Anxiety and genetic polymorphisms in catechol-O-methyltransferase (COMT) and serotonin transportation gene (5HTT) are associated with benign migratory glossitis.

OBJECTIVE: The aim of this case-control study was to investigate whether benign migratory glossitis (BMG) is associated with catechol-O-methyltransferase (COMT) and serotonin transportation gene (5HTT) polymorphisms and anxiety. STUDY DESIGN: The study comprised 43 patients with BMG and 114 patients without a history of BMG. We used the Hamilton Anxiety (HAM-A) rating scale to assess each individual's anxiety. We collected DNA from buccal cells and analyzed polymorphisms of COMT and 5HTT. We conducted statistical evaluations by using SPSS software (SPSS Inc., Chicago, IL) and STATA (StataCorp, College Station, TX). Alpha value was set at 0.05. RESULTS: Overall anxiety level was significantly higher in the case group than in the control group (P < .001). In adjusted multiple logistic regression, the COMT markers were not associated with BMG. Individuals with the CC genotype, in rs3813034 of 5HTT, presented an odds ratio (OR) of 2.85 (95% confidence interval [CI] 1.03-7.82; P = .042). Individuals with the TT genotype, in the rs1042173 of 5HTT, presented an OR of 3.77 (95% CI 1.32-10.74; P = .013). For each incremental increase in the anxiety score, there was an 8% increase in the probability of BMG (ORa=1.08; 95% CI 1.03-1.14; P = .007). CONCLUSIONS: Anxiety increases the risk of BMG. Moreover, the occurrence of BMG was associated with polymorphisms in the 5HTT gene.

Prevalence and heritability of psoriasis and benign migratory glossitis in one Brazilian population

Abstract: Background: An oral condition associated to psoriasis is benign migratory glossitis. The review of the literature does not show any publication about heritability in both soriasis and benign migratory glossitis and prevalence of psoriasis in the Brazilian population. Objective: This research was carried out in order to determine the prevalence of psoriasis and benign migratory glossitis in the Brazilian population from a Brazilian sample, as well as the heritability in these conditions. Methods: Six thousand patients were studied from the records of the outpatient dermatology department. The sample had 129 patients with cutaneous psoriasis, 399 with benign migratory glossitis without psoriasis and a control group with 5,472 patients. After data collection, the statistical analysis was made using Woolf, Chi-square and Falconer tests. Results: The prevalence of psoriasis was 2.15% and the benign migratory glossitis was 7.0%. The prevalence of benign migratory glossitis in the psoriasis group was high (16.3%), and that was statistically significant. Family history in the psoriasis group was 38% for the condition itself and 2,75% for benign migratory glossitis and in the benign migratory glossitis group was 17.54% for the condition itself and 1.5% for psoriasis. The study of heritability was 38.8% for psoriasis and 36.6% for benign migratory glossitis, both with medium heritability. Study limitations: This study was only in the state of São Paulo. Conclusion: This is the first publication that quantifies how much of these conditions have a genetic background and how important the environmental factors are in triggering them.

Prevalence and heritability of psoriasis and benign migratory glossitis in one Brazilian population.

BACKGROUND: An oral condition associated to psoriasis is benign migratory glossitis. The review of the literature does not show any publication about heritability in both soriasis and benign migratory glossitis and prevalence of psoriasis in the Brazilian population. OBJECTIVE: This research was carried out in order to determine the prevalence of psoriasis and benign migratory glossitis in the Brazilian population from a Brazilian sample, as well as the heritability in these conditions. METHODS: Six thousand patients were studied from the records of the outpatient dermatology department. The sample had 129 patients with cutaneous psoriasis, 399 with benign migratory glossitis without psoriasis and a control group with 5,472 patients. After data collection, the statistical analysis was made using Woolf, Chi-square and Falconer tests. RESULTS: The prevalence of psoriasis was 2.15% and the benign migratory glossitis was 7.0%. The prevalence of benign migratory glossitis in the psoriasis group was high (16.3%), and that was statistically significant. Family history in the psoriasis group was 38% for the condition itself and 2,75% for benign migratory glossitis and in the benign migratory glossitis group was 17.54% for the condition itself and 1.5% for psoriasis. The study of heritability was 38.8% for psoriasis and 36.6% for benign migratory glossitis, both with medium heritability. STUDY LIMITATIONS: This study was only in the state of São Paulo. CONCLUSION: This is the first publication that quantifies how much of these conditions have a genetic background and how important the environmental factors are in triggering them.

Host and clinical aspects in patients with benign migratory glossitis.

OBJECTIVE: Investigate the association of clinical, cytological and genetic characteristics with benign migratory glossitis (BMG). STUDY DESIGN: Sample consisted of 175 patients, 44 with BMG and 131 control patients. Clinical examination and DMFT index were assessed. Cytological evaluation determined cell morphology and morphometry. Genetic evaluation was performed by analysing IL6 polymorphisms by real-time PCR. Univariate and multivariate analyses were performed (p<0.05). RESULTS: There was a higher level of anxiety, DMFT score and a prevalence of fissured tongue in BMG group. A high mean nuclear/cytoplasmic area ratio was observed in patients with BMG. There was predominance of Papanicolaou class II I BMG group. IL6 allele G rs2069843 polymorphism was associated with BMG in the dominant model. In multivariate analysis, DMFT and anxiety scale remained associated with BMG.

Mutations in IL36RN are associated with geographic tongue.

Geographic tongue (GT) is a benign inflammatory disorder of unknown etiology. Epidemiology and histopathology in previous studies found that generalized pustular psoriasis (GPP) is a factor associated with GT, but the molecular mechanism remains obscure. To investigate the mechanism of GT, with and without GPP, three cohorts were recruited to conduct genotyping of IL36RN, which is the causative gene of GPP. In a family spanning three generations and diagnosed with only GT ("GT alone"), GT was caused by the c.115+6T>C/p.Arg10ArgfsX1 mutation in the IL36RN gene. An autosomal dominant inheritance pattern with incomplete penetrance was observed. In the cohort consisting of sporadic cases of "GT alone" (n = 48), significant associations between GT and three IL36RN variants (c.115+6T>C/p.Arg10ArgfsX1, c.169G>A/p.Val57Ile and c.29G>A/p.Arg10Gln) were shown. In the GPP patient cohort (n = 56) and GPP family member cohort (n = 67), a significant association between the c.115+6T>C mutation and the simultaneous presence of GPP and GT was observed when compared to the presence of GPP without GT (P < 0.05). Biopsies revealed similarities among GT patients with different genotypes (AA, Aa and aa), with the neutrophils prominently infiltrating the epidermis. Western-blot analysis showed that the expression ratio of IL-36Ra/IL-36γ in lesioned tongues with individuals harboring different genotypes (AA, Aa and aa, n = 3, respectively) decreased significantly compared to controls (n = 3). We describe the mechanism of GT for the first time: some cases of GT are caused by IL36RN mutations, while those lacking mutations are associated with an imbalance in expression between IL-36Ra and IL-36γ proteins in tongue tissue.

Geographic tongue and psoriasis: clinical, histopathological, immunohistochemical and genetic correlation - a literature review.

Geographic tongue is a chronic, inflammatory, and immune-mediated oral lesion of unknown etiology. It is characterized by serpiginous white areas around the atrophic mucosa, which alternation between activity, remission and reactivation at various locations gave the names benign migratory glossitis and wandering rash of the tongue. Psoriasis is a chronic inflammatory disease with frequent cutaneous involvement and an immunogenetic basis of great importance in clinical practice. The association between geographic tongue and psoriasis has been demonstrated in various studies, based on observation of its fundamental lesions, microscopic similarity between the two conditions and the presence of a common genetic marker, human leukocyte antigen (HLA) HLA-C*06. The difficulty however in accepting the diagnosis of geographic tongue as oral psoriasis is the fact that not all patients with geographic tongue present psoriasis. Some authors believe that the prevalence of geographic tongue would be much greater if psoriatic patients underwent thorough oral examination. This study aimed to develop a literature review performed between 1980 and 2014, in which consultation of theses, dissertations and selected scientific articles were conducted through search in Scielo and Bireme databases, from Medline and Lilacs sources, relating the common characteristics between geographic tongue and psoriasis. We observed that the frequency of oral lesions is relatively common, but to establish a correct diagnosis of oral psoriasis, immunohistochemical and genetic histopathological analyzes are necessary, thus highlighting the importance of oral examination in psoriatic patients and cutaneous examination in patients with geographic tongue.

Geographic tongue and psoriasis: clinical, histopathological, immunohistochemical and genetic correlation - a literature review

Abstract: Geographic tongue is a chronic, inflammatory, and immune-mediated oral lesion of unknown etiology. It is characterized by serpiginous white areas around the atrophic mucosa, which alternation between activity, remission and reactivation at various locations gave the names benign migratory glossitis and wandering rash of the tongue. Psoriasis is a chronic inflammatory disease with frequent cutaneous involvement and an immunogenetic basis of great importance in clinical practice. The association between geographic tongue and psoriasis has been demonstrated in various studies, based on observation of its fundamental lesions, microscopic similarity between the two conditions and the presence of a common genetic marker, human leukocyte antigen (HLA) HLA-C*06. The difficulty however in accepting the diagnosis of geographic tongue as oral psoriasis is the fact that not all patients with geographic tongue present psoriasis. Some authors believe that the prevalence of geographic tongue would be much greater if psoriatic patients underwent thorough oral examination. This study aimed to develop a literature review performed between 1980 and 2014, in which consultation of theses, dissertations and selected scientific articles were conducted through search in Scielo and Bireme databases, from Medline and Lilacs sources, relating the common characteristics between geographic tongue and psoriasis. We observed that the frequency of oral lesions is relatively common, but to establish a correct diagnosis of oral psoriasis, immunohistochemical and genetic histopathological analyzes are necessary, thus highlighting the importance of oral examination in psoriatic patients and cutaneous examination in patients with geographic tongue.

A possible relationship of human leucocyte antigens with psoriasis vulgaris and geographic tongue.

BACKGROUND: Geographic tongue (GT) is the most frequent oral lesion in psoriatic patients (PP), and genetic involvement in these conditions has been described. The association of psoriasis with GT is still not clear, and the study of human leucocyte antigen (HLA) may help clarify this relation. OBJECTIVE: The aim of this study was to investigate the association of HLA alleles with psoriasis vulgaris and GT. METHODS: Fifty-eight Brazilian PP, 29 GT patients and 125 healthy controls individuals were selected. Information on demographic and clinical characteristics was collected. All patients underwent an oral examination and blood collection for HLA typing. RESULTS: HLA-A did not show significant differences in frequencies among the groups. HLA-B*57 allele was more frequently found in PP and was not found in GT. HLA-B*58 allele was more frequently found in GT. HLA-C*06 and -C*18 alleles were associated with psoriasis. No significant differences in HLA-DRB1 and HLA-DQB1 were observed. CONCLUSION: HLA-B*58 was associated with GT and HLA-B*57 was possibly associated with psoriasis. This suggested that some GT cases may represent true oral psoriasis and some may represent only GT. Therefore, it is necessary to make this distinction and increase our sample size to improve the correct diagnosis and treatment of these conditions.

Associations of HLA DR and DQ molecules with Lyme borreliosis in Latvian patients.

BACKGROUND: Many autoimmune diseases are associated with variants of HLA genes such as those encoding the MHC complex. This correlation is not absolute, but may help in understanding of the molecular mechanism of disease. The purpose of this study was to determine HLA-DR,-DQ alleles in Latvian patients with Lyme borreliosis and control (healthy) persons. Case patients and control subjects were similar in age, gender and ethnic heritage and differed only as regards the presence of Borrelia burgdorferi infection. The study included 25 patients with clinical stage - erythema migrans and 30 control (healthy) persons. HLA genotyping was performed by PCR with sequence-specific primers. RESULTS: The results show difference in HLA-DRB1 alleles distribution between patients and control subjects. The frequencies of HLA-DRB1 *04 (OR 11.24; p < 0.007) and HLA-DRB1 *17 (03) (OR 8.05; p < 0.033) were increased in the Lyme disease patients. And the frequency of allele DRB1*13 (OR 0.12; p < 0.017) was lower in Borreliosis patients and higher in control group. But, significant differences in frequencies of HLA-DQ alleles we did not detect. CONCLUSIONS: HLA predisposition to Lyme borreliosis appears not to be limited to HLA molecules, but some HLA-DR alleles also have a significant influence, and, may have implications in our understanding of pathogenesis of this disease. In particular, HLA-DRB1*04 and DRB1 *17 (03) may contribute to the Lyme borreliosis development in Latvian population.

Direct molecular detection and genotyping of Borrelia burgdorferi from whole blood of patients with early Lyme disease.

Direct molecular tests in blood for early Lyme disease can be insensitive due to low amount of circulating Borrelia burgdorferi DNA. To address this challenge, we have developed a sensitive strategy to both detect and genotype B. burgdorferi directly from whole blood collected during the initial patient visit. This strategy improved sensitivity by employing 1.25 mL of whole blood, a novel pre-enrichment of the entire specimen extract for Borrelia DNA prior to a multi-locus PCR and electrospray ionization mass spectrometry detection assay. We evaluated the assay on blood collected at the initial presentation from 21 endemic area patients who had both physician-diagnosed erythema migrans (EM) and positive two-tiered serology either at the initial visit or at a follow-up visit after three weeks of antibiotic therapy. Results of this DNA analysis showed detection of B. burgdorferi in 13 of 21 patients (62%). In most cases the new assay also provided the B. burgdorferi genotype. The combined results of our direct detection assay with initial physician visit serology resulted in the detection of early Lyme disease in 19 of 21 (90%) of patients at the initial visit. In 5 of 21 cases we demonstrate the ability to detect B. burgdorferi in early Lyme disease directly from whole blood specimens prior to seroconversion.

Investigation of functional gene polymorphisms: IL-1B, IL-6 and TNFA in benign migratory glossitis in Brazilian individuals.

BACKGROUND: Benign migratory glossitis (BMG) is a very common immunological oral disease of unknown aetiology. METHODS AND SUBJECTS: Fifty-three consecutive subjects affected by BMG and 53 age- and sex-matched control subjects were genotyped for IL-1B, IL-6 and TNFA polymorphisms. Binary logistic regression models were fitted and values of P < 0.05 were considered significant. RESULTS: A significant difference in the distribution of IL-1B genotypes was observed in the group with BMG in univariate analyses (P = 0.01). The multivariate analyses showed that the CT genotype of the IL1-B gene was significantly associated with a high risk to develop BMG (P = 0.02, OR 2.76). The combined presence of IL-1beta high and intermediate producers genotypes was also associated with BMG in multivariate analyses (P = 0.01, OR 3.05). IL-6 and TNFA polymorphisms were not associated with BMG in the univariate and multivariate analyses. CONCLUSION: Our findings demonstrate that the polymorphism +3954 IL-1B is associated with an increased risk of BMG development and suggest a genetic basis for disease development.

Both psoriasis and benign migratory glossitis are associated with HLA-Cw6.

This study was undertaken to investigate human leucocyte antigen (HLA) associations with benign migratory glossitis and psoriasis in Brazilian patients and particularly to determine whether benign migratory glossitis is also associated with HLA-Cw6, the classical association observed in psoriasis. The results showed a highly significant association of Cw6 with both psoriasis and benign migratory glossitis, with this antigen being present in 59.1% of the patients with psoriasis, in 43.8% of the patients with benign migratory glossitis, and in only 12.6% of the controls. Other significant positive associations, although at a lower significance level, were with B13, both in psoriasis and in benign migratory glossitis, and with B17, only in psoriasis. To our knowledge, this is the first report on the association of Cw6 with benign migratory glossitis. We believe that this finding reinforces the concept of a pathogenetic relationship between benign migratory glossitis and psoriasis.

Qual a importância do exame bucal na psoríase? / Which is the importance of a full oral examination in psoriasis?

Os autores discutem a necessidade da avaliaçäo bucal em pacientes psoriásicos, bem como apresentam uma revisäo da literatura concernente às lesöes bucais específicas da psoríase e à associaçäo da mesma com a língua geogrífica, língua fissurada e estomatite geográfica. Os autores concluem que a língua geográfica pode ser uma forma frusta da psoríase, ressaltando a importância do exame estomatológico e a pesquisa de antecedentes familiares para língua geográfica, em psoriásicos

Familial study of fissured tongue.

Clinical and genetic characteristics of histologically defined fissured tongue were examined in a familial study. Fifteen probands with fissured tongue and four probands with geographic tongue were selected from earlier studies. In addition, 12 probands with tongue fissuring, but without changes of papillary structure, were included. The total sample consisted of 31 families; the number of family members examined was 185 (93 men, 92 women), and the mean age of the subjects was 20 yr (range 1-78). Diagnosis of tongue form was emphasized, and this study describes an in vivo method of stereomicroscopy for examining the dorsum of the tongue. According to genetic analysis, fissured tongue with smooth-surfaced papillae was transmitted as a dominant characteristic with incomplete penetrance and was preceded by geographic tongue. The severity of fissured tongue changed with increasing age. Tongue fissuring with normal-appearing filiform papillae was not familial and was not associated with geographic tongue. Fissuring with normal papillary structure should be considered as variations of normal anatomy, whereas fissured tongue and geographic tongue are a clinical and etiological disease entity.

Geographic tongue in two siblings.

We report two illustrative cases of geographic tongue which occurred in 6- and 4-year-old sisters whose father had fissured tongue. The elder sister had mild atopic dermatitis and nail changes, but there was no family history suggestive of psoriasis. Histologically, the geographic tongue in the elder sister showed the same features as the oral lesions in pustular psoriasis. From a review of the literature we suggest that geographic tongue may be classified into two types, one that commonly occurs in atopics and another that develops as an oral manifestation of pustular psoriasis, although both types show similar histopathological features.

Lingual lesions of generalized pustular psoriasis. Report of five cases and a review of the literature.

Geographic tongue and fissured tongue may be mucosal manifestations of generalized pustular psoriasis. All three disorders have polygenic inheritance patterns and affected patients may share genes. Five patients in three families with geographic tongue, fissured tongue, and generalized pustular psoriasis are described and the lingual lesions of generalized pustular psoriasis are reviewed.

HLA antigens in geographic tongue.

HLA-A,B,C phenotyping was performed on 95 patients with geographic tongue to determine whether there is an increased frequency of any particular allele in this condition. An increased frequency of B15 was found in the patients when compared to normal controls. When the patients were divided into atopic and non-atopic groups there was an increased frequency of B15 and a decreased frequency of B40 in the atopic group compared to the controls. B40 was as decreased in the atopic group when compared to the non-atopic group. When the type I correction factor was applied to the probability values the differences in antigen frequencies in all cases became insignificant.

Scrotal tongue and geographic tongue: polygenic and associated traits.

The familial nature of scrotal and geographic tongue was investigated in parents and siblings of 156 probands having these conditions. The prevalence in parents and siblings was significantly higher than that in the control populations. The prevalence in sibilings from families in which at least one parent was also affected was significantly higher than that in siblings from families in which neither parent was affected. The prevalence of scrotal tongue alone in siblins was similar irrespective of the condition in the proband. The prevalence of geographic tongue alone was highest in siblins of probands having only geographic tongue. A polygenic mode of inheritance with some genes common to both conditions is suggested.