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accompanied in many cases by loss of eyebrow hair&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Signs of inflammation&#44; such as erythema and peripheral flaking&#44; are frequently observed around the hairline and the eyebrows&#46; There are 3 described hairline recession patterns &#40;diffuse&#44; linear&#44; and double line&#41; that appear to have prognostic repercussions&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Itching or burning sensations are reported by some patients&#46; Facial papules and hair loss in other body areas&#44; such as the axillae or the pubis&#44; have been described in some cases&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Diagnosis is primarily clinical&#44; and can be supported by trichoscopic findings &#40;peripheral erythema&#44; follicular hyperkeratosis&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> In cases of atypical or ambiguous presentations it is necessary to take a skin biopsy for histopathological study&#46; This type of alopecia is characterized by the presence of lymphocytic infiltrate and peripheral fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Some authors consider FFA a variant of lichen planopilaris&#44; given the common pathological characteristics&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The etiology of FFA is unknown&#46; Some authors have proposed an association between FFA and autoimmune diseases&#44; including thyroid diseases<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and other dermatoses such as mucosal lichen planus<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and rosacea&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Hormonal alterations have also been implicated in FFA&#44; which predominantly affects postmenopausal women&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> although a recent study of women with FFA reported normal blood levels of sex hormones&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The treatment objective is to stabilize the process to prevent progression of hairline recession and achieve symptom control&#46; FFA treatments described in the literature include topical and oral corticosteroids&#44; intralesional corticosteroids&#44; topical immunomodulators&#44; hydroxychloroquine&#44; 5-alpha reductase inhibitors&#44; and retinoids&#46; However&#44; few studies have compared the efficacy of multiple treatments&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The aim of the present study was to describe the characteristics and prescribed treatments of FFA patients treated in a tertiary hospital providing intermediate care in the Community of Madrid&#44; and to identify the factors associated with disease presentation&#44; disease severity&#44; and the need for oral treatment&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and Methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">We designed an observational&#44; descriptive&#44; retrospective cross-sectional study of patients diagnosed with FFA and treated at the trichology unit of the Hospital Universitario Infanta Sof&#237;a &#40;HUIS&#41; between May 2016 and May 2018&#46; Patients eligible for inclusion were those aged over 18 years with a clinical diagnosis of FFA &#40;with or without histological confirmation&#41; who had visited the trichology unit of the HUIS at least once during the study period&#46; Diagnosis was based on the presence of scarring alopecia with recession of the frontotemporal hairline&#44; bilateral diffuse alopecia of the eyebrows&#44; and compatible trichoscopic signs&#46; A biopsy was performed in cases of atypical clinical presentation&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Response variables</span><p id="par0040" class="elsevierStylePara elsevierViewall">The following demographic and clinical variables were collected for each patient&#58; sex&#59; age of alopecia onset&#59; age at the moment of consultation&#59; time since onset&#59; severity &#40;based on measurements taken at the first visit&#44; considering severe FFA as frontal or lateral hairline recession &#8805;3<span class="elsevierStyleHsp" style=""></span>cm&#41;&#59; biopsy confirmation &#40;yes&#44; no&#41;&#59; pattern &#40;diffuse&#44; lineal&#44; double line&#44; or other&#41;&#59; smoking status &#40;nonsmoker&#44; smoker&#44; ex-smoker&#41;&#59; eyebrow involvement &#40;yes&#44; no&#41;&#44; eyebrow involvement from onset &#40;yes&#44; no&#41;&#44; loss of body hair &#40;yes&#44; no&#41;&#44; mucosal lichen planus &#40;yes&#44; no&#41;&#44; signs of rosacea &#40;yes&#44; no&#41;&#44; facial papules &#40;yes&#44; no&#41;&#44; hypothyroidism &#40;yes&#44; no&#41;&#44; association with androgenetic alopecia &#40;yes&#44; no&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The treatment variables selected are shown below&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0050" class="elsevierStylePara elsevierViewall">Type of treatment &#40;topical&#44; systemic &#91;including intralesional corticosteroids&#93;&#41;&#46; Patients with unstable FFA &#40;i&#46;e&#46; hairline recession in preceding months and positive hair-pull test&#41; and those presenting symptoms &#40;pruritus&#44; burning&#41; were prescribed systemic treatment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">Stabilization with systemic treatment &#40;yes&#44; no&#41;&#46; Patients considered stable were those that showed no hairline recession&#44; a negative hair-pull test&#44; and symptom control during treatment follow-up visits &#40;conducted every 3 months during and after treatment&#44; during which comparisons were made with photographs taken prior to beginning treatment&#41;&#46;</p></li></ul></p><p id="par0060" class="elsevierStylePara elsevierViewall">In the descriptive analysis&#44; qualitative variables were expressed as absolute &#40;n&#41; and relative &#40;&#37;&#41; frequencies&#44; and quantitative variables as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation or the median &#91;interquartile range&#93;&#44; depending on data normality as determined using the Shapiro-Wilk test&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Possible associations between the variables of interest were analyzed using the Chi-squared test or Fisher exact test for qualitative variables&#44; and&#44; in the case of quantitative variables&#44; using the Student t test &#40;or Mann Whitney U test&#41; and ANOVA &#40;or Kruskal Wallis test&#41; for comparisons involving 2 and more than 2 study groups&#44; respectively&#46; Multivariate analyses &#40;binary logistic regression&#41; were performed to identify possible factors associated with FFA severity and the need for oral treatment&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">A <span class="elsevierStyleItalic">P</span> value &#60;0&#46;05 was considered indicative of statistical significance&#46; Data were analyzed using the Stata&#47;IC program&#44; v&#46; 14 &#40;StataCorp LLC&#46;&#44; Texas&#44; USA&#41;&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall">In total&#44; 75 patients &#40;73 women and 2 men&#41; fulfilled the inclusion criteria&#46; The median age of self-reported symptom onset was 61 &#91;12&#93; years&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The results of the descriptive analysis together with patient clinical data are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">The key characteristics of the patient population are described below&#46;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0090" class="elsevierStylePara elsevierViewall">A biopsy was performed for histological confirmation of diagnosis in 17&#46;3&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41; of patients&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0095" class="elsevierStylePara elsevierViewall">Onset occurred after menopause in 93&#46;2&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>68&#41; of female patients&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall">Those who had never smoked accounted for 66&#46;7&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&#41; of patients&#44; while 33&#46;3&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41; were active smokers or ex-smokers&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall">Mild hairline recession was observed in 56&#46;0&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>42&#41; of patients at the first consultation&#46; The mean extent of hairline recession was 2&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;50<span class="elsevierStyleHsp" style=""></span>cm&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall">A diffuse hairline recession pattern was observed in 56&#46;9&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>37 cases&#41; of patients&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0115" class="elsevierStylePara elsevierViewall">Data on the involvement of body areas other than the scalp revealed eyebrow involvement in 93&#46;3&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>70&#41; of patients and facial papules in 29&#46;0&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0120" class="elsevierStylePara elsevierViewall">Mucosal lichen planus lesions were observed in 9&#46;6&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41; of patients&#44; hypothyroidism in 14&#46;7&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; and signs of rosacea in 20&#46;0&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></li></ul></p><p id="par0125" class="elsevierStylePara elsevierViewall">Systemic treatment &#40;including intralesional corticosteroid therapy&#41; was instituted in 32&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24&#41; of patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The most commonly prescribed systemic treatment was 5-alpha reductase inhibitors&#44; especially dutasteride &#40;at 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg 1&#44; 2&#44; or 3 times per week&#41;&#59; 64&#46;2&#37; of patients treated with these compounds achieved stabilization lasting 8 to 18 months&#44; except in 3 cases &#40;1 was lost to follow-up&#44; 1 opted to discontinue treatment&#44; and 1 discontinued treatment due to a lack of efficacy after 4 months&#41;&#46; Other treatments used were hydroxychloroquine&#44; oral corticosteroids&#44; isotretinoin&#44; and intralesional corticosteroids &#40;triamcinolone acetonide diluted in saline at a concentration of 8<span class="elsevierStyleHsp" style=""></span>mg&#47;mL&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">The median &#91;interquartile range&#93; duration of treatment was 10 &#91;7&#93; months&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Stabilization of FFA was achieved in 75&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>18&#41; of the 24 patients who were prescribed systemic treatment&#44; and was maintained in all cases during the follow-up period &#40;median follow-up period after stabilization&#44; 11&#46;5 &#91;9&#93; months&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The results of the univariate analysis are presented in the tables in <a class="elsevierStyleCrossRef" href="#sec0045">Appendix B</a> &#40;Supplementary Material&#44; Tables 1&#8211;3&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The degree of involvement was significantly greater in smokers or ex-smokers than in nonsmokers &#40;<span class="elsevierStyleItalic">P</span> &#61; 0&#46;048&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; However&#44; this association was not observed in the multivariate analysis &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; No associations were observed between the severity of hairline recession and eyebrow involvement&#44; eyebrow involvement from onset&#44; body hair loss&#44; the presence of facial papules&#44; concomitant mucosal lichen planus&#44; or signs of rosacea&#46; Age at FFA onset did not differ significantly between patients with severe versus mild hairline recession&#46; However&#44; the median &#91;interquartile range&#93; time since onset tended to be longer in patients with severe versus mild hairline recession &#40;4 &#91;5&#93; and 3 &#91;3&#93; y&#44; respectively&#59; <span class="elsevierStyleItalic">P</span> &#61; 0&#46;095&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">Our results revealed an association between the severity and pattern of hairline recession&#46; Only 21&#46;7&#37; of patients with a linear pattern presented severe hairline recession&#46; By contrast&#44; for the other 2 patterns the proportion of patients with severe recession was significantly higher &#40;<span class="elsevierStyleItalic">P</span> &#61; 0&#46;035&#41;&#46; Logistic regression analysis showed that patients with a diffuse pattern were 4 times more likely to have severe hairline recession than those with a linear pattern &#40;95&#37; CI&#44; 0&#46;07&#8211;0&#46;82&#59; <span class="elsevierStyleItalic">P</span> &#61; 0&#46;022&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Furthermore&#44; the proportion of cases with facial papules differed between the different hairline recession patterns&#44; accounting for only 17&#46;7&#37; of cases among patients with a diffuse pattern but greater proportions of patients with the other 2 patterns &#40;<span class="elsevierStyleItalic">P</span> &#61; 0&#46;065&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; We observed no associations between the different hairline recession patterns and eyebrow involvement&#44; body hair loss&#44; concomitant mucosal lichen planus&#44; or signs of rosacea&#46; Furthermore&#44; age at FFA onset did not differ significantly between patients with different patterns&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">The presence of facial papules was significantly higher in patients under the age of 55 years than in those older &#40;85&#46;7&#37; and 22&#46;6&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">P</span> &#61; 0&#46;002&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0160" class="elsevierStylePara elsevierViewall">We investigated whether there was a correlation between the need for systemic treatment and any of the other variables included in our analysis&#46; Our results show that the need for systemic treatment was significantly greater in patients with rosacea than those without &#40;66&#46;7&#37; and 23&#46;3&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">P</span> &#61; 0&#46;004&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41; and in patients with facial papules than in those without &#40;50&#37; and 24&#46;5&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">P</span> &#61; 0&#46;039&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46; Logistic regression analysis confirmed that these variables were independently associated with the need for systemic treatment&#44; which was 11&#46;33 times greater &#40;95&#37; CI&#58; 2&#46;21&#8211;58&#46;15&#59; <span class="elsevierStyleItalic">P</span> &#61; 0&#46;004&#41; in patients with rosacea than in those without&#44; and 4&#46;25 times greater in patients with papules than in those without &#40;95&#37; CI&#58; 1&#46;08&#8211;16&#46;71&#59; <span class="elsevierStyleItalic">P</span> &#61; 0&#46;038&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; We found no association between the need for systemic treatment and hairline recession pattern&#44; eyebrow involvement&#44; or concomitant mucosal lichen planus &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41;&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0165" class="elsevierStylePara elsevierViewall">FFA is a form of primary scarring alopecia that mainly affects women&#44; especially those of postmenopausal age&#46; The incidence of FFA appears to be increasing in recent years&#44; and available treatments are relatively ineffective&#46; Several published case studies have described the demographic and clinical characteristics of FFA patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#44; and analyzed the outcomes achieved with different treatments &#40;<a class="elsevierStyleCrossRef" href="#fig0035">Fig&#46; 7</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="fig0035"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">We present the results of a retrospective analysis of a series of 75 FFA patients who attended the trichology unit of the HUIS over a 2-year period &#40;2016&#8211;2018&#41;&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">In line with the findings of previous studies&#44; the majority of patients &#40;97&#46;3&#37;&#41; were women&#44; most of whom &#40;93&#46;2&#37;&#41; reported FFA onset after menopause&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Biopsy was required for diagnostic confirmation in only 17&#46;3&#37; of cases&#44; in patients with incipient involvement of recent onset or atypical presentations &#40;e&#46;g&#46; the absence of obvious eyebrow involvement&#41;&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">More than half of our patients &#40;56&#37;&#41; showed mild hairline recession at the time of consultation&#46; Mild hairline recession has also been reported in the majority of subjects in other published series&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;7&#44;14</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">We defined the different clinical patterns based on the series published by Moreno-Arrones et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Those authors found that the linear pattern was the most frequent &#40;48&#46;8&#37;&#41;&#46; By contrast&#44; in our series the diffuse pattern was observed in over half &#40;56&#46;9&#37;&#41; of all patients&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Our data on eyebrow involvement&#44; body hair loss&#44; and the presence of facial papules were similar to those reported in other series&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">In our study population&#44; concomitant lichen planus was observed in 9&#46;6&#37; of patients&#46; This rate is considerably higher than the prevalence of lichen planus in the general population &#40;1&#8211;4&#37;&#41;&#44; suggesting a possible association between the 2 processes&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Other authors have proposed that FFA may be associated with hypothyroidism<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;14&#44;15</span></a> and with rosacea&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;23</span></a> In our series the prevalence of hypothyroidism &#40;14&#46;7&#37;&#41; and rosacea &#40;20&#37;&#41; was strikingly high&#44; far exceeding the estimated prevalence in the general population &#40;4&#46;2&#37; and 2&#8211;5&#37;&#44; respectively&#41;&#46; More than half &#40;56&#46;8&#37;&#41; of our patients also had androgenetic alopecia&#44; in line with the findings of other Spanish series&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;14</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">In agreement with the results of previous studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;12</span></a> patients who received systemic treatments showed generally good outcomes&#58; 75&#37; of this group achieved stabilization of FFA&#46; The most widely used systemic treatment was 5-alpha reductase inhibitors&#44; in particular dutasteride&#46; More than half &#40;64&#46;2&#37;&#41; of all patients treated with these agents achieved stabilization&#44; a proportion similar to that reported in other series&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;13&#44;14</span></a> Stabilization was maintained in all patients during the follow-up period&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Most of our patients were nonsmokers&#46; Univariate analysis revealed a significant association between smoking and mild hairline recession&#44; although this association was not confirmed in the multivariate analysis&#46; In their study&#44; Fonda-Pascual et al<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> reported a higher prevalence of severe FFA among nonsmokers&#44; suggesting a possible protective effect of tobacco against FFA progression&#46; In their series&#44; MacDonald et al<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> reported a greater proportion of nonsmokers among their FFA patients than in the general population&#44; although this observation was not corroborated by other authors&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;14</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">We observed a significant association between the linear pattern and reduced severity&#44; as also reported by Moreno-Arrones et al&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and a trend towards an absence of facial papules in patients with the diffuse pattern&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Furthermore&#44; we observed an association between the presence of facial papules and younger age&#44; as previously reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;26</span></a> The etiology of these noninflammatory facial papules is not well defined&#44; although perifollicular inflammation of facial hair&#44; sebaceous gland hypertrophy&#44; and alterations of elastic fibers are thought to be involved&#46; Because they are more frequently observed in premenopausal women&#44; facial papules may constitute an early sign of FFA&#44; and could be cause to suspect this process in young women with early signs of hairline recession&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">In our series there was a significant association between the need for systemic treatment and the presence of rosacea and facial papules&#46; The logistic regression model revealed that the effects of these 2 factors on the need for treatment were independent of one another&#46; This may indicate a need for earlier and more intensive treatment in FFA patients with concomitant rosacea and&#47;or facial papules&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Our study has certain limitations&#46; Firstly&#44; it is a retrospective study&#44; and therefore the clinical evaluation of the patients was not carried out with the specific purpose of collecting data for this study&#46; Furthermore&#44; owing to short follow-up time after completion of treatment&#44; it was not possible to determine whether the stabilization of FFA achieved by some patients was maintained in the long term&#46; It should also be noted that no trichoscopy data were collected and that smoking-related data did not include the number of packets smoked per year or the number of years since quitting smoking&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">In conclusion&#44; in our series of FFA patients women of post-menopausal age predominated and eyebrow involvement was observed in most cases&#46; The prevalence of mucosal lichen planus among FFA patients was higher than that described in the general population&#46; We found that the likelihood of presenting facial papules was higher in younger patients&#59; patients with a linear hairline recession pattern had less severe FFA&#59; and the need for oral treatment was greater in patients with rosacea and facial papules&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethical Disclosures</span><p id="par0245" class="elsevierStylePara elsevierViewall">Patients&#39; personal data were processed in accordance with Royal Decree-Law 5&#47;2018&#44; of July 27 2018&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">This study was approved by the research commission of the HUIS&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">All patients provided verbal informed consent for the collection of data from their medical records&#44; and were informed that these data could be used for clinical studies&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflicts of Interest</span><p id="par0260" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-07-22"
    "fechaAceptado" => "2020-03-26"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1262785"
          "palabras" => array:6 [
            0 => "Frontal fibrosing alopecia"
            1 => "Rosacea"
            2 => "Tobacco"
            3 => "Treatment"
            4 => "Dutasteride"
            5 => "Hydroxychloroquine"
          ]
        ]
      ]
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1262786"
          "palabras" => array:6 [
            0 => "Alopecia frontal fibrosante"
            1 => "ros&#225;cea"
            2 => "tabaco"
            3 => "tratamiento"
            4 => "dutasteride"
            5 => "hidroxicloroquina"
          ]
        ]
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    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Frontal fibrosing alopecia is an increasingly common form of scarring alopecia&#46; The aim of this study was to describe the demographic and clinical characteristics of patients with FFA seen at the trichology unit of a medium-sized regional hospital and to report on treatments used&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">We reviewed the medical records of all patients with FFA seen at the trichology unit of Hospital Universitario Infanta Sof&#237;a in Madrid&#44; Spain between May 2016 and May 2018&#46; We analyzed associations between disease severity&#44; clinical patterns&#44; need for oral medications&#44; and other characteristics&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Seventy-five patients &#40;73 women and 2 men&#41; were studied&#46; Diagnosis was clinical in most cases and 13 cases &#40;17&#46;3&#37;&#41; were confirmed histologically&#46; Median &#40;interquartile range&#41; age at reported onset of symptoms was 61 &#40;12&#41; years&#46; Involvement of the eyebrows was recorded in 70 patients &#40;93&#46;3&#37;&#41; and signs of oral and genital lichen planus in 7 &#40;9&#46;6&#37;&#41;&#46; Eleven patients &#40;14&#46;7&#37;&#41; had hypothyroidism and 15 &#40;20&#46;0&#37;&#41; had signs of rosacea&#46; Only 5 of the patients who presented a linear pattern &#40;21&#46;7&#37;&#41; had severe hairline recession&#46; Patients with unstable and&#47;or symptomatic disease &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24&#41; were treated with oral medications &#40;5-alpha reductase inhibitors&#44; hydroxychloroquine&#44; corticosteroids&#44; and isotretinoin&#41; or intralesional corticosteroids&#46; Eighteen patients &#40;75&#46;0&#37;&#41; achieved disease stability&#46; Ten of the 15 patients with signs of rosacea and 10 of those with facial papules required systemic treatment&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Most of the patients in this series of FFA were postmenopausal women&#46; The prevalence of oral and genital lichen planus was higher than that observed in the general population&#46; Patients with a linear pattern had less severe disease&#46; Facial papules were more common in younger patients and both facial papules and rosacea were associated with a greater need for oral treatment&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background and objective"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Material and methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivo</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">La alopecia frontal fibrosante &#40;AFF&#41; es un tipo de alopecia cicatricial cuya incidencia est&#225; en aumento&#46; Detallamos las caracter&#237;sticas demogr&#225;ficas&#44; cl&#237;nicas&#44; y los tratamientos utilizados en los pacientes con AFF atendidos en la consulta de Tricolog&#237;a de un hospital de complejidad intermedia&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todo</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Se recopilaron de forma retrospectiva los datos de todos los pacientes diagnosticados de AFF atendidos en la consulta de Tricolog&#237;a del Hospital Universitario Infanta Sof&#237;a desde mayo de 2016 hasta mayo de 2018&#46; Se evalu&#243; la asociaci&#243;n entre la gravedad&#44; el patr&#243;n cl&#237;nico y la necesidad del tratamiento oral con el resto de las caracter&#237;sticas de los pacientes&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron un total de 75 pacientes &#40;73 mujeres y 2 varones&#41;&#46; El diagn&#243;stico en la mayor&#237;a de los casos fue cl&#237;nico&#44; y se realiz&#243; estudio histol&#243;gico en 13 pacientes &#40;17&#44;3&#37;&#41;&#46; La mediana de la edad de inicio del cuadro fue de 61 &#91;12&#93; a&#241;os&#46; En 70 casos &#40;93&#44;3&#37;&#41; se observ&#243; afectaci&#243;n de las cejas&#44; y en 7 pacientes &#40;9&#44;6&#37;&#41; se objetivaron signos de liquen oro-genital&#46; Asociaban hipotiroidismo 11 casos &#40;14&#44;7&#37;&#41;&#44; y en 15 &#40;20&#44;0&#37;&#41; se observaron signos de ros&#225;cea&#46; Solo 5 &#40;21&#44;7&#37;&#41; de los pacientes con patr&#243;n lineal presentaban retroceso grave&#46; En los pacientes inestables y&#47;o sintom&#225;ticos &#40;24 casos&#41; se instaur&#243; tratamiento oral &#40;con inhibidores de 5 alfa reductasa&#44; hidroxicloroquina&#44; corticoides o isotretino&#237;na&#41; o intralesional con corticoides&#44; logrando la estabilizaci&#243;n en 18 pacientes &#40;75&#44;0&#37;&#41;&#46; Un total de 10 pacientes de los 15 que presentaban signos de ros&#225;cea&#44; y 10 de los 20 pacientes que presentaban p&#225;pulas faciales precisaron tratamiento sist&#233;mico&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">La mayor&#237;a de nuestros pacientes son mujeres postmenop&#225;usicas&#46; Hemos encontrado un aumento de la proporci&#243;n de casos con un liquen orogenital en relaci&#243;n con la poblaci&#243;n general&#44; y una menor gravedad en los pacientes con un patr&#243;n lineal&#46; Se ha objetivado la presencia de p&#225;pulas faciales con m&#225;s frecuencia en pacientes m&#225;s j&#243;venes&#44; y una mayor probabilidad de necesitar tratamiento oral en los pacientes con ros&#225;cea y con p&#225;pulas faciales&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Antecedentes y objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Material y m&#233;todo"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
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            "identificador" => "abst0040"
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; Maldonado Cid P&#44; Leis Dosil VM&#44; Garrido Guti&#233;rrez C&#44; Salinas Moreno S&#44; Thuissard Vasallo IJ&#44; Andreu V&#225;zquez C&#44; et al&#46; Alopecia frontal fibrosante&#58; estudio retrospectivo de 75 pacientes&#46; Actas Dermosifiliogr&#46; 2020&#59;111&#58;487&#8211;495&#46;</p>"
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            "apendice" => "<p id="par0270" class="elsevierStylePara elsevierViewall">The following are Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0045"
          ]
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Premenopausal woman with frontal fibrosing alopecia&#46; A&#44; Frontal view&#46; B&#44; Lateral view &#40;note the presence of facial papules&#41;&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Woman with frontal fibrosing alopecia and signs of rosacea&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Association between smoking and less severe hairline recession&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Association between linear pattern and less severe hairline recession&#46;</p>"
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        "etiqueta" => "Figure 5"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Association between facial papules and age &#60;55 years&#46;</p>"
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        "etiqueta" => "Figure 6"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Association between signs of rosacea and the need for systemic treatment&#46;</p>"
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        "etiqueta" => "Figure 7"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Smokers and ex-smoker&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">25 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Nonsmokers&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">50 &#40;66&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Severity</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">&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>75&#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>Severe&#44; No&#46; &#40;&#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">33 &#40;44&#46;0&#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>Mild&#44; No&#46; &#40;&#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">42 &#40;56&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Pattern</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">&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>65&#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>Linear&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;35&#46;4&#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>Diffuse&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">37 &#40;56&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \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>Double line&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;4&#46;6&#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>Other &#40;frontal or lateral hairline recession only&#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;3&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eyebrow involvement&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">&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>75&#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>No eyebrow involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;6&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Partial involvement&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">40 &#40;53&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Complete involvement&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">30 &#40;40&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Eyebrow involvement from onset &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>63&#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">27 &#40;42&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \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">Body hair loss &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>69&#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">30 &#40;43&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Facial papules &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>70&#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">20 &#40;29&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mucosal lichen planus &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>73&#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">7 &#40;9&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Hypothyroidism &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>75&#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">11 &#40;14&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Rosacea &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>75&#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">15 &#40;20&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Androgenetic alopecia &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>74&#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">42 &#40;56&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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">Dose&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No&#46; &#40;&#37;&#41; Patients Treated &#40;Total<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24&#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">Patients That Achieved Stabilization&#44; &#37;&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">No&#46; Patients That Discontinued Treatment due to Adverse Effects&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">Intralesional corticosteroids &#40;triamcinolone acetonide&#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">8<span class="elsevierStyleHsp" style=""></span>mg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;25&#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">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&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">Hydroxychloroquine&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">200&#8211;400<span class="elsevierStyleHsp" style=""></span>mg&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;20&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&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></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">Finasteride&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&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;d&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;8&#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">50&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></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">Dutasteride&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;d 1&#8211;3 times&#47;wk&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">14 &#40;58&#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">64&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;digestive intolerance&#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">Oral corticosteroids &#40;prednisone&#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">50<span class="elsevierStyleHsp" style=""></span>mg &#40;tapering dose&#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">1 &#40;4&#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="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">0&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">Isotretinoin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20<span class="elsevierStyleHsp" style=""></span>mg&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;4&#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="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">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Systemic Treatments Used&#44; Percentage of Patients that Achieved Stabilization for Each Treatment&#44; and Treatment Discontinuation due to Adverse Effects</p>"
        ]
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      9 => array:8 [
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        "etiqueta" => "Table 3"
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          0 => array:3 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Factors Associated With Severity<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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">Odds Ratio&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">95&#37; CI&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> Value&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 " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smoking status</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>Nonsmokers&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">Reference group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></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>Smokers and ex-smokers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;40&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">&#40;0&#46;12&#8211;1&#46;30&#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&#46;128&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 " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pattern</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>Diffuse&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">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></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>Linear&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;25&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">&#40;0&#46;07&#8211;0&#46;82&#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&#46;022&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>Double line&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;32&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">&#40;0&#46;03&#8211;3&#46;91&#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&#46;368&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              ]
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            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Factors associated with the need for oral treatment<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a></th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Odds Ratio &#40;95&#37; CI&#41;</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> Value&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 " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Facial papules</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>No&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">Reference group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></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>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;2&#46;21&#8211;58&#46;15&#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&#46;004&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 " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rosacea</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>No&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">Reference group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></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>Yes&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&#46;25&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">&#40;1&#46;08&#8211;16&#46;71&#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&#46;038&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">Rosacea<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>papules interaction</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">0&#46;24&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">&#40;0&#46;02&#8211;3&#46;12&#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&#46;272&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Binary logistic regression model&#58; N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>63&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;031&#59; pseudo R<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;10&#59; log likelihood<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8211;38&#46;27&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Binary logistic regression model&#58; N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>69&#59; <span class="elsevierStyleItalic">P</span> value<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#58; pseudo R<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;17&#59; log likelihood<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8211;36&#46;02&#46;</p>"
            ]
          ]
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Results of the Multivariate Analysis</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pattern&nbsp;\t\t\t\t\t\t\n
                  \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">Patients &#40;&#37;&#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">Patients with Severe Hairline Recession &#40;&#37;&#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">Patients with Facial Papules &#40;&#37;&#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">Linear&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;4&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">21&#46;7&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">43&#46;5&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">Diffuse&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&#46;9&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">54&#46;1&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">17&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Double line&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&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#46;0&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">Statistical significance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">P</span> &#61; 0&#46;035&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">P</span> &#61; 0&#46;065&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Results According to Presentation</p>"
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      11 => array:8 [
        "identificador" => "tbl0025"
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        "mostrarDisplay" => false
        "detalles" => array:1 [
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            "identificador" => "at0060"
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        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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">HUIS&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">Kanti et al&#44; 2019<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&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">Mervis et al&#44; 2018<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&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">Starace et al&#44; 2018<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&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">Imhof et al&#44; 2018<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&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">Strazzulla et al&#44; 2018<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&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">Heppt et al&#44; 2018<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&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">Kusano et al&#44; 2017<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&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">Moreno-Arrones et al&#44; 2017<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&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">Banka et al&#44; 2014<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&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">Va&#241;&#243; et al&#44; 2014<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&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">Ladizinski et al&#44; 2013<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&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">MacDonald et al&#44; 2012<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&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">Samrao et al&#44; 2010<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&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">Tan et al&#44; 2009<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&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">Tosti et al&#44; 2005<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&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">Moreno-Ramirez et al&#44; 2005<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&#46; of patients&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&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">490&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">91&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">65&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&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">Male &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Single center&#47;multicenter&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">Biopsy&#44; &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Age&#44; y&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  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\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">61&#46;4&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">Age at onset&#44; y&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  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\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  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\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">60&#46;4&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  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></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">Time since onset&#44; y&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  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;5&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">Post-menopausal patients&#44; &#37;&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">93&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">66&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\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">81&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smokers&#47;nonsmokers&#44; &#37;&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">33&#46;3&#47;66&#46;7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">43&#46;1&#47;56&#46;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">36&#46;5&#47;62&#46;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mild hairline recession &#40;&#8804; 3 cm&#41;&#44; &#37;&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  " align="left" valign="\n
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                  \t\t\t\t">71&#46;4&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</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diffuse&#47;linear&#47;double line pattern&#44; &#37;&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">56&#46;9&#47;33&#46;8&#47;6&#46;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">45&#47;48&#46;8&#47;6&#46;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eyebrow involvement&#44; &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eyebrow involvement from onset&#44; &#37;&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</td></tr><tr title="table-row"><td class="td-with-role" title="\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">Body hair loss&#44; &#37;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">37&#46;5&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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Facial papules&#44; &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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">Mucosal lichen planus&#44; &#37;&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 ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Hypothyroidism&#44; &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Rosacea&#44; &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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Vol. 111. Núm. 6.
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7353
Vol. 111. Núm. 6.
Páginas 487-495 (julio - agosto 2020)
Original Article
Open Access
Frontal Fibrosing Alopecia: A Retrospective Study of 75 Patients
Alopecia frontal fibrosante: estudio retrospectivo de 75 pacientes
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7353
P. Maldonado Cida,
Autor para correspondencia
pmaldonadocid@gmail.com

Corresponding author.
, V.M. Leis Dosila, C. Garrido Gutiérreza, S. Salinas Morenob, I.J. Thuissard Vasalloc, C. Andreu Vázquezd, R.M. Díaz Díaza
a Servicio de Dermatología, Hospital Universitario Infanta Sofía, Madrid, Spain
b Servicio de Anatomía Patológica, Hospital Universitario Infanta Sofía, Madrid, Spain
c Escuela de doctorado e investigación (EDI), Universidad Europea de Madrid, Madrid, Spain
d Departamento de Farmacia y Biotecnología, Universidad Europea de Madrid, Madrid, Spain
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Table 1. Demographic and Clinical Characteristics of the Study Population
Table 2. Systemic Treatments Used, Percentage of Patients that Achieved Stabilization for Each Treatment, and Treatment Discontinuation due to Adverse Effects
Table 3. Results of the Multivariate Analysis
Table 4. Results According to Presentation
Table 5. Frontal Fibrosing Alopecia: Comparison of Data from Present and Previously Published Series
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Abstract
Background and objective

Frontal fibrosing alopecia is an increasingly common form of scarring alopecia. The aim of this study was to describe the demographic and clinical characteristics of patients with FFA seen at the trichology unit of a medium-sized regional hospital and to report on treatments used.

Material and methods

We reviewed the medical records of all patients with FFA seen at the trichology unit of Hospital Universitario Infanta Sofía in Madrid, Spain between May 2016 and May 2018. We analyzed associations between disease severity, clinical patterns, need for oral medications, and other characteristics.

Results

Seventy-five patients (73 women and 2 men) were studied. Diagnosis was clinical in most cases and 13 cases (17.3%) were confirmed histologically. Median (interquartile range) age at reported onset of symptoms was 61 (12) years. Involvement of the eyebrows was recorded in 70 patients (93.3%) and signs of oral and genital lichen planus in 7 (9.6%). Eleven patients (14.7%) had hypothyroidism and 15 (20.0%) had signs of rosacea. Only 5 of the patients who presented a linear pattern (21.7%) had severe hairline recession. Patients with unstable and/or symptomatic disease (n=24) were treated with oral medications (5-alpha reductase inhibitors, hydroxychloroquine, corticosteroids, and isotretinoin) or intralesional corticosteroids. Eighteen patients (75.0%) achieved disease stability. Ten of the 15 patients with signs of rosacea and 10 of those with facial papules required systemic treatment.

Conclusions

Most of the patients in this series of FFA were postmenopausal women. The prevalence of oral and genital lichen planus was higher than that observed in the general population. Patients with a linear pattern had less severe disease. Facial papules were more common in younger patients and both facial papules and rosacea were associated with a greater need for oral treatment.

Keywords:
Frontal fibrosing alopecia
Rosacea
Tobacco
Treatment
Dutasteride
Hydroxychloroquine
Resumen
Antecedentes y objetivo

La alopecia frontal fibrosante (AFF) es un tipo de alopecia cicatricial cuya incidencia está en aumento. Detallamos las características demográficas, clínicas, y los tratamientos utilizados en los pacientes con AFF atendidos en la consulta de Tricología de un hospital de complejidad intermedia.

Material y método

Se recopilaron de forma retrospectiva los datos de todos los pacientes diagnosticados de AFF atendidos en la consulta de Tricología del Hospital Universitario Infanta Sofía desde mayo de 2016 hasta mayo de 2018. Se evaluó la asociación entre la gravedad, el patrón clínico y la necesidad del tratamiento oral con el resto de las características de los pacientes.

Resultados

Se incluyeron un total de 75 pacientes (73 mujeres y 2 varones). El diagnóstico en la mayoría de los casos fue clínico, y se realizó estudio histológico en 13 pacientes (17,3%). La mediana de la edad de inicio del cuadro fue de 61 [12] años. En 70 casos (93,3%) se observó afectación de las cejas, y en 7 pacientes (9,6%) se objetivaron signos de liquen oro-genital. Asociaban hipotiroidismo 11 casos (14,7%), y en 15 (20,0%) se observaron signos de rosácea. Solo 5 (21,7%) de los pacientes con patrón lineal presentaban retroceso grave. En los pacientes inestables y/o sintomáticos (24 casos) se instauró tratamiento oral (con inhibidores de 5 alfa reductasa, hidroxicloroquina, corticoides o isotretinoína) o intralesional con corticoides, logrando la estabilización en 18 pacientes (75,0%). Un total de 10 pacientes de los 15 que presentaban signos de rosácea, y 10 de los 20 pacientes que presentaban pápulas faciales precisaron tratamiento sistémico.

Conclusión

La mayoría de nuestros pacientes son mujeres postmenopáusicas. Hemos encontrado un aumento de la proporción de casos con un liquen orogenital en relación con la población general, y una menor gravedad en los pacientes con un patrón lineal. Se ha objetivado la presencia de pápulas faciales con más frecuencia en pacientes más jóvenes, y una mayor probabilidad de necesitar tratamiento oral en los pacientes con rosácea y con pápulas faciales.

Palabras clave:
Alopecia frontal fibrosante
rosácea
tabaco
tratamiento
dutasteride
hidroxicloroquina
Texto completo
Introduction

Frontal fibrosing alopecia (FFA), first described by Kossard in 1994,1 is a type of scarring alopecia, the incidence of which appears to be increasing in recent years.

The demographic and clinical characteristics of FFA patients are described in several published cases series.2–17 This type of alopecia more frequently affects postmenopausal women, although it can also occur in premenopausal women and, less frequently, in men.18,19 It causes progressive and generally irreversible recession of the hairline, accompanied in many cases by loss of eyebrow hair.20 Signs of inflammation, such as erythema and peripheral flaking, are frequently observed around the hairline and the eyebrows. There are 3 described hairline recession patterns (diffuse, linear, and double line) that appear to have prognostic repercussions.16 Itching or burning sensations are reported by some patients. Facial papules and hair loss in other body areas, such as the axillae or the pubis, have been described in some cases.14

Diagnosis is primarily clinical, and can be supported by trichoscopic findings (peripheral erythema, follicular hyperkeratosis).21 In cases of atypical or ambiguous presentations it is necessary to take a skin biopsy for histopathological study. This type of alopecia is characterized by the presence of lymphocytic infiltrate and peripheral fibrosis.20 Some authors consider FFA a variant of lichen planopilaris, given the common pathological characteristics.

The etiology of FFA is unknown. Some authors have proposed an association between FFA and autoimmune diseases, including thyroid diseases22 and other dermatoses such as mucosal lichen planus4 and rosacea.23 Hormonal alterations have also been implicated in FFA, which predominantly affects postmenopausal women,20 although a recent study of women with FFA reported normal blood levels of sex hormones.24

The treatment objective is to stabilize the process to prevent progression of hairline recession and achieve symptom control. FFA treatments described in the literature include topical and oral corticosteroids, intralesional corticosteroids, topical immunomodulators, hydroxychloroquine, 5-alpha reductase inhibitors, and retinoids. However, few studies have compared the efficacy of multiple treatments.13,14

The aim of the present study was to describe the characteristics and prescribed treatments of FFA patients treated in a tertiary hospital providing intermediate care in the Community of Madrid, and to identify the factors associated with disease presentation, disease severity, and the need for oral treatment.

Material and Methods

We designed an observational, descriptive, retrospective cross-sectional study of patients diagnosed with FFA and treated at the trichology unit of the Hospital Universitario Infanta Sofía (HUIS) between May 2016 and May 2018. Patients eligible for inclusion were those aged over 18 years with a clinical diagnosis of FFA (with or without histological confirmation) who had visited the trichology unit of the HUIS at least once during the study period. Diagnosis was based on the presence of scarring alopecia with recession of the frontotemporal hairline, bilateral diffuse alopecia of the eyebrows, and compatible trichoscopic signs. A biopsy was performed in cases of atypical clinical presentation.

Response variables

The following demographic and clinical variables were collected for each patient: sex; age of alopecia onset; age at the moment of consultation; time since onset; severity (based on measurements taken at the first visit, considering severe FFA as frontal or lateral hairline recession ≥3cm); biopsy confirmation (yes, no); pattern (diffuse, lineal, double line, or other); smoking status (nonsmoker, smoker, ex-smoker); eyebrow involvement (yes, no), eyebrow involvement from onset (yes, no), loss of body hair (yes, no), mucosal lichen planus (yes, no), signs of rosacea (yes, no), facial papules (yes, no), hypothyroidism (yes, no), association with androgenetic alopecia (yes, no).

The treatment variables selected are shown below.

  • -

    Type of treatment (topical, systemic [including intralesional corticosteroids]). Patients with unstable FFA (i.e. hairline recession in preceding months and positive hair-pull test) and those presenting symptoms (pruritus, burning) were prescribed systemic treatment.

  • -

    Stabilization with systemic treatment (yes, no). Patients considered stable were those that showed no hairline recession, a negative hair-pull test, and symptom control during treatment follow-up visits (conducted every 3 months during and after treatment, during which comparisons were made with photographs taken prior to beginning treatment).

In the descriptive analysis, qualitative variables were expressed as absolute (n) and relative (%) frequencies, and quantitative variables as the mean±standard deviation or the median [interquartile range], depending on data normality as determined using the Shapiro-Wilk test.

Possible associations between the variables of interest were analyzed using the Chi-squared test or Fisher exact test for qualitative variables, and, in the case of quantitative variables, using the Student t test (or Mann Whitney U test) and ANOVA (or Kruskal Wallis test) for comparisons involving 2 and more than 2 study groups, respectively. Multivariate analyses (binary logistic regression) were performed to identify possible factors associated with FFA severity and the need for oral treatment.

A P value <0.05 was considered indicative of statistical significance. Data were analyzed using the Stata/IC program, v. 14 (StataCorp LLC., Texas, USA).

Results

In total, 75 patients (73 women and 2 men) fulfilled the inclusion criteria. The median age of self-reported symptom onset was 61 [12] years.

The results of the descriptive analysis together with patient clinical data are shown in Table 1.

Table 1.

Demographic and Clinical Characteristics of the Study Population

Sex  (n=75) 
Female  73 (97.3) 
Male  2 (2.7) 
Age at first consultation, y  61 [12] 
Time since onset, y  4 [4] 
Biopsy  13 (17.3) 
Menopause  (n=73) 
Premenopausal  5 (6.8) 
Postmenopausal  68 (93.2) 
Smoking status  (n=75) 
Smokers and ex-smoker  25 (33.3) 
Nonsmokers  50 (66.7) 
Severity  (n=75) 
Severe, No. (%)  33 (44.0) 
Mild, No. (%)  42 (56.0) 
Pattern  (n=65) 
Linear  23 (35.4) 
Diffuse  37 (56.9) 
Double line  3 (4.6) 
Other (frontal or lateral hairline recession only)  2 (3.1) 
Eyebrow involvement  (n=75) 
No eyebrow involvement  5 (6.7) 
Partial involvement  40 (53.3) 
Complete involvement  30 (40.0) 
Eyebrow involvement from onset (n=63)  27 (42.9) 
Body hair loss (n=69)  30 (43.5) 
Facial papules (n=70)  20 (29.0) 
Mucosal lichen planus (n=73)  7 (9.6) 
Hypothyroidism (n=75)  11 (14.7) 
Rosacea (n=75)  15 (20.0) 
Androgenetic alopecia (n=74)  42 (56.8) 

Data are presented as the median [interquartile range] or as n (%).

The key characteristics of the patient population are described below.

  • -

    A biopsy was performed for histological confirmation of diagnosis in 17.3% (n=13) of patients.

  • -

    Onset occurred after menopause in 93.2% (n=68) of female patients.

  • -

    Those who had never smoked accounted for 66.7% (n=50) of patients, while 33.3% (n=25) were active smokers or ex-smokers.

  • -

    Mild hairline recession was observed in 56.0% (n=42) of patients at the first consultation. The mean extent of hairline recession was 2.2±1.50cm.

  • -

    A diffuse hairline recession pattern was observed in 56.9% (n=37 cases) of patients.

  • -

    Data on the involvement of body areas other than the scalp revealed eyebrow involvement in 93.3% (n=70) of patients and facial papules in 29.0% (n=20) (Fig. 1).

    Figure 1.

    Premenopausal woman with frontal fibrosing alopecia. A, Frontal view. B, Lateral view (note the presence of facial papules).

    (0.16MB).
  • -

    Mucosal lichen planus lesions were observed in 9.6% (n=7) of patients, hypothyroidism in 14.7% (n=11), and signs of rosacea in 20.0% (n=15) (Fig. 2).

    Figure 2.

    Woman with frontal fibrosing alopecia and signs of rosacea.

    (0.1MB).

Systemic treatment (including intralesional corticosteroid therapy) was instituted in 32% (n=24) of patients (Table 2). The most commonly prescribed systemic treatment was 5-alpha reductase inhibitors, especially dutasteride (at 0.5mg 1, 2, or 3 times per week); 64.2% of patients treated with these compounds achieved stabilization lasting 8 to 18 months, except in 3 cases (1 was lost to follow-up, 1 opted to discontinue treatment, and 1 discontinued treatment due to a lack of efficacy after 4 months). Other treatments used were hydroxychloroquine, oral corticosteroids, isotretinoin, and intralesional corticosteroids (triamcinolone acetonide diluted in saline at a concentration of 8mg/mL).

Table 2.

Systemic Treatments Used, Percentage of Patients that Achieved Stabilization for Each Treatment, and Treatment Discontinuation due to Adverse Effects

  Dose  No. (%) Patients Treated (Total=24)  Patients That Achieved Stabilization, %  No. Patients That Discontinued Treatment due to Adverse Effects 
Intralesional corticosteroids (triamcinolone acetonide)  8mg/mL  6 (25)  33 
Hydroxychloroquine  200–400mg/d  5 (20.9)  100 
Finasteride  2.5mg/d  2 (8.3)  50 
Dutasteride  0.5mg/d 1–3 times/wk  14 (58.3)  64.2  1 (digestive intolerance) 
Oral corticosteroids (prednisone)  50mg (tapering dose)  1 (4.2) 
Isotretinoin  20mg/d  1 (4.2) 

The median [interquartile range] duration of treatment was 10 [7] months.

Stabilization of FFA was achieved in 75% (n=18) of the 24 patients who were prescribed systemic treatment, and was maintained in all cases during the follow-up period (median follow-up period after stabilization, 11.5 [9] months).

The results of the univariate analysis are presented in the tables in Appendix B (Supplementary Material, Tables 1–3).

The degree of involvement was significantly greater in smokers or ex-smokers than in nonsmokers (P = 0.048) (Fig. 3). However, this association was not observed in the multivariate analysis (Table 3). No associations were observed between the severity of hairline recession and eyebrow involvement, eyebrow involvement from onset, body hair loss, the presence of facial papules, concomitant mucosal lichen planus, or signs of rosacea. Age at FFA onset did not differ significantly between patients with severe versus mild hairline recession. However, the median [interquartile range] time since onset tended to be longer in patients with severe versus mild hairline recession (4 [5] and 3 [3] y, respectively; P = 0.095).

Figure 3.

Association between smoking and less severe hairline recession.

(0.07MB).
Table 3.

Results of the Multivariate Analysis

Factors Associated With Severitya
  Odds Ratio  95% CI  P Value 
Smoking status
Nonsmokers  Reference group     
Smokers and ex-smokers  0.40  (0.12–1.30)  0.128 
Pattern
Diffuse  Reference     
Linear  0.25  (0.07–0.82)  0.022 
Double line  0.32  (0.03–3.91)  0.368 
Factors associated with the need for oral treatmentb
  Odds Ratio (95% CI)P Value 
Facial papules
No  Reference group     
Yes  11.33  (2.21–58.15)  0.004 
Rosacea
No  Reference group     
Yes  4.25  (1.08–16.71)  0.038 
Rosacea×papules interaction  0.24  (0.02–3.12)  0.272 

Abbreviations: 95% CI, 95% confidence interval.

a

Binary logistic regression model: N=63; P=0.031; pseudo R2=0.10; log likelihood=–38.27.

b

Binary logistic regression model: N=69; P value=0.003: pseudo R2=0.17; log likelihood=–36.02.

Our results revealed an association between the severity and pattern of hairline recession. Only 21.7% of patients with a linear pattern presented severe hairline recession. By contrast, for the other 2 patterns the proportion of patients with severe recession was significantly higher (P = 0.035). Logistic regression analysis showed that patients with a diffuse pattern were 4 times more likely to have severe hairline recession than those with a linear pattern (95% CI, 0.07–0.82; P = 0.022) (Fig. 4) (Table 3). Furthermore, the proportion of cases with facial papules differed between the different hairline recession patterns, accounting for only 17.7% of cases among patients with a diffuse pattern but greater proportions of patients with the other 2 patterns (P = 0.065) (Table 4). We observed no associations between the different hairline recession patterns and eyebrow involvement, body hair loss, concomitant mucosal lichen planus, or signs of rosacea. Furthermore, age at FFA onset did not differ significantly between patients with different patterns.

Figure 4.

Association between linear pattern and less severe hairline recession.

(0.08MB).
Table 4.

Results According to Presentation

Pattern  Patients (%)  Patients with Severe Hairline Recession (%)  Patients with Facial Papules (%) 
Linear  35.4  21.7  43.5 
Diffuse  56.9  54.1  17.7 
Double line  4.6  33.3  50.0 
Statistical significance    P = 0.035  P = 0.065 

The presence of facial papules was significantly higher in patients under the age of 55 years than in those older (85.7% and 22.6%, respectively; P = 0.002) (Fig. 5).

Figure 5.

Association between facial papules and age <55 years.

(0.06MB).

We investigated whether there was a correlation between the need for systemic treatment and any of the other variables included in our analysis. Our results show that the need for systemic treatment was significantly greater in patients with rosacea than those without (66.7% and 23.3%, respectively; P = 0.004) (Fig. 4) and in patients with facial papules than in those without (50% and 24.5%, respectively; P = 0.039) (Fig. 5). Logistic regression analysis confirmed that these variables were independently associated with the need for systemic treatment, which was 11.33 times greater (95% CI: 2.21–58.15; P = 0.004) in patients with rosacea than in those without, and 4.25 times greater in patients with papules than in those without (95% CI: 1.08–16.71; P = 0.038) (Table 3). We found no association between the need for systemic treatment and hairline recession pattern, eyebrow involvement, or concomitant mucosal lichen planus (Fig. 6).

Figure 6.

Association between signs of rosacea and the need for systemic treatment.

(0.06MB).
Discussion

FFA is a form of primary scarring alopecia that mainly affects women, especially those of postmenopausal age. The incidence of FFA appears to be increasing in recent years, and available treatments are relatively ineffective. Several published case studies have described the demographic and clinical characteristics of FFA patients (Table 5), and analyzed the outcomes achieved with different treatments (Fig. 7).

Table 5.

Frontal Fibrosing Alopecia: Comparison of Data from Present and Previously Published Series

  HUIS  Kanti et al, 20199  Mervis et al, 20188  Starace et al, 20187  Imhof et al, 20186  Strazzulla et al, 20185  Heppt et al, 20184  Kusano et al, 201717  Moreno-Arrones et al, 201716  Banka et al, 201415  Vañó et al, 201414  Ladizinski et al, 201313  MacDonald et al, 201212  Samrao et al, 201011  Tan et al, 200910  Tosti et al, 20053  Moreno-Ramirez et al, 20052 
No. of patients  75  490  91  65  148  92  72  38  242  62  355  19  60  36  18  14  16 
Male (n)  23  12 
Single center/multicenter  SC  MC  SC  SC  SC  SC  SC  SC  SC  SC  MC  SC  SC  SC  SC  SC  SC 
Biopsy, %  17.3  46%  52.3  82.4  56.5  26.4  8.3  90.3  25  25  94  38.9  100  62.5 
Age, y  65.3  65  59.6  62.5  62.1  64  61.1  61.4  61  64  60  62  61.4 
Age at onset, y  60.8  60  58.2  57.4  55  62  59.8  56  55.9  60.4  59  55.5 
Time since onset, y  4.3  5.3  4.3  3.4  2.5 
Post-menopausal patients, %  93.1  84  66  87.7  87.2  81.4  73.6  80  85.7  89.5  95  83  83  100  81.3 
Smokers/nonsmokers, %  33.3/66.7  10/90  43.1/56.9  36.5/62.2  13/87  29/71 
Mild hairline recession (≤ 3 cm), %  56  75.3  63  71.4 
Diffuse/linear/double line pattern, %  56.9/33.8/6.2  45/48.8/6.2 
Eyebrow involvement, %  92  81  69  86.1  60.1  94.6  61.1  89.5  77.3  81  80  95  73  75  83.3  64.3  50 
Eyebrow involvement from onset, %  42.9  9.2  39  15 
Body hair loss, %a  43.5  47.5  37  52.3  15.5  5.6  73.7  53  21  26  25  22.2  14.3  37.5 
Facial papules, %  29  26  33.8  15.5  17.8  14  37  11.1 
Mucosal lichen planus, %  9.6  1.5  5.4  4.3  4.2  3.2  3.4  3.3  5.5  16.6 
Hypothyroidism, %  14.7  12.2  18  27.7  44.6  7.6  29.2  28  21  15  23  11.1 
Rosacea, %  20  1.8  4.4  15.5  3.2 
Androgenetic alopecia, %  56.8  16  33.8  23.9  34.7  68  40  11  1.6  14  43.8 
a

In our series we specified the percentage of patients with axillary and/or pubic hair involvement. For all other series, values represent the percentage of patients with body hair involvement (if affected location was not specified), or the percentage of patients with axillary hair involvement alone or axillary and pubic hair involvement.

Figure 7.

Association between facial papules and the need for systemic treatment.

(0.07MB).

We present the results of a retrospective analysis of a series of 75 FFA patients who attended the trichology unit of the HUIS over a 2-year period (2016–2018).

In line with the findings of previous studies, the majority of patients (97.3%) were women, most of whom (93.2%) reported FFA onset after menopause.

Biopsy was required for diagnostic confirmation in only 17.3% of cases, in patients with incipient involvement of recent onset or atypical presentations (e.g. the absence of obvious eyebrow involvement).

More than half of our patients (56%) showed mild hairline recession at the time of consultation. Mild hairline recession has also been reported in the majority of subjects in other published series.3,7,14

We defined the different clinical patterns based on the series published by Moreno-Arrones et al.16 Those authors found that the linear pattern was the most frequent (48.8%). By contrast, in our series the diffuse pattern was observed in over half (56.9%) of all patients.

Our data on eyebrow involvement, body hair loss, and the presence of facial papules were similar to those reported in other series.7

In our study population, concomitant lichen planus was observed in 9.6% of patients. This rate is considerably higher than the prevalence of lichen planus in the general population (1–4%), suggesting a possible association between the 2 processes.

Other authors have proposed that FFA may be associated with hypothyroidism6,14,15 and with rosacea.6,23 In our series the prevalence of hypothyroidism (14.7%) and rosacea (20%) was strikingly high, far exceeding the estimated prevalence in the general population (4.2% and 2–5%, respectively). More than half (56.8%) of our patients also had androgenetic alopecia, in line with the findings of other Spanish series.2,14

In agreement with the results of previous studies,5,12 patients who received systemic treatments showed generally good outcomes: 75% of this group achieved stabilization of FFA. The most widely used systemic treatment was 5-alpha reductase inhibitors, in particular dutasteride. More than half (64.2%) of all patients treated with these agents achieved stabilization, a proportion similar to that reported in other series.3,13,14 Stabilization was maintained in all patients during the follow-up period.

Most of our patients were nonsmokers. Univariate analysis revealed a significant association between smoking and mild hairline recession, although this association was not confirmed in the multivariate analysis. In their study, Fonda-Pascual et al25 reported a higher prevalence of severe FFA among nonsmokers, suggesting a possible protective effect of tobacco against FFA progression. In their series, MacDonald et al12 reported a greater proportion of nonsmokers among their FFA patients than in the general population, although this observation was not corroborated by other authors.7,14

We observed a significant association between the linear pattern and reduced severity, as also reported by Moreno-Arrones et al,16 and a trend towards an absence of facial papules in patients with the diffuse pattern.

Furthermore, we observed an association between the presence of facial papules and younger age, as previously reported.8,26 The etiology of these noninflammatory facial papules is not well defined, although perifollicular inflammation of facial hair, sebaceous gland hypertrophy, and alterations of elastic fibers are thought to be involved. Because they are more frequently observed in premenopausal women, facial papules may constitute an early sign of FFA, and could be cause to suspect this process in young women with early signs of hairline recession.

In our series there was a significant association between the need for systemic treatment and the presence of rosacea and facial papules. The logistic regression model revealed that the effects of these 2 factors on the need for treatment were independent of one another. This may indicate a need for earlier and more intensive treatment in FFA patients with concomitant rosacea and/or facial papules.

Our study has certain limitations. Firstly, it is a retrospective study, and therefore the clinical evaluation of the patients was not carried out with the specific purpose of collecting data for this study. Furthermore, owing to short follow-up time after completion of treatment, it was not possible to determine whether the stabilization of FFA achieved by some patients was maintained in the long term. It should also be noted that no trichoscopy data were collected and that smoking-related data did not include the number of packets smoked per year or the number of years since quitting smoking.

In conclusion, in our series of FFA patients women of post-menopausal age predominated and eyebrow involvement was observed in most cases. The prevalence of mucosal lichen planus among FFA patients was higher than that described in the general population. We found that the likelihood of presenting facial papules was higher in younger patients; patients with a linear hairline recession pattern had less severe FFA; and the need for oral treatment was greater in patients with rosacea and facial papules.

Ethical Disclosures

Patients' personal data were processed in accordance with Royal Decree-Law 5/2018, of July 27 2018.

This study was approved by the research commission of the HUIS.

All patients provided verbal informed consent for the collection of data from their medical records, and were informed that these data could be used for clinical studies.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Appendix A
Supplementary data

The following are Supplementary data to this article:

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Please cite this article as: Maldonado Cid P, Leis Dosil VM, Garrido Gutiérrez C, Salinas Moreno S, Thuissard Vasallo IJ, Andreu Vázquez C, et al. Alopecia frontal fibrosante: estudio retrospectivo de 75 pacientes. Actas Dermosifiliogr. 2020;111:487–495.

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