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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Bullous pemphigoid is the most common autoimmune bullous disease in our setting&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It is caused by the presence of circulating autoantibodies against proteins that make up the hemidesmosomes of the dermal-epidermal junction &#40;the antigens BP180 and BP230&#41; and is characterized by the formation of intensely pruritic urticarial plaques and tense blisters affecting the whole skin surface&#44; with a predilection for the skinfolds&#46; Mucous involvement is uncommon&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The incidence of the disease has increased 2- to 4-fold during the last 20 years&#46; This increase is associated with the administration of various drugs&#44; such as spironolactone&#46; An association was recently observed between bullous pemphigoid and administration of oral antidiabetic drugs belonging to the dipeptidylpeptidase-4 inhibitor &#40;DPP-4i&#41; family&#44; which are also known as gliptins&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> This association was not observed in clinical trials before these drugs were marketed&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The objective of the present study was to estimate the prevalence of DPP-4i in patients with a histological diagnosis of bullous pemphigoid in the Dermatology Department of Hospital General Universitario de Valencia&#44; Valencia&#44; Spain between October 2015 and October 2018&#46; We also evaluated whether there were differences in the time of onset of bullous pemphigoid according to the type of gliptin used&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">We designed a single-center&#44; retrospective&#44; descriptive&#44; observational study to be performed in the Dermatology Department of Hospital General de Valencia&#44; Valencia&#44; Spain between October 2015 and October 2018&#46; All patients with a histological diagnosis of bullous pemphigoid were included&#46; The patients were selected continuously via a biopsy database in our department&#46; We excluded patients with other bullous skin diseases or with cicatricial pemphigoid or paraneoplastic pemphigus&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Once the sample was selected&#44; we performed a retrospective search of the electronic clinical history of each patient in order to record data for the study variables&#44; as follows&#58; sex&#44; age&#44; history of diabetes&#44; current treatment with a DPP-4i&#44; type of gliptin&#44; months between prescription of the drug and consultation in our department because of symptoms&#44; direct immunofluorescence pattern&#44; and response to treatment according to whether the DPP-4i was withdrawn or not&#46; The direct immunofluorescence patterns analyzed were linear deposition of immunoglobulin &#40;Ig&#41; G and complement factor 3 &#40;C3&#41; and deposition of IgM&#46; All patients were treated with oral corticosteroids&#44; and those in treatment with a DPP-4i were referred to their primary care physician to have the drug withdrawn and replaced by an antidiabetic agent from a different family&#46; A complete response was defined as the total disappearance of the lesions&#44; and a partial response was defined as the presence of lesions requiring treatment with oral or topical corticosteroids&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The statistical analysis was performed using the software application IBM SPSS Statistics&#44; Version 21&#46;0 &#40;IBM Corp&#46;&#41;&#46; Continuous variables are expressed as median &#40;interquartile range &#91;IQR&#93;&#41;&#46; Qualitative variables are expressed as a whole number and percentage&#46; Hypotheses for quantitative variables were tested using the Pearson &#967;<span class="elsevierStyleSup">2</span> test&#46; Survival was analyzed using Kaplan-Meier plots of the time to onset of bullous pemphigoid &#40;in months&#41; and the different gliptins used&#46; The log-rank test was used for comparisons&#46; Statistical significance was set at <span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;05&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0030" class="elsevierStylePara elsevierViewall">A total of 70 patients were histologically diagnosed with bullous pemphigoid during the 3-year study period&#46; Of these&#44; 35 &#40;50&#37;&#41; were men and 35 &#40;50&#37;&#41; were women&#46; The median age was 82 &#40;38-97&#41; years&#46; Thirty-five patients &#40;50&#37;&#41; had type 2 diabetes&#59; of these&#44; 31 &#40;88&#46;5&#37;&#41; were receiving a DPP-4i&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the demographic characteristics of the patients according to whether or not they were receiving gliptins&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">At diagnosis&#44; the most commonly used DPP-4i was linagliptin &#40;13 patients &#91;18&#46;6&#37;&#93;&#41;&#44; followed by vildagliptin &#40;12 &#91;17&#46;1&#37;&#93;&#41;&#44; sitagliptin &#40;5 &#91;7&#46;1&#37;&#93;&#41;&#44; and saxagliptin &#40;1 &#91;1&#46;4&#37;&#93;&#41;&#46; In 8 patients &#40;11&#46;4&#37;&#41;&#44; this was the second gliptin the patient had been prescribed&#46; Six patients had previously been treated with sitagliptin&#44; 1 with linagliptin&#44; and 1 with vildagliptin&#44; with a median time of treatment with the drug of 9 &#40;4&#41; months&#46; Of the 31 patients receiving treatment with a DPP-4i&#44; 25 &#40;80&#46;64&#37;&#41; were taking the drug in combination with metformin&#44; 5 &#40;16&#46;13&#37;&#41; in monotherapy&#44; and 1 &#40;3&#46;22&#37;&#41; in combination with sulfonylurea&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">All patients were diagnosed with bullous pemphigoid after initiation of treatment with gliptins&#44; with a median time of 27&#46;5 &#40;33&#41; months&#46; The median time from the initiation of treatment for each of the gliptins until onset of bullous pemphigoid lesions was 39 &#40;13&#41; months for vildagliptin&#44; 36 &#40;7&#41; months for sitagliptin&#44; 16 &#40;3&#41; months for linagliptin&#44; and 53 &#40;0&#41; months for saxagliptin &#40;log-rank&#44; &#60;&#46;011&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the survival plots for the different types of gliptin with respect to onset of bullous pemphigoid&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Direct immunofluorescence testing was applied in 67 patients &#40;95&#46;7&#37;&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the results of direct immunofluorescence testing according to the different patterns analyzed&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">All of the 31 patients receiving treatment with a DPP-4i were advised to discontinue therapy&#46; The DPP-4i was eventually withdrawn in 27 cases &#40;87&#37;&#41;&#46; A complete response was achieved in 26 cases &#40;83&#46;8&#37;&#41; &#40;1 patient died&#41;&#46; Of the 4 patients in whom the drug was not discontinued&#44; 3 &#40;9&#46;6&#37;&#41; achieved a partial response&#44; and 1 was lost to follow-up&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">The association between DPP-4i and bullous pemphigoid has been demonstrated in several case-control studies&#44; although not in our setting&#46; The underlying pathogenic mechanism remains unclear&#46; We know that DPP-4 is a cell surface plasminogen receptor that is expressed in keratinocytes and in other types of cell&#44; such as endothelial cells and T lymphocytes&#46; Activation of DPP-4 in vitro leads to the formation of plasmin&#44; a protease that cleaves BP-180 via the NC-16A domain&#46; Furthermore&#44; it has been demonstrated in vivo that inhibition of this receptor by DPP-4i can increase the activity of proinflammatory cytokines such as eotaxin&#47;CCL11&#44; thus leading to recruitment of eosinophils in the dermis and the formation of blisters&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Over the 3-year period we studied&#44; a total of 70 patients were diagnosed with bullous pemphigoid&#46; Given the catchment population of Hospital General de Valencia &#40;approximately 370 000 people&#41;&#44; this incidence is approximately 3 times higher than that published in a French study on the incidence of bullous pemphigoid &#40;21&#46;7 cases per million people per year&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> There may be several explanations for this finding&#46; In recent years&#44; the number of cases of bullous pemphigoid has increased&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Possible reasons include increased use of DPP-4i and other drugs&#46; In addition&#44; the French study was published almost 8 years ago&#59; therefore&#44; we might expect the incidence to have increased&#46; Furthermore&#44; it is difficult to estimate prevalence based only on the hospital catchment population&#44; since some of the patients diagnosed with bullous pemphigoid in the last few years were from outside our area&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">These drugs are thought to increase the risk of bullous pemphigoid by up to 2&#46;8-fold&#44; especially in the case of vildagliptin and&#44; to a lesser extent&#44; linagliptin&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;7</span></a> Moreover&#44; small case series have reported a noninflammatory phenotype of bullous pemphigoid induced by DPP-4i&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a> In their major case-control study&#44; Kridin and Bergman<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> found no differences in the clinical pattern of presentation of bullous pemphigoid &#40;beyond greater involvement of the mucous membranes&#41;&#46; Since the study was retrospective&#44; the clinical description of the lesions was very poor&#44; as was the explicit evaluation of the mucous membrane&#44; and no differences were found in the cases we collected&#46; While many of these drugs are combined with metformin &#40;80&#46;64&#37; in the present cohort&#41;&#44; this drug was not associated with an increased risk of bullous pemphigoid in the univariate or the multivariate analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The median latency period between initiation of therapy with these antidiabetic agents and disease onset varies considerably depending on the study&#44; from 6 to 26&#46;4 months&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The median latency in our cohort was slightly higher &#40;27&#46;5 months&#41;&#44; perhaps because we defined onset as the point at which the patients came to our department&#46; Given that there may have been some delay until consultation&#44; our results seem consistent with those reported elsewhere&#46; We were unable to find studies that compared the latency of onset of bullous pemphigoid according to the type of gliptin used&#46; In our cohort&#44; linagliptin was the drug with which bullous pemphigoid appeared earliest&#46; A review of the literature indicates that the latency periods reported with this gliptin are similar to those we report&#44; although the cases are usually isolated&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The direct immunofluorescence pattern is similar in bullous pemphigoid associated with DPP-4i and in cases in which these drugs are not involved&#46; In the present cohort&#44; a negative direct immunofluorescence result was statistically significantly associated with the absence of DPP-4i&#44; whereas the presence of linear IgG at the dermal-epidermal junction was statistically significantly more common in cases of bullous pemphigoid associated with DPP-4i&#46; Although infrequent&#44; there have been reports of patients diagnosed with bullous pemphigoid in whom direct immunofluorescence is initially negative or indeterminate&#44; thus necessitating a second biopsy to confirm the diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> According to our cohort&#44; false negatives were less common in patients treated with DPP-4i&#44; although this was not confirmed with a second direct immunofluorescence assay&#46; Furthermore&#44; detection of linear IgG with or without C3 in these patients seems to be more sensitive in the diagnosis of bullous pemphigoid&#46; This is a common finding in patients with bullous pemphigoid induced by drugs in general&#44; and not only in those cases where the disease is induced by DPP-4i&#46; We found no studies that evaluate the difference in direct immunofluorescence patterns of bullous pemphigoid according to the presence of these antidiabetic drugs&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Discontinuation of treatment was associated with complete clinical remission in most patients&#44; thus confirming similar data reported elsewhere&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In contrast&#44; other authors did not find differences in the clinical response between patients who discontinued therapy with gliptins and those who continued therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The main limitation of our study is that data were collected retrospectively&#46; This prevented us from evaluating the clinical characteristics of patients&#44; since this information was not available in the clinical history in many cases&#46; In addition&#44; it would have been interesting to study the serological values of the patients&#8217; anti&#8211;basement membrane antibodies and to determine whether there are differences between patients taking gliptins and patients who were not&#44; even though other authors report no differences&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> We do not routinely use these analytical markers&#44; except in patients with discrepant clinical-pathological data in whom direct immunofluorescence testing is negative&#46; Our study has an advantage over other studies in that we avoided Berkson bias by selecting patients in whom bullous pemphigoid was diagnosed based on histology&#46; The small sample is a disadvantage when attempting to draw robust conclusions&#44; although our sample was very similar to or even larger than those of similar previously published studies&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In conclusion&#44; the prevalence of treatment with DPP-4i in patients diagnosed with bullous pemphigoid is high&#46; The direct immunofluorescence pattern observed in these patients may differ from that observed in those who are not receiving DPP-4i&#44; with a higher frequency of positive results in direct immunofluorescence testing for the combination linear IgG-C3&#46; We also observed that the latency period between initiation of the drug and onset of bullous pemphigoid was significantly shorter with linagliptin than with the other gliptins&#46; Discontinuation of DPP-4i combined with the usual treatment for bullous pemphigoid results in a complete clinical response in almost all patients&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflicts of interest</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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            0 => "Bullous pemphigoid"
            1 => "Dipeptidyl peptidase 4 inhibitors"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The association between dipeptidyl peptidase 4 inhibitors &#40;DPP-4i&#41; and bullous pemphigoid &#40;BP&#41; has been demonstrated in several studies&#46; The main aim of this study was to estimate the use of DPP-4i treatment in patients diagnosed with BP in our setting&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">We selected patients histologically diagnosed with BP in our department between October 2015 and October 2018 and performed a retrospective chart review to assess clinical and epidemiological data and direct immunofluorescence &#40;DIF&#41; patterns&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Of the 70 patients diagnosed with BP during the study period&#44; 50&#37; were diabetic and 88&#46;57&#37; of these were being treated with a DPP-4i when diagnosed with BP&#46; The most common DPP-4i was linagliptin &#40;used in 18&#46;6&#37; of patients&#41;&#44; followed by vildagliptin &#40;17&#46;1&#37;&#41;&#46; The median latency period between initiation of DPP-4i treatment and diagnosis of BP was 27&#46;5 months for all treatments&#44; 16 months for linagliptin&#44; and 39 months for vildagliptin &#40;log rank &#60; 0&#46;01&#41;&#46; A negative DIF result was significantly more common in patients not being treated with a DPP-4i&#46; The DIF pattern most strongly &#40;and significantly&#41; associated with DPP-4i treatment was linear immunoglobulin G deposits along the dermal-epidermal junction&#46; DPP-4i treatment was withdrawn in 87&#37; of patients and 96&#37; of these achieved a complete response&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">DPP-4i treatment is very common in patients with BP in our setting&#46; The latency period between start of treatment and onset of BP seems to be shorter with linagliptin than with other types of gliptins&#46; Patients receiving DPP-4i treatment may show different DIF patterns to those not receiving treatment&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La asociaci&#243;n entre los inhibidores de la dipeptidil peptidasa 4 &#40;iDPP-4&#41; y el penfigoide ampolloso &#40;PA&#41; se ha demostrado en varios estudios&#46; El objetivo principal de este estudio era estimar el uso del tratamiento con iDPP-4i en pacientes diagnosticados de PA en nuestro entorno&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Seleccionamos pacientes diagnosticados histol&#243;gicamente de PA en nuestro departamento entre octubre de 2015 y octubre de 2018&#46; Realizamos una revisi&#243;n retrospectiva para evaluar los datos cl&#237;nicos-epidemiol&#243;gicos y los patrones de inmunofluorescencia directa &#40;IFD&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">De los 70 pacientes diagnosticados con PA durante el per&#237;odo de estudio&#44; el 50&#37; eran diab&#233;ticos y el 88&#44;57&#37; de ellos estaban siendo tratados con un iDPP-4 en el momento del diagn&#243;stico de PA&#46; El iDPP-4 m&#225;s frecuente era la linagliptina &#40;utilizada en el 18&#44;6&#37; de los pacientes&#41;&#44; seguida de la vildagliptina &#40;el 17&#44;1&#37;&#41;&#46; La mediana de tiempo de latencia entre el inicio del tratamiento con iDPP-4 y el diagn&#243;stico de PA fue de 27&#44;5 meses&#44; siendo de 16 meses para la linagliptina y 39 meses para la vildagliptina &#40;log Rank &#60; 0&#44;01&#41;&#46; La IFD fue negativaUn resultado negativo de DIF fue significativamente m&#225;s com&#250;n en pacientes que no fueron tratados con un DPP-4i&#46; El patr&#243;n DIF m&#225;s fuertemente &#40;y significativamente&#41; asociado con el tratamiento con DPP-4i fueron los dep&#243;sitos lineales de inmunoglobulina G a lo largo de la uni&#243;n dermoepid&#233;rmica&#46; El tratamiento con DPP-4i se retir&#243; en el 87&#37; de los pacientes y el 96&#37; de ellos logr&#243; una respuesta completa&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">El tratamiento con DPP-4i es muy com&#250;n en pacientes con BP en nuestro entorno&#46; El per&#237;odo de latencia entre el inicio del tratamiento y el inicio de la PA parece ser m&#225;s corto con linagliptina que con otros tipos de gliptinas&#46; Los pacientes que reciben tratamiento con DPP-4i pueden mostrar patrones DIF diferentes a los que no reciben tratamiento&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Magdaleno-Tapial J&#44; Valenzuela-O&#241;ate C&#44; Esteban Hurtado &#193;&#44; Ortiz-Salvador JM&#44; Subiabre-Ferrer D&#44; Ferrer-Guill&#233;n B&#44; et al&#46; Asociaci&#243;n entre penfigoide ampolloso e inhibidores de la dipeptidilpeptidasa-4&#58; estudio de cohortes retrospectivo&#46; Actas Dermosifiliogr&#46; 2020&#59;111&#58;249&#8211;253&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Median latency time between initiation of therapy with DPP-4i and the diagnosis of bullous pemphigoid&#46; DPP-4i indicates dipeptidyl peptidase 4 inhibitor&#46;</p>"
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                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
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\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">Receiving DPP-4i&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Not Receiving DPP-4i&nbsp;\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
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&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
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                  \t\t\t\t">39&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">&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\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \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">&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">&#46;09&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>Male&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">19 &#40;54&#46;3&#37;&#41;&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">16 &#40;47&#46;3&#41;&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">&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>Female&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">12 &#40;34&#46;3&#37;&#41;&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">23 &#40;65&#46;7&#37;&#41;&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">&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">Mean &#40;SD&#41; age&#44; y</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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&#46;71 &#40;8&#46;4&#41;&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">77&#46;38 &#40;12&#46;9&#41;&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">&#46;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="elsevierStyleItalic">Clinical picture</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="left" 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">&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">&#46;7&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>Urticarial phase &#47;eczema&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">10 &#40;32&#37;&#41;&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">13 &#40;33&#37;&#41;&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">&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>Bullous phase&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">6 &#40;19&#37;&#41;&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">10 &#40;25&#37;&#41;&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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Abbreviation&#58; DDP-4i&#44; dipeptidyl peptidase-4 inhibitor&#46;</p>"
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            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">Pattern&nbsp;\t\t\t\t\t\t\n
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                  \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">Receiving DPP-4i&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Not Receiving DPP-4i&nbsp;\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
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> Value<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\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">Negative&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&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&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"><span class="elsevierStyleBold">&#46;04</span>&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">Linear IgG positive&#47;negative&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">24&#47;6&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">20&#47;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"><span class="elsevierStyleBold">&#46;02</span>&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">Linear C3 positive&#47;negative&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">24&#47;6&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">22&#47;15&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">&#46;72&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">Granular C3 positive&#47;negative&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&#47;30&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&#47;36&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">&#46;3&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">IgA in inflammatory cells positive&#47;negative&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&#47;27&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">4&#47;33&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">&#46;9&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">Linear IgA positive&#47;negative&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&#47;27&nbsp;\t\t\t\t\t\t\n
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Original Article
Association Between Bullous Pemphigoid and Dipeptidyl Peptidase 4 Inhibitors: A Retrospective Cohort Study
Asociación entre penfigoide ampolloso e inhibidores de la dipeptidilpeptidasa-4: estudio de cohortes retrospectivo
J. Magdaleno-Tapial
Autor para correspondencia
magdaleno_jor@gva.es

Corresponding author.
, C. Valenzuela-Oñate, Á. Esteban Hurtado, J.M. Ortiz-Salvador, D. Subiabre-Ferrer, B. Ferrer-Guillén, M. Giacaman-von der Weth, M. García-Legaz Martínez, Á. Martínez-Domenech, P. Hernández-Bel, A. Esteve-Martínez, G. Pérez-Pastor, V. Zaragoza-Ninet, A. García-Rabasco, A. Martínez-Aparicio, J.L. Sánchez-Carazo, A. Pérez-Ferriols, V. Alegre-de Miquel
Servicio de Dermatología, Hospital General Universitario de Valencia, Valencia, Spain
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Median latency time between initiation of therapy with DPP-4i and the diagnosis of bullous pemphigoid&#46; DPP-4i indicates dipeptidyl peptidase 4 inhibitor&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Bullous pemphigoid is the most common autoimmune bullous disease in our setting&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It is caused by the presence of circulating autoantibodies against proteins that make up the hemidesmosomes of the dermal-epidermal junction &#40;the antigens BP180 and BP230&#41; and is characterized by the formation of intensely pruritic urticarial plaques and tense blisters affecting the whole skin surface&#44; with a predilection for the skinfolds&#46; Mucous involvement is uncommon&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The incidence of the disease has increased 2- to 4-fold during the last 20 years&#46; This increase is associated with the administration of various drugs&#44; such as spironolactone&#46; An association was recently observed between bullous pemphigoid and administration of oral antidiabetic drugs belonging to the dipeptidylpeptidase-4 inhibitor &#40;DPP-4i&#41; family&#44; which are also known as gliptins&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> This association was not observed in clinical trials before these drugs were marketed&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The objective of the present study was to estimate the prevalence of DPP-4i in patients with a histological diagnosis of bullous pemphigoid in the Dermatology Department of Hospital General Universitario de Valencia&#44; Valencia&#44; Spain between October 2015 and October 2018&#46; We also evaluated whether there were differences in the time of onset of bullous pemphigoid according to the type of gliptin used&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">We designed a single-center&#44; retrospective&#44; descriptive&#44; observational study to be performed in the Dermatology Department of Hospital General de Valencia&#44; Valencia&#44; Spain between October 2015 and October 2018&#46; All patients with a histological diagnosis of bullous pemphigoid were included&#46; The patients were selected continuously via a biopsy database in our department&#46; We excluded patients with other bullous skin diseases or with cicatricial pemphigoid or paraneoplastic pemphigus&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Once the sample was selected&#44; we performed a retrospective search of the electronic clinical history of each patient in order to record data for the study variables&#44; as follows&#58; sex&#44; age&#44; history of diabetes&#44; current treatment with a DPP-4i&#44; type of gliptin&#44; months between prescription of the drug and consultation in our department because of symptoms&#44; direct immunofluorescence pattern&#44; and response to treatment according to whether the DPP-4i was withdrawn or not&#46; The direct immunofluorescence patterns analyzed were linear deposition of immunoglobulin &#40;Ig&#41; G and complement factor 3 &#40;C3&#41; and deposition of IgM&#46; All patients were treated with oral corticosteroids&#44; and those in treatment with a DPP-4i were referred to their primary care physician to have the drug withdrawn and replaced by an antidiabetic agent from a different family&#46; A complete response was defined as the total disappearance of the lesions&#44; and a partial response was defined as the presence of lesions requiring treatment with oral or topical corticosteroids&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The statistical analysis was performed using the software application IBM SPSS Statistics&#44; Version 21&#46;0 &#40;IBM Corp&#46;&#41;&#46; Continuous variables are expressed as median &#40;interquartile range &#91;IQR&#93;&#41;&#46; Qualitative variables are expressed as a whole number and percentage&#46; Hypotheses for quantitative variables were tested using the Pearson &#967;<span class="elsevierStyleSup">2</span> test&#46; Survival was analyzed using Kaplan-Meier plots of the time to onset of bullous pemphigoid &#40;in months&#41; and the different gliptins used&#46; The log-rank test was used for comparisons&#46; Statistical significance was set at <span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;05&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0030" class="elsevierStylePara elsevierViewall">A total of 70 patients were histologically diagnosed with bullous pemphigoid during the 3-year study period&#46; Of these&#44; 35 &#40;50&#37;&#41; were men and 35 &#40;50&#37;&#41; were women&#46; The median age was 82 &#40;38-97&#41; years&#46; Thirty-five patients &#40;50&#37;&#41; had type 2 diabetes&#59; of these&#44; 31 &#40;88&#46;5&#37;&#41; were receiving a DPP-4i&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the demographic characteristics of the patients according to whether or not they were receiving gliptins&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">At diagnosis&#44; the most commonly used DPP-4i was linagliptin &#40;13 patients &#91;18&#46;6&#37;&#93;&#41;&#44; followed by vildagliptin &#40;12 &#91;17&#46;1&#37;&#93;&#41;&#44; sitagliptin &#40;5 &#91;7&#46;1&#37;&#93;&#41;&#44; and saxagliptin &#40;1 &#91;1&#46;4&#37;&#93;&#41;&#46; In 8 patients &#40;11&#46;4&#37;&#41;&#44; this was the second gliptin the patient had been prescribed&#46; Six patients had previously been treated with sitagliptin&#44; 1 with linagliptin&#44; and 1 with vildagliptin&#44; with a median time of treatment with the drug of 9 &#40;4&#41; months&#46; Of the 31 patients receiving treatment with a DPP-4i&#44; 25 &#40;80&#46;64&#37;&#41; were taking the drug in combination with metformin&#44; 5 &#40;16&#46;13&#37;&#41; in monotherapy&#44; and 1 &#40;3&#46;22&#37;&#41; in combination with sulfonylurea&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">All patients were diagnosed with bullous pemphigoid after initiation of treatment with gliptins&#44; with a median time of 27&#46;5 &#40;33&#41; months&#46; The median time from the initiation of treatment for each of the gliptins until onset of bullous pemphigoid lesions was 39 &#40;13&#41; months for vildagliptin&#44; 36 &#40;7&#41; months for sitagliptin&#44; 16 &#40;3&#41; months for linagliptin&#44; and 53 &#40;0&#41; months for saxagliptin &#40;log-rank&#44; &#60;&#46;011&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the survival plots for the different types of gliptin with respect to onset of bullous pemphigoid&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Direct immunofluorescence testing was applied in 67 patients &#40;95&#46;7&#37;&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the results of direct immunofluorescence testing according to the different patterns analyzed&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">All of the 31 patients receiving treatment with a DPP-4i were advised to discontinue therapy&#46; The DPP-4i was eventually withdrawn in 27 cases &#40;87&#37;&#41;&#46; A complete response was achieved in 26 cases &#40;83&#46;8&#37;&#41; &#40;1 patient died&#41;&#46; Of the 4 patients in whom the drug was not discontinued&#44; 3 &#40;9&#46;6&#37;&#41; achieved a partial response&#44; and 1 was lost to follow-up&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">The association between DPP-4i and bullous pemphigoid has been demonstrated in several case-control studies&#44; although not in our setting&#46; The underlying pathogenic mechanism remains unclear&#46; We know that DPP-4 is a cell surface plasminogen receptor that is expressed in keratinocytes and in other types of cell&#44; such as endothelial cells and T lymphocytes&#46; Activation of DPP-4 in vitro leads to the formation of plasmin&#44; a protease that cleaves BP-180 via the NC-16A domain&#46; Furthermore&#44; it has been demonstrated in vivo that inhibition of this receptor by DPP-4i can increase the activity of proinflammatory cytokines such as eotaxin&#47;CCL11&#44; thus leading to recruitment of eosinophils in the dermis and the formation of blisters&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Over the 3-year period we studied&#44; a total of 70 patients were diagnosed with bullous pemphigoid&#46; Given the catchment population of Hospital General de Valencia &#40;approximately 370 000 people&#41;&#44; this incidence is approximately 3 times higher than that published in a French study on the incidence of bullous pemphigoid &#40;21&#46;7 cases per million people per year&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> There may be several explanations for this finding&#46; In recent years&#44; the number of cases of bullous pemphigoid has increased&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Possible reasons include increased use of DPP-4i and other drugs&#46; In addition&#44; the French study was published almost 8 years ago&#59; therefore&#44; we might expect the incidence to have increased&#46; Furthermore&#44; it is difficult to estimate prevalence based only on the hospital catchment population&#44; since some of the patients diagnosed with bullous pemphigoid in the last few years were from outside our area&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">These drugs are thought to increase the risk of bullous pemphigoid by up to 2&#46;8-fold&#44; especially in the case of vildagliptin and&#44; to a lesser extent&#44; linagliptin&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;7</span></a> Moreover&#44; small case series have reported a noninflammatory phenotype of bullous pemphigoid induced by DPP-4i&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a> In their major case-control study&#44; Kridin and Bergman<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> found no differences in the clinical pattern of presentation of bullous pemphigoid &#40;beyond greater involvement of the mucous membranes&#41;&#46; Since the study was retrospective&#44; the clinical description of the lesions was very poor&#44; as was the explicit evaluation of the mucous membrane&#44; and no differences were found in the cases we collected&#46; While many of these drugs are combined with metformin &#40;80&#46;64&#37; in the present cohort&#41;&#44; this drug was not associated with an increased risk of bullous pemphigoid in the univariate or the multivariate analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The median latency period between initiation of therapy with these antidiabetic agents and disease onset varies considerably depending on the study&#44; from 6 to 26&#46;4 months&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The median latency in our cohort was slightly higher &#40;27&#46;5 months&#41;&#44; perhaps because we defined onset as the point at which the patients came to our department&#46; Given that there may have been some delay until consultation&#44; our results seem consistent with those reported elsewhere&#46; We were unable to find studies that compared the latency of onset of bullous pemphigoid according to the type of gliptin used&#46; In our cohort&#44; linagliptin was the drug with which bullous pemphigoid appeared earliest&#46; A review of the literature indicates that the latency periods reported with this gliptin are similar to those we report&#44; although the cases are usually isolated&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The direct immunofluorescence pattern is similar in bullous pemphigoid associated with DPP-4i and in cases in which these drugs are not involved&#46; In the present cohort&#44; a negative direct immunofluorescence result was statistically significantly associated with the absence of DPP-4i&#44; whereas the presence of linear IgG at the dermal-epidermal junction was statistically significantly more common in cases of bullous pemphigoid associated with DPP-4i&#46; Although infrequent&#44; there have been reports of patients diagnosed with bullous pemphigoid in whom direct immunofluorescence is initially negative or indeterminate&#44; thus necessitating a second biopsy to confirm the diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> According to our cohort&#44; false negatives were less common in patients treated with DPP-4i&#44; although this was not confirmed with a second direct immunofluorescence assay&#46; Furthermore&#44; detection of linear IgG with or without C3 in these patients seems to be more sensitive in the diagnosis of bullous pemphigoid&#46; This is a common finding in patients with bullous pemphigoid induced by drugs in general&#44; and not only in those cases where the disease is induced by DPP-4i&#46; We found no studies that evaluate the difference in direct immunofluorescence patterns of bullous pemphigoid according to the presence of these antidiabetic drugs&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Discontinuation of treatment was associated with complete clinical remission in most patients&#44; thus confirming similar data reported elsewhere&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In contrast&#44; other authors did not find differences in the clinical response between patients who discontinued therapy with gliptins and those who continued therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The main limitation of our study is that data were collected retrospectively&#46; This prevented us from evaluating the clinical characteristics of patients&#44; since this information was not available in the clinical history in many cases&#46; In addition&#44; it would have been interesting to study the serological values of the patients&#8217; anti&#8211;basement membrane antibodies and to determine whether there are differences between patients taking gliptins and patients who were not&#44; even though other authors report no differences&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> We do not routinely use these analytical markers&#44; except in patients with discrepant clinical-pathological data in whom direct immunofluorescence testing is negative&#46; Our study has an advantage over other studies in that we avoided Berkson bias by selecting patients in whom bullous pemphigoid was diagnosed based on histology&#46; The small sample is a disadvantage when attempting to draw robust conclusions&#44; although our sample was very similar to or even larger than those of similar previously published studies&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In conclusion&#44; the prevalence of treatment with DPP-4i in patients diagnosed with bullous pemphigoid is high&#46; The direct immunofluorescence pattern observed in these patients may differ from that observed in those who are not receiving DPP-4i&#44; with a higher frequency of positive results in direct immunofluorescence testing for the combination linear IgG-C3&#46; We also observed that the latency period between initiation of the drug and onset of bullous pemphigoid was significantly shorter with linagliptin than with the other gliptins&#46; Discontinuation of DPP-4i combined with the usual treatment for bullous pemphigoid results in a complete clinical response in almost all patients&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflicts of interest</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The association between dipeptidyl peptidase 4 inhibitors &#40;DPP-4i&#41; and bullous pemphigoid &#40;BP&#41; has been demonstrated in several studies&#46; The main aim of this study was to estimate the use of DPP-4i treatment in patients diagnosed with BP in our setting&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">We selected patients histologically diagnosed with BP in our department between October 2015 and October 2018 and performed a retrospective chart review to assess clinical and epidemiological data and direct immunofluorescence &#40;DIF&#41; patterns&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Of the 70 patients diagnosed with BP during the study period&#44; 50&#37; were diabetic and 88&#46;57&#37; of these were being treated with a DPP-4i when diagnosed with BP&#46; The most common DPP-4i was linagliptin &#40;used in 18&#46;6&#37; of patients&#41;&#44; followed by vildagliptin &#40;17&#46;1&#37;&#41;&#46; The median latency period between initiation of DPP-4i treatment and diagnosis of BP was 27&#46;5 months for all treatments&#44; 16 months for linagliptin&#44; and 39 months for vildagliptin &#40;log rank &#60; 0&#46;01&#41;&#46; A negative DIF result was significantly more common in patients not being treated with a DPP-4i&#46; The DIF pattern most strongly &#40;and significantly&#41; associated with DPP-4i treatment was linear immunoglobulin G deposits along the dermal-epidermal junction&#46; DPP-4i treatment was withdrawn in 87&#37; of patients and 96&#37; of these achieved a complete response&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">DPP-4i treatment is very common in patients with BP in our setting&#46; The latency period between start of treatment and onset of BP seems to be shorter with linagliptin than with other types of gliptins&#46; Patients receiving DPP-4i treatment may show different DIF patterns to those not receiving treatment&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La asociaci&#243;n entre los inhibidores de la dipeptidil peptidasa 4 &#40;iDPP-4&#41; y el penfigoide ampolloso &#40;PA&#41; se ha demostrado en varios estudios&#46; El objetivo principal de este estudio era estimar el uso del tratamiento con iDPP-4i en pacientes diagnosticados de PA en nuestro entorno&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Seleccionamos pacientes diagnosticados histol&#243;gicamente de PA en nuestro departamento entre octubre de 2015 y octubre de 2018&#46; Realizamos una revisi&#243;n retrospectiva para evaluar los datos cl&#237;nicos-epidemiol&#243;gicos y los patrones de inmunofluorescencia directa &#40;IFD&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">De los 70 pacientes diagnosticados con PA durante el per&#237;odo de estudio&#44; el 50&#37; eran diab&#233;ticos y el 88&#44;57&#37; de ellos estaban siendo tratados con un iDPP-4 en el momento del diagn&#243;stico de PA&#46; El iDPP-4 m&#225;s frecuente era la linagliptina &#40;utilizada en el 18&#44;6&#37; de los pacientes&#41;&#44; seguida de la vildagliptina &#40;el 17&#44;1&#37;&#41;&#46; La mediana de tiempo de latencia entre el inicio del tratamiento con iDPP-4 y el diagn&#243;stico de PA fue de 27&#44;5 meses&#44; siendo de 16 meses para la linagliptina y 39 meses para la vildagliptina &#40;log Rank &#60; 0&#44;01&#41;&#46; La IFD fue negativaUn resultado negativo de DIF fue significativamente m&#225;s com&#250;n en pacientes que no fueron tratados con un DPP-4i&#46; El patr&#243;n DIF m&#225;s fuertemente &#40;y significativamente&#41; asociado con el tratamiento con DPP-4i fueron los dep&#243;sitos lineales de inmunoglobulina G a lo largo de la uni&#243;n dermoepid&#233;rmica&#46; El tratamiento con DPP-4i se retir&#243; en el 87&#37; de los pacientes y el 96&#37; de ellos logr&#243; una respuesta completa&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">El tratamiento con DPP-4i es muy com&#250;n en pacientes con BP en nuestro entorno&#46; El per&#237;odo de latencia entre el inicio del tratamiento y el inicio de la PA parece ser m&#225;s corto con linagliptina que con otros tipos de gliptinas&#46; Los pacientes que reciben tratamiento con DPP-4i pueden mostrar patrones DIF diferentes a los que no reciben tratamiento&#46;</p></span>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">31&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" 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">&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">&#46;09&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>Male&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">19 &#40;54&#46;3&#37;&#41;&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">16 &#40;47&#46;3&#41;&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">&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\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female&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">12 &#40;34&#46;3&#37;&#41;&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">23 &#40;65&#46;7&#37;&#41;&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
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Mean &#40;SD&#41; age&#44; y</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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&#46;71 &#40;8&#46;4&#41;&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">77&#46;38 &#40;12&#46;9&#41;&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
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                  \t\t\t\t">&#46;1&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
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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">&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">&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">&#46;7&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>Urticarial phase &#47;eczema&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">10 &#40;32&#37;&#41;&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">13 &#40;33&#37;&#41;&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">&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>Bullous phase&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">6 &#40;19&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;25&#37;&#41;&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
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pattern&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Not Receiving DPP-4i&nbsp;\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
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                  \t\t\t\t">Negative&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">3&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">11&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"><span class="elsevierStyleBold">&#46;04</span>&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">Linear IgG positive&#47;negative&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">24&#47;6&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">20&#47;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"><span class="elsevierStyleBold">&#46;02</span>&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">Linear C3 positive&#47;negative&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">24&#47;6&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">22&#47;15&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">&#46;72&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">Granular C3 positive&#47;negative&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&#47;30&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&#47;36&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">&#46;3&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">IgA in inflammatory cells positive&#47;negative&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&#47;27&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#47;33&nbsp;\t\t\t\t\t\t\n
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                            1 => "F&#46; T&#233;tart"
                            2 => "L&#46; Fardet"
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Información del artículo
ISSN: 15782190
Idioma original: Inglés
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