Geographic tongue: Predisposing factors, diagnosis and treatment. A systematic review

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A systematic review" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "481" "paginaFinal" => "488" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "L. González-Álvarez, M.J. García-Pola, J.M. García-Martín" "autores" => array:3 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "González-Álvarez" ] 1 => array:4 [ "nombre" => "M.J." "apellidos" => "García-Pola" "email" => array:1 [ 0 => "mjgarcia@uniovi.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:2 [ "nombre" => "J.M." 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Revisión sistemática" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1377 "Ancho" => 2596 "Tamanyo" => 221556 ] ] "descripcion" => array:1 [ "en" => "Management and treatment algorithm for patients with geographic tongue." ] ] ] "textoCompleto" => "BackgroundGeographic tongue (GT) or benign migratory glossitis is a condition characterized by the appearance of 1 or more atrophic areas on the dorsum and lateral edges of the tongue due to the absence of filiform papillae.<a class="elsevierStyleCrossRef" href="#bib0215">1</a>Precisely defining the epidemiological data regarding the condition's incidence is difficult, given that different rates are reported within the same country. In Sweden, for example, there have been fluctuations in sample size and selection and in the year the study was conducted, with reported prevalence rates in the general population of up to 8.45%.<a class="elsevierStyleCrossRefs" href="#bib0220">2–4</a>GT is clinically classified as (a) active or typical, when demarcated by a white (or intense red), slightly elevated, keratotic edge and (b) passive, abortive or atypical if this edge is missing or disappears before completing the GT formation process. Depending on its dynamism, GT can also be classified as migratory or fixed. Lesions are occasionally found in other locations of the oral cavity and are commonly known as migratory stomatitis, geographical stomatitis or ectopic GT.<a class="elsevierStyleCrossRef" href="#bib0235">5</a>The cause of GT is still unknown but has been reported in patients with a family history of this disease and is frequently found in patients with underlying immune diseases, diseases with systemic repercussions and after administering various treatments.<a class="elsevierStyleCrossRef" href="#bib0240">6</a> The lesion is dynamic, because it changes morphology within hours, is self-limiting by healing in days or weeks and can reoccur within a variable period.<a class="elsevierStyleCrossRef" href="#bib0245">7</a>The objective of this systematic review was to search for information on the comorbid diseases of GT to develop an updated algorithm for its management, which can be applied as guidelines or a reference for practitioners who most often diagnose this disease. To this end, we selected observational, cross-sectional studies, cohort studies, case–control studies and clinical trials on the diagnosis of GT and its associated diseases and its therapeutic alternatives.Materials and methodsThis section was planned by following the Preferred Reporting Items for Systematic Reviews and Meta-analyses system criteria.<a class="elsevierStyleCrossRef" href="#bib0250">8</a>Question at hand: Is there a relationship between GT and some disease that facilitates its management, prevention and treatment?Eligibility criteria: The condition of GT should be defined (1) as the presence of a lesion with atrophy of the lingual filiform papillae surrounded by a white-yellowish border<a class="elsevierStyleCrossRefs" href="#bib0215">1,5</a> or (2) by referring to its source.We also considered as inclusion criteria the articles published in journals, designed on cross-sectional studies, cohort studies, case–control studies and randomized clinical trials. These articles had to be written in English, accompanied or not, by another language. As exclusion criteria, we ruled out prevalence (or epidemiological) studies, reviews, letters to the editor, and contributions to congresses (conferences, presentations and posters).Search strategy: The search was conducted on the PubMed, EMBASE, Web of Science and Cochrane databases. The search strategy included the following keywordsGeographic tongue and Benign migratory glossitis.Study selection: The publications were initially identified by title and author to exclude duplicates. Using the title, abstract and/or directly from the full text, we selected the potentially relevant articles related to diseases associated with GT, its diagnosis, symptoms and treatment. The screening process for the articles was performed by two authors (GA and GP), whose agreement rate was 97.2%. The articles that met the eligibility criteria were fully read and analyzed by the three authors.Data recording: We recorded data on the author(s)’ last name and year of publication. We also included the following variables: the number of examined patients with GT, their age, sex, symptoms and associated diseases. The complementary diagnostic technique (cytology and biopsy) and treatment prescribed was also provided.Prioritization of results: We described the results covering the context of prevalence of the associated diseases, their clinical manifestation, diagnosis and therapeutics. The data analysis was descriptive, providing values on frequency, ranges and mean.Risk of bias in the studies and between the studies: Due to the plurality of the objectives of each research study and the clinical–pathological diversity associated with the participants of these studies, we did not evaluate the individual quality or interstudy quality.ResultsInitially, the PubMed search found 1296 studies (1951 to October 31, 2017), EMBASE provided 983 (1952 to October 31, 2017), Web of Science provided 468 (1910 to December 31, 2017), and the Cochrane database included 11 articles (1964 to 2017), resulting in a total of 2758 publications. After discarding the duplicates by title and author, we reduced the sample to 1021 articles.As we mentioned, we first differentiated the titles and abstracts and excluded publications not directly related to the topic (n=939). After reading the abstracts (or full text in cases where the abstract provided insufficient information or was not available), we selected 82 publications. Of these, we discarded 49, 11 for not meeting the inclusion criteria and 38 for not defining the GT disease. Ultimately, 33 studies met the inclusion criteria, referencing 12 different authors to express the concept of GT. The selected articles were published between 1956 and 2017. <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the flow diagram for the study selection.<a class="elsevierStyleCrossRefs" href="#bib0255">9–41</a><elsevierMultimedia ident="fig0005"></elsevierMultimedia>Demographic characteristics and toxic habitsA total of 4998 patients were analyzed with GT in the sample of 33 articles that made up the review. The studies’ sample sizes ranged from 10<a class="elsevierStyleCrossRef" href="#bib0370">32</a> to 801 cases of GT (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0385">35</a> The patients’ sex was provided in all but six studies.<a class="elsevierStyleCrossRefs" href="#bib0255">9,10,13,19,24,40</a> A total of 2069 patients were male (50.13%), and 2058 were female (49.87%). The age range of the patients with GT was 0–85 years, with a mean age (excluding nine studies) of 42.6 years.<a class="elsevierStyleCrossRefs" href="#bib0270">12–17,20,21,37,41</a> Two patients presented GT at birth.<a class="elsevierStyleCrossRef" href="#bib0345">27</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Tobacco use was recorded in seven studies<a class="elsevierStyleCrossRefs" href="#bib0285">15,17,20–23,26</a> and alcohol use was recorded in 2,<a class="elsevierStyleCrossRefs" href="#bib0315">21,23</a> with 17.45% using tobacco (217/1243) and 42.2% consuming alcohol (187/443). These data corresponded to patients who were in their 30s.Patient characteristicsThe GT symptoms were defined in 5 articles, evaluating pain using the visual analog scale (VAS)<a class="elsevierStyleCrossRef" href="#bib0310">20</a> and through the presence or absence of a burning sensation,<a class="elsevierStyleCrossRefs" href="#bib0270">12,15,18,24,27</a> which presented especially when consuming hot, spicy, acidic or bitter food or drink.<a class="elsevierStyleCrossRef" href="#bib0300">18</a> In the analyzed adult samples, these types of symptoms were reported at rates of 9.2% (12/130),<a class="elsevierStyleCrossRef" href="#bib0285">15</a> 24.5% (46/188)<a class="elsevierStyleCrossRef" href="#bib0300">18</a> and 47% in 2 studies (45/96 and 29/47).<a class="elsevierStyleCrossRefs" href="#bib0270">12,15</a> The VAS scale was applied to 19 patients with GT, with scores lower than 30 for 10 patients, between 30 and 60 for 5 patients and greater than 60 for 4 patients.<a class="elsevierStyleCrossRef" href="#bib0310">20</a> The complication of pain versus no pain without quantification was reported in 3 of 188 patients (1.59%).<a class="elsevierStyleCrossRef" href="#bib0300">18</a>The presence of dysgeusia in young and adolescent patients with GT was mostly from the perception of a bitter or sour taste, with no statistically significant differences compared with a control group.<a class="elsevierStyleCrossRef" href="#bib0410">40</a> Although GT can progress with symptoms in children, it has been observed that, by analyzing the Early Childhood Oral Health Impact Scale, GT does not have a statistically significant effect on their quality of life.<a class="elsevierStyleCrossRef" href="#bib0330">24</a>In terms of the number of lesions in an article, mild symptoms (1 lesion) were observed in 19% of the sample (59/296), moderate symptoms (2–5 lesions) were observed in 46.3% (137/296) and severe symptoms (more than 6 lesions) were observed in 33% (100/296).<a class="elsevierStyleCrossRef" href="#bib0285">15</a> GT was most prevalent at the lateral edges of the tongue (68.6%, 129/188), followed by the anterior area (58.5%,110/188), dorsum (42%; 79/188) and ventral face (10.6%, 20/188).<a class="elsevierStyleCrossRef" href="#bib0300">18</a>For patients with psoriasis, the most common location for GT was on the dorsum (20/29), followed by the lateral edges (12/39).<a class="elsevierStyleCrossRef" href="#bib0270">12</a> The keratosis halo that accompanied the lesion was thinner for patients with GT and psoriasis, providing a lesser burning sensation, despite the onset of more lesions than in patients with GT without psoriasis, results that were statistically significant.<a class="elsevierStyleCrossRef" href="#bib0270">12</a>PsoriasisThe prevalence of GT among patients with psoriasis of the present sample was 12.5% (128/1017),<a class="elsevierStyleCrossRefs" href="#bib0255">9,10,13,14</a> and the prevalence of psoriasis among those with GT was 13.5% (43/318).<a class="elsevierStyleCrossRefs" href="#bib0270">12,15,18</a> GT has also been reported more frequently among patients with psoriasis (10.3%) than in a control group (2.5%).<a class="elsevierStyleCrossRef" href="#bib0265">11</a> These findings were confirmed as statistically significant,<a class="elsevierStyleCrossRef" href="#bib0280">14</a> with an odds ratio of experiencing GT in psoriasis of 4.76 (95% CI 2.3–10.8)<a class="elsevierStyleCrossRef" href="#bib0275">13</a> and 5.0 (95% CI 1.5–16.8) in 2 studies.<a class="elsevierStyleCrossRef" href="#bib0255">9</a> Demographically, GT has been reported more frequently in men with psoriasis<a class="elsevierStyleCrossRefs" href="#bib0270">12,14</a> and older patients in a statistically significant manner.<a class="elsevierStyleCrossRef" href="#bib0265">11</a> The clinical form most often associated with GT has been chronic plaque psoriasis (15/251).<a class="elsevierStyleCrossRef" href="#bib0280">14</a> GT has been considered a marker of greater severity of psoriatic skin lesions using the Psoriasis Area and Severity Index.<a class="elsevierStyleCrossRef" href="#bib0280">14</a> In terms of pathogenesis, when the age at onset of psoriasis was less than 30 years, the prevalence of GT was higher,<a class="elsevierStyleCrossRef" href="#bib0280">14</a> which was corroborated in a statistically significant manner in the study by Picciani et al.<a class="elsevierStyleCrossRef" href="#bib0275">13</a>Allergies/atopy/asthmaThe presence of GT has been reported in patients with allergies (31.08%, 9/27).<a class="elsevierStyleCrossRef" href="#bib0295">17</a> The total number of patients with GT and a history of allergies was 81 (81/639; 12.6%). This prevalence ranged from 3.1% (5/166) to 9.2% (12/130) in the population of a single city, who underwent a study in various diagnostic centers (Borås, Sweden).<a class="elsevierStyleCrossRef" href="#bib0285">15</a> In other geographical areas, the relationship between patients with GT and a history of allergies is as follows: 8/58 (8.6%),<a class="elsevierStyleCrossRef" href="#bib0355">29</a> 23/188 (12.2%),<a class="elsevierStyleCrossRef" href="#bib0300">18</a> 2/13 (15.3%),<a class="elsevierStyleCrossRef" href="#bib0350">28</a> 12/44 (27.2%)<a class="elsevierStyleCrossRef" href="#bib0315">21</a> and 19/40 (47.5%)<a class="elsevierStyleCrossRef" href="#bib0290">16</a>. GT has also been reported (in a statistically significant manner) in patients with a history of atopy<a class="elsevierStyleCrossRef" href="#bib0295">17</a> and of asthma and rhinitis, regardless of the presence of atopy.<a class="elsevierStyleCrossRef" href="#bib0305">19</a> Goregen et al. revealed the statistical significance between the positivity of the Stallergen skin test and the presence of GT.<a class="elsevierStyleCrossRef" href="#bib0290">16</a> The types of allergies mentioned in patients with GT include food, metals and chemical products, pollen and animal skin.<a class="elsevierStyleCrossRef" href="#bib0310">20</a>Psychological/psychiatric factorsIn one study, GT was present in 7.6% (5/66) of the patients with psychological disorders.<a class="elsevierStyleCrossRef" href="#bib0295">17</a> When analyzing the psychosomatic factors frequently related to GT, the statistically significant presence of anxiety measured with the Hamilton Scale (13/44; 29.5%) has been observed.<a class="elsevierStyleCrossRef" href="#bib0315">21</a> Stress was present in 46.2% of a sample collected from 3 studies on patients with GT (304/657).<a class="elsevierStyleCrossRefs" href="#bib0325">23,27</a> However, another study found that GT was not associated with periods of depression (7/121; 5.78%).<a class="elsevierStyleCrossRef" href="#bib0320">22</a>DiabetesWysocki and Daley observed a greater prevalence of GT among patients with juvenile diabetes (7/87; 87%) and with HLA-B15,<a class="elsevierStyleCrossRef" href="#bib0335">25</a> although these findings were not corroborated by other authors (2/65; 3.07%).<a class="elsevierStyleCrossRef" href="#bib0295">17</a>Gastrointestinal diseasesA prevalence of celiac disease of 15% (9/60) has been reported in patients with GT, which was statistically significant despite the lack of this significance in the quantification of antigens HLA-DQ2 and HLA-DQ8, which are frequently found in this disease.<a class="elsevierStyleCrossRef" href="#bib0340">26</a> Other authors have not related GT to a history of gastrointestinal disease.<a class="elsevierStyleCrossRef" href="#bib0295">17</a>Hematological disordersBánóczy et al. detected the presence of anemia in 17% (12/70) of patients with LG.<a class="elsevierStyleCrossRef" href="#bib0345">27</a> Cigic et al. observed statistically significant iron-deficiency among patients with GT compared with a control group, but the authors did not specify whether these patients had celiac disease.<a class="elsevierStyleCrossRef" href="#bib0340">26</a>Other diseasesAlthough a significant relationship with systemic diseases is not always present,<a class="elsevierStyleCrossRefs" href="#bib0315">21,28</a> a number of authors have reported the absence of a relationship with certain diseases such as cardiovascular disease,<a class="elsevierStyleCrossRef" href="#bib0295">17</a> hepatic genitourinary disease,<a class="elsevierStyleCrossRef" href="#bib0295">17</a> thyroid diseases<a class="elsevierStyleCrossRef" href="#bib0300">18</a> and dyslipidemia.<a class="elsevierStyleCrossRef" href="#bib0300">18</a> A relationship with systemic diseases has also not been observed in the pediatric population.<a class="elsevierStyleCrossRef" href="#bib0355">29</a>Association between geographic tongue and oral diseasesThe presence of Helicobacter pylori was reported in 1 of 37 patients with GT.<a class="elsevierStyleCrossRef" href="#bib0365">31</a> The statistically significant prevalence of candidiasis was reported in 14.2% of patients with GT (10/70)<a class="elsevierStyleCrossRef" href="#bib0345">27</a> and in smaller series (90%; 9/10).<a class="elsevierStyleCrossRef" href="#bib0370">32</a> In larger GT samples, mycosis was diagnosed in 2.12% of patients (5/235)<a class="elsevierStyleCrossRef" href="#bib0360">30</a>; the mean involvement was therefore 7.61% (24/315).Another reported infection was caries, with a higher statistically significant index of decayed, missing and filled teeth among patients with GT than in a control group of adults.<a class="elsevierStyleCrossRef" href="#bib0315">21</a> Variations in the quantity of saliva secretion were not recorded,<a class="elsevierStyleCrossRef" href="#bib0370">32</a> and their pH was qualitatively more acidic when compared with a healthy control group.<a class="elsevierStyleCrossRef" href="#bib0370">32</a>GT was concomitant with fissured tongue in up to 49.2% of a sample<a class="elsevierStyleCrossRef" href="#bib0285">15</a> and has been reported in a statistically significant manner in other studies.<a class="elsevierStyleCrossRefs" href="#bib0295">17,18,32,35</a> Although a high rate of the 2 diseases has been found in the pediatric population,<a class="elsevierStyleCrossRef" href="#bib0355">29</a> a statistically significant association between GT and fissured tongue has not been observed in this age group.<a class="elsevierStyleCrossRefs" href="#bib0350">28,33</a> The association between GT and fissured tongue among siblings was manifested in 17.7% of patients (14/79).<a class="elsevierStyleCrossRef" href="#bib0400">38</a> Rahamimoff and Muhsma<a class="elsevierStyleCrossRef" href="#bib0405">39</a> described the progression of GT toward fissured tongue in a number of patients in the third year of monitoring (37.5%; 140/373).GT has been diagnosed in association with serrated tongue (20.9%; 62/296)<a class="elsevierStyleCrossRef" href="#bib0285">15</a> and in a statistically significant manner among patients with burning mouth syndrome (32.9%; 53/161) when comparing them with patients with temporomandibular dysfunction.<a class="elsevierStyleCrossRef" href="#bib0380">34</a>Cytological and histological characteristicsThe cytological peculiarities of GT were described by Scariot et al.<a class="elsevierStyleCrossRef" href="#bib0315">21</a> who specified a Papanicolaou grade of 2, i.e. a normal smear with inflammatory changes. The authors distinguished the increase in nuclear size, thereby increasing its relationship with respect to the cytoplasm. The nuclei showed a perinuclear halo due to its thickening of binuclear appearance. The cytological analysis performed on 96 patients to rule out candidiasis did not report the findings of this test.<a class="elsevierStyleCrossRef" href="#bib0270">12</a>Biopsy studies and sample staining with hematoxylin-eosin were performed for 37 patients. Banoczy et al.<a class="elsevierStyleCrossRef" href="#bib0345">27</a> described 2 areas. In the area corresponding to the red patches, there was greater intracellular and extracellular edema of the epithelial acanthosis and an inflammatory infiltrate, mainly of neutrophils. This inflammatory infiltrate was also observed in the more superficial layers of the epithelium, forming microabscesses (Munro's abscesses). The center of the atrophy corresponds histologically with epithelial exfoliation triggered by the microabscesses, identifying with the absence of filiform papillae and the parakeratotic layer.<a class="elsevierStyleCrossRef" href="#bib0260">10</a>TreatmentThe treatments come from 3 articles on 101 patients. Banoczy et al. proposed the alternative of vitamins A, B, C and B12, iron and sex hormone replenishment, as well as antifungal regimens, although these were effective in <3% of the treated patients.<a class="elsevierStyleCrossRef" href="#bib0345">27</a> Another 3 patients with pain (out of 188) were treated with topical antihistamines, the results of which were not reported.<a class="elsevierStyleCrossRef" href="#bib0300">18</a> The third article was a comparative clinical trial between the topical use of 0.1% triamcinolone acetonide alone and the combination with 0.05% retinoic acid, twice daily, for 10 days in symptomatic GT (without specifying its quantification). Of their results from 28 patients, the authors noted that both treatments provided clinical improvement, without showing significant differences in the use of the corticosteroid in isolation or combined with retinoid.<a class="elsevierStyleCrossRef" href="#bib0415">41</a>DiscussionThe present systematic review covers 33 studies developed using 4 methodological designs: cases and controls (n=19), cross-sectional studies (n=11), cohort (n=2) and a randomized clinical trial. A total of 4998 patients with GT were analyzed from the perspective of their clinical manifestations, diagnosis and treatment.The various authors included in this review followed the classical definition of GT proposed by Hume.<a class="elsevierStyleCrossRef" href="#bib0235">5</a> Thus, GT appears as irregular erythematous patches due to a loss of filiform papillae, typically circumscribed by bands or white keratotic lines that are slightly raised, preserving the fungiform papillae, which have a self-limiting and migratory character.GT is a disorder that has an interchangeable prevalence between the sexes, whose ratio is approximately 1 to 1 (50.13% and 49.87% for males and females, respectively). Tobacco use was considered in 7 studies, reporting tobacco consumption by 17.45% of registered patients (217/1243). The prevalence of alcohol consumption was more relevant, however, although the sample size for their preparation was smaller (42.2%; 187/443).The symptom criteria were difficult to interpret because the degree of pain (measured with the VAS) was only considered in 19 patients.<a class="elsevierStyleCrossRef" href="#bib0310">20</a> Another symptom criterion was expressed through the presence or absence of a burning sensation, a symptom that defines burning mouth syndrome in the absence of clinical and pathological signs.<a class="elsevierStyleCrossRef" href="#bib0420">42</a> This symptom appeared in 9.2% to 47% of patients with GT<a class="elsevierStyleCrossRefs" href="#bib0270">12,15,20</a> and in 32.9% of patients with burning mouth syndrome.<a class="elsevierStyleCrossRef" href="#bib0380">34</a>The patients with GT did not report total dysgeusia in a statistically significant manner.<a class="elsevierStyleCrossRef" href="#bib0410">40</a> This result could be due to the concept of GT, because lingual atrophy mostly affects the filiform papillae (papillae that are not involved in taste) and preserves the fungiform papillae that contain the taste buds.The extensive documentation that examined the association between GT and other ailments requires an understanding of its comorbidity with various systemic and local conditions of the oral cavity. This understanding helps focus on whether this condition involves an oral disease with systemic repercussion or an oral manifestation of a systemic disease. Thus, the link between GT psoriasis, between GT and certain allergies and between GT and certain psychological disorders can be considered bidirectional. Patients with GT have been observed to have psoriasis (at a mean rate of 12.5% of the sample<a class="elsevierStyleCrossRefs" href="#bib0255">9,10,13,14</a>), allergies (12.6%<a class="elsevierStyleCrossRefs" href="#bib0285">15,16,18,21,28</a>) and anxiety (29.5%; 13/44<a class="elsevierStyleCrossRef" href="#bib0315">21</a>). GT manifested in 13.5% of patients with psoriasis,<a class="elsevierStyleCrossRefs" href="#bib0270">12,15,18</a> in 31.08% (9/27)<a class="elsevierStyleCrossRef" href="#bib0295">17</a> of patients with allergies and in 7.6% (5/66) of those with psychological disorders.<a class="elsevierStyleCrossRef" href="#bib0295">17</a> Other diseases that can be present in GT include diabetes, iron-deficiency anemia and celiac disease.Two of the most prevalent oral infections reported in patients with GT are caries and oral candidiasis. The statistically significant evidence of caries in patients with GT, when compared with a healthy control group, is explained by the qualitative findings of a more acidic saliva, thereby promoting the cariogenic process despite the lack of hyposalivation (quantitative reduction in saliva).<a class="elsevierStyleCrossRef" href="#bib0370">32</a> Oral candidiasis was manifested in 7.6% (24/315) of the patients with GT. The differential diagnosis of these 2 diseases can be initially established through examination. The keratotic lesions that define GT cannot be eliminated by scraping and normally self-resolve, although they can reoccur within a variable period.The previous description of GT, along with the self-limiting behavior, helps with the clinical diagnosis. Only 1.19% of the analyzed sample was examined using complementary techniques of cytological diagnosis and biopsy. In atypical forms, a cytological study may be used to confirm the clinical diagnosis. Despite only being used in 17 samples, the cytological description can define the disease due to the inflammatory characteristics (Papanicolaou type 2), with the characteristic image of nuclear demarcation.<a class="elsevierStyleCrossRef" href="#bib0315">21</a> In rare cases, a biopsy that identifies the Munro abscesses may be performed.<a class="elsevierStyleCrossRef" href="#bib0345">27</a>Given the chronicity and fear of cancer generated in the patient by asymptomatic GT lesions, the first step is to inform the patient of the nature and benign behavior of the lesion,<a class="elsevierStyleCrossRef" href="#bib0345">27</a> reserving drug treatment for lesions that the patient reports as painful. Furthermore, the only relevant clinical trial that has confirmed a therapeutic response proposed the application of 0.1% triamcinolone acetonide in orabase (combined or not with 0.05% retinoic acid), twice daily, for 10 days.<a class="elsevierStyleCrossRef" href="#bib0415">41</a><a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows the clinical management of the diagnosis and therapy resulting from the present review.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>There are a number of limitations in this review. The number of studies was small, which was mainly due to the lack of a GT definition in the methodology, which prompted us to exclude 38 articles. No less important was the heterogeneity in the studies’ design and objectives, which is why their comparative analysis was not performed. In most of the research studies, the focus was on the comorbidity with specific diseases, lacking documentation related to the symptoms and therapy.Future studies should aim at completing the therapeutic understanding of GT, as well as the implication of the presence of GT as a marker of severity for the comorbid diseases proposed in the present study, such as psoriasis, various allergies and anxiety.Conflicts of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1118085" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1054263" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1118084" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1054264" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Materials and methods" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Results" "secciones" => array:12 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Demographic characteristics and toxic habits" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Patient characteristics" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Psoriasis" ] 3 => array:2 [ "identificador" => "sec0035" "titulo" => "Allergies/atopy/asthma" ] 4 => array:2 [ "identificador" => "sec0040" "titulo" => "Psychological/psychiatric factors" ] 5 => array:2 [ "identificador" => "sec0045" "titulo" => "Diabetes" ] 6 => array:2 [ "identificador" => "sec0050" "titulo" => "Gastrointestinal diseases" ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Hematological disorders" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Other diseases" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Association between geographic tongue and oral diseases" ] 10 => array:2 [ "identificador" => "sec0070" "titulo" => "Cytological and histological characteristics" ] 11 => array:2 [ "identificador" => "sec0075" "titulo" => "Treatment" ] ] ] 7 => array:2 [ "identificador" => "sec0080" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-03-12" "fechaAceptado" => "2018-05-12" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1054263" "palabras" => array:6 [ 0 => "Benign migratory glossitis" 1 => "Geographic tongue" 2 => "Comorbidity" 3 => "Caries" 4 => "Treatment" 5 => "Systematic review" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1054264" "palabras" => array:6 [ 0 => "Glositis migratoria benigna" 1 => "Lengua geográfica" 2 => "Comorbilidad" 3 => "Caries" 4 => "Tratamiento" 5 => "Revisión sistemática" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionGeographic tongue (GT) is a lesion of unknown origin associated with systemic diseases and therefore involves multidisciplinary care. MethodsWe performed a literature search of the PubMed, EMBASE, Web of Science and Cochrane databases. The selection criteria were consistent with the Preferred Reporting Items for Systematic Reviews protocol. We considered as inclusion criteria journal articles designed on cases of cohorts, cross-sectional studies, cases and controls and randomized clinical trials in the pathogenic, clinical and therapeutic context. ResultsA total of 33 articles met these criteria. We analyzed 4998 patients with GT, with an age range of 0–85 years, and the burning sensation symptom was present in 9.2–47% of these patients. The GT diagnosis was clinical in 98.81% of the cases, and GT displayed an association with psoriasis, allergies and anxiety. Candida infection was present in 7.6% (24/315) of the cases, and the presence of caries was statistically significant. The only analyzed clinical trial proposed treatment through the topical application of 0.1% triamcinolone acetonide combined or not with 0.05% retinoic acid. ConclusionsThe diagnosis of GT is mainly clinical. GT is an asymptomatic disorder that usually requires no treatment. Understanding GT is necessary due to the comorbid intraoral and extraoral diseases that accompany the condition." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónLa lengua geográfica (LG) es una lesión de origen desconocido asociada a enfermedades sistémicas, por lo que su atención plantea una validez multidisciplinar. MétodosLa búsqueda de los artículos fue realizada a partir de las bases de datos de PubMed, Embase, Web of Science y Cochrane Database. Los criterios de selección fueron en concordancia con el protocolo Preferred Reporting Items for Systematic Reviews. Hemos considerado como criterios de inclusión los artículos en revistas diseñados sobre casos de cohortes, estudios transversales, casos y controles, y ensayos clínicos aleatorizados en el contexto patogénico, clínico y terapéutico. ResultadosUn total de 33 artículos cumplieron dichos criterios. El número de pacientes analizados con LG fue de 4.998 con un rango de edad entre los 0 y 85 años. La sintomatología de sensación de ardor estuvo presente en entre el 9,2% y el 47% de los pacientes. El diagnóstico de la LG fue clínico en el 98,81%. Se ha manifestado en la LG una asociación con la psoriasis, las alergias y la ansiedad. La infección por Candida se presentó en el 7,6% (24/315) y la presencia de caries fue estadísticamente significativa. El único ensayo clínico analizado propone como tratamiento el uso tópico de acetónido de triamcinolona al 0,1%, combinado o no con el ácido retinoico al 0,05%. ConclusionesEl diagnóstico de la lengua geográfica es principalmente clínico. Es un desorden asintomático que habitualmente no requiere tratamiento. El conocimiento de la LG es necesario debido a las enfermedades comórbidas intra y extraorales que la acompañan." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: González-Álvarez L, García-Pola MJ, García-Martín JM. Lengua geográfica: factores predisponentes, diagnóstico y tratamiento. Revisión sistemática. Rev Clín Español. 2018;218:481–488." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2685 "Ancho" => 2001 "Tamanyo" => 341011 ] ] "descripcion" => array:1 [ "en" => "Literature search algorithm according to PRISMA criteria." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1377 "Ancho" => 2596 "Tamanyo" => 221556 ] ] "descripcion" => array:1 [ "en" => "Management and treatment algorithm for patients with geographic tongue." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients with GT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4998 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex: male/female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2069/2058 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0–85 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tobacco use, yes/no \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">217/926 (n=1243) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alcohol use, yes/no \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">187/256 (n=443) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">GT+FT, yes/no \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">890/2611 (n=3501) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oral candidiasis, ± \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24/291 (n=315) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Burning sensation, yes/no \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">132/461 (n=593) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Visual analog scale (VAS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">VAS<30 (n=10); VAS 30–60 (n=5); VAS≥60 (n=4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severity according to the no. of lesions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mild: 100 (23.5%); moderate: 214 (50.2%); severe: 112 (26.3%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatments \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.01% triamcinolone acetonide alone or in combination with 0.05% retinoic acid (n=28) Iron plus vitamin B12 (n=25) Vitamin A (n=11) Vitamin C (n=6) Sex hormones (n=3) Antifungals (n=12) Topical antihistamines (n=3) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1907777.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Demographic, clinical and therapeutic characteristics of patients with geographic tongue." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:42 [ 0 => array:3 [ "identificador" => "bib0215" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oral & Maxillofacial Pathology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "B.W. 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Geographic tongue: Predisposing factors, diagnosis and treatment. A systematic review

Lengua geográfica: factores predisponentes, diagnóstico y tratamiento. Revisión sistemática

L. González-Álvarez, M.J. García-Pola

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mjgarcia@uniovi.es

Corresponding author.

, J.M. García-Martín

Departamento de Cirugía y Especialidades Médico-Quirúrgicas, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Geographic tongue &#40;GT&#41; or benign migratory glossitis is a condition characterized by the appearance of 1 or more atrophic areas on the dorsum and lateral edges of the tongue due to the absence of filiform papillae&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Precisely defining the epidemiological data regarding the condition&#39;s incidence is difficult&#44; given that different rates are reported within the same country&#46; In Sweden&#44; for example&#44; there have been fluctuations in sample size and selection and in the year the study was conducted&#44; with reported prevalence rates in the general population of up to 8&#46;45&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">GT is clinically classified as &#40;a&#41; active or typical&#44; when demarcated by a white &#40;or intense red&#41;&#44; slightly elevated&#44; keratotic edge and &#40;b&#41; passive&#44; abortive or atypical if this edge is missing or disappears before completing the GT formation process&#46; Depending on its dynamism&#44; GT can also be classified as migratory or fixed&#46; Lesions are occasionally found in other locations of the oral cavity and are commonly known as migratory stomatitis&#44; geographical stomatitis or ectopic GT&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The cause of GT is still unknown but has been reported in patients with a family history of this disease and is frequently found in patients with underlying immune diseases&#44; diseases with systemic repercussions and after administering various treatments&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">6</span></a> The lesion is dynamic&#44; because it changes morphology within hours&#44; is self-limiting by healing in days or weeks and can reoccur within a variable period&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The objective of this systematic review was to search for information on the comorbid diseases of GT to develop an updated algorithm for its management&#44; which can be applied as guidelines or a reference for practitioners who most often diagnose this disease&#46; To this end&#44; we selected observational&#44; cross-sectional studies&#44; cohort studies&#44; case&#8211;control studies and clinical trials on the diagnosis of GT and its associated diseases and its therapeutic alternatives&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">This section was planned by following the Preferred Reporting Items for Systematic Reviews and Meta-analyses system criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Question at hand</span>&#58; Is there a relationship between GT and some disease that facilitates its management&#44; prevention and treatment&#63;</p><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Eligibility criteria</span>&#58; The condition of GT should be defined &#40;1&#41; as the presence of a lesion with atrophy of the lingual filiform papillae surrounded by a white-yellowish border<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">1&#44;5</span></a> or &#40;2&#41; by referring to its source&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">We also considered as inclusion criteria the articles published in journals&#44; designed on cross-sectional studies&#44; cohort studies&#44; case&#8211;control studies and randomized clinical trials&#46; These articles had to be written in English&#44; accompanied or not&#44; by another language&#46; As exclusion criteria&#44; we ruled out prevalence &#40;or epidemiological&#41; studies&#44; reviews&#44; letters to the editor&#44; and contributions to congresses &#40;conferences&#44; presentations and posters&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Search strategy</span>&#58; The search was conducted on the PubMed&#44; EMBASE&#44; Web of Science and Cochrane databases&#46; The search strategy included the following keywords</p><p id="par0055" class="elsevierStylePara elsevierViewall">Geographic tongue and Benign migratory glossitis&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Study selection</span>&#58; The publications were initially identified by title and author to exclude duplicates&#46; Using the title&#44; abstract and&#47;or directly from the full text&#44; we selected the potentially relevant articles related to diseases associated with GT&#44; its diagnosis&#44; symptoms and treatment&#46; The screening process for the articles was performed by two authors &#40;GA and GP&#41;&#44; whose agreement rate was 97&#46;2&#37;&#46; The articles that met the eligibility criteria were fully read and analyzed by the three authors&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Data recording</span>&#58; We recorded data on the author&#40;s&#41;&#8217; last name and year of publication&#46; We also included the following variables&#58; the number of examined patients with GT&#44; their age&#44; sex&#44; symptoms and associated diseases&#46; The complementary diagnostic technique &#40;cytology and biopsy&#41; and treatment prescribed was also provided&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Prioritization of results</span>&#58; We described the results covering the context of prevalence of the associated diseases&#44; their clinical manifestation&#44; diagnosis and therapeutics&#46; The data analysis was descriptive&#44; providing values on frequency&#44; ranges and mean&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Risk of bias in the studies and between the studies</span>&#58; Due to the plurality of the objectives of each research study and the clinical&#8211;pathological diversity associated with the participants of these studies&#44; we did not evaluate the individual quality or interstudy quality&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">Initially&#44; the PubMed search found 1296 studies &#40;1951 to October 31&#44; 2017&#41;&#44; EMBASE provided 983 &#40;1952 to October 31&#44; 2017&#41;&#44; Web of Science provided 468 &#40;1910 to December 31&#44; 2017&#41;&#44; and the Cochrane database included 11 articles &#40;1964 to 2017&#41;&#44; resulting in a total of 2758 publications&#46; After discarding the duplicates by title and author&#44; we reduced the sample to 1021 articles&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">As we mentioned&#44; we first differentiated the titles and abstracts and excluded publications not directly related to the topic &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>939&#41;&#46; After reading the abstracts &#40;or full text in cases where the abstract provided insufficient information or was not available&#41;&#44; we selected 82 publications&#46; Of these&#44; we discarded 49&#44; 11 for not meeting the inclusion criteria and 38 for not defining the GT disease&#46; Ultimately&#44; 33 studies met the inclusion criteria&#44; referencing 12 different authors to express the concept of GT&#46; The selected articles were published between 1956 and 2017&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the flow diagram for the study selection&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">9&#8211;41</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Demographic characteristics and toxic habits</span><p id="par0090" class="elsevierStylePara elsevierViewall">A total of 4998 patients were analyzed with GT in the sample of 33 articles that made up the review&#46; The studies&#8217; sample sizes ranged from 10<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">32</span></a> to 801 cases of GT &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">35</span></a> The patients&#8217; sex was provided in all but six studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">9&#44;10&#44;13&#44;19&#44;24&#44;40</span></a> A total of 2069 patients were male &#40;50&#46;13&#37;&#41;&#44; and 2058 were female &#40;49&#46;87&#37;&#41;&#46; The age range of the patients with GT was 0&#8211;85 years&#44; with a mean age &#40;excluding nine studies&#41; of 42&#46;6 years&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#8211;17&#44;20&#44;21&#44;37&#44;41</span></a> Two patients presented GT at birth&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Tobacco use was recorded in seven studies<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">15&#44;17&#44;20&#8211;23&#44;26</span></a> and alcohol use was recorded in 2&#44;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">21&#44;23</span></a> with 17&#46;45&#37; using tobacco &#40;217&#47;1243&#41; and 42&#46;2&#37; consuming alcohol &#40;187&#47;443&#41;&#46; These data corresponded to patients who were in their 30s&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Patient characteristics</span><p id="par0100" class="elsevierStylePara elsevierViewall">The GT symptoms were defined in 5 articles&#44; evaluating pain using the visual analog scale &#40;VAS&#41;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a> and through the presence or absence of a burning sensation&#44;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#44;15&#44;18&#44;24&#44;27</span></a> which presented especially when consuming hot&#44; spicy&#44; acidic or bitter food or drink&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> In the analyzed adult samples&#44; these types of symptoms were reported at rates of 9&#46;2&#37; &#40;12&#47;130&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">15</span></a> 24&#46;5&#37; &#40;46&#47;188&#41;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> and 47&#37; in 2 studies &#40;45&#47;96 and 29&#47;47&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#44;15</span></a> The VAS scale was applied to 19 patients with GT&#44; with scores lower than 30 for 10 patients&#44; between 30 and 60 for 5 patients and greater than 60 for 4 patients&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a> The complication of pain versus no pain without quantification was reported in 3 of 188 patients &#40;1&#46;59&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">The presence of dysgeusia in young and adolescent patients with GT was mostly from the perception of a bitter or sour taste&#44; with no statistically significant differences compared with a control group&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">40</span></a> Although GT can progress with symptoms in children&#44; it has been observed that&#44; by analyzing the Early Childhood Oral Health Impact Scale&#44; GT does not have a statistically significant effect on their quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">24</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In terms of the number of lesions in an article&#44; mild symptoms &#40;1 lesion&#41; were observed in 19&#37; of the sample &#40;59&#47;296&#41;&#44; moderate symptoms &#40;2&#8211;5 lesions&#41; were observed in 46&#46;3&#37; &#40;137&#47;296&#41; and severe symptoms &#40;more than 6 lesions&#41; were observed in 33&#37; &#40;100&#47;296&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">15</span></a> GT was most prevalent at the lateral edges of the tongue &#40;68&#46;6&#37;&#44; 129&#47;188&#41;&#44; followed by the anterior area &#40;58&#46;5&#37;&#44;110&#47;188&#41;&#44; dorsum &#40;42&#37;&#59; 79&#47;188&#41; and ventral face &#40;10&#46;6&#37;&#44; 20&#47;188&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">For patients with psoriasis&#44; the most common location for GT was on the dorsum &#40;20&#47;29&#41;&#44; followed by the lateral edges &#40;12&#47;39&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">12</span></a> The keratosis halo that accompanied the lesion was thinner for patients with GT and psoriasis&#44; providing a lesser burning sensation&#44; despite the onset of more lesions than in patients with GT without psoriasis&#44; results that were statistically significant&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Psoriasis</span><p id="par0120" class="elsevierStylePara elsevierViewall">The prevalence of GT among patients with psoriasis of the present sample was 12&#46;5&#37; &#40;128&#47;1017&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">9&#44;10&#44;13&#44;14</span></a> and the prevalence of psoriasis among those with GT was 13&#46;5&#37; &#40;43&#47;318&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#44;15&#44;18</span></a> GT has also been reported more frequently among patients with psoriasis &#40;10&#46;3&#37;&#41; than in a control group &#40;2&#46;5&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a> These findings were confirmed as statistically significant&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> with an odds ratio of experiencing GT in psoriasis of 4&#46;76 &#40;95&#37; CI 2&#46;3&#8211;10&#46;8&#41;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">13</span></a> and 5&#46;0 &#40;95&#37; CI 1&#46;5&#8211;16&#46;8&#41; in 2 studies&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">9</span></a> Demographically&#44; GT has been reported more frequently in men with psoriasis<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#44;14</span></a> and older patients in a statistically significant manner&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a> The clinical form most often associated with GT has been chronic plaque psoriasis &#40;15&#47;251&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> GT has been considered a marker of greater severity of psoriatic skin lesions using the Psoriasis Area and Severity Index&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> In terms of pathogenesis&#44; when the age at onset of psoriasis was less than 30 years&#44; the prevalence of GT was higher&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> which was corroborated in a statistically significant manner in the study by Picciani et al&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Allergies&#47;atopy&#47;asthma</span><p id="par0125" class="elsevierStylePara elsevierViewall">The presence of GT has been reported in patients with allergies &#40;31&#46;08&#37;&#44; 9&#47;27&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> The total number of patients with GT and a history of allergies was 81 &#40;81&#47;639&#59; 12&#46;6&#37;&#41;&#46; This prevalence ranged from 3&#46;1&#37; &#40;5&#47;166&#41; to 9&#46;2&#37; &#40;12&#47;130&#41; in the population of a single city&#44; who underwent a study in various diagnostic centers &#40;Bor&#229;s&#44; Sweden&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">15</span></a> In other geographical areas&#44; the relationship between patients with GT and a history of allergies is as follows&#58; 8&#47;58 &#40;8&#46;6&#37;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">29</span></a> 23&#47;188 &#40;12&#46;2&#37;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> 2&#47;13 &#40;15&#46;3&#37;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">28</span></a> 12&#47;44 &#40;27&#46;2&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a> and 19&#47;40 &#40;47&#46;5&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">16</span></a>&#46; GT has also been reported &#40;in a statistically significant manner&#41; in patients with a history of atopy<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> and of asthma and rhinitis&#44; regardless of the presence of atopy&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> Goregen et al&#46; revealed the statistical significance between the positivity of the Stallergen skin test and the presence of GT&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">16</span></a> The types of allergies mentioned in patients with GT include food&#44; metals and chemical products&#44; pollen and animal skin&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Psychological&#47;psychiatric factors</span><p id="par0130" class="elsevierStylePara elsevierViewall">In one study&#44; GT was present in 7&#46;6&#37; &#40;5&#47;66&#41; of the patients with psychological disorders&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> When analyzing the psychosomatic factors frequently related to GT&#44; the statistically significant presence of anxiety measured with the Hamilton Scale &#40;13&#47;44&#59; 29&#46;5&#37;&#41; has been observed&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a> Stress was present in 46&#46;2&#37; of a sample collected from 3 studies on patients with GT &#40;304&#47;657&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">23&#44;27</span></a> However&#44; another study found that GT was not associated with periods of depression &#40;7&#47;121&#59; 5&#46;78&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Diabetes</span><p id="par0135" class="elsevierStylePara elsevierViewall">Wysocki and Daley observed a greater prevalence of GT among patients with juvenile diabetes &#40;7&#47;87&#59; 87&#37;&#41; and with HLA-B15&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">25</span></a> although these findings were not corroborated by other authors &#40;2&#47;65&#59; 3&#46;07&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Gastrointestinal diseases</span><p id="par0140" class="elsevierStylePara elsevierViewall">A prevalence of celiac disease of 15&#37; &#40;9&#47;60&#41; has been reported in patients with GT&#44; which was statistically significant despite the lack of this significance in the quantification of antigens HLA-DQ2 and HLA-DQ8&#44; which are frequently found in this disease&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">26</span></a> Other authors have not related GT to a history of gastrointestinal disease&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Hematological disorders</span><p id="par0145" class="elsevierStylePara elsevierViewall">B&#225;n&#243;czy et al&#46; detected the presence of anemia in 17&#37; &#40;12&#47;70&#41; of patients with LG&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a> Cigic et al&#46; observed statistically significant iron-deficiency among patients with GT compared with a control group&#44; but the authors did not specify whether these patients had celiac disease&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Other diseases</span><p id="par0150" class="elsevierStylePara elsevierViewall">Although a significant relationship with systemic diseases is not always present&#44;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">21&#44;28</span></a> a number of authors have reported the absence of a relationship with certain diseases such as cardiovascular disease&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> hepatic genitourinary disease&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> thyroid diseases<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> and dyslipidemia&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> A relationship with systemic diseases has also not been observed in the pediatric population&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">29</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Association between geographic tongue and oral diseases</span><p id="par0155" class="elsevierStylePara elsevierViewall">The presence of <span class="elsevierStyleItalic">Helicobacter pylori</span> was reported in 1 of 37 patients with GT&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">31</span></a> The statistically significant prevalence of candidiasis was reported in 14&#46;2&#37; of patients with GT &#40;10&#47;70&#41;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a> and in smaller series &#40;90&#37;&#59; 9&#47;10&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">32</span></a> In larger GT samples&#44; mycosis was diagnosed in 2&#46;12&#37; of patients &#40;5&#47;235&#41;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">30</span></a>&#59; the mean involvement was therefore 7&#46;61&#37; &#40;24&#47;315&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Another reported infection was caries&#44; with a higher statistically significant index of decayed&#44; missing and filled teeth among patients with GT than in a control group of adults&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a> Variations in the quantity of saliva secretion were not recorded&#44;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">32</span></a> and their pH was qualitatively more acidic when compared with a healthy control group&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">32</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">GT was concomitant with fissured tongue in up to 49&#46;2&#37; of a sample<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">15</span></a> and has been reported in a statistically significant manner in other studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#44;18&#44;32&#44;35</span></a> Although a high rate of the 2 diseases has been found in the pediatric population&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">29</span></a> a statistically significant association between GT and fissured tongue has not been observed in this age group&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">28&#44;33</span></a> The association between GT and fissured tongue among siblings was manifested in 17&#46;7&#37; of patients &#40;14&#47;79&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">38</span></a> Rahamimoff and Muhsma<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">39</span></a> described the progression of GT toward fissured tongue in a number of patients in the third year of monitoring &#40;37&#46;5&#37;&#59; 140&#47;373&#41;&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">GT has been diagnosed in association with serrated tongue &#40;20&#46;9&#37;&#59; 62&#47;296&#41;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">15</span></a> and in a statistically significant manner among patients with burning mouth syndrome &#40;32&#46;9&#37;&#59; 53&#47;161&#41; when comparing them with patients with temporomandibular dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">34</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Cytological and histological characteristics</span><p id="par0175" class="elsevierStylePara elsevierViewall">The cytological peculiarities of GT were described by Scariot et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a> who specified a Papanicolaou grade of 2&#44; i&#46;e&#46; a normal smear with inflammatory changes&#46; The authors distinguished the increase in nuclear size&#44; thereby increasing its relationship with respect to the cytoplasm&#46; The nuclei showed a perinuclear halo due to its thickening of binuclear appearance&#46; The cytological analysis performed on 96 patients to rule out candidiasis did not report the findings of this test&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">12</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Biopsy studies and sample staining with hematoxylin-eosin were performed for 37 patients&#46; Banoczy et al&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a> described 2 areas&#46; In the area corresponding to the red patches&#44; there was greater intracellular and extracellular edema of the epithelial acanthosis and an inflammatory infiltrate&#44; mainly of neutrophils&#46; This inflammatory infiltrate was also observed in the more superficial layers of the epithelium&#44; forming microabscesses &#40;Munro&#39;s abscesses&#41;&#46; The center of the atrophy corresponds histologically with epithelial exfoliation triggered by the microabscesses&#44; identifying with the absence of filiform papillae and the parakeratotic layer&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Treatment</span><p id="par0185" class="elsevierStylePara elsevierViewall">The treatments come from 3 articles on 101 patients&#46; Banoczy et al&#46; proposed the alternative of vitamins A&#44; B&#44; C and B<span class="elsevierStyleInf">12</span>&#44; iron and sex hormone replenishment&#44; as well as antifungal regimens&#44; although these were effective in &#60;3&#37; of the treated patients&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a> Another 3 patients with pain &#40;out of 188&#41; were treated with topical antihistamines&#44; the results of which were not reported&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> The third article was a comparative clinical trial between the topical use of 0&#46;1&#37; triamcinolone acetonide alone and the combination with 0&#46;05&#37; retinoic acid&#44; twice daily&#44; for 10 days in symptomatic GT &#40;without specifying its quantification&#41;&#46; Of their results from 28 patients&#44; the authors noted that both treatments provided clinical improvement&#44; without showing significant differences in the use of the corticosteroid in isolation or combined with retinoid&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">41</span></a></p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Discussion</span><p id="par0190" class="elsevierStylePara elsevierViewall">The present systematic review covers 33 studies developed using 4 methodological designs&#58; cases and controls &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41;&#44; cross-sectional studies &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; cohort &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; and a randomized clinical trial&#46; A total of 4998 patients with GT were analyzed from the perspective of their clinical manifestations&#44; diagnosis and treatment&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The various authors included in this review followed the classical definition of GT proposed by Hume&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">5</span></a> Thus&#44; GT appears as irregular erythematous patches due to a loss of filiform papillae&#44; typically circumscribed by bands or white keratotic lines that are slightly raised&#44; preserving the fungiform papillae&#44; which have a self-limiting and migratory character&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">GT is a disorder that has an interchangeable prevalence between the sexes&#44; whose ratio is approximately 1 to 1 &#40;50&#46;13&#37; and 49&#46;87&#37; for males and females&#44; respectively&#41;&#46; Tobacco use was considered in 7 studies&#44; reporting tobacco consumption by 17&#46;45&#37; of registered patients &#40;217&#47;1243&#41;&#46; The prevalence of alcohol consumption was more relevant&#44; however&#44; although the sample size for their preparation was smaller &#40;42&#46;2&#37;&#59; 187&#47;443&#41;&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">The symptom criteria were difficult to interpret because the degree of pain &#40;measured with the VAS&#41; was only considered in 19 patients&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a> Another symptom criterion was expressed through the presence or absence of a burning sensation&#44; a symptom that defines burning mouth syndrome in the absence of clinical and pathological signs&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">42</span></a> This symptom appeared in 9&#46;2&#37; to 47&#37; of patients with GT<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#44;15&#44;20</span></a> and in 32&#46;9&#37; of patients with burning mouth syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">34</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">The patients with GT did not report total dysgeusia in a statistically significant manner&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">40</span></a> This result could be due to the concept of GT&#44; because lingual atrophy mostly affects the filiform papillae &#40;papillae that are not involved in taste&#41; and preserves the fungiform papillae that contain the taste buds&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">The extensive documentation that examined the association between GT and other ailments requires an understanding of its comorbidity with various systemic and local conditions of the oral cavity&#46; This understanding helps focus on whether this condition involves an oral disease with systemic repercussion or an oral manifestation of a systemic disease&#46; Thus&#44; the link between GT psoriasis&#44; between GT and certain allergies and between GT and certain psychological disorders can be considered bidirectional&#46; Patients with GT have been observed to have psoriasis &#40;at a mean rate of 12&#46;5&#37; of the sample<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">9&#44;10&#44;13&#44;14</span></a>&#41;&#44; allergies &#40;12&#46;6&#37;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">15&#44;16&#44;18&#44;21&#44;28</span></a>&#41; and anxiety &#40;29&#46;5&#37;&#59; 13&#47;44<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a>&#41;&#46; GT manifested in 13&#46;5&#37; of patients with psoriasis&#44;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#44;15&#44;18</span></a> in 31&#46;08&#37; &#40;9&#47;27&#41;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> of patients with allergies and in 7&#46;6&#37; &#40;5&#47;66&#41; of those with psychological disorders&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> Other diseases that can be present in GT include diabetes&#44; iron-deficiency anemia and celiac disease&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Two of the most prevalent oral infections reported in patients with GT are caries and oral candidiasis&#46; The statistically significant evidence of caries in patients with GT&#44; when compared with a healthy control group&#44; is explained by the qualitative findings of a more acidic saliva&#44; thereby promoting the cariogenic process despite the lack of hyposalivation &#40;quantitative reduction in saliva&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">32</span></a> Oral candidiasis was manifested in 7&#46;6&#37; &#40;24&#47;315&#41; of the patients with GT&#46; The differential diagnosis of these 2 diseases can be initially established through examination&#46; The keratotic lesions that define GT cannot be eliminated by scraping and normally self-resolve&#44; although they can reoccur within a variable period&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">The previous description of GT&#44; along with the self-limiting behavior&#44; helps with the clinical diagnosis&#46; Only 1&#46;19&#37; of the analyzed sample was examined using complementary techniques of cytological diagnosis and biopsy&#46; In atypical forms&#44; a cytological study may be used to confirm the clinical diagnosis&#46; Despite only being used in 17 samples&#44; the cytological description can define the disease due to the inflammatory characteristics &#40;Papanicolaou type 2&#41;&#44; with the characteristic image of nuclear demarcation&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a> In rare cases&#44; a biopsy that identifies the Munro abscesses may be performed&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">Given the chronicity and fear of cancer generated in the patient by asymptomatic GT lesions&#44; the first step is to inform the patient of the nature and benign behavior of the lesion&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a> reserving drug treatment for lesions that the patient reports as painful&#46; Furthermore&#44; the only relevant clinical trial that has confirmed a therapeutic response proposed the application of 0&#46;1&#37; triamcinolone acetonide in orabase &#40;combined or not with 0&#46;05&#37; retinoic acid&#41;&#44; twice daily&#44; for 10 days&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">41</span></a><a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> shows the clinical management of the diagnosis and therapy resulting from the present review&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0235" class="elsevierStylePara elsevierViewall">There are a number of limitations in this review&#46; The number of studies was small&#44; which was mainly due to the lack of a GT definition in the methodology&#44; which prompted us to exclude 38 articles&#46; No less important was the heterogeneity in the studies&#8217; design and objectives&#44; which is why their comparative analysis was not performed&#46; In most of the research studies&#44; the focus was on the comorbidity with specific diseases&#44; lacking documentation related to the symptoms and therapy&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Future studies should aim at completing the therapeutic understanding of GT&#44; as well as the implication of the presence of GT as a marker of severity for the comorbid diseases proposed in the present study&#44; such as psoriasis&#44; various allergies and anxiety&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflicts of interest</span><p id="par0245" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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              "titulo" => "Patient characteristics"
            ]
            2 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Psoriasis"
            ]
            3 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Allergies&#47;atopy&#47;asthma"
            ]
            4 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Psychological&#47;psychiatric factors"
            ]
            5 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Diabetes"
            ]
            6 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Gastrointestinal diseases"
            ]
            7 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Hematological disorders"
            ]
            8 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Other diseases"
            ]
            9 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Association between geographic tongue and oral diseases"
            ]
            10 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Cytological and histological characteristics"
            ]
            11 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Treatment"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conflicts of interest"
        ]
        9 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-03-12"
    "fechaAceptado" => "2018-05-12"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1054263"
          "palabras" => array:6 [
            0 => "Benign migratory glossitis"
            1 => "Geographic tongue"
            2 => "Comorbidity"
            3 => "Caries"
            4 => "Treatment"
            5 => "Systematic review"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1054264"
          "palabras" => array:6 [
            0 => "Glositis migratoria benigna"
            1 => "Lengua geogr&#225;fica"
            2 => "Comorbilidad"
            3 => "Caries"
            4 => "Tratamiento"
            5 => "Revisi&#243;n sistem&#225;tica"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Geographic tongue &#40;GT&#41; is a lesion of unknown origin associated with systemic diseases and therefore involves multidisciplinary care&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We performed a literature search of the PubMed&#44; EMBASE&#44; Web of Science and Cochrane databases&#46; The selection criteria were consistent with the Preferred Reporting Items for Systematic Reviews protocol&#46; We considered as inclusion criteria journal articles designed on cases of cohorts&#44; cross-sectional studies&#44; cases and controls and randomized clinical trials in the pathogenic&#44; clinical and therapeutic context&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 33 articles met these criteria&#46; We analyzed 4998 patients with GT&#44; with an age range of 0&#8211;85 years&#44; and the burning sensation symptom was present in 9&#46;2&#8211;47&#37; of these patients&#46; The GT diagnosis was clinical in 98&#46;81&#37; of the cases&#44; and GT displayed an association with psoriasis&#44; allergies and anxiety&#46; <span class="elsevierStyleItalic">Candida</span> infection was present in 7&#46;6&#37; &#40;24&#47;315&#41; of the cases&#44; and the presence of caries was statistically significant&#46; The only analyzed clinical trial proposed treatment through the topical application of 0&#46;1&#37; triamcinolone acetonide combined or not with 0&#46;05&#37; retinoic acid&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The diagnosis of GT is mainly clinical&#46; GT is an asymptomatic disorder that usually requires no treatment&#46; Understanding GT is necessary due to the comorbid intraoral and extraoral diseases that accompany the condition&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          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">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La lengua geogr&#225;fica &#40;LG&#41; es una lesi&#243;n de origen desconocido asociada a enfermedades sist&#233;micas&#44; por lo que su atenci&#243;n plantea una validez multidisciplinar&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La b&#250;squeda de los art&#237;culos fue realizada a partir de las bases de datos de PubMed&#44; Embase&#44; Web of Science y Cochrane Database&#46; Los criterios de selecci&#243;n fueron en concordancia con el protocolo <span class="elsevierStyleItalic">Preferred Reporting Items for Systematic Reviews</span>&#46; Hemos considerado como criterios de inclusi&#243;n los art&#237;culos en revistas dise&#241;ados sobre casos de cohortes&#44; estudios transversales&#44; casos y controles&#44; y ensayos cl&#237;nicos aleatorizados en el contexto patog&#233;nico&#44; cl&#237;nico y terap&#233;utico&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Un total de 33 art&#237;culos cumplieron dichos criterios&#46; El n&#250;mero de pacientes analizados con LG fue de 4&#46;998 con un rango de edad entre los 0 y 85 a&#241;os&#46; La sintomatolog&#237;a de sensaci&#243;n de ardor estuvo presente en entre el 9&#44;2&#37; y el 47&#37; de los pacientes&#46; El diagn&#243;stico de la LG fue cl&#237;nico en el 98&#44;81&#37;&#46; Se ha manifestado en la LG una asociaci&#243;n con la psoriasis&#44; las alergias y la ansiedad&#46; La infecci&#243;n por <span class="elsevierStyleItalic">Candida</span> se present&#243; en el 7&#44;6&#37; &#40;24&#47;315&#41; y la presencia de caries fue estad&#237;sticamente significativa&#46; El &#250;nico ensayo cl&#237;nico analizado propone como tratamiento el uso t&#243;pico de acet&#243;nido de triamcinolona al 0&#44;1&#37;&#44; combinado o no con el &#225;cido retinoico al 0&#44;05&#37;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El diagn&#243;stico de la lengua geogr&#225;fica es principalmente cl&#237;nico&#46; Es un desorden asintom&#225;tico que habitualmente no requiere tratamiento&#46; El conocimiento de la LG es necesario debido a las enfermedades com&#243;rbidas intra y extraorales que la acompa&#241;an&#46;</p></span>"
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            "titulo" => "M&#233;todos"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0040"
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    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Gonz&#225;lez-&#193;lvarez L&#44; Garc&#237;a-Pola MJ&#44; Garc&#237;a-Mart&#237;n JM&#46; Lengua geogr&#225;fica&#58; factores predisponentes&#44; diagn&#243;stico y tratamiento&#46; Revisi&#243;n sistem&#225;tica&#46; Rev Cl&#237;n Espa&#241;ol&#46; 2018&#59;218&#58;481&#8211;488&#46;</p>"
      ]
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients with GT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4998&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex&#58; male&#47;female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2069&#47;2058&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age &#40;range&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#8211;85 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tobacco use&#44; yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">217&#47;926 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1243&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alcohol use&#44; yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">187&#47;256 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>443&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top">GT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>FT&#44; yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">890&#47;2611 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3501&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oral candidiasis&#44; &#177;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#47;291 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>315&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Burning sensation&#44; yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">132&#47;461 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>593&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Visual analog scale &#40;VAS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">VAS<span class="elsevierStyleHsp" style=""></span>&#60;30 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41;&#59; VAS 30&#8211;60 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41;&#59; VAS<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>60 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severity according to the no&#46; of lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mild&#58; 100 &#40;23&#46;5&#37;&#41;&#59; moderate&#58; 214 &#40;50&#46;2&#37;&#41;&#59; severe&#58; 112 &#40;26&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatments&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;01&#37; triamcinolone acetonide alone or in combination with 0&#46;05&#37; retinoic acid &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#41;<br>Iron plus vitamin B<span class="elsevierStyleInf">12</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41;<br>Vitamin A &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;<br>Vitamin C &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;<br>Sex hormones &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;<br>Antifungals &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41;<br>Topical antihistamines &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:42 [
            0 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Oral &#38; Maxillofacial Pathology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "B&#46;W&#46; Neville"
                            1 => "D&#46;D&#46; Damm"
                            2 => "C&#46;M&#46; Allen"
                            3 => "J&#46;E&#46; Bouquot"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:4 [
                        "edicion" => "3rd edition"
                        "fecha" => "2009"
                        "editorial" => "Saunders"
                        "editorialLocalizacion" => "Philadelphia"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "2"
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                      "autores" => array:1 [
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                          "etal" => false
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                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
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                        ]
                      ]
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            ]
            2 => array:3 [
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              "etiqueta" => "3"
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "T&#46; Ax&#233;ll"
                          ]
                        ]
                      ]
                    ]
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              "identificador" => "bib0230"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Occurrence of oral mucosal lesions&#44; the influence of tobacco habits and an estimate of treatment time in an adult Swedish population"
                      "autores" => array:1 [
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                          "etal" => false
                          "autores" => array:3 [
                            0 => "L&#46; Salonen"
                            1 => "T&#46; Ax&#233;ll"
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                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
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            4 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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Article information

ISSN: 22548874
Original language: English

DOI:10.1016/j.rceng.2018.05.009

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