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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Beh&#231;et&#39;s disease &#40;BD&#41; is a systemic vasculitis of unknown cause&#44; classified among the Variable Vessel Vasculitis by the 2012 Revised International Chapel Hill Consensus Conference&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> It was first described in 1937&#44; by Hulusi Beh&#231;et&#44; as a triad of recurrent oral and genital aphthosis and uveitis&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> In addition to these classic symptoms&#44; BD is a chronic disease&#44; with a cumulative course&#44; marked by periods of exacerbations and remissions&#44; that may affect several systems such as articular&#44; vascular&#44; neurological&#44; gastrointestinal&#44; cardiac&#44; pulmonary&#44; or others&#46; Therefore&#44; the disease spectrum ranges from mucocutaneous manifestations to deep organ disease with relevant morbidity and life-threatening involvement&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Although BD has a worldwide distribution&#44; its prevalence is higher along the ancient &#8220;silk route&#8221; extending from the Mediterranean region to the Middle East and Far East countries&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;4</span></a> BD prevalence varies from 20&#8211;420&#47;100&#44;000 inhabitants in Turkey to 0&#46;27&#8211;0&#46;63&#47;100&#44;000 inhabitants in the United Kingdom&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Organic involvement and BD&#39;s clinical course exhibit different phenotypes in different regions&#44; although the factors that lead to these differences are not exact&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;4&#44;7</span></a> To date&#44; the etiological factors of BD remains speculative&#46; Nevertheless&#44; infectious agents&#44; genetic causes&#44; immunological susceptibility factors&#44; and fibrinolysis defects have been implicated in BD&#39;s etiopathogenesis&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> An association of BD with the presence of HLA-B&#42;51 allele has been reported&#44; which was associated with greater susceptibility to the disease in the countries with the highest prevalence&#46; However&#44; this association does not appear in western countries&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> HLA-B&#42;51 positivity is not related to BD severity&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The severity of BD manifestations is known to be greater in men due to an increase in morbidity related to ocular&#44; vascular&#44; and neurological manifestations of BD<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#44;10&#8211;16</span></a> and in younger patients at the onset of disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#44;17&#8211;19</span></a> It has also been described in cohorts of patients with ocular involvement who present erythema nodosum&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11&#44;13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The purpose of this study was to evaluate clinical factors that are associated with the manifestations of severe BD in a single-center cohort&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Setting&#44; patients&#44; and study design</span><p id="par0030" class="elsevierStylePara elsevierViewall">In our center&#44; we carried out a prospective&#44; longitudinal cohort study including all patients with diagnostic criteria for BD according to the International Study Group &#40;ISG&#41; in 1990&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> followed as an outpatient in Clinical Immunology Unit of Centro Hospitalar e Universit&#225;rio do Porto&#44; between January-1981 and January-2020&#46; &#40;Centro Hospitalar e Universit&#225;rio do Porto&#41; is a tertiary-care university hospital in Porto&#44; northern Portugal&#46; The patients that were referred to our consultation with signs or symptoms suggestive of BD or with BD diagnosis were included in our database and the manifestations were recorded as they arose during the follow-up period&#46; Some manifestations&#44; namely those that were already present before admission to consultation&#44; were registered according to the patient&#39;s information&#44; as the onset of the first symptoms&#46; Therefore&#44; although the study is essentially prospective&#44; it has a retrospective component that must be considered&#46; On the other hand&#44; for the purpose of this study&#44; we included only patients with BD criteria&#44; according to the ISG&#44; based on the manifestations presented throughout the follow-up&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Due to the long follow-up period&#44; it was not possible to obtain informed consent from all patients&#46; Thus&#44; institutional authorizations were requested to carry out this study&#46; Hospital Ethics Committee approved the study design&#44; and informed consent was waived &#91;study number 2020-162&#40;127-DEFI-129-CE&#41;&#93;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Data and definitions</span><p id="par0040" class="elsevierStylePara elsevierViewall">We collected data regarding demographic features and symptoms of BD &#40;each time of appearance of mucosae manifestations &#8211; oral aphthosis&#44; genital aphthosis&#59; skin manifestations &#8211; erythema nodosum&#44; pseudofolliculitis&#59; joint manifestations &#8211; arthralgias&#44; monoarthritis&#44; polyarthritis&#44; spondyloarthritis&#59; ocular&#44; neurological&#44; vascular&#44; gastrointestinal and cardiac involvement&#41;&#46; Ocular manifestations include uveitis&#44; retinal vasculitis&#44; papillitis&#44; conjunctivitis&#44; and scleritis&#46; Neurological manifestations include the hemispheric&#44; brainstem&#44; and spinal cord syndromes&#44; dural sinus thrombosis&#44; and arterial occlusion of the central nervous system &#40;CNS&#41; vessels&#46; Vascular manifestations include deep vein thrombosis&#44; thrombophlebitis&#44; arterial aneurysms&#44; and arterial occlusion other than CNS vessels&#46; Esophageal&#44; gastroduodenal&#44; intestinal&#44; and perianal ulcers&#44; digestive bleeding from ulcers&#44; bowel perforation&#44; and chronic inflammatory diarrhea were reported as gastrointestinal manifestations&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">To evaluate BD severity&#44; we used Krause&#39;s total clinical severity score &#40;CSS&#41; as it was the most commonly used index in previous studies&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> This score<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> was calculated as the sum of 1 point each for mild symptoms &#40;oral aphthosis&#44; genital ulcers&#44; arthralgia&#44; and typical skin lesions such as erythema nodosum&#44; papulopustular lesions&#44; and folliculitis&#41;&#44; 2 points each for moderate symptoms &#40;arthritis&#44; deep vein thrombosis of the legs&#44; anterior uveitis&#44; and gastrointestinal involvement&#41;&#44; and 3 points each for severe disease manifestations &#40;posterior&#47;panuveitis&#44; retinal vasculitis&#44; arterial thrombosis&#44; neuro-Beh&#231;et&#39;s and bowel perforation&#41;&#46; The data used for analysis comprises the cumulative manifestations that have ever occurred in a specific patient&#46; The BD patients were categorized according to the CSS as follows&#58; severe BD a score<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleUnderline">&#62;</span><span class="elsevierStyleHsp" style=""></span>4 points and mild BD a score<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>4 points&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> We have also evaluate the overall damage associated with BD according to the Beh&#231;et&#39;s Syndrome Overall Damage Index &#40;BODI&#41; score&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The presence of HLA-B&#42;51 allele was also collected&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The age at the beginning of the first manifestations attributed to BD&#44; reported by the patient&#44; was considered the age at onset&#44; regardless of the time the diagnosis was made&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Our sample refers to a population followed in a specialized outpatient clinic&#44; including patients referred from primary health care and other hospitals and&#44; therefore&#44; includes the most severe disease cases&#46; Thus&#44; this selection bias can mean that our sample may be underrepresented in terms of milder cases&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Categorical variables are presented as an absolute value and relative frequency&#44; and the numerical variables as mean<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleUnderline">&#43;</span><span class="elsevierStyleHsp" style=""></span>standard deviation &#40;SD&#41;&#46; For comparison between groups&#44; the Pearson Chi-square test was used for categorical variables or the Fisher&#39;s exact test&#59; the Student <span class="elsevierStyleItalic">t</span>-test was used for numerical variables&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The multivariate analysis included the variables with a statistically significant association with severe BD in the univariate analysis &#40;defined as <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1&#41; and the demographic data&#46; A multivariate&#44; forward stepwise&#44; logistic regression analysis was performed&#44; defining severe BD as the dependent variable&#46; We constructed three different models for the multivariate analysis&#46; Each of them used age at different times&#44; as presented along with this work &#40;age at onset&#44; age at diagnosis&#44; and current age&#41;&#46; Multivariate analysis results are expressed as odds ratios &#40;OR&#41; with a 95&#37; confidence interval &#40;95&#37; CI&#41; and <span class="elsevierStyleItalic">p</span>-value&#46; The goodness of fit for all regressions was checked using the Hosmer&#8211;Lemeshow test&#46; Statistical significance was set for <span class="elsevierStyleItalic">p</span> values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; All statistical tests were 2-sided&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Statistical analyses were performed using SPSS software &#40;SPSS for Windows&#44; version 24&#44; Chicago&#44; IL&#44; USA&#41;&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">Our cohort includes 243 patients followed between 1981 and 2020&#44; of which 75 &#40;31&#37;&#41; patients are male&#46; The current age was 49&#46;9 &#40;<span class="elsevierStyleUnderline">&#43;</span>14&#46;3&#41; years old &#40;y&#46;o&#46;&#41;&#44; the follow-up time was 14&#46;6 &#40;<span class="elsevierStyleUnderline">&#43;</span>8&#46;1&#41; years&#46; The first signs and symptoms of the disease started at 28 &#40;<span class="elsevierStyleUnderline">&#43;</span>13&#46;3&#41; y&#46;o&#46; B&#46;D diagnosis were established when patients had&#44; at the mean&#44; 34&#46;7 &#40;<span class="elsevierStyleUnderline">&#43;</span>12&#46;3&#41; y&#46;o&#46; BD diagnosis was established&#44; on average&#44; 6&#46;6 &#40;<span class="elsevierStyleUnderline">&#43;</span>7&#46;8&#41; years after the onset of the first symptoms&#44; and 0&#46;6 &#40;<span class="elsevierStyleUnderline">&#43;</span>2&#46;2&#41; years after admission to our consultation&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The HLA-B&#42;51 allele was only accessed in 200 &#40;82&#37;&#41; patients and present in 108 &#40;54&#37;&#41;&#46; The mean Krause CSS was 5&#46;7 &#40;<span class="elsevierStyleUnderline">&#43;</span>3&#46;5&#41; points and a BODI score of 0&#46;7 &#40;<span class="elsevierStyleUnderline">&#43;</span>1&#46;5&#41; points&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Regarding organ manifestations&#44; during the follow-up period&#44; all patients had mucosae manifestations &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>243&#44; 100&#37;&#41;&#44; 133 &#40;55&#37;&#41; had cutaneous&#44; 104 &#40;43&#37;&#41; joint&#44; 71 &#40;29&#37;&#41; ocular&#44; 48 &#40;20&#37;&#41; vascular&#44; 47 &#40;19&#37;&#41; neurological&#44; 22 &#40;9&#37;&#41; gastrointestinal and 1 &#40;0&#46;4&#37;&#41; cardiac involvement by BD&#46; Manifestations by organ are detailed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">In most patients&#44; mucosae manifestations were the first symptoms of BD &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>234&#44; 96&#37;&#41;&#46; Skin involvement was present at BD onset in 29 &#40;12&#37;&#41; patients&#46; Patients exhibited signs of skin involvement seven years after the appearance of first signs of BD&#46; Articular&#44; ocular&#44; vascular&#44; gastrointestinal&#44; and cardiac manifestations appear later in the disease course&#44; more than nine years after the first BD signs&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> presents the time elapsed between first signs of BD and each organ manifestation&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Besides BD&#44; 22 patients presented overlap with other autoimmune diseases&#44; namely&#44; seven patients with Sj&#246;gren&#39;s syndrome&#44; five with ankylosing spondylitis&#44; two with psoriatic arthritis&#44; two with psoriasis without joint involvement&#44; two with antiphospholipid syndrome&#44; one with rheumatoid arthritis&#44; one with idiopathic thrombocytopenic purpura and another with temporal arteritis&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Severe BD</span><p id="par0105" class="elsevierStylePara elsevierViewall">Considering Krause&#39;s CSS&#44; 156 &#40;64&#46;2&#37;&#41; patients were classified as having severe BD&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> summarizes the data regarding the comparison of subgroups with mild and severe BD&#46; The proportion of men with severe DB was higher &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;029&#41;&#46; Although patients with severe BD were older &#40;51&#46;1 <span class="elsevierStyleItalic">vs&#46;</span> 47&#46;8 y&#46;o&#46;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;087&#41;&#44; we found no differences regarding age at onset of disease &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;755&#41; nor the age of diagnosis &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;553&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">The HLA-B&#42;51 allele was only accessed in 128 patients with severe BD&#44; and was present in 72 &#40;56&#37;&#41; of them&#46; We found no differences regarding the presence of HLA-B&#42;51 allele positivity comparing mild and severe BD &#40;51&#46;4&#37; <span class="elsevierStyleItalic">vs&#46;</span>56&#46;3&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;555&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">In our cohort&#44; all patients had oral aphthosis during the follow-up period&#44; and 75&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>181&#41; had genital ulcers&#46; We found no differences regarding the presence of genital aphthosis between mild and severe BD patients &#40;77&#37; <span class="elsevierStyleItalic">vs&#46;</span> 73&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;542&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">On the other hand&#44; among the 133 patients that had cutaneous manifestations&#44; we found skin involvement more frequent in the group of patients with severe BD&#44; both at onset and cumulative BD manifestations &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; specifically erythema nodosum &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and pseudofolliculitis &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; No significant differences were found regarding the frequency of manifestations at mucosae&#44; joint&#44; ocular&#44; vascular&#44; neurological&#44; and gastrointestinal at BD onset&#46; On the other hand&#44; the presence of articular&#44; ocular&#44; vascular&#44; neurological and gastrointestinal manifestations is higher in patients with severe BD&#44; as is excepted by the Krause&#39;s CSS calculus&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">No differences were found regarding the prevalence of other autoimmune diseases&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">BD damage&#44; evaluated by the BODI score&#44; was significantly higher among patients with severe BD &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows the variables related to severe BD&#44; expressed in simple OR&#44; and the multivariate analysis results&#44; including clinical and demographic features&#46; In the univariate and multivariate analysis models&#44; in addition to demographic data&#44; we included only mucosae and skin manifestations&#46; Using the Krause&#39;s CSS&#44; patients who present articular&#44; vascular&#44; neurological and gastrointestinal manifestations will be included in a severe disease category due to the score attributed to this type of manifestations&#44; together with the point assigned to the classical features of BD&#46; Thus&#44; if we included those variables in the models&#44; we would be evaluating the same factor twice&#44; so we chose not to include them&#46; We constructed three different models for the multivariate analysis&#44; in each one of them using a different age &#8211; current age&#44; age at onset&#44; and age at diagnosis&#46; The results were the same in those three models&#59; none of them returned age as an output&#46; Variables independently associated with severe BD were male gender &#40;<span class="elsevierStyleItalic">Adjusted OR</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;961&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;047&#41;&#44; erythema nodosum &#40;<span class="elsevierStyleItalic">Adjusted OR</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#46;561&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; and pseudofolliculitis &#40;<span class="elsevierStyleItalic">Adjusted OR</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;372&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0135" class="elsevierStylePara elsevierViewall">Although associations between clinical manifestations of BD and a more severe course of the disease have been described&#44; most of these associations were described in subgroups of patients who have a specific type of organ involvement&#44; such as ocular&#44; intestinal&#44; among others&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#44;10&#8211;13&#44;15&#8211;19&#44;25</span></a> Our cohort included all patients followed at our center&#44; regardless of specific organ involvement&#46; This study revealed the association of the male gender as well as the presence of erythema nodosum and pseudofolliculitis&#44; as clinical characteristics that are independently associated with manifestations of severe BD&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">As for gender differences&#44; several studies reported a higher incidence of ocular&#44; vascular&#44; and neurological impairment in men&#44;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">10&#44;12&#44;15&#44;16</span></a> although in the latter case&#44; the results were sometimes contradictory&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> Using a modified form of the BD total activity index to access BD severity&#44; G&#252;l<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> in a cohort of 148 patients&#44; described an increased risk of severe disease in men&#44; in a logistic regression including demographic data&#44; family history&#44; and HLA-B&#42;51 allele positivity&#44; without including other clinical features in the analysis&#46; Furthermore&#44; Balta<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> described a higher incidence of ocular&#44; neurological&#44; and vascular manifestations in men&#44; comparing each organic manifestation&#39;s prevalence between men and women&#46; Likewise&#44; Cansu<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> described a higher incidence of vascular and ocular damage in men&#44; just as Davatchi<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> described a strong association between male sex and vascular damage&#46; In a study that addresses BD&#39;s mortality conducted by Saadoun&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> male sex and arterial involvement were independently associated with mortality&#46; On the other hand&#44; Bang<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> reported a higher prevalence of neurological disorders in women compared to men&#46; Based on these studies&#44; it is known that the disease has a more severe phenotype in men&#46; However&#44; the variability in the BD severity definition used in different studies makes it difficult to compare results&#46; Our study corroborates this association&#44; demonstrating the independent association of male gender with the most severe forms of BD in the global expression of the disease and not only limited to a subgroup of clinical manifestations&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The presence of erythema nodosum as a prognostic factor for the severe disease was only described in patients with ocular disease&#46; Likewise&#44; the definitions used to address BD&#39;s severity in these ocular cohorts differ&#46; Using a worse visual prognosis as an outcome in a cohort of ocular BD&#44; Hu<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> described a more severe BD in males presenting erythema nodosum&#46; On the other hand&#44; defining severe disease as death&#44; blindness&#44; vascular&#44; neurological&#44; lung&#44; gastrointestinal and articular BD involvement&#44; Zouboulis<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> described a more severe disease in patients presenting a triad of symptoms&#58; ocular BD&#44; erythema nodosum&#44; and thrombophlebitis&#46; Our study shows that erythema nodosum is independently associated with the most severe manifestations of BD and that this association is not limited to ocular BD cohorts&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">A higher incidence of pseudofolliculitis has been more described in males than in females in several studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">12&#44;18&#44;19</span></a> although others found no differences between genders&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> The presence of pseudofolliculitis had not previously been described as a factor independently associated with severe BD manifestations&#46; The prevalence of pseudofolliculitis is very variable in different geographical locations&#44; with a reported prevalence of 39&#37; from Egypt to 91&#37; in Jordan&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> In our population&#44; the prevalence of pseudofolliculitis is low &#40;39&#46;5&#37;&#41; compared to other series with many patients included&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">25&#44;27&#44;28</span></a> However&#44; given BD&#39;s phenotypic variation in different locations&#44; this association described in our cohort may not be reproducible in other populations&#46; Further studies extended to other population groups are necessary to confirm it&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">In our study&#44; the increase of the current age is associated with severe BD&#44; with the odds for severe BD increasing 2&#37; per year&#44; without considering interaction with other factors&#46; This finding is in accordance with the disease&#39;s progressive course and the appearance of organ manifestations over the years&#46; However&#44; when age was analyzed together with other factors&#44; we found no association between severe BD and the patient&#39;s age&#46; The onset of BD clinical manifestations is around the third decade of life in most studies&#44;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> the same in our population&#44; 28&#46;1 years&#46; We did not find any association between the age of onset of symptoms and severe BD&#46; Studies that reported this association analyzed the effect of age without considering interaction with other factors<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">18&#44;19</span></a> or considered only a group of patients with a specific organ target&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17&#44;29&#44;30</span></a> Yazici<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> demonstrated that men with the onset of symptoms before 24 y&#46;o&#46; had more eye disease&#46; Alpsoy<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> showed that patients with age at onset under 40 y&#46;o&#46; had more ocular involvement and genital ulcers&#46; In patients with intestinal BD&#44; Jung<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> reported that age at onset&#44; greater severity of the intestinal disease&#44; and the prevalence of volcano-shaped ulcers are associated with a worse prognosis&#46; Also&#44; in patients with intestinal BD&#44; Zhang<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> associated the earlier age at onset with shorter event-free survival&#46; Similarly&#44; in a cohort with ocular BD&#44; Belkhadir<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> describes a worse ocular outcome in patients with earlier age at onset and with a higher number of recurrences&#46; The authors raise the hypothesis that this association with age may be due to greater exposure to BD flares throughout life&#44; with periods of exacerbation and cumulative damage and not precisely more severe manifestations when they appear at an earlier age&#44; however&#44; this study does not allow us to draw these connections&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">As in previous studies&#44; there was no association between the HLA-B&#42;51 allele&#39;s positivity and the presence of severe BD&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Regarding the sequence of manifestations&#8217; appearance&#44; in most patients of our cohort&#44; mucosae manifestations were the first to appear&#44; followed by skin involvement&#44; around seven years later&#46; Other organ manifestations arose almost a decade later&#46; Thus&#44; we believe that these clinical characteristics can assist the clinician in the follow-up of these patients and serve as a warning sign for earlier detection and timely treatment and prevention of deep organ damage&#46; It is important to notice in these time interval&#39;s analysis&#44; that the real differences may not be that big&#46; On the one hand&#44; both mucosal and cutaneous manifestations are detectable without the use of complementary exams and&#44; therefore&#44; they can either be either noticed by the patient or be observed by the clinic&#44; and thus&#44; be detected practically at the onset time&#46; On the other hand&#44; usually deep organ involvement diagnosis requires complementary tests and&#44; therefore&#44; can be detected later&#46; Over the past few years&#44; technological developments in terms of complementary tests have increased the detection of BD&#39;s deep organ manifestations&#44; namely vascular and neurological involvement&#44; among others&#46; In our study&#44; due to the long follow-up period&#44; these manifestations&#44; especially for the patients included within the first years&#44; may be underrepresented&#44; although the long inclusion period together with the cumulative BD manifestations presented&#44; tends to lessen this problem&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">BD diagnosis relies basically on the identification of several clinical characteristics&#44; that can emerge separated by several years&#44; enough to fulfill the classification criteria &#40;with a specificity above 95&#37; <a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">31</span></a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">32&#44;33</span></a> This can represent underdiagnosis in the initial stages and accounts for the lag time between the BD onset and diagnosis&#44; on average&#44; 7 years in our study&#46; Furthermore&#44; some BD phenotypes can mimic other autoinflammatory diseases&#44; especially the antineutrophil cytoplasmatic antibodies &#40;ANCA&#41;-associated vasculitis &#40;AAV&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">34</span></a> The distinction between these entities can be a challenge&#44; due to manifestations overlap&#46; ANCA positivity does not always help in the diagnosis&#58; there are ANCA-negative AAV&#44; and&#44; on the other hand&#44; ANCA has been detected in a wide range of diseases&#44; other than AAV<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">35</span></a>&#44; including BD with vascular involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">34</span></a> To date&#44; no known biomarker has been reported for BD&#39;s&#44; but efforts have been made&#46;32 Both factors can introduce a diagnostic bias in our study&#44; underrepresenting BD cases at an earlier stage and&#44; also&#44; patients with atypical presentations&#46; The authors believe that&#44; in the future&#44; the identification of such biomarkers can help to distinguish these diseases&#44; and possibly allow an earlier diagnosis&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Our study&#39;s main strengths lie in the fact that we have considered the multiorgan manifestations of BD and were not limited to a specific organ&#44; in the high number of patients followed in our center&#44; and in the long follow-up period&#46; The main weaknesses of this study are due to its observational nature with its inherent limitations as well as to the fact that we used a definition for severe BD a score with a final result that can translate just one or an association of organs&#44; which can hide whether these associations are due to a preferential organ achievement&#46; In our opinion&#44; our study raises future questions&#44; namely whether these associations vary with gender or with the involvement of a specific organ&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0175" class="elsevierStylePara elsevierViewall">Male gender&#44; erythema nodosum&#44; and pseudofolliculitis were associated with severe DB&#46; Mucous manifestations are usually the first sign of the disease and&#44; together with skin involvement&#44; usually&#44; appear before other organs are affected&#46; Thus&#44; these manifestations can help as an alert for the clinician&#44; indicating that the patient who presents them may develop severe BD manifestations in the future&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Funding sources</span><p id="par0180" 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="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interest</span><p id="par0185" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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          "titulo" => "Keywords"
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          "titulo" => "Resumen"
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              "titulo" => "Introducci&#243;n"
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            1 => array:2 [
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              "titulo" => "Objetivos"
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              "titulo" => "M&#233;todos"
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              "titulo" => "Resultados"
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              "titulo" => "Discusi&#243;n"
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          "titulo" => "Palabras clave"
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          "titulo" => "Introduction"
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          "titulo" => "Methods"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Setting&#44; patients&#44; and study design"
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          "identificador" => "sec0055"
          "titulo" => "Conflict of interest"
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        11 => array:2 [
          "identificador" => "xack672400"
          "titulo" => "Acknowledgements"
        ]
        12 => array:1 [
          "titulo" => "References"
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      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-12-06"
    "fechaAceptado" => "2021-03-25"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1655050"
          "palabras" => array:6 [
            0 => "Beh&#231;et&#39;s disease"
            1 => "Adamantiades&#8211;Beh&#231;et disease"
            2 => "Vasculitis"
            3 => "Prognosis"
            4 => "Erythema nodosum"
            5 => "Pseudofolliculitis"
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      ]
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          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1655049"
          "palabras" => array:6 [
            0 => "Enfermedad de Beh&#231;et"
            1 => "Enfermedad de Adamantiades-Beh&#231;et"
            2 => "Vasculitis"
            3 => "Pron&#243;stico"
            4 => "eritema nudoso"
            5 => "Pseudofoliculitis"
          ]
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Beh&#231;et&#39;s disease &#40;BD&#41; is a systemic vasculitis of unknown cause&#46; The spectrum of the disease ranges from mucocutaneous manifestations to other organ diseases with relevant morbidity&#46; Associations between disease severity and male sex&#44; earlier age at onset&#44; and the presence of erythema nodosum have been described&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To evaluate clinical factors associated with manifestations of severe disease in a single-center cohort&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A longitudinal&#44; prospective&#44; unicentric cohort study with patients followed in a specialized outpatient clinic between 1981 and 2020&#46; Severe BD was defined as a Krause total clinical severity score <span class="elsevierStyleUnderline">&#62;</span>4 points&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We included 243 patients&#44; of whom 31&#37; were male&#44; with an average follow-up time of 14&#46;6 years&#46; Regarding organ manifestations&#44; all patients had mucous manifestations &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>243&#44; 100&#37;&#41;&#44; 133 &#40;55&#37;&#41; skin&#44; 104 &#40;43&#37;&#41; joint&#44; 71 &#40;29&#37;&#41; ocular&#44; 48 &#40;20&#37;&#41; vascular&#44; 47 &#40;19&#37;&#41; neurological&#44; 22 &#40;9&#37;&#41; gastrointestinal and 1 &#40;0&#46;4&#37;&#41; cardiac involvement by BD&#46; One hundred fifty-six &#40;64&#37;&#41; patients were classified as having severe BD&#46; Severe BD was more frequent in men &#40;<span class="elsevierStyleItalic">OR</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;004&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#41;&#44; increasing with age &#40;<span class="elsevierStyleItalic">OR</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;021 per year&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;037&#41;&#44; in the presence of skin manifestations &#40;<span class="elsevierStyleItalic">OR</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;711&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; specifically erythema nodosum &#40;<span class="elsevierStyleItalic">OR</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#46;381&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; and pseudofolliculitis &#40;<span class="elsevierStyleItalic">OR</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;910&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In the multivariate model&#44; variables independently associated with severe BD were male gender &#40;<span class="elsevierStyleItalic">Adjusted OR</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;961&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;047&#41;&#44; erythema nodosum &#40;<span class="elsevierStyleItalic">Adjusted OR</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#46;561&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and pseudofolliculitis &#40;<span class="elsevierStyleItalic">Adjusted OR</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;372&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discussion</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Male gender&#44; erythema nodosum&#44; and pseudofolliculitis were independently associated with severe BD forms and therefore should serve as warning signs to the clinician&#46;</p></span>"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La enfermedad de Beh&#231;et &#40;EB&#41; es una vasculitis sist&#233;mica de causa desconocida&#46; El espectro de la enfermedad abarca desde manifestaciones mucocut&#225;neas hasta otras enfermedades de &#243;rganos con morbilidad relevante&#46; Se han descrito asociaciones entre la gravedad de la enfermedad y el sexo masculino&#44; la edad de inicio m&#225;s temprana y la presencia de eritema nudoso&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Evaluar los factores cl&#237;nicos asociados con las manifestaciones de enfermedad grave en una cohorte de un solo centro&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Estudio de cohorte longitudinal&#44; prospectivo y unic&#233;ntrico con pacientes seguidos en una cl&#237;nica ambulatoria especializada entre 1981 y 2020&#46; La EB grave se defini&#243; como una puntuaci&#243;n <span class="elsevierStyleItalic">Krause total clinical severity score</span><span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>4 puntos&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 243 pacientes&#44; de los cuales el 31&#37; eran varones&#44; con un tiempo de seguimiento medio de 14&#44;6 a&#241;os&#46; En cuanto a las manifestaciones org&#225;nicas&#44; todos los pacientes presentaron manifestaciones mucosas &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>243&#44; 100&#37;&#41;&#44; 133 &#40;55&#37;&#41; piel&#44; 104 &#40;43&#37;&#41; articular&#44; 71 &#40;29&#37;&#41; ocular&#44; 48 &#40;20&#37;&#41; afectaci&#243;n vascular&#44; 47 &#40;19&#37;&#41; neurol&#243;gica&#44; 22 &#40;9&#37;&#41; gastrointestinal y 1 &#40;0&#44;4&#37;&#41; cardiaca por EB&#59; 156 &#40;64&#37;&#41; pacientes fueron clasificados como con EB grave&#46; La EB severa fue m&#225;s frecuente en hombres &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;004&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;024&#41;&#44; aumentando con la edad &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;021 por a&#241;o&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;037&#41;&#44; en presencia de manifestaciones cut&#225;neas &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44;711&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; espec&#237;ficamente eritema nodosum &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#44;381&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y pseudofoliculitis &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;910&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">En el modelo multivariado&#44; las variables asociadas de forma independiente con el EB grave fueron el sexo masculino &#40;OR ajustado<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;961&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;047&#41;&#44; eritema nudoso &#40;OR ajustado<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#44;561&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y pseudofoliculitis &#40;OR ajustado<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;372&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discusi&#243;n</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">El sexo masculino&#44; el eritema nudoso y la pseudofoliculitis se asociaron de forma independiente con formas graves de DB y&#44; por lo tanto&#44; deber&#237;an servir como signos de advertencia para el m&#233;dico&#46;</p></span>"
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            "titulo" => "Resultados"
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            "identificador" => "abst0050"
            "titulo" => "Discusi&#243;n"
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        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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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">Manifestations&#44; by organ&#44; <span class="elsevierStyleItalic">N</span> &#40;&#37;&#41;&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">243 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">22 &#40;9&#46;1&#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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Arthralgias</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">80 &#40;32&#46;9&#37;&#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
                  \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">Ocular</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">71 &#40;29&#46;2&#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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Uveitis</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">63 &#40;25&#46;9&#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
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\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\ttop\n
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                  \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">4 &#40;1&#46;6&#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 ; 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
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                  \t\t\t\t">5 &#40;2&#46;1&#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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Amaurosis</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
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                  \t\t\t\t\ttable-entry\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
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                  \t\t\t\t</td><td class="td" title="\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
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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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;11&#46;5&#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\ttop\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\ttable-entry\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
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                  \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\ttable-entry\n
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                  \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\ttop\n
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                  \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\ttop\n
                  \t\t\t\t">12 &#40;4&#46;9&#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
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                  \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\ttop\n
                  \t\t\t\t">5 &#40;2&#46;1&#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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Chronic headache</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\ttop\n
                  \t\t\t\t">20 &#40;8&#46;2&#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\ttop\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
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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">22 &#40;9&#46;1&#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
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                  \t\t\t\t\ttop\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\ttable-entry\n
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                  \t\t\t\t\ttop\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">4 &#40;1&#46;6&#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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Perianal ulcer</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">5 &#40;2&#46;1&#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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Digestive bleeding from ulcer</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\ttop\n
                  \t\t\t\t">4 &#40;1&#46;6&#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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Bowel perforation</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">5 &#40;2&#46;1&#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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Chronic inflammatory diarrhea</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">16 &#40;6&#46;6&#37;&#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
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  """
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            0 => array:1 [
              "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">&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">Time elapsed between onset of BD and each organ manifestation&#44; in years&#44; mean &#40;SD&#41;&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">Mucosae&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">0&#46;1 &#40;0&#46;04&#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">Skin&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">7&#46;4 &#40;0&#46;74&#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">Joint&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">11&#46;6 &#40;0&#46;96&#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">Ocular&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">11&#46;0 &#40;1&#46;12&#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">Vascular&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">9&#46;7 &#40;1&#46;32&#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">Neurological&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">14&#46;4 &#40;1&#46;66&#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">Gastrointestinal&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">9&#46;2 &#40;1&#46;58&#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">Cardiac&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">31 &#40;&#8211;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Time elapsed between first signs of Beh&#231;et&#39;s disease &#40;BD&#41; and each organ involvement&#46;</p>"
        ]
      ]
      2 => 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" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Statistical significance was set for p values &#60; 0&#46;05&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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">&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">Total &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>243&#41;&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">Mild BD &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>87&#41;&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">Severe BD &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>156&#41;&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"><span class="elsevierStyleItalic">p</span>&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"><span class="elsevierStyleItalic">Male gender&#44; N &#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75 &#40;30&#46;9&#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">19 &#40;21&#46;8&#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">56 &#40;35&#46;9&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;029</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"><span class="elsevierStyleItalic">Age &#40;current&#41; &#40;years&#41;&#44; mean &#40;<span class="elsevierStyleUnderline">&#43;</span>SD&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#46;9 &#40;<span class="elsevierStyleUnderline">&#43;</span>14&#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">47&#46;3 &#40;<span class="elsevierStyleUnderline">&#43;</span>13&#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">51&#46;3 &#40;<span class="elsevierStyleUnderline">&#43;</span>14&#46;2&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;036&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">Age at onset &#40;years&#41;&#44; mean &#40;<span class="elsevierStyleUnderline">&#43;</span>SD&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;1 &#40;<span class="elsevierStyleUnderline">&#43;</span>13&#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">27&#46;7 &#40;<span class="elsevierStyleUnderline">&#43;</span>14&#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">28&#46;3 &#40;<span class="elsevierStyleUnderline">&#43;</span>12&#46;7&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;755&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">Age at diagnosis &#40;years&#41;&#44; mean &#40;<span class="elsevierStyleUnderline">&#43;</span>SD&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#46;7 &#40;<span class="elsevierStyleUnderline">&#43;</span>12&#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">35&#46;3 &#40;<span class="elsevierStyleUnderline">&#43;</span>13&#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">34&#46;4 &#40;<span class="elsevierStyleUnderline">&#43;</span>11&#46;7&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;553&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="5" 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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Manifestations&#44; N &#40;&#37;&#41;</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="elsevierStyleHsp" style=""></span>Mucosae &#40;at onset&#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">234 &#40;96&#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">86 &#40;98&#46;9&#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">148 &#40;94&#46;9&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;163&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>Mucosae &#40;cumulative&#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">243 &#40;100&#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">87 &#40;100&#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">156 &#40;100&#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="char" 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="elsevierStyleHsp" style=""></span>Oral aphthosis&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">243 &#40;100&#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">87 &#40;100&#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">156 &#40;100&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&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>Genital aphthosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">67 &#40;77&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">114 &#40;73&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;542&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Skin &#40;at onset&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">29 &#40;11&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;2&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">27 &#40;17&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;0&#46;001</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Skin &#40;cumulative&#41;&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">133 &#40;54&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">27 &#40;31&#46;0&#37;&#41;&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">106 &#40;67&#46;9&#37;&#41;&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"><span class="elsevierStyleBold">&#60;0&#46;001</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"><span class="elsevierStyleHsp" style=""></span>Erythema nodosum&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">72 &#40;29&#46;6&#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
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                  \t\t\t\t">7 &#40;8&#46;0&#37;&#41;&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">66 &#40;42&#46;3&#37;&#41;&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"><span class="elsevierStyleBold">&#60;0&#46;001</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"><span class="elsevierStyleHsp" style=""></span>Pseudofolliculitis&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
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                  \t\t\t\t">96 &#40;39&#46;5&#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
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                  \t\t\t\t">21 &#40;24&#46;1&#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
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                  \t\t\t\t">75 &#40;48&#46;1&#37;&#41;&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"><span class="elsevierStyleBold">&#60;0&#46;001</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"><span class="elsevierStyleHsp" style=""></span>Joint &#40;at onset&#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
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                  \t\t\t\t">5 &#40;2&#46;1&#37;&#41;&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">1 &#40;1&#46;1&#37;&#41;&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">4 &#40;2&#46;6&#37;&#41;&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
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                  \t\t\t\t">0&#46;657&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>Joint &#40;cumulative&#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">104 &#40;42&#46;8&#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
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                  \t\t\t\t">17 &#40;19&#46;5&#37;&#41;&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="left" valign="\n
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                  \t\t\t\t">87 &#40;55&#46;8&#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="char" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;0&#46;001</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"><span class="elsevierStyleHsp" style=""></span>Ocular &#40;at onset&#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">5 &#40;2&#46;1&#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
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                  \t\t\t\t">0&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">5 &#40;3&#46;2&#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="char" valign="\n
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                  \t\t\t\t">0&#46;163&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>Ocular &#40;cumulative&#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">71 &#40;29&#46;2&#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">0&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="left" valign="\n
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                  \t\t\t\t">71 &#40;45&#46;5&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;0&#46;001</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"><span class="elsevierStyleHsp" style=""></span>Vascular &#40;at onset&#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">3 &#40;1&#46;2&#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
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                  \t\t\t\t">0&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">3 &#40;1&#46;9&#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="char" valign="\n
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                  \t\t\t\t">0&#46;555&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>Vascular &#40;cumulative&#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">48 &#40;19&#46;8&#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">4 &#40;4&#46;6&#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
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                  \t\t\t\t">44 &#40;28&#46;9&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;0&#46;001</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"><span class="elsevierStyleHsp" style=""></span>Neurological &#40;at onset&#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">2 &#40;0&#46;8&#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">0&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;1&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;538&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>Neurological &#40;cumulative&#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">47 &#40;19&#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">0&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">47 &#40;30&#46;1&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;0&#46;001</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"><span class="elsevierStyleHsp" style=""></span>Gastrointestinal &#40;at onset&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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        "texto" => "<p id="par0190" class="elsevierStylePara elsevierViewall">The authors would like to thank all members of Clinical Immunology Unit of Centro Hospitalar e Universit&#225;rio do Porto&#44; namely&#44; Isabel Almeida&#44; MD&#44; Ph&#46;D&#46;&#59; Ant&#243;nio Marinho&#44; MD&#44; Ph&#46;D&#46;&#59; Ana Campar&#44; MD&#59; Mariana Brand&#227;o&#44; MD&#59; Raquel Faria&#44; MD&#59; Teresa Mendon&#231;a&#44; MD&#59; Fernanda Almeida&#44; MD&#59; Margarida Fran&#231;a&#44; MD&#59; &#193;lvaro Ferreira&#44; MD&#59; Graziela Carvalheiras&#44; MD&#59; Pedro Vita&#44; MD&#59; Ana Martins da Silva&#44; MD&#44; Ph&#46;D&#46;&#59; Guilherme Rocha&#44; MD&#59; Manuela Magalh&#227;es&#44; NP&#59; S&#243;nia Ruivo&#44; NP&#59; Ana Tavares&#59; Daniela Boleixa&#59; and Jacqueline Ferreira&#46;</p>"
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