Oral mucosa and cutaneous manifestations of psoriasis in an older patient: A case report.

BACKGROUND: Psoriasis is a common cutaneous disease; however, information about psoriasis-related oral mucosal lesions is scarce in the literature. CASE DESCRIPTION: We report a case of a 73-year-old male patient with cutaneous and oral palatal alterations. An incisional biopsy of these lesions revealed psoriasis. CONCLUSION: The current case highlights the importance of a systematic examination of the oral cavity in psoriasis patients for the appropriate diagnosis and management on the control of these lesions.

S100A9 Drives the Chronification of Psoriasiform Inflammation by Inducing IL-23/Type 3 Immunity.

Psoriasis is a chronic inflammatory skin disorder driven by the IL-23/type 3 immune response. However, molecular mechanisms sustaining the chronicity of inflammation and psoriatic lesions remain elusive. Combining systematic analyses of several transcriptomic datasets, we delineated gene signatures across human psoriatic skin, identifying S100A9 as one of the most up-regulated genes, which was confirmed in lesioned skin from patients with psoriasis and preclinical psoriasiform skin inflammation models. Genetic ablation or pharmacologic inhibition of S100A9 alleviated Aldara-induced skin inflammation. By single-cell mapping of human psoriatic skin and bone marrow chimeric mice experiments, we identified keratinocytes as the major source of S100A9. Mechanistically, S100A9 induced IL-23 production by dendritic cells, driving the IL-23/type 3 immunity in psoriasiform skin inflammation. In addition, the cutaneous IL-23/IL-17 axis induced epidermal S100A9 expression in human and experimental psoriasis. Thus, we showed an autoregulatory circuit between keratinocyte-derived S100A9 and IL-23/type 3 immunity during psoriasiform inflammation, identifying a crucial function of S100A9 in the chronification of psoriasis.

Expression of B lymphocyte-induced maturation protein 1 (Blimp-1) in keratinocyte and cytokine signalling drives human Th17 response in psoriasis.

Transcriptional factor B lymphocyte-induced maturation protein 1 (Blimp-1) is pivotally implicated in T helper 17 (Th17) cell differentiation. This study investigated expression of the Blimp-1 protein, positive regulatory domain 1 (PRDM1), and cytokine genes in psoriasis (PsO). Affected (AS-PsO) and non-affected skin (nAS-PsO) samples were used to assess gene and protein expressions by reverse transcription-quantitative PCR (RT-qPCR), and immunostaining and confocal microscopy, respectively; the normalised public transcriptomic data permitted differential gene expression analyses. On RT-qPCR, PRDM1 and IL17A transcripts showed higher expression in AS-PsO than in nAS-PsO (n = 34) (p < 0.001; p < 0.0001, respectively). Confocal microscopy showed Blimp-1 protein expression in epidermal layer keratinocytes in AS-PsO, but not in nAS-PsO. Bioinformatic analysis of the transcriptomic dataset GSE13355 corroborated the increased PRDM1, signal transducer and activator of transcription 3 (STAT3), IL12B, TNF, IL17A, IL6, IL1B, IL22, and IL10 gene expression in AS-PsO, when compared to normal skin and nAS-PsO (p < 0.001). PRDM1 expression correlated positively (p < 0.0001) with that of IL17A (r = 0.7), IL1B (r = 0.67), IL12B (r = 0.6), IL6 (r = 0.59), IL22 (r = 0.53), IL23A (r = 0.47), IL21 (r = 0.47), IL27 (r = 0.34), IL23R (r = 0.32), S100 calcium binding protein A9 (r = 0.63), and lipocalin 2 (r = 0.50), and negatively with that of TGFB1 (r = - 0.28) and RORC (r = - 0.60). Blimp-1 may be critical in the pathogenesis of PsO dysregulation involving the Th17 inflammatory pathway. This knowledge may accelerate the development of new treatments.

Clinical Specialty Setting as Determinant of Management of Psoriatic Arthritis: A Cross-Sectional Brazilian Study.

OBJECTIVE: The aim of this study was to examine the effect of clinical specialty setting on the management of psoriatic arthritis (PsA) as well as disease activity/burden in Brazil. METHODS: This study is a post hoc analysis of the Brazilian population in a cross-sectional, observational study conducted in 17 countries. Patients were 18 years or older with suspected or confirmed PsA attending routine visits at participating sites. Primary end points were time from symptom onset to PsA diagnosis, from diagnosis to first conventional systemic disease-modifying antirheumatic drug (DMARD) or first biologic DMARD, and from first conventional systemic DMARD to first biologic DMARD. Potential associations were assessed using the Student t test or the Mann-Whitney U nonparametric test. Normality was tested using the Shapiro-Wilk and Kolmogorov-Smirnov tests. For qualitative variables, the χ2 test was adopted. RESULTS: Patients (n = 130) visited dermatology (n = 75) or rheumatology (n = 55) sites. All primary end points were similar between the 2 settings; however, dermatology patients had significantly greater enthesitis counts (2.1 vs 0.6; p = 0.002), absenteeism at work (Work Productivity and Activity Impairment, 19.7% vs 5.2%; p = 0.03), and pain (Health Assessment Questionnaire-Disability Index pain scale, 1.39 vs 1.01; p = 0.032), as well as worse quality of life related to psoriasis (Dermatology Life Quality Index total score, 8.5 vs 5.0; p = 0.019) and mental health (12-item Short-Form Health Survey, version 2.0 subscale, 42.4 vs 47.4; p = 0.029). CONCLUSIONS: In Brazil, PsA disease burden and disease activity were influenced by clinical specialty. Irrespective of setting, patients experienced a delay in being diagnosed with PsA, reinforcing the need for collaborative management of PsA by rheumatologists and dermatologists for better outcomes in these patients.

HLA-G, cytokines, and cytokine receptors in the non-aggressive basal cell carcinoma microenvironment.

Non-aggressive basal cell carcinoma (BCC) growth is slow and might be mediated by the immune system. This study analysed the human leukocyte antigen (HLA)-G expression and cytokine profile in non-aggressive BCC subtypes from distinct locations. HLA-G was evaluated via immunohistochemistry and cytokine expression was analysed by a quantitative real-time polymerase chain reaction in 26 primary BCC samples, including nodular BCC (nBCC, n = 16) and superficial BCC (n = 10) from cephalic (ceBCC, n = 12) and non-cephalic (n = 14) locations, and by bioinformatics analysis of public GEO databases. Inflammatory infiltrate was concentrated around the tumour nests. HLA-G-positive inflammatory cells (53.85%) were more abundant than HLA-G-positive tumour cells (21.54%, p < 0.001). HLA-G immunoreactivity was predominantly cytoplasmic in BCC cells and was primarily associated with lymphocytes and macrophages surrounding the tumour. nBCC showed a higher percentage of HLA-G-positive tumour cells (p = 0.04), and ceBCC showed stronger intensity (p = 0.04). IFN-gamma and IL-10 expression were 1.95 and 1.22-fold higher, respectively, relative to that in normal skin, with a positive correlation between them (r = 0.61; p = 0.002). IL-23 expression was higher in nBCC (p = 0.04) and positively correlated (r = 0.47; p = 0.05) with slight intensity of HLA-G-positive tumour cells. The up-regulation of IL23A and IL10RB and down-regulation of IFNGR1 and IL4R gene expression in BCC compared to levels in adjacent tissues were demonstrated in the GSE125285 dataset. The exhibited cytokine profile was consistent with the induction of HLA-G expression in non-aggressive BCC subtypes. HLA-G expression in tumour cells and inflammatory cells surrounding BCCs supports the generation of inhibitory signals on various immune cells that exert anti-tumour responses.

Attributes and risk factors of positive margins on 864 excisions of basal cell carcinomas: a single-center retrospective study.

Background: Residual tumors increase the likelihood of recurrence of basal cell carcinoma (BCC).Objective: We determined the attributes and risk factors for positive surgical margins (+SM) of excised BCC in a university hospital.Methods: In this cross-sectional retrospective study, we reviewed the histologic reports of BCC removed via conventional surgical excision (CSE) by specialists from different fields.Results: Among excised BCCs (n = 864), there was a predominance of nodular BCC (82.64%) in the facial H-area (72.81%; average diameter = 9.12 mm), which had the highest + SM rate (20.17%). Most cephalic (ce-BCC; 69.01%) and non-cephalic (91.11%) BCCs were excised by dermatologists, with low rates of + SM (4.53%; 1.46%, respectively); the overall + SM rate was 12.73%. Men had larger (p < .001) and more ulcerated (p = .04) BCC. An aggressive histologic pattern (Ag-P) (p < .04) and ulceration (p < .001) were correlated with tumor size on multivariate analysis. The risk for + SM increased in ulcerated ce-BCC (p = .02), BCC with Ag-P (p = .02), and in the H-area (p < .001), nasal (p = .007), and labial (p = .05) regions. ce-BCC excised by head-neck surgeons had a high chance of ulceration (p < .001) and Ag-P (p = .002).Conclusions: Ag-P and H-zone remain critical risk factors for + SM. Accordingly appropriate treatment protocols should be used to ensure low + SM rates via CSE.

Sarcoid-Like Paracoccidioidomycosis in a Female Urban Dweller: Reviewing a Rare Clinical Condition in Brazil.

We discuss the sarcoid-like clinical presentation, a rare type of infiltrative paracoccidioidomycosis (PCM) that is almost exclusively cutaneous, involves the face and histologically has a tuberculoid granulomatous pattern with few fungi. It is often misdiagnosed. In endemic regions of Brazil, PCM is more common among men from rural areas, while women of a reproductive age appear to be protected. We report the sarcoid-like PCM in a female urban dweller and highlight the main findings of a literature review.

Fluorescence spectroscopy as a tool to in vivo discrimination of distinctive skin disorders.

BACKGROUND: Fast and non-invasive analytical methods, as in fluorescence spectroscopy, have potential applications to detect modifications of biochemical and morphologic properties of malignant tissues. In this study, we propose to analyze the fluorescence spectra using k-Nearest Neighbours algorithm (k-NN) and ratio of the fluorescence intensity (FI) to differentiate skin disorders of distinctive etiologies and morphologies. MATERIALS AND METHODS: Laser-induced autofluorescence spectra upon excitation at 408nm were collected from basal cell carcinoma (BCC) subtypes (n=45/212 spectra), psoriasis (PS) (n=37/193 spectra) and Bowen's disease (BD) (n=04/19 spectra) lesions and respective normal skin at sun-exposed (EXP) and non-exposed (NEXP) sites of the same patient. RESULTS: The mean ratios of FI values at selected wavelengths of emission (FI600nm/FI500nm) were significantly lower in BCC and PS lesions compared to EXP [P=0.0001; P=0.0002, respectively]; but there were no significant differences between abnormal conditions. The analysis of fluorescence spectra using k-NN can discriminate normal or abnormal skin conditions (EXP, BCC, BD, PS) of distinctive etiology, neoplastic or inflammatory (BCC, BD and PS) and morphologies (nodular and superficial BCC, BD and PS) as high as 88% and 93% sensitivity and specificity means, respectively; also, similar erythematous-squamous features (superficial BCC, BD and PS) with 98% and 97% sensitivity and specificity means, respectively. The k-NN computational analysis appears to be a promising approach to distinguish skin disorders.

Pharmacokinetics of venlafaxine enantiomers and their metabolites in psoriasis patients.

Psoriasis is a chronic inflammatory disease associated with several comorbidities, including depression. Previous studies have shown that inflammatory diseases downregulate the expression and suppress activity of CYP isoforms. Venlafaxine (VLX) is an antidepressant metabolized mainly by CYP2D6 to O-desmethylvenlafaxine (ODV), CYP3A to N-desmethylvenlafaxine (NDV), and CYP2D6 and CYP3A to N,O-didesmethylvenlafaxine (DDV). This study evaluated the influence of psoriasis on the enantioselective pharmacokinetics of VLX. Psoriasis patients (n = 13) and healthy volunteers (n = 11) phenotyped as CYP2D6 extensive (EM) or poor metabolizers (n = 1) received a single oral dose of 150 mg racemic VLX. Plasma concentrations of TNF-α, IFN-γ, IL-6, IL-8, and IL-17 cytokines were higher in EM psoriasis patients when compared with healthy volunteers. IL-6 plasma concentrations varied from 0.4 to 12.9 pg/mL (mean, 2.1 pg/mL) in healthy volunteers and from 0.4 to 29.3 pg/mL (mean, 4.2 pg/mL) in psoriatic patients. VLX pharmacokinetics are enantioselective in healthy volunteers and psoriasis patients phenotyped as EM. Higher AUC values for the (S)-VLX, (S)-NDV, and (S)-DDV enantiomers were observed in healthy volunteers, whereas higher AUC values for (S)-VLX and (R)-ODV were found in psoriasis patients phenotyped as EM. Psoriasis does not alter the pharmacokinetics of the VLX enantiomers probably because of the low levels of IL-6 plasma concentrations.

Delayed diagnosis of leprosy and the potential role of educational activities in Brazil.

This study identifies possible obstacles to the early diagnosis of leprosy. Semi-structured interviews were held with 40 patients at a secondary health service in upstate São Paulo, Brazil. The data concerning the sample were: 75% males, age range 13-76 years, 85% with elementary school education, 85% multibacillary. Skin lesions associated with sensory alterations had been noticed by 55% of the patients; 32.5% of the patients had been misdiagnosed as having conditions other than leprosy. The diagnosis was made 1 year after the awareness of signs/symptoms in 55% of the patients. In this group, 54% had impairment grade 1, while 23% had no disabilities. Forty-five percent of all patients interviewed had some information about the disease prior to diagnosis. Eleven patients (27.5%) had previous contact with leprosy patients, but this did not prevent late diagnosis in 64%. After the disease was confirmed, about half of the interviewed patients (47.5%) showed mainly positive feelings due to the prospect of treatment and cure. Our results suggest that misdiagnoses and unawareness of the disease were the main factors that influenced the delayed diagnosis. We consider the effective involvement of various segments of society, particularly the integration and partnership of the public health services and health education centres to be valuable tools for the planning and execution of educational activities directed at risk groups and the community.