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Abstract Early diagnosis of leprosy remains primarily clinical, based on recognition of skin lesions with altered sensation and peripheral nerve involvement. However, complementary tests play crucial roles in confirming uncertain cases, guiding operational classification, detecting subclinical neural involvement, and distinguishing late reactions from relapse. This review synthesizes the practical application of diagnostic methods available to dermatologists. Slit-skin smear microscopy demonstrates high specificity but limited sensitivity in paucibacillary forms, while histopathology reveals the characteristic immunopathological spectrum, with perineural acid-fast bacilli being pathognomonic for leprosy. Molecular detection by PCR enhances diagnosis in paucibacillary cases (34%‒80% sensitivity) but cannot distinguish viable from non-viable bacilli, limiting its utility in post-treatment assessment. Anti-PGL-1 serology aids contact surveillance, with seropositive individuals showing 3.5-fold increased risk of developing disease, though sensitivity remains below 30% in tuberculoid forms. For neural evaluation, Semmes-Weinstein monofilament testing provides a standardized tactile threshold assessment, while the histamine test maps autonomic dysfunction, particularly valuable in indeterminate forms. Electrodiagnostic studies reveal early subclinical changes and monitor reaction-related neural deterioration. Peripheral nerve ultrasonography demonstrates superior sensitivity over palpation for detecting thickening (97.4% vs. 30% concordance) and identifies inflammatory activity through Doppler assessment. When evaluating post-treatment complications, an integrated approach combining bacteriological index trajectory, histopathological patterns, PCR cycle threshold values, and serological trends enables reliable differentiation between therapeutic failure, late reactions, and relapse. No single laboratory test confirms early leprosy in isolation; clinical dermato-neurological expertise remains paramount, with complementary tests interpreted within the epidemiological context to optimize diagnostic accuracy and therapeutic decisions.

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Abstract Background Graft-versus-host disease (GVHD) is a frequent complication of hematopoietic stem cell transplantation (HSCT), with the skin being the most commonly affected organ. However, its risk factors remain poorly defined. Objective To assess the risk factors associated with chronic cutaneous GVHD (ccGVHD) in a children’s hospital in Chile. Methods This retrospective cohort study examined children under 18-years who underwent HSCT between 2007 and 2017, with a follow-up period of at least 2-years. Survival analysis and Cox regression analysis were performed. Results 150 children with HSCT were included with a median age of 7.3 (3.7‒10.6) years. 17.3% of the children developed ccGVHD, with a median onset after HSCT of 8 (4‒11) months. In the univariate analysis, patients with ccGVHD were significantly older at transplantation, with a higher proportion of bone marrow as graft source, related donor, and acute GVHD compared to those who did not develop ccGVHD (for all p< 0.05). In the multivariate analysis, the main risk factors were male sex (Hazard Ratio [HR] 2.51), total body irradiation as conditioning regimen (HR = 3.53), and bone marrow as graft source (HR = 7.28). Study limitations Its retrospective, single-center design may reduce generalizability and introduce selection bias. Conclusions This study is one of the largest series of ccGVHD in children. Early identification of patients at higher risk of ccGVHD allows for timely initiation of treatment, thereby reducing the morbidity associated with this debilitating complication.

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Abstract Background Acral cutaneous melanoma (ACM) is an aggressive skin cancer, especially when diagnosed in the advanced stage. The Ki-67 is a rapid tool for proliferation rate analysis. Previous data indicated that its staining pattern is distinct during the several stages of the cell cycle among epithelial cells. Objective To evaluate the prognostic impact of Ki-67 expression pattern classification among advanced acral cutaneous melanoma cases. Methods Two pathologists classified staining nuclear patterns of Ki-67 in the hot spot of scanning slides of advanced ACM (pT4): NP1 (randomly Ki-67 immunopositive fine or coarse granules), NP2 (Ki-67 stained in one or two well defined and centralized nodules), NP3 (Ki-67 seen as granules or nodules occupying most of the nucleus), NP4 (nucleoplasm with intense and homogeneous Ki-67 staining) and NP5 (empty central area with peripheral Ki-67). For analysis, seven cases per group ‒ Alive (Al) and Melanoma-Related Death (De) ‒ were randomly selected. Results This pilot study analyzed 5676 Ki-67 positive nuclei. Means comparison between the two groups revealed differences in nuclear patterns NP1 (p = 0.0014), NP4 (p = 0.038), NP5 (p = 0.0193), and the total number of stained nuclei (p = 0.0258). Study limitations Small number of cases and biased value of 6.35 through the Bland-Altman analysis. Conclusion The present analysis highlights the importance of Ki-67 staining patterns as a potential prognostic marker among ACM. High Ki-67 positive nuclei were associated with worse outcomes (death), particularly in staining patterns before and after mitosis (NP1, NP4, and NP5).

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Abstract Background Mycosis fungoides is the commonest type of cutaneous T-Cell lymphoma. Janus kinases are intracellular tyrosine kinases that have recently been proven to have a crucial role in the pathogenesis and progression of several dermatological and malignant diseases. Objective The aim of this study was to investigate the immunohistochemical expression of Janus Kinase-1 (JAK1) and Janus Kinase-3 (JAK3) in the skin of mycosis fungoides . Methods The current study included 46 patients with early-stage MF, and 7 patients with late-stage MF, and 53 control samples. Immunohistochemical staining using JAK1 and JAK3 monoclonal antibodies was done in the skin specimens obtained from patients and controls. The evaluation of JAK1 and JAK3 gene expression using RT-PCR will be included in part 2 of the study. Results JAK1 immunohistochemical expression was nuclear, and JAK3 was cytoplasmic in MF patients. Immunoreactivity scores for JAK1 and JAK3 in MF patients were significantly increased compared to healthy controls (p < 0.001 and < 0.001, respectively). JAK1 and JAK3 immunoreactivity scores were significantly higher in the tumor than in the patch and plaque stages of MF (P7 = 0.001 and 0.004, respectively). Study limitations This study is limited by the relatively small sample size of some clinical variants of mycosis fungoides, particularly advanced forms such as erythrodermic and tumor-stage MF. Further studies are needed to evaluate JAK1 and JAK3 expression following therapeutic interventions, including phototherapy and JAK inhibitors. Conclusions JAK1 and JAK3 were significantly expressed in MF skin lesions in comparison to normal controls. JAK1 and JAK3 were more expressed in the tumor stage than patch and plaque stage MF, suggesting that JAK1 and JAK3 could play a crucial role in MF pathogenesis, progression, and prognosis.

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Abstract Background Mycosis Fungoides (MF) is the commonest type of primary cutaneous T-Cell lymphomas representing about 50% of all lymphomas arising primarily in the skin. Janus kinases are non-receptor intracellular tyrosine kinases that play an important role in the pathogenesis of variant skin disorders and several hematological malignancies. Objective The aim of this study was to investigate the gene expression of Janus Kinase-1 (JAK1) and Janus Kinase-3 (JAK3) in the skin of different types of MF patients using Real-time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR). Methods The current study included 53 patients with MF, and 53 control samples. RT-PCR for JAK1 and JAK3 was done in the skin specimens obtained from patients and controls. Results Both JAK1 and JAK3 fold changes showed stepwise upregulation in lesional MF skin than normal control skin, with statistically significant increase in MF patients than healthy controls (p < 0.001 and < 0.001 respectively). JAK1 was significantly upregulated in early-stage MF than JAK3 (p < 0.001). Study limitations Limitations of this study include the small sample size of some mycosis fungoides variants, such as erythrodermic MF. Further studies are needed to clarify the functional role of Janus kinase signaling pathways in MF pathogenesis. Conclusions Both JAK1 and JAK3 play a role in the pathogenesis of MF. JAK1 may have a pathogenic role, particularly in the early stage of cutaneous T-cell lymphoma. This potentiates the idea of using JAK1 and JAK3 inhibitors for MF treatment.

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Abstract Background Leprosy is associated with social exclusion and discrimination. Historical records of compulsory isolation, severe clinical manifestations, and fear of contagion have contributed to the perpetuation of prejudice and discriminatory attitudes. In Brazil, the psychosocial impact of leprosy among patients, contacts, and the general population remains poorly understood. Objective To assess the stigma associated with leprosy and to identify factors influencing its impact among patients, contacts, and the General Population (GP). Methods A cross-sectional study was conducted, including three groups (patients, contacts, and GPs) from the metropolitan region of Manaus - AM (Brazil). Demographic and clinical data were collected, and stigma was evaluated using the Explanatory Model Interview Catalogue-Affected People (EMIC-AP) for patients and the EMIC-Community Stigma Scale (EMIC-CSS) for contacts and GPs. The impact of different aspects was assessed within each group, and clinicodemographic factors associated with higher stigma were explored. Results A total of 214 patients, 104 contacts, and 393 GPs were evaluated. The EMIC-AP mean (SD) score among patients was 16 (9), whereas the EMIC-CSS scores were 15 (7) for contacts and 12 (6) for the GP group. Network analysis revealed that feelings of shame, negative self-opinion, and social avoidance were central elements of stigma across groups. Female sex among patients (β = -2.9; p = 0.03), higher education among contacts (β = 3.2; p = 0.03); and younger age and religious practice among the GPs (β = -1.3 and 1.3; p < 0.05) were associated with higher stigma scores. After standardization, contacts and GP exhibited greater stigma perception than patients (θ = 0.02 and -0.06 vs. -0.26; p < 0.05). Study limitations Non-randomized sample from a single center. Conclusions Leprosy-related stigma persists across patients, contacts, and GPs, reflecting deep-rooted social and cultural misconceptions. Beyond medical cure, achieving the “Zero Leprosy” goals demands integrated actions that promote education, community engagement, and psychosocial support to reduce prejudice and promote social inclusion.

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Abstract Isotretinoin is an extremely successful treatment for acne, widely prescribed for moderate to severe cases unresponsive to conventional therapy that is commonly used in dermatology. While its systemic side effects, particularly those related to hepatic and lipid metabolism, are extensively documented, its impact on cardiac electrophysiology is little understood. Metabolic abnormalities are frequent, with hypertriglyceridemia occurring in up to 44% of patients, elevated total cholesterol in 30%, and transient liver enzyme elevation in approximately 10%-11%. This focused review summarizes the existing research on electrocardiographic (ECG) alterations associated with isotretinoin medication. Reported cardiac abnormalities are rare, with isolated case reports and small studies describing transient arrhythmias in fewer than 1%-2% of users, including premature ventricular contractions (PVCs), atrial tachycardia, and, in exceptionally rare instances, cardiomyopathy < 0.01%. Mechanistic ideas suggest changes in human ether-a-go-go-related gene (hERG) potassium channels, dyslipidemia-induced atherosclerosis, electrolyte imbalances, and sympathetic overactivity. However, large population-based studies have not found a significant increase in major cardiovascular events. Most ECG abnormalities, when noted, appear to be reversible with discontinuing isotretinoin. This review is unique in that it focuses on isotretinoin from both dermatological and cardiac viewpoints. It identifies important shortcomings in standardized ECG monitoring procedures and underscores the scarcity of large, prospective, controlled trials. Future research should focus on longitudinal, multicenter trials using serial ECG evaluations to better define risk profiles and guide clinical monitoring. Understanding infrequent but potentially serious cardiac effects is critical for improving isotretinoin's safety profile and guiding evidence-based therapy.

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Abstract Background The prevalence of allergic contact dermatitis (ACD) differs across various populations, and the sensitization rate can change constantly as new products are introduced to the market. The current Brazilian standard series of patch tests has been used for over two decades. Therefore, the development of a new Brazilian standard series is important to ensure that contact tests remain a reliable diagnostic tool. Methods A Brazilian multicenter, cross-sectional, prospective study was conducted using a modified series of patch tests between 2023 and 2025. The factors under study were the substances used in the contact tests, and the outcomes were the frequencies of positivity and relevance. Demographic and clinical variables of the participants, who had contact dermatitis without a defined etiology prior to the tests, were evaluated. The required sample size was defined as 523 patients, estimating the prevalence of positivity with a 1.8% confidence interval. Wald's test was considered a 95% confidence level and a 1% expected prevalence of positivity. Results A total of 567 participants were included, 77.3% female, with a mean age of 53.3 years, and most belonged to phototypes II, III, and IV. Cleaning services were the most frequent occupational activity, and 43.3% of patients had a personal history of atopy. The overall reactivity of the tests was 69.3%, with 70.2% relevance. Nickel sulfate was the most frequently reactive allergen (28.9%), and 29 substances reached at least 1% positivity. Study limitations Lack of representatives from all regions of Brazil and absence of prospective follow-up. Conclusion The authors propose a new Brazilian standard series of patch tests, with 40 substances, considering the 29 that achieved 1% positivity and another 11 with clinical importance and supported by current literature as emerging and current allergens.