Abstract in English:

Abstract Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios.

Abstract in English:

Abstract Background Alopecia Areata (AA) is an acquired autoimmune form of non-scarring hair loss. Adiponectin and its gene polymorphism were related to many autoimmune disorders. Objective Assessment of adiponectin serum levels and adiponectin gene (ADIPOQ) (rs2241766) Single Nucleoid Polymorphism (SNP) in AA patients and correlating the results with the disease severity in those patients. Methods This study included 75 AA patients and 75 age and gender-matched healthy subjects (controls). The severity of Alopecia Tool (SALT) score assessment to evaluate AA severity was done. Adiponectin serum levels by ELISA and ADIPOQ (rs2241766) SNP using PCR were performed. Results Adiponectin serum levels were significantly lower in AA patients than controls (p = 0.001). ADIPOQ (rs2241766) TG genotype and G allele were significantly predominant in AA patients increasing its risk by 5 and 4 folds (OR = 5.17, p = 0.001), (OR = 3.82, p = 0.001) respectively. Serum adiponectin levels were negatively correlated with SALT score (r = -0.435, p = 0.001) and associated with alopecia totalis (p = 0.016). ADIPOQ (rs2241766) TG genotype was significantly associated with low serum adiponectin levels and higher SALT score (p = 0.001). Study limitations The small sample size. Conclusions ADIPOQ (rs2241766) gene polymorphism (TG genotype and G allele) may modulate AA risk and contribute to the development of AA in Egyptian populations. Decreased circulating adiponectin levels may have a dynamic role in AA etiopathogenesis. Adiponectin serum concentration can be considered a severity marker of hair loss in AA.

Abstract in English:

Abstract Background The development of rosacea is suggested to be closely associated with lipid metabolism, inflammation, and anxiety/depression. Gamma linolenic acid (GLA) is a key factor participating in lipid metabolism, which is also confirmed to regulate the inflammatory response. However, the associations of serum GLA levels with rosacea severity and psychological status still remain unclear. Objective and limitations of the study The present study aimed to investigate the associations of gamma linolenic acid (GLA), a key factor participating in lipid metabolism and the inflammatory response, with rosacea severity and psychological status. The present study still had some limitations. First, this study is a cross-sectional study and does not provide longitudinal evidence about the relationship between GLA and rosacea; Second, the cohort in this study is also relatively small, and a larger cohort is needed in further investigation to reveal the potential role of lipid metabolism in the pathogenesis of rosacea. Methods A total of 62 rosacea patients were consecutively recruited. Patient’s Self-Assessment (PSA) scale and Clinician Erythema Assessment (CEA) as well as 7-item Generalized Anxiety Disorder (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9) were conducted to evaluate the degree of erythema severity and anxiety/depression, respectively. Serum GLA levels were determined by gas chromatography mass. Results Lower levels of serum GLA in rosacea patients were observed (p < 0.001), and subgroup analysis revealed that patients with higher-level GLA had lower scores of PSA, CEA, GAD-7 and PHQ-9. Moreover, Spearman correlation analysis uncovered that serum GLA levels were negatively associated with PSA, CEA, GAD-7 as well and PHQ-9 scores, respectively. Linear regression model found that serum GLA levels at baseline were a predictive factor for prognosis of clinical outcomes after 1-month conventional treatment. Conclusion The present study indicates that lower levels of serum GLA in rosacea patients are negatively associated with the degree of erythema and anxiety/depression status.

Abstract in English:

Abstract Background Vitiligo is the most common pigmentary disorder and is considered a chronic, cumulative, multifactorial disease. The crucial role of cytotoxic CD8+ T lymphocytes and the IFNγ/CXCL10 axis has been demonstrated in its pathogenesis. Objective To evaluate the clinical profile and immuno-inflammatory markers in patients with vitiligo in a reference medical center. Methods Cross-sectional study in which all patients with vitiligo seen at the medical center the from 2019 to 2022 were evaluated, to outline the clinical profile. Moreover, cardiovascular risk biomarkers (neutrophil/lymphocyte ratio and C-reactive protein levels) were measured, as well as cytokines and chemokines (TNFα, IFNγ, IL10, IL15 and CXCL10) in the serum of a subgroup of 30 patients. Results There was a predominance of females, with a mean age of 43 years. Most were phototypes IV or V (71.3%), without comorbidities (77.55%), and without a family history of vitiligo (70.41%). Higher levels of neutrophil/lymphocyte ratio, C-reactive protein, and inflammatory cytokines/chemokines were documented in vitiligo patients when compared to the control group (non-significant). As relevant data, the highest values of CXCL10 were detected in patients with vitiligo versus controls, as well as in patients with disease of shorter duration (p < 0.05). Study limitations The number of assessed patients was small due to recruitment difficulties caused by the COVID-19 pandemic. Conclusion The present data contribute to confirming the relevant role of the IFNγ/CXCL10 axis in the pathogenesis of vitiligo, highlighting CXCL10 as a possible activity marker.

Abstract in English:

Abstract Background Skin cancer is the most frequent cancer worldwide and the most frequent periocular tumor. Keratinocyte Carcinomas (KC) located in periorificial areas, such as periocular tumors, are considered high-risk tumors. Mohs Micrographic Surgery (MMS) is considered the first line for the treatment of high-risk KC, providing a lower recurrence rate than conventional wide excision. Objective To describe the clinical-pathological features of periocular KC treated with MMS in a tertiary university center in Chile. Methods A single-center, retrospective study of patients with KC located on the periocular area, that underwent MMS between 2017‒2022. MMS details were recorded. Results One hundred thirteen patients with periocular carcinomas were included. The mean age was 59 ± 13 years; 52% were women. The most frequent location was the medial canthus (53%), followed by the lower eyelid (30.1%). The most frequent BCC histology was the nodular variant (59.3%). Regarding MMS, the average number of stages was 1.5 ± 0.7, and 54% of the cases required only 1 stage to achieve clear margins. To date, no recurrence has been reported. Tumors larger than 8.5 mm in largest diameter or 43.5 mm2 were more likely to require complex reconstruction. Study limitations Retrospective design and a relatively low number of patients in the SCC group. Possible selection bias, as larger or more complex cases, may have been referred to oculoplastic surgeons directly. Conclusion The present study confirms the role of MMS for the treatment of periocular KCs. Periocular KCs larger than 8.5 mm might require complex reconstruction. These results can be used to counsel patients during pre-surgical visits.

Abstract in English:

Abstract Background Cutaneous squamous cell carcinoma (cSCC) develops from epithelial keratinocytes by dysregulation of self-renewal and differentiation. Recent studies have found that the size and number of cSCC tumors gradually decrease or even disappear after HPV vaccination. However, the role of the HPV vaccine in the cSCC mechanism is poorly understood. Objective The aim of this study is to investigate the effect and mechanism of the HPV vaccine in cSCC. Methods Immunofluorescence was used to study the immune infiltrating cells in the tumor tissues of patients with cSCC. The effects of the HPV vaccine on cSCC cells and tissues were studied by Cell Culture, Real-time PCR, Western Blot, Cytotoxicity Assay, Enzyme-linked Immunosorbent Assay, m6A Blotting, CCK-8 Assay, m6A Ribonucleic acid Methylation Quantification and tumor transplantation. Results The HPV vaccine enhanced the toxic effect of CD8+T cells on cSCC cells and promoted the secretion of multiple cytokines by CD8+T cells. In addition, HPV vaccines can increase tumor sensitivity to anti-PD-1 therapy by downregulating METTL3 in tumor tissue, with the combination of HPV vaccine and PD-1 monoclonal antibodies producing enhanced immune cell infiltration compared to PD-1 blockade alone. Study limitations It is important to note the limitations of this study, including the small sample size, the construction of the mouse model, and the choice of HPV vaccine and PD-1 monoclonal antibody, which may limit the generalization of our findings to a wider population. Conclusions It is hoped that this research will contribute to a deeper understanding of the role of the HPV vaccine in the treatment of cSCC. HPV vaccine is expected to become an important approach to alleviate the development of cSCC.

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Abstract Background Systematic reviews of Randomized Controlled Trials (RCTs) are considered high-level evidence to support a decision on therapeutic interventions, and their methodological quality is essential to provide reliable and applicable results. Objective This meta-epidemiological study aimed to map and critically appraise systematic reviews assessing treatments for vesiculobullous skin diseases. Methods We conducted a comprehensive search strategy on MEDLINE (via Pubmed) in December 2022 without restrictions to find systematic reviews evaluating pharmacological interventions for vesiculobullous skin diseases. The methodological quality was assessed using the AMSTAR-2 tool, and additional information was extracted. We identified nine systematic reviews published between 2002 and 2021, seven assessing pemphigus. Results According to the AMSTAR-2 tool, 55.6% were classified as critically low quality, 22.2% as moderate quality, 11.1% as low and 11.1% as high quality. No review assessed the certainty of the evidence (GRADE); 86% of pemphigus reviews had at least two overlapping RCTs. There were some limitations regarding methodological flaws and the AMSTAR-2 tool use Conclusions These findings reveal a frail methodological quality of systematic reviews about vesiculobullous diseases treatment that may impact the results. Therefore, methodological rigor is mandatory for future systematic reviews to avoid duplication of effort and increase the certainty of the evidence supporting decision-making.

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Abstract Background Talaromyces Marneffei (TM) is a rare opportunistic pathogen that mostly infects patients with low immunity compared to those with normal immunity. It may be related to immune deficiency or genetic factors. Objective To evaluate the gene mutation of a patient infected with TM in an endemic area with negative anti-interferon-γ autoantibodies, and negative human immunodeficiency virus (HIV) infection. Methods Extract deoxyribonucleic acid (DNA) samples from the patient's peripheral blood, detect the mutation gene by whole exome sequencing (WES), and carry out Sanger sequencing verification for the detected mutation gene. Results The authors detected a mutation in the IFNGR1 gene (NM_001363526.1) and validated the detected gene mutation using Sanger sequencing. The results showed a heterozygous mutation c.4C>T (p.L2F) located in the IFNGR1 gene (NM_001363526.1). Study limitations The mechanism of the IFNGR1 gene has not been further investigated in this study. Conclusions The IFNGR1 gene mutation may be a potential risk factor for TM infection, and the presence of anti-interferon-γ autoantibodies can aggravate disease symptoms.

Abstract in English:

Abstract Background Glomus Tumor (GT) are benign neoplasms that originate from mesenchymal cells. It presents as tenderness and cold allodynia in the digits, especially in the subungual region. There are a few studies that investigated the mechanism of pain. Objectives To analyze the clinical-pathologic characteristics of GT and to identify the expression of IL-1β, IL-6, and CGRP in it, further, to explore the possible mechanism of pain. Methods The clinical and pathological data of 60 GT patients were retrospectively analyzed. Tissue microarrays and immunohistochemistry were used to measure the expression of IL-1β, IL-6 and CGRP. Results GT is more common in females and the ratio of male to was near to 1:2, mostly in middle-aged people. It often occurs in fingertips, especially the thumbs. Patients often present with spontaneous pain, tenderness, and cold hypersensitivity. Both the two pain mediators IL-1β and IL-6 were highly expressed in GT cells of patients with and without cold hypersensitivity. While CGRP was not expressed in GT. Study limitations Low sample size and further research is needed to explore the specific mechanism. Conclusions IL-1β and IL-6 were highly expressed in GT cells, suggesting that IL-1β and IL-6 have certain nociceptive roles in GT. In the 4 patients with cold intolerance, the intensity of IL-1β and IL-6 staining was also strong, suggesting that they may not play a role in the cold hypersensitivity. However, since there are only 4 patients with cold intolerance, it’s necessary to conduct further in-depth research using a larger sample size. The specific role of CGRP in GT has not been found yet.

Abstract in English:

Abstract Background Psoriasis is a chronic, systemic inflammatory disease with a worldwide prevalence of approximately 2%. Currently, despite the difficulties faced every day by patients and physicians in low-resource countries, literature describing the exact needs of psoriasis treatment in Latin America remains scarce. Objective To investigate the unmet needs in psoriasis treatment in Latin America. Methods The authors conducted a systematic review following PRISMA statements in PubMed, Embase, and LILACS of studies published from January 2011 to March 2021 addressing challenges in psoriasis treatment in Latin America. Results The search strategy identified 3,837 articles, of which 19 were included in the final analysis. Most were from Brazil (58%; n = 11), all were observational, and most were cross-sectional (84%; n = 16). Difficulties faced by psoriasis patients in Latin America included the high prevalence of opportunistic and endemic infections (42% of the studies addressed this matter; n = 8), delay in diagnosis (5%; n = 1), work productivity impairment (16%; n = 3), limited access to medication/medical care (37%; n = 7), poor adherence to treatment (5%; n = 1) and poor adherence to guidelines (11%; n = 2). Study limitations Number and quality of studies currently available on this subject. Conclusions Current psoriasis guidelines do not always account for epidemiological, financial, and cultural characteristics. Most studies available are from Brazil, which might not accurately represent Latin America as a whole. In a region where neglected diseases and scarce resources remain a reality, it is imperative that dermatological training be offered to primary care providers, allowing for standardized conduct and earlier diagnosis.

Abstract in English:

Abstract In dermatologists' clinical practice, the use of systemic glucocorticoids is recurrent for the management of different comorbidities that require chronic immunosuppression. The prescription of this medication requires caution and basic clinical knowledge due to the several adverse effects inherent to the treatment. However, different doubts may arise or inappropriate conduct may be adopted due to the lack of objective and specific guidelines for the screening, prophylaxis and management of complications from chronic corticosteroid therapy. Considering this problem, the authors carried out a narrative review of the literature to gather up-to-date data on adverse effects secondary to the chronic use of systemic glucocorticoids. The broad approach to this topic made it possible to review the pathophysiology and risk factors for these complications, as well as to develop updated orientation that can be used as a learning tool and quick reference for dermatologists during their clinical practice with glucocorticoids.

Abstract in English:

Abstract The concept of “Cumulative Life Course Impairment” (CLCI) characterizes the set of factors harmful to the lives of patients resulting from the stigma and physical and psychological impairment associated with different chronic diseases, which can accumulate irreversibly over the course of patients lives. The sum of these factors often makes it impossible for these individuals to enjoy their lives fully, intensely and adequately. On the other hand, CLCI also incorporates coping strategies, including external factors and personality characteristics, which may act as modulating or protective factors of vulnerability to the CLCI. Although psoriasis is the most studied dermatological disease in relation to its impact on quality of life and CLCI, several other chronic inflammatory diseases such as atopic dermatitis, hidradenitis suppurativa, and alopecia areata have also been evaluated in relation to the magnitude of the damage to patients lives.