoporosis<break/>&#x0160;e&#x0107;erna bolest<break/>/ Diabetes mellitus<break/>Hipertenzija<break/>/ Hypertension</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.75pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Pretrage prije uvo&#x0111;enja terapije<break/>/ Laboratory assessments at baseline</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.75pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Kompletna krvna slika<break/>/ Complete blood count<break/>Diferencijalna krvna slika<break/>/ Differential blood count<break/>Urin / Urinalysis<break/>Testovi za renalnu funkciju (kreatinin, klirens kreatinina)<break/>/ Renal function tests (creatinine, creatinine clearance)<break/>Kreatinin fosfokinaza<break/>/ Creatine phosphokinase<break/>Jetreni enzimi<break/>/ Liver function tests<break/>Urati / Uric acid<break/>Elektroliti / Electrolytes<break/>Magnezij / Magnesium<break/>Lipidogram / Lipids<break/>HIV test<break/>Quantiferonski test<break/>/ Quantiferon test<break/>Hepatitis B i/and C<break/>Krvni tlak / Blood pressure<break/>IgM i IgG na VZV*<break/>/ IgM and IgG for VZV*</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.75pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Kompletna krvna slika<break/>/ Complete blood count<break/>Diferencijalna krvna slika<break/>/ Differential blood count<break/>Testovi za renalnu funkciju<break/>/ Renal function tests<break/>Jetreni enzimi<break/>/ Liver function tests<break/>Hepatitis B i/and C<break/>HIV test<break/>Quantiferonski test<break/>/ Quantiferon test<break/>IgM i IgG na VZV*<break/>/ IgM and IgG for VZV*</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.75pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Kompletna krvna slika<break/>/ Complete blood count<break/>Diferencijalna krvna slika<break/>/ Differential blood count<break/>Testovi za renalnu funkciju<break/>/ Renal function tests<break/>Jetreni enzimi<break/>/ Liver function tests<break/>Amilaze / Amylase<break/>TPMT<break/>Hepatitis B i/and C<break/>HIV test<break/>Quantiferonski test<break/>/ Quantiferon test<break/>IgM i IgG na VZV*<break/>/ IgM and IgG for VZV*</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.75pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Kompletna krvna slika<break/>/ Complete blood count<break/>Diferencijalna krvna slika<break/>/ Differential blood count<break/>Testovi za renalnu funkciju<break/>/ Renal function tests<break/>Jetreni enzimi<break/>/ Liver function tests<break/>HIV test<break/>Quantiferonski test<break/>/ Quantiferon test<break/>IgM i IgG na VZV*<break/>/ IgM and IgG for VZV*</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.75pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Nije potrebno<break/>/ None</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Kontrolne pretrage tijekom terapije<break/>/ Laboratory assessments at follow-up monitoring</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Kompletna krvna slika<break/>/ Complete blood count<break/>Diferencijalna krvna slika<break/>/ Differential blood count<break/>Urin / Urinalysis<break/>Odre&#x0111;ivanje renalne funkcije<break/>/ Renal function tests<break/>Jetreni enzimi<break/>/ Liver function tests<break/>Lipidi / Lipids<break/>Mg, K, mokra&#x0107;na kiselina<break/>/ Mg, K, uric acid<break/>Krvni tlak / Blood pressure</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Kompletna krvna slika<break/>/ Complete blood count<break/>Diferencijalna krvna slika<break/>/ Differential blood count<break/>Testovi za renalnu funkciju<break/>/ Renal function tests<break/>Jetreni enzimi<break/>/ Liver function tests</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Kompletna krvna slika<break/>/ Complete blood count<break/>Diferencijalna krvna slika<break/>/ Differential blood count<break/>Testovi za renalnu funkciju<break/>/ Renal function tests<break/>Jetreni enzimi<break/>/ Liver function tests<break/>Amilaze / Amylase</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Kompletna krvna slika<break/>/ Complete blood count<break/>Diferencijalna krvna slika<break/>/ Differential blood count<break/>Testovi za renalnu funkciju<break/>/ Renal function tests<break/>Jetreni enzimi<break/>/ Liver function tests<break/>Quantiferonski test<break/>/ Quantiferon test</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Ne savjetuje se dugotrajna terapija<break/>/ Long-term therapy is not advised</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.75pt" scope="row">Razine preporuka; Razine dokaza<break/>/ Strength of recommendation; Evidence grade</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.75pt">A; 1a</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.75pt">C; 4</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.75pt">A; 1b</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.75pt">C; 4</td>
<td valign="top" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.75pt">D; &#x2013;</td>
</tr>
</tbody>
</table><table-wrap-foot>
<p>* Ukoliko bolesnik nije prebolio ili se ne sje&#x0107;a da je prebolio vari&#x010D;ele / If the patient has not had or does not remember having chickenpox</p>
<p>VZV: varicella zoster virus TPMT: enzim tiopurin metil-transferaza/ thiopurine methyltransferase; K: Kalij/Potassium; Mg: magnezij/magnesium</p>
</table-wrap-foot></table-wrap>
<p>Osnova lije&#x010D;enja svakog bolesnika s AD-om uklju&#x010D;uje edukaciju oboljelih i &#x010D;lanova obitelji, redovitu primjenu emolijensa, prepoznavanje i izbjegavanje &#x010D;imbenika pogor&#x0161;anja dermatitisa.</p>
<p>Kod blagih oblika AD-a (SCORAD &lt;25, EASI 1,1-7,0) uz svakodnevnu njegu ko&#x017E;e (emolijensi), u lokalnoj terapiji u razdobljima pogor&#x0161;anja dermatitisa savjetuje se lokalna protuupalna terapija (lokalni glukokortikoidi slabije ja&#x010D;ine djelovanja) te prema potrebi (u slu&#x010D;aju sekundarne infekcije) antimikrobna terapija. Za lije&#x010D;enje dermatitisa na licu, vratu, pregibima i genitalnoj regiji savjetuje se aplikacija inhibitora kalcineurina (takrolimus mast 0,03% ili 0,1%, pimekrolimus krema 1%).</p>
<p>Za srednje te&#x0161;ke oblike AD-a (SCORAD 25-50, EASI 7,1-21) uz svakodnevnu njegu ko&#x017E;e (emolijensi), savjetuje se reaktivna i proaktivna aplikacija lokalnih protuupalnih preparata (glukokortikoidi ja&#x010D;e potentnosti i inhibitori kalcineurina). Ako lokalna terapija nije dostatna i/ili po prestanku njene aplikacije brzo nastaju recidivi, savjetuje se provo&#x0111;enje fototerapije (uskospektralna UVB terapija, iznimno UVA1 terapija ili PUVA terapija). Ako unato&#x010D; primjeni lokalne protuupalne terapije i fototerapije ne do&#x0111;e do pobolj&#x0161;anja, savjetuje se uvo&#x0111;enje sustavne konvencionalne terapije.</p>
<p>Za te&#x0161;ke oblike AD-a (SCORAD &gt;50, EASI &gt;21,1) kod kojih nema pobolj&#x0161;anja na lokalnu terapiju i/ili fototerapiju, indicirano je uz svakodnevnu njegu ko&#x017E;e (emolijensi) i sustavno imunosupresivno lije&#x010D;enje (ciklosporin ili metotreksat ili azatioprin ili mikofenolat mofetil) u prosje&#x010D;nom trajanju 1 &#x2013; 8,5 mjeseci.</p>
<p>Za srednje te&#x0161;ke i te&#x0161;ke oblike AD-a kod kojih nema pobolj&#x0161;anja na lokalnu terapiju i/ili fototerapiju, nema odgovaraju&#x0107;eg odgovora i/ili postoje nuspojave na jedan sustavni konvencionalni imunosupresivni lijek, indicirano je lije&#x010D;enje biolo&#x0161;kom terapijom ili terapijom JAK-inhibitorima. Ukoliko po ukidanju sustavnoga konvencionalnog imunosupresiva nastupi pogor&#x0161;anje, kod bolesnika je indicirano lije&#x010D;enje biolo&#x0161;kom terapijom ili terapija JAK-inhibitorima.</p>
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<ref-list>
<title>LITERATURA</title>
<ref id="r1"><label>1</label><mixed-citation publication-type="other">Ljubojevi&#x0107; Had&#x017E;avdi&#x0107; S, Pusti&#x0161;ek N. Atopijski dermatitis. Zagreb: Medicinska naknada; 2019.</mixed-citation></ref>
<ref id="r2"><label>2</label><mixed-citation publication-type="other">Lipozen&#x010D;i&#x0107; J, Ljubojevi&#x0107; S, Marinovi&#x0107; Kuli&#x0161;i&#x0107; S. Atopijski dermatitis u odraslih. U: Lipozen&#x010D;i&#x0107; J, et al. Alergijske i imunosne bolesti. Zagreb: Medicinska naklada; 2011, str. 239&#x2013;46.</mixed-citation></ref>
<ref id="r3"><label>3</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Silverberg</surname><given-names>JI</given-names></name><name><surname>Thyssen</surname><given-names>JP</given-names></name><name><surname>Paller</surname><given-names>AS</given-names></name><name><surname>Drucker</surname><given-names>AM</given-names></name><name><surname>Wollenberg</surname><given-names>A</given-names></name><name><surname>Lee</surname><given-names>KH</given-names></name><etal/></person-group> <article-title>What&#x2019;s in a name? Atopic dermatitis or atopic eczema, but not eczema alone.</article-title> <source>Allergy</source>. <year>2017</year>;<volume>72</volume>:<fpage>2026</fpage>&#x2013;<lpage>30</lpage>. <pub-id pub-id-type="doi">10.1111/all.13225</pub-id><pub-id pub-id-type="pmid">28605026</pub-id></mixed-citation></ref>
<ref id="r4"><label>4</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mortz</surname><given-names>CG</given-names></name><name><surname>Andersen</surname><given-names>KE</given-names></name><name><surname>Dellgren</surname><given-names>C</given-names></name><name><surname>Barington</surname><given-names>T</given-names></name><name><surname>Bindslev-Jensen</surname><given-names>C</given-names></name></person-group>. <article-title>Atopic dermatitis from adolescence to adulthood in the TOACS cohort: prevalence, persistence and comorbidities.</article-title> <source>Allergy</source>. <year>2015</year>;<volume>70</volume>:<fpage>836</fpage>&#x2013;<lpage>45</lpage>. <pub-id pub-id-type="doi">10.1111/all.12619</pub-id><pub-id pub-id-type="pmid">25832131</pub-id></mixed-citation></ref>
<ref id="r5"><label>5</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bieber</surname><given-names>T</given-names></name></person-group>. <article-title>Atopic dermatitis.</article-title> <source>Ann Dermatol</source>. <year>2010</year>;<volume>22</volume>(<issue>2</issue>):<fpage>125</fpage>&#x2013;<lpage>37</lpage>. <pub-id pub-id-type="doi">10.5021/ad.2010.22.2.125</pub-id><pub-id pub-id-type="pmid">20548901</pub-id></mixed-citation></ref>
<ref id="r6"><label>6</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yaghmaie</surname><given-names>P</given-names></name><name><surname>Koudelka</surname><given-names>CW</given-names></name><name><surname>Simpson</surname><given-names>EL</given-names></name></person-group>. <article-title>Mental health comorbidity in patients with atopic dermatitis.</article-title> <source>J Allergy Clin Immunol</source>. <year>2013</year>;<volume>131</volume>:<fpage>428</fpage>&#x2013;<lpage>33</lpage>. <pub-id pub-id-type="doi">10.1016/j.jaci.2012.10.041</pub-id><pub-id pub-id-type="pmid">23245818</pub-id></mixed-citation></ref>
<ref id="r7"><label>7</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Patel</surname><given-names>KR</given-names></name><name><surname>Immaneni</surname><given-names>S</given-names></name><name><surname>Singam</surname><given-names>V</given-names></name><name><surname>Rastogi</surname><given-names>S</given-names></name><name><surname>Silverberg</surname><given-names>JI</given-names></name></person-group>. <article-title>Association between atopic dermatitis, depression, and suicidal ideation: A systematic review and meta-analysis.</article-title> <source>J Am Acad Dermatol</source>. <year>2019</year>;<volume>80</volume>:<fpage>402</fpage>&#x2013;<lpage>10</lpage>. <pub-id pub-id-type="doi">10.1016/j.jaad.2018.08.063</pub-id><pub-id pub-id-type="pmid">30365995</pub-id></mixed-citation></ref>
<ref id="r8"><label>8</label><mixed-citation publication-type="other">Ring J, Alomar A, Bieber T, Deleuran M, Fink-Wagner A, Gelmetti C, et al. Guidelines for treatment of atopic eczema (atopic dermatitis). Part I. J Eur Acad Derm Venereol. 2012;26(8):1045&#x2013;60.</mixed-citation></ref>
<ref id="r9"><label>9</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wollenberg</surname><given-names>A</given-names></name><name><surname>Barbarot</surname><given-names>S</given-names></name><name><surname>Bieber</surname><given-names>T</given-names></name><name><surname>Christen-Zaech</surname><given-names>S</given-names></name><name><surname>Deleuran</surname><given-names>M</given-names></name></person-group>, Fink-Wagner, et al. <article-title>Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I.</article-title> <source>J Eur Acad Dermatol Venereol</source>. <year>2018</year>;<volume>32</volume>(<issue>5</issue>):<fpage>657</fpage>&#x2013;<lpage>82</lpage>. <pub-id pub-id-type="doi">10.1111/jdv.14891</pub-id><pub-id pub-id-type="pmid">29676534</pub-id></mixed-citation></ref>
<ref id="r10"><label>10</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wollenberg</surname><given-names>A</given-names></name><name><surname>Barbarot</surname><given-names>S</given-names></name><name><surname>Bieber</surname><given-names>T</given-names></name><name><surname>Christen-Zaech</surname><given-names>S</given-names></name><name><surname>Deleuran</surname><given-names>M</given-names></name><name><surname>Fink-Wagner</surname><given-names>A</given-names></name><etal/></person-group> <article-title>Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II.</article-title> <source>J Eur Acad Dermatol Venereol</source>. <year>2018</year>;<volume>32</volume>(<issue>6</issue>):<fpage>850</fpage>&#x2013;<lpage>78</lpage>. <pub-id pub-id-type="doi">10.1111/jdv.14888</pub-id><pub-id pub-id-type="pmid">29878606</pub-id></mixed-citation></ref>
<ref id="r11"><label>11</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Damiani</surname><given-names>G</given-names></name><name><surname>Calzavara-Pinton</surname><given-names>P</given-names></name><name><surname>Stingeni</surname><given-names>L</given-names></name><name><surname>Hansel</surname><given-names>K</given-names></name><name><surname>Cusano</surname><given-names>F</given-names></name></person-group>, &#x201C;Skin Allergy&#x201D; Group of SIDeMaST; &#x201C;ADOI&#x201D; (Associazione Dermatologi Ospedalieri Italiani), et al. <article-title>Italian guidelines for therapy of atopic dermatitis &#x2013; Adapted from consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis).</article-title> <source>Dermatol Ther</source>. <year>2019</year>;<volume>32</volume>(<issue>6</issue>):<elocation-id>e13121</elocation-id>.<pub-id pub-id-type="pmid">31625221</pub-id></mixed-citation></ref>
<ref id="r12"><label>12</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hanifin</surname><given-names>JM</given-names></name><name><surname>Rajka</surname><given-names>G</given-names></name></person-group>. <article-title>Diagnostic features of atopic dermatitis.</article-title> <source>Acta Derm Venereol Suppl (Stockh)</source>. <year>1980</year>;<volume>92</volume>(<issue>2</issue>):<fpage>44</fpage>&#x2013;<lpage>7</lpage>.</mixed-citation></ref>
<ref id="r13"><label>13</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schram</surname><given-names>ME</given-names></name><name><surname>Leeflang</surname><given-names>MMG</given-names></name><name><surname>Den Ottolander</surname><given-names>JP</given-names></name><name><surname>Spuls</surname><given-names>PI</given-names></name><name><surname>Bos</surname><given-names>JD</given-names></name></person-group>. <article-title>Validation and refinement of the Millennium Criteria for atopic dermatitis.</article-title> <source>J Dermatol</source>. <year>2011</year>;<volume>38</volume>(<issue>9</issue>):<fpage>850</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1111/j.1346-8138.2011.01202.x</pub-id><pub-id pub-id-type="pmid">21453318</pub-id></mixed-citation></ref>
<ref id="r14"><label>14</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eichenfield</surname><given-names>LF</given-names></name><name><surname>Tom</surname><given-names>WL</given-names></name><name><surname>Chamlin</surname><given-names>SL</given-names></name><name><surname>Feldman</surname><given-names>SR</given-names></name><name><surname>Hanifin</surname><given-names>JM</given-names></name><name><surname>Simpson</surname><given-names>EL</given-names></name><etal/></person-group> <article-title>Guidelines of care for management of atopic dermatitis. Section 1. Diagnosis and assessment of atopic dermatitis.</article-title> <source>J Am Acad Dermatol</source>. <year>2014</year>;<volume>70</volume>(<issue>2</issue>):<fpage>338</fpage>&#x2013;<lpage>51</lpage>. <pub-id pub-id-type="doi">10.1016/j.jaad.2013.10.010</pub-id><pub-id pub-id-type="pmid">24290431</pub-id></mixed-citation></ref>
<ref id="r15"><label>15</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eichenfield</surname><given-names>LF</given-names></name><name><surname>Hanifin</surname><given-names>JM</given-names></name><name><surname>Luger</surname><given-names>TA</given-names></name><name><surname>Stevens</surname><given-names>SR</given-names></name><name><surname>Pride</surname><given-names>HB</given-names></name></person-group>. <article-title>Consensus conference on pediatric atopic dermatitis.</article-title> <source>J Am Acad Dermatol</source>. <year>2003</year>;<volume>49</volume>(<issue>6</issue>):<fpage>1088</fpage>&#x2013;<lpage>95</lpage>. <pub-id pub-id-type="doi">10.1016/S0190-9622(03)02539-8</pub-id><pub-id pub-id-type="pmid">14639390</pub-id></mixed-citation></ref>
<ref id="r16"><label>16</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kabashima</surname><given-names>K</given-names></name></person-group>. <article-title>New concept of the pathogenesis of atopic dermatitis: interplay among barrier, allergy, and pruritus as a trinitiy.</article-title> <source>J Dermatol Sci</source>. <year>2013</year>;<volume>70</volume>(<issue>1</issue>):<fpage>3</fpage>&#x2013;<lpage>11</lpage>. <pub-id pub-id-type="doi">10.1016/j.jdermsci.2013.02.001</pub-id><pub-id pub-id-type="pmid">23473856</pub-id></mixed-citation></ref>
<ref id="r17"><label>17</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>W&#x00FC;thrich</surname><given-names>B</given-names></name><name><surname>Schmid-Grendelmeier</surname><given-names>P</given-names></name></person-group>. <article-title>The atopic eczema/dermatitis syndrome. Epidemilogy, natural course, and immunology of IgE-associated (&#x201C;extrinsic&#x201D;) and the nonallergic (&#x201C;intrinsic&#x201D;) AEDS.</article-title> <source>J Investig Allergol Clin Immunol</source>. <year>2003</year>;<volume>13</volume>(<issue>1</issue>):<fpage>1</fpage>&#x2013;<lpage>5</lpage>.<pub-id pub-id-type="pmid">12861844</pub-id></mixed-citation></ref>
<ref id="r18"><label>18</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schmitt</surname><given-names>J</given-names></name><name><surname>Langan</surname><given-names>S</given-names></name><name><surname>Deckert</surname><given-names>S</given-names></name><name><surname>Svensson</surname><given-names>A</given-names></name><name><surname>von Kobyletzki</surname><given-names>L</given-names></name><name><surname>Thomas</surname><given-names>K</given-names></name><etal/></person-group> <article-title>Assessment of clinical signs of atopic dermatitis: A systematic review and recommendation.</article-title> <source>J Allergy Clin Immunol</source>. <year>2013</year>;<volume>132</volume>(<issue>6</issue>):<fpage>1337</fpage>&#x2013;<lpage>47</lpage>. <pub-id pub-id-type="doi">10.1016/j.jaci.2013.07.008</pub-id><pub-id pub-id-type="pmid">24035157</pub-id></mixed-citation></ref>
<ref id="r19"><label>19</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><collab>European Task Force on Atopic Dermatitis</collab></person-group>. <article-title>Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis.</article-title> <source>Dermatology</source>. <year>1993</year>;<volume>186</volume>(<issue>1</issue>):<fpage>23</fpage>&#x2013;<lpage>31</lpage>. <pub-id pub-id-type="doi">10.1159/000247298</pub-id><pub-id pub-id-type="pmid">8435513</pub-id></mixed-citation></ref>
<ref id="r20"><label>20</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hanifin</surname><given-names>JM</given-names></name><name><surname>Thurston</surname><given-names>M</given-names></name><name><surname>Omoto</surname><given-names>M</given-names></name><name><surname>Cherill</surname><given-names>R</given-names></name><name><surname>Tofte</surname><given-names>SJ</given-names></name><name><surname>Graeber</surname><given-names>M</given-names></name></person-group>. <article-title>The eczema area and severity index: assessment of reliability in atopic dermatitis. EASI Evaluator Group.</article-title> <source>Exp Dermatol</source>. <year>2001</year>;<volume>10</volume>(<issue>1</issue>):<fpage>11</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1034/j.1600-0625.2001.100102.x</pub-id><pub-id pub-id-type="pmid">11168575</pub-id></mixed-citation></ref>
<ref id="r21"><label>21</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lewis-Jones</surname><given-names>MS</given-names></name><name><surname>Finlay</surname><given-names>Ay</given-names></name></person-group>. <article-title>The children&#x2019;s dermatology life quality index (CDLQI): Initial validation and practical use.</article-title> <source>Br J Dermatol</source>. <year>1995</year>;<volume>132</volume>(<issue>6</issue>):<fpage>942</fpage>&#x2013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1111/j.1365-2133.1995.tb16953.x</pub-id><pub-id pub-id-type="pmid">7662573</pub-id></mixed-citation></ref>
<ref id="r22"><label>22</label><mixed-citation publication-type="web">Cardiff University School of Medicine. Quality of life questionnaires. 2019 Mar. Dostupno na: <ext-link ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://www.cardiff.ac.uk/medicine/resources/quality-of-life-questionnaires">https://www.cardiff.ac.uk/medicine/resources/quality-of-life-questionnaires</ext-link>. Pristupljeno: 26. rujna 2021.</mixed-citation></ref>
<ref id="r23"><label>23</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rehal</surname><given-names>B</given-names></name><name><surname>Armstrong</surname><given-names>A</given-names></name></person-group>. <article-title>Health outcomes measures in atopic dermatitis: A systematic review of trends in disease severity and Quality of-life instruments 1985&#x2013;2010.</article-title> <source>PLoS One</source>. <year>2011</year>;<volume>6</volume>(<issue>4</issue>):<elocation-id>e17520</elocation-id>. <pub-id pub-id-type="doi">10.1371/journal.pone.0017520</pub-id><pub-id pub-id-type="pmid">21533286</pub-id></mixed-citation></ref>
<ref id="r24"><label>24</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Basra</surname><given-names>MKA</given-names></name><name><surname>Sue-Ho</surname><given-names>R</given-names></name><name><surname>Finlay</surname><given-names>AY</given-names></name></person-group>. <article-title>The Family Dermatology Life Quality Index: measuring the secondary impact of skin disease.</article-title> <source>Br J Dermatol</source>. <year>2007</year>;<volume>156</volume>(<issue>3</issue>):<fpage>528</fpage>&#x2013;<lpage>38</lpage>. <pub-id pub-id-type="doi">10.1111/j.1365-2133.2006.07617.x</pub-id><pub-id pub-id-type="pmid">17300244</pub-id></mixed-citation></ref>
<ref id="r25"><label>25</label><mixed-citation publication-type="web">Mediately Baza Lijekova. Dostupno na: <ext-link ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://mediately.co/hr/tools">https://mediately.co/hr/tools</ext-link>. Pristupljeno: 21. rujna 2021.</mixed-citation></ref>
<ref id="r26"><label>26</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eichenfield</surname><given-names>LF</given-names></name><name><surname>Tom</surname><given-names>WL</given-names></name><name><surname>Berger</surname><given-names>TG</given-names></name><name><surname>Krol</surname><given-names>A</given-names></name><name><surname>Paller</surname><given-names>AS</given-names></name><name><surname>Schwarzenberger</surname><given-names>K</given-names></name><etal/></person-group> <article-title>Guidelines of care for the management of atopic dermatitis. Section 2. Management and treatment of atopic dermatitis with topical therapies.</article-title> <source>J Am Acad Dermatol</source>. <year>2014</year>;<volume>71</volume>(<issue>1</issue>):<fpage>116</fpage>&#x2013;<lpage>32</lpage>. <pub-id pub-id-type="doi">10.1016/j.jaad.2014.03.023</pub-id><pub-id pub-id-type="pmid">24813302</pub-id></mixed-citation></ref>
<ref id="r27"><label>27</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gelmetti</surname><given-names>C</given-names></name><name><surname>Wollenberg</surname><given-names>A</given-names></name></person-group>. <article-title>Atopic dermatitis &#x2013; all you can do from the outside.</article-title> <source>Br J Dermatol</source>. <year>2014</year>;<volume>170</volume> <supplement>Suppl 1</supplement>:<fpage>19</fpage>&#x2013;<lpage>24</lpage>. <pub-id pub-id-type="doi">10.1111/bjd.12957</pub-id><pub-id pub-id-type="pmid">24720530</pub-id></mixed-citation></ref>
<ref id="r28"><label>28</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ryan</surname><given-names>C</given-names></name><name><surname>Shaw</surname><given-names>RE</given-names></name><name><surname>Cockerell</surname><given-names>CJ</given-names></name><name><surname>Hand</surname><given-names>S</given-names></name><name><surname>Ghali</surname><given-names>FE</given-names></name></person-group>. <article-title>Novel sodium hypochlorite cleanser shows clinical response and excellent acceptability in the treatment of atopic dermatitis.</article-title> <source>Pediatr Dermatol</source>. <year>2013</year>;<volume>30</volume>(<issue>3</issue>):<fpage>308</fpage>&#x2013;<lpage>15</lpage>. <pub-id pub-id-type="doi">10.1111/pde.12150</pub-id><pub-id pub-id-type="pmid">23617366</pub-id></mixed-citation></ref>
<ref id="r29"><label>29</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wong</surname><given-names>SM</given-names></name><name><surname>Ng</surname><given-names>TG</given-names></name><name><surname>Baba</surname><given-names>R</given-names></name></person-group>. <article-title>Efficacy and safety of sodium hypochlorite (bleach) baths in patients with moderate to severe atopic dermatitis in Malaysia.</article-title> <source>J Dermatol</source>. <year>2013</year>;<volume>40</volume>(<issue>11</issue>):<fpage>874</fpage>&#x2013;<lpage>80</lpage>. <pub-id pub-id-type="doi">10.1111/1346-8138.12265</pub-id><pub-id pub-id-type="pmid">24111816</pub-id></mixed-citation></ref>
<ref id="r30"><label>30</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hon</surname><given-names>KL</given-names></name><name><surname>Tsang</surname><given-names>YC</given-names></name><name><surname>Lee</surname><given-names>VW</given-names></name><name><surname>Pong</surname><given-names>NH</given-names></name><name><surname>Ha</surname><given-names>G</given-names></name><name><surname>Lee</surname><given-names>ST</given-names></name><etal/></person-group> <article-title>Efficacy of sodium hypochlorite (bleach) baths to reduce Staphylococcus aureus colonization in childhood onset moderate-to-severe eczema: A randomized, placebo-controlled cross-over trial.</article-title> <source>J Dermatolog Treat</source>. <year>2016</year>;<volume>27</volume>(<issue>2</issue>):<fpage>156</fpage>&#x2013;<lpage>62</lpage>. <pub-id pub-id-type="doi">10.3109/09546634.2015.1067669</pub-id><pub-id pub-id-type="pmid">26270469</pub-id></mixed-citation></ref>
<ref id="r31"><label>31</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barnes</surname><given-names>TM</given-names></name><name><surname>Kerryn</surname><given-names>AG</given-names></name></person-group>. <article-title>Use of bleach baths for the treatment of infected atopic eczema.</article-title> <source>Australas J Dermatol</source>. <year>2013</year>;<volume>54</volume>(<issue>4</issue>):<fpage>251</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1111/ajd.12015</pub-id><pub-id pub-id-type="pmid">23330843</pub-id></mixed-citation></ref>
<ref id="r32"><label>32</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wollenberg</surname><given-names>A</given-names></name><name><surname>Christen-Zach</surname><given-names>E</given-names></name><name><surname>Taieb</surname><given-names>A</given-names></name><name><surname>Paul</surname><given-names>C</given-names></name><name><surname>Thyssen</surname><given-names>JP</given-names></name><name><surname>de Bruin-Weller</surname><given-names>M</given-names></name><etal/></person-group> <article-title>ETFAD/EADV Eczema task force 2020 position paper of diagnosis and treatment of atopic dermatitis in adults and children.</article-title> <source>J Eur Acad Dermatol Venereol</source>. <year>2020</year>;<volume>34</volume>:<fpage>2717</fpage>&#x2013;<lpage>44</lpage>. <pub-id pub-id-type="doi">10.1111/jdv.16892</pub-id><pub-id pub-id-type="pmid">33205485</pub-id></mixed-citation></ref>
<ref id="r33"><label>33</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Saeki</surname><given-names>H</given-names></name><name><surname>Nakahara</surname><given-names>T</given-names></name><name><surname>Tanaka</surname><given-names>A</given-names></name><name><surname>Kabashima</surname><given-names>K</given-names></name><name><surname>Sugaya</surname><given-names>M</given-names></name><name><surname>Murota</surname><given-names>H</given-names></name><etal/></person-group> <article-title>Clinical practice guidelines for the management of atopic dermatitis 2016.</article-title> <source>J Dermatol</source>. <year>2016</year>;<volume>43</volume>(<issue>10</issue>):<fpage>1117</fpage>&#x2013;<lpage>45</lpage>. <pub-id pub-id-type="doi">10.1111/1346-8138.13392</pub-id><pub-id pub-id-type="pmid">27076388</pub-id></mixed-citation></ref>
<ref id="r34"><label>34</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chalmers</surname><given-names>JR</given-names></name><name><surname>Haines</surname><given-names>RH</given-names></name><name><surname>Bradshaw</surname><given-names>LE</given-names></name><name><surname>Montgomery</surname><given-names>AA</given-names></name><name><surname>Thomas</surname><given-names>KS</given-names></name><name><surname>Brown</surname><given-names>SJ</given-names></name><etal/></person-group> <article-title>Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trial.</article-title> <source>Lancet</source>. <year>2020</year>;<volume>395</volume>(<issue>10228</issue>):<fpage>962</fpage>&#x2013;<lpage>72</lpage>. <pub-id pub-id-type="doi">10.1016/S0140-6736(19)32984-8</pub-id><pub-id pub-id-type="pmid">32087126</pub-id></mixed-citation></ref>
<ref id="r35"><label>35</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barbarot</surname><given-names>S</given-names></name><name><surname>Bernier</surname><given-names>C</given-names></name><name><surname>Deleuran</surname><given-names>M</given-names></name><name><surname>De Raeve</surname><given-names>L</given-names></name><name><surname>Eichenfield</surname><given-names>L</given-names></name><name><surname>El Hachem</surname><given-names>M</given-names></name><etal/></person-group> <article-title>Therapeutic patient education in children with atopic dermatitis: position paper on objectives and recommendation.</article-title> <source>Pediatr Dermatol</source>. <year>2013</year>;<volume>30</volume>(<issue>2</issue>):<fpage>199</fpage>&#x2013;<lpage>206</lpage>. <pub-id pub-id-type="doi">10.1111/pde.12045</pub-id><pub-id pub-id-type="pmid">23461685</pub-id></mixed-citation></ref>
<ref id="r36"><label>36</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stalder</surname><given-names>JF</given-names></name><name><surname>Bernier</surname><given-names>C</given-names></name><name><surname>Ball</surname><given-names>A</given-names></name><name><surname>De Raeve</surname><given-names>L</given-names></name><name><surname>Gieler</surname><given-names>U</given-names></name><name><surname>Deleuran</surname><given-names>M</given-names></name><etal/></person-group> <article-title>Therapeutic patient education in atopic dermatitis: worldwide experience.</article-title> <source>Pediatr Dermatol</source>. <year>2013</year>;<volume>30</volume>(<issue>3</issue>):<fpage>329</fpage>&#x2013;<lpage>34</lpage>. <pub-id pub-id-type="doi">10.1111/pde.12024</pub-id><pub-id pub-id-type="pmid">23406346</pub-id></mixed-citation></ref>
<ref id="r37"><label>37</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pusti&#x0161;ek</surname><given-names>N</given-names></name><name><surname>&#x0160;itum</surname><given-names>M</given-names></name><name><surname>Vurnek &#x017D;ivkovi&#x0107;</surname><given-names>M</given-names></name><name><surname>Ljubojevi&#x0107; Had&#x017E;avdi&#x0107;</surname><given-names>S</given-names></name><name><surname>Vurnek</surname><given-names>M</given-names></name><name><surname>Niseteo</surname><given-names>T</given-names></name></person-group>. <article-title>The significance of structured parental educational intervention on childhood atopic dermatitis: a randomized controlled trial.</article-title> <source>J Eur Acad Dermatol Venereol</source>. <year>2016</year>;<volume>30</volume>:<fpage>806</fpage>&#x2013;<lpage>12</lpage>. <pub-id pub-id-type="doi">10.1111/jdv.13519</pub-id><pub-id pub-id-type="pmid">26616256</pub-id></mixed-citation></ref>
<ref id="r38"><label>38</label><mixed-citation publication-type="web">Ruxolitinib Cream Approved for Short-term Treatment of Atopic Dermatitis. Dostupno na: <ext-link ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://www.ajmc.com/view/ruxolitinib-cream-approved-for-short-term-treatment-of-atopic-dermatitis">https://www.ajmc.com/view/ruxolitinib-cream-approved-for-short-term-treatment-of-atopic-dermatitis</ext-link>. Pristupljeno: 10. o&#x017E;ujka 2022.</mixed-citation></ref>
<ref id="r39"><label>39</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Niedner</surname><given-names>R</given-names></name><name><surname>Iliev</surname><given-names>D</given-names></name></person-group>. <article-title>Dermatological local therapy. How to control eczema.</article-title> <source>MMW Fortschr Med</source>. <year>2001</year>;<volume>143</volume>(<issue>24</issue>):<fpage>33</fpage>&#x2013;<lpage>8</lpage>.<pub-id pub-id-type="pmid">11469016</pub-id></mixed-citation></ref>
<ref id="r40"><label>40</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Long</surname><given-names>CC</given-names></name><name><surname>Finlay</surname><given-names>AY</given-names></name></person-group>. <article-title>The finger-tip unit &#x2014; a new practical measure.</article-title> <source>Clin Exp Dermatol</source>. <year>1991</year>;<volume>16</volume>(<issue>6</issue>):<fpage>444</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1111/j.1365-2230.1991.tb01232.x</pub-id><pub-id pub-id-type="pmid">1806320</pub-id></mixed-citation></ref>
<ref id="r41"><label>41</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Reitamo</surname><given-names>S</given-names></name><name><surname>Rustin</surname><given-names>M</given-names></name><name><surname>Harper</surname><given-names>J</given-names></name><name><surname>Kalimo</surname><given-names>K</given-names></name><name><surname>Rubins</surname><given-names>A</given-names></name><name><surname>Cambazard</surname><given-names>F</given-names></name><etal/></person-group> <article-title>A 4-year follow-up study of atopic dermatitis therapy with 0.1% tacrolimus ointment in children and adult patients.</article-title> <source>Br J Dermatol</source>. <year>2008</year>;<volume>159</volume>:<fpage>942</fpage>&#x2013;<lpage>51</lpage>. <pub-id pub-id-type="doi">10.1111/j.1365-2133.2008.08747.x</pub-id><pub-id pub-id-type="pmid">18637898</pub-id></mixed-citation></ref>
<ref id="r42"><label>42</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sigurgeirsson</surname><given-names>B</given-names></name><name><surname>Boznanski</surname><given-names>A</given-names></name><name><surname>Todd</surname><given-names>G</given-names></name><name><surname>Vertruyen</surname><given-names>A</given-names></name><name><surname>Schuttelaar</surname><given-names>ML</given-names></name><name><surname>Zhu</surname><given-names>X</given-names></name><etal/></person-group> <article-title>Safety and efficacy of pimecrolimus in atopic dermatitis: a 5-year randomized trial.</article-title> <source>Pediatrics</source>. <year>2015</year>;<volume>135</volume>:<fpage>597</fpage>&#x2013;<lpage>606</lpage>. <pub-id pub-id-type="doi">10.1542/peds.2014-1990</pub-id><pub-id pub-id-type="pmid">25802354</pub-id></mixed-citation></ref>
<ref id="r43"><label>43</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alexander</surname><given-names>H</given-names></name><name><surname>Paller</surname><given-names>AS</given-names></name><name><surname>Traidl-Hoffmann</surname><given-names>C</given-names></name><name><surname>Beck</surname><given-names>LA</given-names></name><name><surname>De Benedetto</surname><given-names>A</given-names></name><name><surname>Dhar</surname><given-names>S</given-names></name></person-group>. <article-title>The role of bacterial skin infections in atopic dermatitis: expert statement and review from the International Eczema Council Skin Infection Group.</article-title> <source>Br J Dermatol</source>. <year>2020</year>;<volume>182</volume>(<issue>6</issue>):<fpage>1331</fpage>&#x2013;<lpage>42</lpage>. <pub-id pub-id-type="doi">10.1111/bjd.18643</pub-id><pub-id pub-id-type="pmid">31677162</pub-id></mixed-citation></ref>
<ref id="r44"><label>44</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sidbury</surname><given-names>R</given-names></name><name><surname>Davis</surname><given-names>DM</given-names></name><name><surname>Cohen</surname><given-names>DE</given-names></name><name><surname>Cordoro</surname><given-names>KM</given-names></name><name><surname>Berger</surname><given-names>TG</given-names></name><name><surname>Bergman</surname><given-names>JN</given-names></name><etal/></person-group> <article-title>Guidelines of care for the management of atopic dermatitis. Section 3. Management and treatment of atopic dermatitis with phototerapy and systemic agents.</article-title> <source>J Am Acad Dermatol</source>. <year>2014</year>;<volume>71</volume>(<issue>2</issue>):<fpage>327</fpage>&#x2013;<lpage>49</lpage>. <pub-id pub-id-type="doi">10.1016/j.jaad.2014.03.030</pub-id><pub-id pub-id-type="pmid">24813298</pub-id></mixed-citation></ref>
<ref id="r45"><label>45</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Young</surname><given-names>A</given-names></name></person-group>. <article-title>Carcinogenicity of UVB phototherapy assesed.</article-title> <source>Lancet</source>. <year>1995</year>;<volume>346</volume>:<fpage>1431</fpage>&#x2013;<lpage>2</lpage>. <pub-id pub-id-type="doi">10.1016/S0140-6736(95)92617-8</pub-id></mixed-citation></ref>
<ref id="r46"><label>46</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moela</surname><given-names>T</given-names></name><name><surname>Soter</surname><given-names>NA</given-names></name><name><surname>Lim</surname><given-names>HW</given-names></name></person-group>. <article-title>Soter NA, Lim HW. Are topical corticosteroids useful adjunctive therapy for the treatment of psoriasis with ultraviolet radiation? A review of the literature.</article-title> <source>Arch Dermatol</source>. <year>1991</year>;<volume>127</volume>:<fpage>1708</fpage>&#x2013;<lpage>13</lpage>. <pub-id pub-id-type="doi">10.1001/archderm.1991.01680100108015</pub-id><pub-id pub-id-type="pmid">1952979</pub-id></mixed-citation></ref>
<ref id="r47"><label>47</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Paul</surname><given-names>BS</given-names></name><name><surname>Momtaz</surname><given-names>K</given-names></name><name><surname>Stern</surname><given-names>RS</given-names></name><name><surname>Arndt</surname><given-names>KA</given-names></name><name><surname>Parrish</surname><given-names>JA</given-names></name></person-group>. <article-title>Combined methotreaxate-ultraviolet B therapy in the treatment of psoriasis.</article-title> <source>J Am Acad Dermatol</source>. <year>1982</year>;<volume>7</volume>:<fpage>758</fpage>&#x2013;<lpage>62</lpage>. <pub-id pub-id-type="doi">10.1016/S0190-9622(82)70157-4</pub-id><pub-id pub-id-type="pmid">7174914</pub-id></mixed-citation></ref>
<ref id="r48"><label>48</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Seccombe</surname><given-names>E</given-names></name><name><surname>Wynne</surname><given-names>MD</given-names></name><name><surname>Clancy</surname><given-names>C</given-names></name><name><surname>Godfrey</surname><given-names>KM</given-names></name><name><surname>Fityan</surname><given-names>A</given-names></name></person-group>. <article-title>A retrospective review of phototherapy in children, at a tertiary paediatric unit.</article-title> <source>Photodermatol Photoimmunol Photomed</source>. <year>2021</year>;<volume>37</volume>:<fpage>34</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1111/phpp.12604</pub-id><pub-id pub-id-type="pmid">32860720</pub-id></mixed-citation></ref>
<ref id="r49"><label>49</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hunjan</surname><given-names>MK</given-names></name><name><surname>Brockley</surname><given-names>JR</given-names></name><name><surname>Buka</surname><given-names>R</given-names></name><name><surname>Ramesh</surname><given-names>R</given-names></name></person-group>. <article-title>Treatment of paediatric eczema with narrowband ultraviolet light B therapy.</article-title> <source>Photodermatol Photoimmunol Photomed</source>. <year>2021</year>;<volume>37</volume>:<fpage>105</fpage>&#x2013;<lpage>10</lpage>. <pub-id pub-id-type="doi">10.1111/phpp.12615</pub-id><pub-id pub-id-type="pmid">33012054</pub-id></mixed-citation></ref>
<ref id="r50"><label>50</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Feld</surname><given-names>M</given-names></name><name><surname>Garcia</surname><given-names>R</given-names></name><name><surname>Buddenkotte</surname><given-names>J</given-names></name><name><surname>Katayama</surname><given-names>S</given-names></name><name><surname>Lewis</surname><given-names>K</given-names></name><name><surname>Muirhead</surname><given-names>GI</given-names></name><etal/></person-group> <article-title>The pruritus- and TH2-associated cytokine IL-31 promotes growth of sensory nerves.</article-title> <source>J Allergy Clin Immunol</source>. <year>2016</year>;<volume>138</volume>(<issue>2</issue>):<fpage>500</fpage>&#x2013;<lpage>8.e24</lpage>. <pub-id pub-id-type="doi">10.1016/j.jaci.2016.02.020</pub-id><pub-id pub-id-type="pmid">27212086</pub-id></mixed-citation></ref>
<ref id="r51"><label>51</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Berth-Jones</surname><given-names>J</given-names></name><name><surname>Exton</surname><given-names>LS</given-names></name><name><surname>Ladoyanni</surname><given-names>E</given-names></name><name><surname>Mohd Mustapa</surname><given-names>MF</given-names></name><name><surname>Tebbs</surname><given-names>VM</given-names></name><name><surname>Yesudian</surname><given-names>PD</given-names></name></person-group>. <article-title>British Association of Dermatologists guidelines for the safe and effective prescribing of oral ciclosporin in dermatology 2018.</article-title> <source>Br J Dermatol</source>. <year>2019</year>;<volume>180</volume>(<issue>6</issue>):<fpage>1312</fpage>&#x2013;<lpage>38</lpage>. <pub-id pub-id-type="doi">10.1111/bjd.17587</pub-id><pub-id pub-id-type="pmid">30653672</pub-id></mixed-citation></ref>
<ref id="r52"><label>52</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Holst</surname><given-names>R</given-names></name><name><surname>Gieler</surname><given-names>U</given-names></name><name><surname>Kahle</surname><given-names>J</given-names></name><name><surname>Kapp</surname><given-names>A</given-names></name><name><surname>Nast</surname><given-names>A</given-names></name><name><surname>Nemat</surname><given-names>K</given-names></name><etal/></person-group> <article-title>S2k guideline on diagnosis and treatment of atopic dermatitis &#x2013; short version.</article-title> <source>Allergo J Int</source>. <year>2016</year>;<volume>25</volume>:<fpage>82</fpage>&#x2013;<lpage>95</lpage>. <pub-id pub-id-type="doi">10.1007/s40629-016-0110-8</pub-id><pub-id pub-id-type="pmid">27239428</pub-id></mixed-citation></ref>
<ref id="r53"><label>53</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Davari</surname><given-names>DR</given-names></name><name><surname>Nieman</surname><given-names>EL</given-names></name><name><surname>McShane</surname><given-names>DB</given-names></name><name><surname>Morrell</surname><given-names>DS</given-names></name></person-group>. <article-title>Current Perspectives on the Management of Infantile Atopic Dermatitis.</article-title> <source>J Asthma Allergy</source>. <year>2020</year>;<volume>13</volume>:<fpage>563</fpage>&#x2013;<lpage>73</lpage>. <pub-id pub-id-type="doi">10.2147/JAA.S246175</pub-id><pub-id pub-id-type="pmid">33177843</pub-id></mixed-citation></ref>
<ref id="r54"><label>54</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vestergaard</surname><given-names>C</given-names></name><name><surname>Wollenberg</surname><given-names>A</given-names></name><name><surname>Barbarot</surname><given-names>S</given-names></name><name><surname>Christen-Zaech</surname><given-names>S</given-names></name><name><surname>Deleuran</surname><given-names>M</given-names></name><name><surname>Spuls</surname><given-names>P</given-names></name><etal/></person-group> <article-title>European task force on atopic dermatitis position paper: treatment of parental atopic dermatitis during preconception, pregnancy and lactation period.</article-title> <source>J Eur Acad Dermatol Venereol</source>. <year>2019</year>;<volume>33</volume>:<fpage>1644</fpage>&#x2013;<lpage>59</lpage>. <pub-id pub-id-type="doi">10.1111/jdv.15709</pub-id><pub-id pub-id-type="pmid">31231864</pub-id></mixed-citation></ref>
<ref id="r55"><label>55</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chalmers</surname><given-names>RJ</given-names></name><name><surname>Kirby</surname><given-names>B</given-names></name><name><surname>Smith</surname><given-names>A</given-names></name><name><surname>Burrows</surname><given-names>P</given-names></name><name><surname>Little</surname><given-names>R</given-names></name><name><surname>Horan</surname><given-names>M</given-names></name><etal/></person-group> <article-title>Raplacement of routine liver biopsy by procollagen III aminopeptide for monitoring patients with psoriasis receiving long-term methotrexate: a multicentre audit and health economic analysis.</article-title> <source>Br J Dermatol</source>. <year>2005</year>;<volume>152</volume>:<fpage>444</fpage>&#x2013;<lpage>80</lpage>. <pub-id pub-id-type="doi">10.1111/j.1365-2133.2005.06422.x</pub-id><pub-id pub-id-type="pmid">15787812</pub-id></mixed-citation></ref>
<ref id="r56"><label>56</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yin</surname><given-names>LVC</given-names></name><name><surname>Cadwaladr</surname><given-names>B</given-names></name><name><surname>Chen</surname><given-names>KS</given-names></name><name><surname>Yesudian</surname><given-names>PD</given-names></name></person-group>. <article-title>Subcutaneous methotrexate in the management of atopic dermatitis: A series of 12 patients.</article-title> <source>Am Acad Dermatol.</source> <year>2015</year>;<volume>72</volume>: <pub-id pub-id-type="doi">10.1016/j.jaad.2015.02.310</pub-id></mixed-citation></ref>
<ref id="r57"><label>57</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Drucker</surname><given-names>AM</given-names></name><name><surname>Eyerich</surname><given-names>K</given-names></name><name><surname>de Bruin-Weller</surname><given-names>MS</given-names></name><name><surname>Thyssen</surname><given-names>JP</given-names></name><name><surname>Spuls</surname><given-names>PI</given-names></name><name><surname>Irvine</surname><given-names>AD</given-names></name><etal/></person-group> <article-title>Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement.</article-title> <source>Br J Dermatol</source>. <year>2018</year>;<volume>178</volume>(<issue>3</issue>):<fpage>768</fpage>&#x2013;<lpage>75</lpage>. <pub-id pub-id-type="doi">10.1111/bjd.15928</pub-id><pub-id pub-id-type="pmid">28865094</pub-id></mixed-citation></ref>
<ref id="r58"><label>58</label><mixed-citation publication-type="web">Dupixent (dupilumab) injection (package insert). United States Food and Drug Published June 2019. Dostupno na: <ext-link ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761055s014lbl.pdf">https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761055s014lbl.pdf</ext-link>. Pristupljeno: 1 listopada 2021.</mixed-citation></ref>
<ref id="r59"><label>59</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Beck</surname><given-names>LA</given-names></name><name><surname>Tha&#x00E7;i</surname><given-names>D</given-names></name><name><surname>Hamilton</surname><given-names>JD</given-names></name><name><surname>Graham</surname><given-names>NM</given-names></name><name><surname>Bieber</surname><given-names>T</given-names></name><name><surname>Rocklin</surname><given-names>R</given-names></name><etal/></person-group> <article-title>Dupilumab treatment in adults with moderate-to-severe atopic dermatitis.</article-title> <source>N Engl J Med</source>. <year>2014</year>;<volume>371</volume>:<fpage>130</fpage>&#x2013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1056/NEJMoa1314768</pub-id><pub-id pub-id-type="pmid">25006719</pub-id></mixed-citation></ref>
<ref id="r60"><label>60</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tha&#x00E7;i</surname><given-names>D</given-names></name><name><surname>Simpson</surname><given-names>EL</given-names></name><name><surname>Beck</surname><given-names>LA</given-names></name><name><surname>Bieber</surname><given-names>T</given-names></name><name><surname>Blauvelt</surname><given-names>A</given-names></name><name><surname>Papp</surname><given-names>K</given-names></name><etal/></person-group> <article-title>Efficacy and safety of dupilumab in adults with moderate to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose ranging phase 2b trial.</article-title> <source>Lancet</source>. <year>2016</year>;<volume>387</volume>:<fpage>40</fpage>&#x2013;<lpage>52</lpage>. <pub-id pub-id-type="doi">10.1016/S0140-6736(15)00388-8</pub-id><pub-id pub-id-type="pmid">26454361</pub-id></mixed-citation></ref>
<ref id="r61"><label>61</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wollenberg</surname><given-names>A</given-names></name><name><surname>Blauvelt</surname><given-names>A</given-names></name><name><surname>Guttman-Yassky</surname><given-names>E</given-names></name><name><surname>Worm</surname><given-names>M</given-names></name><name><surname>Lynde</surname><given-names>C</given-names></name><name><surname>Lacour</surname><given-names>JP</given-names></name><etal/></person-group> <article-title>Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2).</article-title> <source>Br J Dermatol</source>. <year>2021</year>;<volume>184</volume>(<issue>3</issue>):<fpage>437</fpage>&#x2013;<lpage>49</lpage>. <pub-id pub-id-type="doi">10.1111/bjd.19574</pub-id><pub-id pub-id-type="pmid">33000465</pub-id></mixed-citation></ref>
<ref id="r62"><label>62</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wollenberg</surname><given-names>A</given-names></name><name><surname>Blauvelt</surname><given-names>A</given-names></name><name><surname>Guttman-Yassky</surname><given-names>E</given-names></name><name><surname>Worm</surname><given-names>M</given-names></name><name><surname>Lynde</surname><given-names>C</given-names></name><name><surname>Lacour</surname><given-names>JP</given-names></name><etal/></person-group> <article-title>Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2).</article-title> <source>Br J Dermatol</source>. <year>2021</year>;<volume>184</volume>(<issue>3</issue>):<fpage>437</fpage>&#x2013;<lpage>49</lpage>. <pub-id pub-id-type="doi">10.1111/bjd.19574</pub-id><pub-id pub-id-type="pmid">33000465</pub-id></mixed-citation></ref>
<ref id="r63"><label>63</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Simpson</surname><given-names>EL</given-names></name><name><surname>Lacour</surname><given-names>JP</given-names></name><name><surname>Spelman</surname><given-names>L</given-names></name><name><surname>Galimberti</surname><given-names>R</given-names></name><name><surname>Eichenfield</surname><given-names>LF</given-names></name><name><surname>Bissonnette</surname><given-names>R</given-names></name><etal/></person-group> <article-title>Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials.</article-title> <source>Br J Dermatol</source>. <year>2020</year>;<volume>183</volume>:<fpage>242</fpage>&#x2013;<lpage>55</lpage>. <pub-id pub-id-type="doi">10.1111/bjd.18898</pub-id><pub-id pub-id-type="pmid">31995838</pub-id></mixed-citation></ref>
<ref id="r64"><label>64</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Guttman-Yassky</surname><given-names>E</given-names></name><name><surname>Tha&#x00E7;i</surname><given-names>D</given-names></name><name><surname>Pangan</surname><given-names>AL</given-names></name><name><surname>Chih-Ho Hong</surname><given-names>H</given-names></name><name><surname>Papp</surname><given-names>KA</given-names></name><name><surname>Reichet</surname><given-names>K</given-names></name><etal/></person-group> <article-title>Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial.</article-title> <source>J Allergy Clin Immunol</source>. <year>2020</year>;<volume>145</volume>(<issue>3</issue>):<fpage>877</fpage>&#x2013;<lpage>84</lpage>. <pub-id pub-id-type="doi">10.1016/j.jaci.2019.11.025</pub-id><pub-id pub-id-type="pmid">31786154</pub-id></mixed-citation></ref>
<ref id="r65"><label>65</label><mixed-citation publication-type="web">Pfizer provides update on u. <italic>S.</italic> FDA review of abrocitinib and xeljanz&#x00AE; filings | pfpfizeruscom. Dostupno na: <ext-link ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-provides-update-us-fda-review-abrocitinib-and">https://www.pfizer.com/news/press-release/press-release-detail/pfizer-provides-update-us-fda-review-abrocitinib-and</ext-link>. Pristupljeno 1. listopada 2021.</mixed-citation></ref>
<ref id="r66"><label>66</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Silverberg</surname><given-names>JI</given-names></name><name><surname>Simpson</surname><given-names>EL</given-names></name><name><surname>Thyssen</surname><given-names>JP</given-names></name><name><surname>Gooderham</surname><given-names>M</given-names></name><name><surname>Chan</surname><given-names>G</given-names></name><name><surname>Feeney</surname><given-names>C</given-names></name><etal/></person-group> <article-title>Efficacy and Safety of Abrocitinib in Patients With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial.</article-title> <source>JAMA Dermatol</source>. <year>2020</year>;<volume>156</volume>(<issue>8</issue>):<fpage>863</fpage>&#x2013;<lpage>73</lpage>. <pub-id pub-id-type="doi">10.1001/jamadermatol.2020.1406</pub-id><pub-id pub-id-type="pmid">32492087</pub-id></mixed-citation></ref>
<ref id="r67"><label>67</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Montgomery</surname><given-names>K</given-names></name><name><surname>Thompson</surname><given-names>AR</given-names></name></person-group>. <article-title>The potential role of mindfulness in psychosocial support for dermatology patients.</article-title> <source>Clin Dermatol</source>. <year>2018</year>;<volume>36</volume>(<issue>6</issue>):<fpage>743</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1016/j.clindermatol.2018.08.010</pub-id><pub-id pub-id-type="pmid">30446198</pub-id></mixed-citation></ref>
</ref-list>
</back>
</article>
