Omalizumab treatment in adolescents with chronic spontaneous urticaria: Efficacy and safety

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Demir, Ö.F. Akmeşe, H. Erbay, A. Taylan-Özkan, K.Y. Mumcuoğlu" "autores" => array:5 [ 0 => array:2 [ "nombre" => "E." "apellidos" => "Demir" ] 1 => array:2 [ "nombre" => "Ö.F." "apellidos" => "Akmeşe" ] 2 => array:2 [ "nombre" => "H." "apellidos" => "Erbay" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Taylan-Özkan" ] 4 => array:2 [ "nombre" => "K.Y." 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Wang, L. Jin, S.-X. Liu, K. Fan, M.-L. Qin, S.-Q. Yu" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Y." "apellidos" => "Wang" ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Jin" ] 2 => array:2 [ "nombre" => "S.-X." "apellidos" => "Liu" ] 3 => array:2 [ "nombre" => "K." "apellidos" => "Fan" ] 4 => array:2 [ "nombre" => "M.-L." "apellidos" => "Qin" ] 5 => array:2 [ "nombre" => "S.-Q." "apellidos" => "Yu" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054620300264?idApp=UINPBA00004N" "url" => "/03010546/0000004800000004/v2_202012180835/S0301054620300264/v2_202012180835/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "Omalizumab treatment in adolescents with chronic spontaneous urticaria: Efficacy and safety" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "368" "paginaFinal" => "373" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M. Ocak, O. Soyer, B. Buyuktiryaki, B.E. Sekerel, U.M. Sahiner" "autores" => array:5 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Ocak" ] 1 => array:2 [ "nombre" => "O." "apellidos" => "Soyer" ] 2 => array:2 [ "nombre" => "B." "apellidos" => "Buyuktiryaki" ] 3 => array:2 [ "nombre" => "B.E." "apellidos" => "Sekerel" ] 4 => array:4 [ "nombre" => "U.M." "apellidos" => "Sahiner" "email" => array:1 [ 0 => "umsahner@yahoo.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Hacettepe University Faculty of Medicine, Department of Pediatric Allergy, 06100 Ankara, Turkey" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1167 "Ancho" => 1667 "Tamanyo" => 72175 ] ] "descripcion" => array:1 [ "en" => "The number of complete responders by each dose i.e., seven patients responded at first dose, six patients responded at second dose etc." ] ] ] "textoCompleto" => "IntroductionChronic spontaneous urticaria (CSU) is a disease characterized by itchy hives and/or angioedema that occur daily or almost daily for at least six weeks without any external stimulus.<a class="elsevierStyleCrossRef" href="#bib0180">1</a> Inducible urticaria and urticarial vasculitis form the other types of chronic urticaria (CU).<a class="elsevierStyleCrossRef" href="#bib0185">2</a> Chronic urticaria in children may affect up to 3% of the pediatric population.<a class="elsevierStyleCrossRef" href="#bib0190">3</a> According to current guidelines, the treatment for chronic urticaria involves H1 antihistamines as the first-line, which can be increased up to fourfold the licensed dosage. However, one-third of adults and more than 10% of children do not respond to high dose H1 antihistamines and require third-line treatment such as omalizumab, cyclosporine, and montelukast.<a class="elsevierStyleCrossRefs" href="#bib0195">4,5</a> Omalizumab is a recombinant humanized monoclonal anti-IgE antibody that binds to free IgE and indirectly downregulates FcɛRI receptor expression on mast cells and basophils.<a class="elsevierStyleCrossRef" href="#bib0205">6</a> Omalizumab was approved by the FDA in March 2014 for CSU in adults and adolescents 12 years of age and older in cases of antihistamine refractoriness.<a class="elsevierStyleCrossRef" href="#bib0210">7</a> A multicenter study from Italy included 322 patients with refractory CSU aged 15–83 years showed that omalizumab is a well-tolerated and effective therapy for this wide age range population.<a class="elsevierStyleCrossRef" href="#bib0215">8</a>Even though the current literature on the treatment of CSU with omalizumab is rapidly increasing, information about the efficacy and safety of omalizumab treatment in children with CSU is limited. Large pivotal phase III trials have demonstrated a good safety and efficacy profile.<a class="elsevierStyleCrossRefs" href="#bib0220">9–11</a> A recent systematic literature review of omalizumab treatment of children with CSU less than 12 years of age suggested that omalizumab could be a safe treatment option in this age group.<a class="elsevierStyleCrossRef" href="#bib0235">12</a> There is also a published information gap on the use of omalizumab in the subgroup of patients from 12 to younger than 18 years old with CSU. A study that analyzed a total of 39 adolescents with CSU in three phase III studies reported potential differences in baseline demographic and clinical characteristics between adult and adolescent patients.<a class="elsevierStyleCrossRef" href="#bib0240">13</a> Considering these limited data in children, this study aimed to evaluate the effectiveness and safety of omalizumab in adolescents with recalcitrant chronic spontaneous urticaria.MethodsThis study was conducted at Hacettepe University School of Medicine, Department of Pediatric Allergy, between January 2015 and August 2018 and was approved by the Institutional Review Board of Hacettepe University. Informed written consent was obtained from all patients and parents.Chronic urticaria was the presence of recurrent urticaria, angioedema, or both, for six weeks or longer. Patients without a clinical response who were treated with second-generation antihistamines at a four-fold increased dose were defined as refractory CSU.<a class="elsevierStyleCrossRef" href="#bib0245">14</a> Twenty-nine refractory CSU patients from 12 to 18 years old with a diagnosis of symptomatic CSU were included in the study population. The study had both retrospective and prospective aspects. First, the medical reports of CSU patients were evaluated retrospectively. Then the clinical status of each patient was evaluated firstly by a telephone visit and then by hospital visits. Urticaria activity score of 7 (UAS7) was used to evaluate disease activity. Itching severity and urticarial plaque number were graded and the sum of seven days of UAS gave the UAS7.<a class="elsevierStyleCrossRef" href="#bib0180">1</a> All the patients had an UAS7 of 16 or greater. Patients were treated with 300mg omalizumab subcutaneously once every four weeks. The treatment continued until the patient had no symptoms for three months. If this time was less than six months, the total duration of the treatment was completed to six months. The patients were evaluated at each visit for the effectiveness of the therapy.The degree of response was classified into complete responders (UAS7=0), partial responders (UAS7≤6 but not 0) and non-responders (UAS7>6).<a class="elsevierStyleCrossRef" href="#bib0250">15</a> Relapse was considered to be the reappearance of CSU symptoms after the end of the omalizumab treatment.We also evaluated demographic and clinical features of patients, including gender, age at onset, frequency and duration of symptoms, presence of angioedema, concomitant symptoms other than urticaria or angioedema, personal and familial history of allergic diseases, chronic diseases and laboratory findings. Triggering factors that increase symptoms such as cold, heat, sunlight, exercise, stress, infection, food additives, menstrual cycle, and drugs were questioned. Medications (H1 receptor antagonists, H2 receptor antagonists, oral corticosteroids, leukotriene receptor antagonists (LTRA), immunosuppressants) administered before omalizumab treatment, treatments administered concurrently with omalizumab and side effects during omalizumab treatment were recorded.Complete blood cell count, eosinophil percentage, total immunoglobulin E (IgE), specific IgE levels, C-reactive protein level, erythrocyte sedimentation rate, C3 and C4 levels, thyroid hormones, thyroid autoantibodies, antinuclear antibody, anti-double-stranded DNA antibody, urine analysis and stool examination for parasites were reviewed from the database.<a class="elsevierStyleCrossRefs" href="#bib0255">16,17</a> The normal limits of the laboratory results were evaluated as follows: thyroid-stimulating hormone: 0.38–5.33μIU/mL; thyroxine: 7.86–14.41pmol/L; sedimentation rate: 0–20mm/h; C-reactive protein: 0–0.8mg/dl; C3: 79–152mg/dl; C4: 16–38mg/dl.The data were analyzed with SPSS statistical software, version 20.0 (SPSS Inc, Chicago, IL, USA). The proportions in different groups were compared by using the Pearson χ2 test or the Fisher exact test. All numeric variables were non-normally distributed and compared with Mann–Whitney U or Kruskal–Wallis tests, when appropriate; the results were given as median and interquartile ranges (IQR). A p-value of 0.05 indicated a statistically significant result.<a class="elsevierStyleCrossRef" href="#bib0265">18</a>ResultsA total of 29 patients who met the study criteria were evaluated. The patients were predominantly females (n=16; 55%). The median age and symptom onset age of the patients were 15.2 years (IQR, 12.8–16.5 years) and 14.0 years (IQR, 11.8–15.9 years), respectively. The median duration of urticaria before omalizumab treatment was eight months (IQR, 4–24 months). Eleven (37.9%) patients had angioedema and 10 (34.5%) patients had concomitant allergic diseases. A family history of allergic diseases was present in seven (24.1%) patients. The characteristics of the patients are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Triggering factors that increased the symptoms of patients are given in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia>High antinuclear antibody titers (>1/160) were found in 15/26 (57.6%) patients but none of them were diagnosed as having the rheumatologic disease during the study period. Skin prick tests (SPT) and autolog serum skin testing were performed on only 10 patients due to the use of antihistamines. Autolog serum skin testing was positive in 2/10 (20%) patients and SPT was positive in 5/10 (50%) patients. The leukocyte and eosinophil counts, C3 and C4 levels were within normal limits. All the patients had normal thyroid function tests and negative thyroid autoantibody results. Stool parasite examination was positive in 2/17 (11.7%) patients and Blastocystis hominis eggs were detected (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Medications used before the start of omalizumab treatment were H1 antihistamines (100%), H2 receptor antagonists (34.5%), montelukast (37.9%) and oral corticosteroids (17.2%) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The median age of onset of omalizumab was 15.4 years (IQR 12.9–16.9 years). The median symptom duration was 12 months (IQR 6.5–27.5 months) before the omalizumab treatment. A total of 28 (96.5%) [26 (89.6%) complete, two (6.9%) partial] patients achieved remission with omalizumab. The number of patients who had more than a 30% decline in UAS7 within 12 weeks of treatment is indicated in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> according to the weeks. At week 12, after three doses of omalizumab, complete response was reported in 17 (58%) patients (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The median time to achieve a complete response was 7.5 (IQR 3–14.7) weeks. One (3.5%) patient showed no significant change in UAS7 at week 12 so omalizumab was discontinued and the case was accepted as a non-responder. The omalizumab dose interval was extended to six weeks in eight (27.5%) patients.<elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia>The adverse effect was observed in only one (3.4%) patient as angioedema after the third dose of omalizumab and asymptomatic two months. Allergy skin tests were performed with omalizumab solution and an intradermal skin test at a dilution of 1:10 was detected positive with a wheal of 10mm. There was no effect of pre-treatment symptom duration (p=0.167) and associated angioedema on symptom disappearance time (p=0.41). Twenty-three of 26 patients who had a complete response and completed the treatment were followed-up for a median of 18 months (IQR, 13–27 months). Relapse was observed in three (13%) patients. The relapse times of three patients were 4, 6, and 12 months after the end of omalizumab therapy.DiscussionThe omalizumab treatment in adolescents with CSU seems to be highly effective. Nearly 90% of our patients showed a complete response rate and another 6.5% showed a partial response. We experienced only one adverse effect as angioedema, which did not preclude the continuation of the therapy. Within a one-and-a-half-year follow-up period after cessation of omalizumab treatment, 13% of the children with CSU relapsed. Relapses occurred within the first year after cessation of treatment. Omalizumab is considered as an effective and safe treatment for CSU in adolescents.There are few studies in the literature on the use of omalizumab in children with CSU. Most studies of omalizumab in adult patients guide this treatment option in adolescents and children. Three randomized, double-blind, placebo-controlled clinical trials, ASTERIA I,<a class="elsevierStyleCrossRef" href="#bib0225">10</a> ASTERIA II<a class="elsevierStyleCrossRef" href="#bib0220">9</a> and GLACIAL,<a class="elsevierStyleCrossRef" href="#bib0230">11</a> demonstrated the efficacy and safety of omalizumab in adults. In these three pivotal studies, ASTERIA I and ASTERIA II included patients who remained symptomatic with H1-antihistamines at approved doses but GLACIAL enrolled patients who were symptomatic despite the suggested combination therapies (up to four-fold dose of H1-antihistamines, plus H2 antihistamines, LTRAs or both H2-antihistamines and LTRAs). Although the methodologies of the studies were different, the similarities in efficacy were emphasized.<a class="elsevierStyleCrossRefs" href="#bib0220">9–11</a> In our study, the inclusion criteria were similar to GLACIAL and the number of previous CSU medications was a median of two (IQR, 1–3). Because the adolescents were not the focus of these study populations, they had not been evaluated separately for the efficacy of omalizumab. In a clinical review that had 975 patients with CSU, 39 (4%) were from 12 to under 18 years old. That statistical study had the highest number of adolescent cases in the literature. The mean age of the adolescent group was 15.1 years and most patients were female (69.2%).<a class="elsevierStyleCrossRef" href="#bib0240">13</a> Similarly, the mean age of the group in our study was 15.2 years and most patients were female (56.2%).A systematic review of 84 observational studies reported the effectiveness of different dosing regimens, such as 150mg/dose every two weeks or every four weeks (Q4W), but most frequently, omalizumab was commenced at 300mg/dose (62.7%) at a frequency of Q4W (83.9%).<a class="elsevierStyleCrossRef" href="#bib0270">19</a> Another study that described response patterns using the data of three pivotal omalizumab trials demonstrated that 300mg of omalizumab could control CSU symptoms well. <a class="elsevierStyleCrossRef" href="#bib0250">15</a> In our study, we initiated with 300mg/dose Q4W. The omalizumab dose interval was prolonged to six weeks in eight (27.5%) patients since they showed lower UAS7 scores and good responses. It should be noted that individualizing the dose and frequency may increase treatment success.UAS7 provides semi-quantitative information on disease activity between clinical visits.<a class="elsevierStyleCrossRef" href="#bib0275">20</a> There are variations among studies on the definition of response to treatment in CSU. In most of the studies, the degree of response was classified into complete responders (UAS7=0), partial responders (UAS7≤6 but not 0) and non-responders (UAS>6).<a class="elsevierStyleCrossRef" href="#bib0280">21</a> In our study, we also evaluated our patients according to previous definitions. In ASTERIA II the median time to achieve complete response was eight weeks for the patients who received 300mg omalizumab. The median time for complete response was 12 and 13 weeks in the studies ASTERIA I and GLACIAL for 300mg omalizumab, respectively. At week 12, patients treated with 300mg omalizumab reported UAS7=0; 35.8% for ASTERIA I, 44.3% for ASTERIA II and 33.7% for GLACIAL.<a class="elsevierStyleCrossRefs" href="#bib0220">9–11</a> An earlier study by Sussman et al. found a complete response rate of 79% for any point during the study.<a class="elsevierStyleCrossRef" href="#bib0285">22</a> A recent retrospective study by Nettis et al. reported a complete response of 67% <a class="elsevierStyleCrossRef" href="#bib0290">23</a> In the present study, we found an overall response rate of 96.5%, with only one patient not responding. By week 12, 96.5% of our patients achieved a response (partial or complete), however, 31% of patients gained complete response after the 12th week. These findings were similar to previous adult studies. After the initiation of omalizumab, the possibility of response at different time points may be observed. The time to respond to treatment may vary in adults and children.In the literature, there is no marked consensus related to the time of discontinuation of omalizumab treatment. Metz et al.<a class="elsevierStyleCrossRef" href="#bib0295">24</a> reported that omalizumab treatment could be continued for 6–12 months. However, the general approach is to specify the treatment period according to the patient's clinical response.<a class="elsevierStyleCrossRef" href="#bib0300">25</a> Some patients may experience relapse after cessation of omalizumab. It is important to know when the medication can be stopped and whether the patients have to be retreated in the event of recurrence of symptoms. A study investigating patients who were at risk of relapse after stopping omalizumab treatment suggested that the speed of symptom return was independent of baseline characteristics of the patients, including duration of CSU, angioedema, previous treatments received, or patient demographics. However, they considered that symptom return could be estimated based on baseline UAS7 and early treatment response.<a class="elsevierStyleCrossRef" href="#bib0305">26</a> In a retrospective study that included 31 patients with refractory CSU it was found that the mean time to achieve complete therapy response was a statistically significant difference between the time to complete response with the first and third course. It was faster as the number of retreatments increased.<a class="elsevierStyleCrossRef" href="#bib0310">27</a>A multicenter, randomized, double-blind, placebo-controlled study that enrolled patients with antihistamine-resistant CSU was designed to answer questions regarding the benefit of omalizumab treatment after 24 and 48 weeks. It was suggested that continuous treatment with omalizumab was beneficial both for preventing the return of symptoms as well as for achieving sustained control through 48 weeks of treatment.<a class="elsevierStyleCrossRef" href="#bib0315">28</a> In the present study, we continued treatment for at least six months. Only three of our patients experienced a relapse at 4, 6, and 12 months after the end of omalizumab therapy.The safety of omalizumab has been evaluated in numerous adult studies. The most common adverse events reported were headache (6.1%), sinusitis (4.9%), arthralgia (2.9%) and injection-site reaction (2.7%).<a class="elsevierStyleCrossRef" href="#bib0320">29</a> There were no reports of omalizumab related anaphylaxis in three pivotal studies, ASTERIA I, ASTERIA II or GLACIAL.<a class="elsevierStyleCrossRef" href="#bib0325">30</a> However, one case was reported who experienced anaphylaxis 36h after omalizumab administration.<a class="elsevierStyleCrossRef" href="#bib0330">31</a> Angioedema and urticaria following omalizumab for CSU were stated in four cases.<a class="elsevierStyleCrossRef" href="#bib0335">32</a> In the present study, we observed angioedema in one (3.4%) patient after the third dose of omalizumab.Clinical and laboratory criteria have not been defined to predict the effectiveness of omalizumab treatment. Positive determinants of omalizumab response, such as absence of angioedema, advanced age, history of short-term disease, no history of immunosuppressant use and negative result on a histamine release test were reported in a study that had 154 CSU patients treated with omalizumab.<a class="elsevierStyleCrossRef" href="#bib0340">33</a> Angioedema has been reported to occur in 40% of patients with CSU and 23.1% in omalizumab clinical trials involving adolescents.<a class="elsevierStyleCrossRefs" href="#bib0240">13,34</a> Angioedema was detected in 37.7% of our study population. No significant association was observed between treatment response and demographics, concomitant diseases. In a multicenter study that assessed the safety, efficacy, and predictors of poor treatment outcome of omalizumab in patients with CSU, higher pretreatment IgE levels were found less likely to be associated with poor treatment response.<a class="elsevierStyleCrossRef" href="#bib0350">35</a> In the present study, we did not find any laboratory predictors for poor treatment outcome. However, prospective studies including children under 18 years old would be informative in this setting.In conclusion, our results indicate that treatment with 300mg/4QW of omalizumab for at least six months is effective and safe for adolescents with CSU. Additional double-blind and placebo-controlled randomized studies are needed to assess the safety and efficacy of omalizumab in this special population.FundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Author contributionsMK wrote the article, ABB and OUS examined the patients and carried out the follow-ups. BES supervised the study and contributed to the discussion. UMS performed the statistical analysis, supervised the study and contributed to the writing process.Conflict of interestThe authors declare that there is no conflict of interest and no funding." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1437439" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1312171" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xpalclavsec1312172" "titulo" => "Abbreviations" ] 3 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 4 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 5 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 6 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 8 => array:2 [ "identificador" => "sec0030" "titulo" => "Author contributions" ] 9 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of interest" ] 10 => array:2 [ "identificador" => "xack501516" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-11-23" "fechaAceptado" => "2020-03-12" "PalabrasClave" => array:1 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1312171" "palabras" => array:5 [ 0 => "Adolescents" 1 => "Chronic urticaria" 2 => "Efficacy" 3 => "Omalizumab" 4 => "Safety" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec1312172" "palabras" => array:8 [ 0 => "CSU" 1 => "CU" 2 => "IgE" 3 => "IQR" 4 => "LTRA" 5 => "Q4W" 6 => "SPT" 7 => "UAS" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundOmalizumab is useful as an add-on treatment in patients unresponsive to high doses of second-generation antihistamines. This study aimed to evaluate the efficacy and safety of omalizumab treatment in adolescents with refractory chronic spontaneous urticaria (CSU). MethodsCSU patients aged 12–18 years old with the diagnosis of symptomatic CSU and unresponsive to classical treatment were included in the study. All patients had an urticaria-activity-score (UAS7) of ≥16 or and were treated with 300mg omalizumab every four weeks. The degree of response was classified into complete, partial and non-responders due to UAS7. ResultsA total of 29 patients were evaluated. The median age and symptom onset age of the patients was 15.2 (IQR, 12.8–16.5) years and 14.0 (IQR, 11.8–15.9) years, respectively. The median duration of urticaria was eight (IQR, 4–24) months at admission. Eleven (37.9%) patients had angioedema and ten (34.5%) patients had concomitant allergic diseases. The median age at the beginning of treatment with omalizumab was 15.4 (IQR, 12.9–16.9) years. The median symptom duration was 12 (IQR, 6.5–27.5) months before the omalizumab treatment. Twenty-eight (96.5%) of the patients (89.6% complete, 6.9% partial) achieved response; however, one patient was a non-responder (3.5%). The adverse effect was observed in one (3.4%) patient as angioedema after the third dose. Twenty-three patients were followed up for a median of 18 (IQR, 13–27) months. Relapse was observed in three (13%) patients. ConclusionsOmalizumab is considered as an effective and safe treatment for CSU in adolescents. Relapses mostly occur within the first year after the cessation of treatment." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1316 "Ancho" => 1667 "Tamanyo" => 68385 ] ] "descripcion" => array:1 [ "en" => "Triggering factors that increased the symptoms of chronic spontaneous urticaria." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1111 "Ancho" => 1667 "Tamanyo" => 42313 ] ] "descripcion" => array:1 [ "en" => "Response time of patients according to UAS7 scores. The number of patients who had more than a 30% decline in UAS7 within 12 weeks of treatment." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1167 "Ancho" => 1667 "Tamanyo" => 72175 ] ] "descripcion" => array:1 [ "en" => "The number of complete responders by each dose i.e., seven patients responded at first dose, six patients responded at second dose etc." ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n=29 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (44.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (years)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.2 (12.8–16.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age at symptom onset (years)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (11.8–15.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Symptom duration at admission (months)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (4–24) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Concomitant angioedema, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (37.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Concomitant allergic disease, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (34.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allergic rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (13.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Asthma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (10.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Atopic dermatitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (3.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allergic rhinitis+atopic dermatitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (3.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allergic rhinitis+asthma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (3.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total IgE level (IU/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">99 (13–328) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age at omalizumab treatment (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.4 (12.9–16.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Baseline UAS7 scores† \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 (30–42) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2472565.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Median, IQR=interquartile range." ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of the study population." ] ] 4 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Laboratory findings \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No. patients evaluated \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CU (n=29) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leukocyte count (mm3)<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8300 (6500–9050) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Eosinophil count (mm3)<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100 (100–200) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total IgE level (IU/L)<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">99 (13.1–328.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ESR level (mm/h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.5 (2.0–8.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CRP level (mg/dL)<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.22 (0.1–0.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TSH level (μIU/mL)<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.7 (1.1–2.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">fT4 level (pmol/L)<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.55 (9.4–12.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tryptase level (μg/l)<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.87 (1.8–6.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antinuclear antibody positivity, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (51.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-double stranded DNA antibody positivity, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thyroid autoantibody positivity, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autolog serum skin test positivity, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (6.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Skin prick test positivity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (7.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Animal dander \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mold \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dust mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Food \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parasite in stool, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (6.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2472566.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "Median, IQR=interquartile range." ] ] ] "descripcion" => array:1 [ "en" => "Laboratory findings of children with CSU." ] ] 5 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations. CSU: chronic spontaneous urticaria; H1: histamine1; H2: histamine2; LTRA: leukotriene receptor antagonist." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No. of previous CSU medications, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (1–3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">H1 antihistamines, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (100) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">H2 receptor antagonists, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (34.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LTRAs, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (37.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Corticosteroids, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (17.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other medications, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2472564.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Treatments of CSU patients before the start of omalizumab." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:35 [ 0 => array:3 [ "identificador" => "bib0180" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The EAACI/GA(2)LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Zuberbier" 1 => "W. Aberer" 2 => "R. Asero" 3 => "A.H. Abdul Latiff" 4 => "D. Baker" 5 => "B. Ballmer-Weber" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/all.13397" "Revista" => array:6 [ "tituloSerie" => "Allergy" "fecha" => "2018" "volumen" => "73" "paginaInicial" => "1393" "paginaFinal" => "1414" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29336054" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0185" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The diagnosis and management of acute and chronic urticaria: 2014 update" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.A. Bernstein" 1 => "D.M. Lang" 2 => "D.A. Khan" 3 => "T. Craig" 4 => "D. Dreyfus" 5 => "F. 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"vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/03010546/0000004800000004/v2_202012180835/S0301054620300720/v2_202012180835/en/main.assets" "Apartado" => array:4 [ "identificador" => "5554" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03010546/0000004800000004/v2_202012180835/S0301054620300720/v2_202012180835/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054620300720?idApp=UINPBA00004N"]

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M. Ocak, O. Soyer, B. Buyuktiryaki, B.E. Sekerel, U.M. Sahiner

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umsahner@yahoo.com

Corresponding author.

Hacettepe University Faculty of Medicine, Department of Pediatric Allergy, 06100 Ankara, Turkey

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic spontaneous urticaria &#40;CSU&#41; is a disease characterized by itchy hives and&#47;or angioedema that occur daily or almost daily for at least six weeks without any external stimulus&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">1</span></a> Inducible urticaria and urticarial vasculitis form the other types of chronic urticaria &#40;CU&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">2</span></a> Chronic urticaria in children may affect up to 3&#37; of the pediatric population&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">3</span></a> According to current guidelines&#44; the treatment for chronic urticaria involves H1 antihistamines as the first-line&#44; 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information about the efficacy and safety of omalizumab treatment in children with CSU is limited&#46; Large pivotal phase III trials have demonstrated a good safety and efficacy profile&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">9&#8211;11</span></a> A recent systematic literature review of omalizumab treatment of children with CSU less than 12 years of age suggested that omalizumab could be a safe treatment option in this age group&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">12</span></a> There is also a published information gap on the use of omalizumab in the subgroup of patients from 12 to younger than 18 years old with CSU&#46; A study that analyzed a total of 39 adolescents with CSU in three phase III studies reported potential differences in baseline demographic and clinical characteristics between adult and adolescent patients&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">13</span></a> Considering these limited data in children&#44; this study aimed to evaluate the effectiveness and safety of omalizumab in adolescents with recalcitrant chronic spontaneous urticaria&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">This study was conducted at Hacettepe University School of Medicine&#44; Department of Pediatric Allergy&#44; between January 2015 and August 2018 and was approved by the Institutional Review Board of Hacettepe University&#46; Informed written consent was obtained from all patients and parents&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Chronic urticaria was the presence of recurrent urticaria&#44; angioedema&#44; or both&#44; for six weeks or longer&#46; Patients without a clinical response who were treated with second-generation antihistamines at a four-fold increased dose were defined as refractory CSU&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">14</span></a> Twenty-nine refractory CSU patients from 12 to 18 years old with a diagnosis of symptomatic CSU were included in the study population&#46; The study had both retrospective and prospective aspects&#46; First&#44; the medical reports of CSU patients were evaluated retrospectively&#46; Then the clinical status of each patient was evaluated firstly by a telephone visit and then by hospital visits&#46; Urticaria activity score of 7 &#40;UAS7&#41; was used to evaluate disease activity&#46; Itching severity and urticarial plaque number were graded and the sum of seven days of UAS gave the UAS7&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">1</span></a> All the patients had an UAS7 of 16 or greater&#46; Patients were treated with 300<span class="elsevierStyleHsp" style=""></span>mg omalizumab subcutaneously once every four weeks&#46; The treatment continued until the patient had no symptoms for three months&#46; If this time was less than six months&#44; the total duration of the treatment was completed to six months&#46; The patients were evaluated at each visit for the effectiveness of the therapy&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The degree of response was classified into complete responders &#40;UAS7<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#41;&#44; partial responders &#40;UAS7<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>6 but not 0&#41; and non-responders &#40;UAS7<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>6&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a> Relapse was considered to be the reappearance of CSU symptoms after the end of the omalizumab treatment&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">We also evaluated demographic and clinical features of patients&#44; including gender&#44; age at onset&#44; frequency and duration of symptoms&#44; presence of angioedema&#44; concomitant symptoms other than urticaria or angioedema&#44; personal and familial history of allergic diseases&#44; chronic diseases and laboratory findings&#46; Triggering factors that increase symptoms such as cold&#44; heat&#44; sunlight&#44; exercise&#44; stress&#44; infection&#44; food additives&#44; menstrual cycle&#44; and drugs were questioned&#46; Medications &#40;H<span class="elsevierStyleInf">1</span> receptor antagonists&#44; H<span class="elsevierStyleInf">2</span> receptor antagonists&#44; oral corticosteroids&#44; leukotriene receptor antagonists &#40;LTRA&#41;&#44; immunosuppressants&#41; administered before omalizumab treatment&#44; treatments administered concurrently with omalizumab and side effects during omalizumab treatment were recorded&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Complete blood cell count&#44; eosinophil percentage&#44; total immunoglobulin E &#40;IgE&#41;&#44; specific IgE levels&#44; C-reactive protein level&#44; erythrocyte sedimentation rate&#44; C3 and C4 levels&#44; thyroid hormones&#44; thyroid autoantibodies&#44; antinuclear antibody&#44; anti-double-stranded DNA antibody&#44; urine analysis and stool examination for parasites were reviewed from the database&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">16&#44;17</span></a> The normal limits of the laboratory results were evaluated as follows&#58; thyroid-stimulating hormone&#58; 0&#46;38&#8211;5&#46;33<span class="elsevierStyleHsp" style=""></span>&#956;IU&#47;mL&#59; thyroxine&#58; 7&#46;86&#8211;14&#46;41<span class="elsevierStyleHsp" style=""></span>pmol&#47;L&#59; sedimentation rate&#58; 0&#8211;20<span class="elsevierStyleHsp" style=""></span>mm&#47;h&#59; C-reactive protein&#58; 0&#8211;0&#46;8<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#59; C<span class="elsevierStyleInf">3</span>&#58; 79&#8211;152<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#59; C<span class="elsevierStyleInf">4</span>&#58; 16&#8211;38<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The data were analyzed with SPSS statistical software&#44; version 20&#46;0 &#40;SPSS Inc&#44; Chicago&#44; IL&#44; USA&#41;&#46; The proportions in different groups were compared by using the Pearson <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test or the Fisher exact test&#46; All numeric variables were non-normally distributed and compared with Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> or Kruskal&#8211;Wallis tests&#44; when appropriate&#59; the results were given as median and interquartile ranges &#40;IQR&#41;&#46; A <span class="elsevierStyleItalic">p</span>-value of 0&#46;05 indicated a statistically significant result&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">A total of 29 patients who met the study criteria were evaluated&#46; The patients were predominantly females &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#59; 55&#37;&#41;&#46; The median age and symptom onset age of the patients were 15&#46;2 years &#40;IQR&#44; 12&#46;8&#8211;16&#46;5 years&#41; and 14&#46;0 years &#40;IQR&#44; 11&#46;8&#8211;15&#46;9 years&#41;&#44; respectively&#46; The median duration of urticaria before omalizumab treatment was eight months &#40;IQR&#44; 4&#8211;24 months&#41;&#46; Eleven &#40;37&#46;9&#37;&#41; patients had angioedema and 10 &#40;34&#46;5&#37;&#41; patients had concomitant allergic diseases&#46; A family history of allergic diseases was present in seven &#40;24&#46;1&#37;&#41; patients&#46; The characteristics of the patients are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Triggering factors that increased the symptoms of patients are given in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">High antinuclear antibody titers &#40;&#62;1&#47;160&#41; were found in 15&#47;26 &#40;57&#46;6&#37;&#41; patients but none of them were diagnosed as having the rheumatologic disease during the study period&#46; Skin prick tests &#40;SPT&#41; and autolog serum skin testing were performed on only 10 patients due to the use of antihistamines&#46; Autolog serum skin testing was positive in 2&#47;10 &#40;20&#37;&#41; patients and SPT was positive in 5&#47;10 &#40;50&#37;&#41; patients&#46; The leukocyte and eosinophil counts&#44; C3 and C4 levels were within normal limits&#46; All the patients had normal thyroid function tests and negative thyroid autoantibody results&#46; Stool parasite examination was positive in 2&#47;17 &#40;11&#46;7&#37;&#41; patients and <span class="elsevierStyleItalic">Blastocystis hominis</span> eggs were detected &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Medications used before the start of omalizumab treatment were H1 antihistamines &#40;100&#37;&#41;&#44; H2 receptor antagonists &#40;34&#46;5&#37;&#41;&#44; montelukast &#40;37&#46;9&#37;&#41; and oral corticosteroids &#40;17&#46;2&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">The median age of onset of omalizumab was 15&#46;4 years &#40;IQR 12&#46;9&#8211;16&#46;9 years&#41;&#46; The median symptom duration was 12 months &#40;IQR 6&#46;5&#8211;27&#46;5 months&#41; before the omalizumab treatment&#46; A total of 28 &#40;96&#46;5&#37;&#41; &#91;26 &#40;89&#46;6&#37;&#41; complete&#44; two &#40;6&#46;9&#37;&#41; partial&#93; patients achieved remission with omalizumab&#46; The number of patients who had more than a 30&#37; decline in UAS7 within 12 weeks of treatment is indicated in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> according to the weeks&#46; At week 12&#44; after three doses of omalizumab&#44; complete response was reported in 17 &#40;58&#37;&#41; patients &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The median time to achieve a complete response was 7&#46;5 &#40;IQR 3&#8211;14&#46;7&#41; weeks&#46; One &#40;3&#46;5&#37;&#41; patient showed no significant change in UAS7 at week 12 so omalizumab was discontinued and the case was accepted as a non-responder&#46; The omalizumab dose interval was extended to six weeks in eight &#40;27&#46;5&#37;&#41; patients&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The adverse effect was observed in only one &#40;3&#46;4&#37;&#41; patient as angioedema after the third dose of omalizumab and asymptomatic two months&#46; Allergy skin tests were performed with omalizumab solution and an intradermal skin test at a dilution of 1&#58;10 was detected positive with a wheal of 10<span class="elsevierStyleHsp" style=""></span>mm&#46; There was no effect of pre-treatment symptom duration &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;167&#41; and associated angioedema on symptom disappearance time &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;41&#41;&#46; Twenty-three of 26 patients who had a complete response and completed the treatment were followed-up for a median of 18 months &#40;IQR&#44; 13&#8211;27 months&#41;&#46; Relapse was observed in three &#40;13&#37;&#41; patients&#46; The relapse times of three patients were 4&#44; 6&#44; and 12 months after the end of omalizumab therapy&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">The omalizumab treatment in adolescents with CSU seems to be highly effective&#46; Nearly 90&#37; of our patients showed a complete response rate and another 6&#46;5&#37; showed a partial response&#46; We experienced only one adverse effect as angioedema&#44; which did not preclude the continuation of the therapy&#46; Within a one-and-a-half-year follow-up period after cessation of omalizumab treatment&#44; 13&#37; of the children with CSU relapsed&#46; Relapses occurred within the first year after cessation of treatment&#46; Omalizumab is considered as an effective and safe treatment for CSU in adolescents&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">There are few studies in the literature on the use of omalizumab in children with CSU&#46; Most studies of omalizumab in adult patients guide this treatment option in adolescents and children&#46; Three randomized&#44; double-blind&#44; placebo-controlled clinical trials&#44; ASTERIA I&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">10</span></a> ASTERIA II<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">9</span></a> and GLACIAL&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">11</span></a> demonstrated the efficacy and safety of omalizumab in adults&#46; In these three pivotal studies&#44; ASTERIA I and ASTERIA II included patients who remained symptomatic with H1-antihistamines at approved doses but GLACIAL enrolled patients who were symptomatic despite the suggested combination therapies &#40;up to four-fold dose of H1-antihistamines&#44; plus H2 antihistamines&#44; LTRAs or both H2-antihistamines and LTRAs&#41;&#46; Although the methodologies of the studies were different&#44; the similarities in efficacy were emphasized&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">9&#8211;11</span></a> In our study&#44; the inclusion criteria were similar to GLACIAL and the number of previous CSU medications was a median of two &#40;IQR&#44; 1&#8211;3&#41;&#46; Because the adolescents were not the focus of these study populations&#44; they had not been evaluated separately for the efficacy of omalizumab&#46; In a clinical review that had 975 patients with CSU&#44; 39 &#40;4&#37;&#41; were from 12 to under 18 years old&#46; That statistical study had the highest number of adolescent cases in the literature&#46; The mean age of the adolescent group was 15&#46;1 years and most patients were female &#40;69&#46;2&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">13</span></a> Similarly&#44; the mean age of the group in our study was 15&#46;2 years and most patients were female &#40;56&#46;2&#37;&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">A systematic review of 84 observational studies reported the effectiveness of different dosing regimens&#44; such as 150<span class="elsevierStyleHsp" style=""></span>mg&#47;dose every two weeks or every four weeks &#40;Q4W&#41;&#44; but most frequently&#44; omalizumab was commenced at 300<span class="elsevierStyleHsp" style=""></span>mg&#47;dose &#40;62&#46;7&#37;&#41; at a frequency of Q4W &#40;83&#46;9&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a> Another study that described response patterns using the data of three pivotal omalizumab trials demonstrated that 300<span class="elsevierStyleHsp" style=""></span>mg of omalizumab could control CSU symptoms well&#46; <a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a> In our study&#44; we initiated with 300<span class="elsevierStyleHsp" style=""></span>mg&#47;dose Q4W&#46; The omalizumab dose interval was prolonged to six weeks in eight &#40;27&#46;5&#37;&#41; patients since they showed lower UAS7 scores and good responses&#46; It should be noted that individualizing the dose and frequency may increase treatment success&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">UAS7 provides semi-quantitative information on disease activity between clinical visits&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">20</span></a> There are variations among studies on the definition of response to treatment in CSU&#46; In most of the studies&#44; the degree of response was classified into complete responders &#40;UAS7<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#41;&#44; partial responders &#40;UAS7<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>6 but not 0&#41; and non-responders &#40;UAS<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>6&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">21</span></a> In our study&#44; we also evaluated our patients according to previous definitions&#46; In ASTERIA II the median time to achieve complete response was eight weeks for the patients who received 300<span class="elsevierStyleHsp" style=""></span>mg omalizumab&#46; The median time for complete response was 12 and 13 weeks in the studies ASTERIA I and GLACIAL for 300<span class="elsevierStyleHsp" style=""></span>mg omalizumab&#44; respectively&#46; At week 12&#44; patients treated with 300<span class="elsevierStyleHsp" style=""></span>mg omalizumab reported UAS7<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#59; 35&#46;8&#37; for ASTERIA I&#44; 44&#46;3&#37; for ASTERIA II and 33&#46;7&#37; for GLACIAL&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">9&#8211;11</span></a> An earlier study by Sussman et al&#46; found a complete response rate of 79&#37; for any point during the study&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a> A recent retrospective study by Nettis et al&#46; reported a complete response of 67&#37; <a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">23</span></a> In the present study&#44; we found an overall response rate of 96&#46;5&#37;&#44; with only one patient not responding&#46; By week 12&#44; 96&#46;5&#37; of our patients achieved a response &#40;partial or complete&#41;&#44; however&#44; 31&#37; of patients gained complete response after the 12th week&#46; These findings were similar to previous adult studies&#46; After the initiation of omalizumab&#44; the possibility of response at different time points may be observed&#46; The time to respond to treatment may vary in adults and children&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In the literature&#44; there is no marked consensus related to the time of discontinuation of omalizumab treatment&#46; Metz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">24</span></a> reported that omalizumab treatment could be continued for 6&#8211;12 months&#46; However&#44; the general approach is to specify the treatment period according to the patient&#39;s clinical response&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">25</span></a> Some patients may experience relapse after cessation of omalizumab&#46; It is important to know when the medication can be stopped and whether the patients have to be retreated in the event of recurrence of symptoms&#46; A study investigating patients who were at risk of relapse after stopping omalizumab treatment suggested that the speed of symptom return was independent of baseline characteristics of the patients&#44; including duration of CSU&#44; angioedema&#44; previous treatments received&#44; or patient demographics&#46; However&#44; they considered that symptom return could be estimated based on baseline UAS7 and early treatment response&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">26</span></a> In a retrospective study that included 31 patients with refractory CSU it was found that the mean time to achieve complete therapy response was a statistically significant difference between the time to complete response with the first and third course&#46; It was faster as the number of retreatments increased&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">A multicenter&#44; randomized&#44; double-blind&#44; placebo-controlled study that enrolled patients with antihistamine-resistant CSU was designed to answer questions regarding the benefit of omalizumab treatment after 24 and 48 weeks&#46; It was suggested that continuous treatment with omalizumab was beneficial both for preventing the return of symptoms as well as for achieving sustained control through 48 weeks of treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">28</span></a> In the present study&#44; we continued treatment for at least six months&#46; Only three of our patients experienced a relapse at 4&#44; 6&#44; and 12 months after the end of omalizumab therapy&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The safety of omalizumab has been evaluated in numerous adult studies&#46; The most common adverse events reported were headache &#40;6&#46;1&#37;&#41;&#44; sinusitis &#40;4&#46;9&#37;&#41;&#44; arthralgia &#40;2&#46;9&#37;&#41; and injection-site reaction &#40;2&#46;7&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">29</span></a> There were no reports of omalizumab related anaphylaxis in three pivotal studies&#44; ASTERIA I&#44; ASTERIA II or GLACIAL&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">30</span></a> However&#44; one case was reported who experienced anaphylaxis 36<span class="elsevierStyleHsp" style=""></span>h after omalizumab administration&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">31</span></a> Angioedema and urticaria following omalizumab for CSU were stated in four cases&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">32</span></a> In the present study&#44; we observed angioedema in one &#40;3&#46;4&#37;&#41; patient after the third dose of omalizumab&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Clinical and laboratory criteria have not been defined to predict the effectiveness of omalizumab treatment&#46; Positive determinants of omalizumab response&#44; such as absence of angioedema&#44; advanced age&#44; history of short-term disease&#44; no history of immunosuppressant use and negative result on a histamine release test were reported in a study that had 154 CSU patients treated with omalizumab&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">33</span></a> Angioedema has been reported to occur in 40&#37; of patients with CSU and 23&#46;1&#37; in omalizumab clinical trials involving adolescents&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">13&#44;34</span></a> Angioedema was detected in 37&#46;7&#37; of our study population&#46; No significant association was observed between treatment response and demographics&#44; concomitant diseases&#46; In a multicenter study that assessed the safety&#44; efficacy&#44; and predictors of poor treatment outcome of omalizumab in patients with CSU&#44; higher pretreatment IgE levels were found less likely to be associated with poor treatment response&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">35</span></a> In the present study&#44; we did not find any laboratory predictors for poor treatment outcome&#46; However&#44; prospective studies including children under 18 years old would be informative in this setting&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In conclusion&#44; our results indicate that treatment with 300<span class="elsevierStyleHsp" style=""></span>mg&#47;4QW of omalizumab for at least six months is effective and safe for adolescents with CSU&#46; Additional double-blind and placebo-controlled randomized studies are needed to assess the safety and efficacy of omalizumab in this special population&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Funding</span><p id="par0115" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public&#44; commercial&#44; or not-for-profit sectors&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Author contributions</span><p id="par0120" class="elsevierStylePara elsevierViewall">MK wrote the article&#44; ABB and OUS examined the patients and carried out the follow-ups&#46; BES supervised the study and contributed to the discussion&#46; UMS performed the statistical analysis&#44; supervised the study and contributed to the writing process&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflict of interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that there is no conflict of interest and no funding&#46;</p></span></span>"
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    "fechaRecibido" => "2019-11-23"
    "fechaAceptado" => "2020-03-12"
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          "titulo" => "Abbreviations"
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            0 => "CSU"
            1 => "CU"
            2 => "IgE"
            3 => "IQR"
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            7 => "UAS"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Omalizumab is useful as an add-on treatment in patients unresponsive to high doses of second-generation antihistamines&#46; This study aimed to evaluate the efficacy and safety of omalizumab treatment in adolescents with refractory chronic spontaneous urticaria &#40;CSU&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">CSU patients aged 12&#8211;18 years old with the diagnosis of symptomatic CSU and unresponsive to classical treatment were included in the study&#46; All patients had an urticaria-activity-score &#40;UAS7&#41; of &#8805;16 or and were treated with 300<span class="elsevierStyleHsp" style=""></span>mg omalizumab every four weeks&#46; The degree of response was classified into complete&#44; partial and non-responders due to UAS7&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 29 patients were evaluated&#46; The median age and symptom onset age of the patients was 15&#46;2 &#40;IQR&#44; 12&#46;8&#8211;16&#46;5&#41; years and 14&#46;0 &#40;IQR&#44; 11&#46;8&#8211;15&#46;9&#41; years&#44; respectively&#46; The median duration of urticaria was eight &#40;IQR&#44; 4&#8211;24&#41; months at admission&#46; Eleven &#40;37&#46;9&#37;&#41; patients had angioedema and ten &#40;34&#46;5&#37;&#41; patients had concomitant allergic diseases&#46; The median age at the beginning of treatment with omalizumab was 15&#46;4 &#40;IQR&#44; 12&#46;9&#8211;16&#46;9&#41; years&#46; The median symptom duration was 12 &#40;IQR&#44; 6&#46;5&#8211;27&#46;5&#41; months before the omalizumab treatment&#46; Twenty-eight &#40;96&#46;5&#37;&#41; of the patients &#40;89&#46;6&#37; complete&#44; 6&#46;9&#37; partial&#41; achieved response&#59; however&#44; one patient was a non-responder &#40;3&#46;5&#37;&#41;&#46; The adverse effect was observed in one &#40;3&#46;4&#37;&#41; patient as angioedema after the third dose&#46; Twenty-three patients were followed up for a median of 18 &#40;IQR&#44; 13&#8211;27&#41; months&#46; Relapse was observed in three &#40;13&#37;&#41; patients&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Omalizumab is considered as an effective and safe treatment for CSU in adolescents&#46; Relapses mostly occur within the first year after the cessation of treatment&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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        ]
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    ]
    "multimedia" => array:6 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Triggering factors that increased the symptoms of chronic spontaneous urticaria&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Response time of patients according to UAS7 scores&#46; The number of patients who had more than a 30&#37; decline in UAS7 within 12 weeks of treatment&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The number of complete responders by each dose i&#46;e&#46;&#44; seven patients responded at first dose&#44; six patients responded at second dose etc&#46;</p>"
        ]
      ]
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                  \t\t\t\t">13 &#40;44&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Age &#40;years&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15&#46;2 &#40;12&#46;8&#8211;16&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Age at symptom onset &#40;years&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">14 &#40;11&#46;8&#8211;15&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Symptom duration at admission &#40;months&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">8 &#40;4&#8211;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">11 &#40;37&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Concomitant allergic disease&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">10 &#40;34&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Allergic rhinitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">4 &#40;13&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Asthma&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3 &#40;10&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Atopic dermatitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1 &#40;3&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Allergic rhinitis<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>atopic dermatitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;3&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Allergic rhinitis</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#43;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">asthma</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Total IgE level &#40;IU&#47;ml&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  <table border="0" frame="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Laboratory findings&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CU &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>29&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">29&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8300 &#40;6500&#8211;9050&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Eosinophil count &#40;mm</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">3</span></span><span class="elsevierStyleItalic">&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">29&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">100 &#40;100&#8211;200&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Total IgE level &#40;IU&#47;L&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99 &#40;13&#46;1&#8211;328&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">ESR level &#40;mm&#47;h&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">2&#46;5 &#40;2&#46;0&#8211;8&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">CRP level &#40;mg&#47;dL&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;22 &#40;0&#46;1&#8211;0&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">TSH level &#40;&#956;IU&#47;mL&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7 &#40;1&#46;1&#8211;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">fT4 level &#40;pmol&#47;L&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;55 &#40;9&#46;4&#8211;12&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tryptase level &#40;&#956;g&#47;l&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;87 &#40;1&#46;8&#8211;6&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Antinuclear antibody positivity&#44; no&#46; &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;51&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Anti-double stranded DNA antibody positivity&#44; no&#46; &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Thyroid autoantibody positivity&#44; no&#46; &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Autolog serum skin test positivity&#44; no&#46; &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;6&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;7&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pollen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Animal dander&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mold&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dust mites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Food&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Parasite in stool&#44; no&#46; &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;6&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">No&#46; of previous CSU medications&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2 &#40;1&#8211;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">H<span class="elsevierStyleInf">1</span> antihistamines&#44; no&#46; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">29 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">H<span class="elsevierStyleInf">2</span> receptor antagonists&#44; no&#46; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;34&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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Article information

ISSN: 03010546
Original language: English

DOI:10.1016/j.aller.2020.03.011

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	7	0	7
2024 October	37	22	59
2024 September	78	27	105
2024 August	66	15	81
2024 July	70	14	84
2024 June	48	11	59
2024 May	35	24	59
2024 April	26	18	44
2024 March	62	8	70
2024 February	63	26	89
2024 January	76	20	96
2023 December	60	10	70
2023 November	81	14	95
2023 October	82	14	96
2023 September	80	12	92
2023 August	44	9	53
2023 July	58	10	68
2023 June	70	7	77
2023 May	122	12	134
2023 April	99	7	106
2023 March	54	11	65
2023 February	48	20	68
2023 January	23	8	31
2022 December	29	13	42
2022 November	79	9	88
2022 October	35	17	52
2022 September	31	13	44
2022 August	29	21	50
2022 July	35	15	50
2022 June	32	11	43
2022 May	29	21	50
2022 April	35	28	63
2022 March	42	22	64
2022 February	29	14	43
2022 January	27	31	58
2021 December	119	18	137
2021 November	35	18	53
2021 October	35	25	60
2021 September	31	27	58
2021 August	15	18	33
2021 July	28	28	56
2021 June	31	25	56
2021 May	25	25	50
2021 April	75	52	127
2021 March	36	19	55
2021 February	27	14	41
2021 January	19	21	40
2020 December	8	9	17
2020 November	1	2	3
2020 October	2	2	4
2020 September	2	0	2
2020 July	3	1	4
2020 June	0	2	2

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Allergologia et Immunopathologia is no longer published on Elsevier since the 2021 year.Transferred to Codon Publications

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Allergologia et Immunopathologia is no longer published on Elsevier since the 2021 year.Transferred to Codon Publications

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