Islam AW, Motdhare P, Mohan S
… +2 more, Bejoy S, Wilkhoo HS
An Bras Dermatol
· 2026 · PMID 41861760
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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, parti...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.
El-Amawy HS, Mohamed Ali BM, Salem ML
… +1 more, Elgarhy L
An Bras Dermatol
· 2026 · PMID 41861759
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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...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.
An Bras Dermatol
· 2026 · PMID 41861758
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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 staini...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).
Cruz PT, Miot HA, Talhari C
… +8 more, Pedrosa VL, Serique RDM, Cordeiro AGDS, Mendes JDS, Doria SS, Sales JEDS, Costa AF, Talhari S
An Bras Dermatol
· 2026 · PMID 41806758
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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 prejud...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.
El-Amawy HS, Mohamed Ali BM, Shareef MM
… +1 more, Elgarhy L
An Bras Dermatol
· 2026 · PMID 41806757
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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...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.
An Bras Dermatol
· 2026 · PMID 41604967
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BACKGROUND: Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease with heterogeneous clinical manifestations that is hard to diagnose. Direct immunofluorescence (DIF) is critical, but its role in multimoda...BACKGROUND: Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease with heterogeneous clinical manifestations that is hard to diagnose. Direct immunofluorescence (DIF) is critical, but its role in multimodal frameworks is unclear. OBJECTIVE: To assess DIF's diagnostic performance in MMP and explore factors affecting its positivity patterns in multimodal workflows. METHODS: We retrospectively analyzed 79 suspected MMP patients, categorizing them into confirmed and non-confirmed groups based on clinical, histopathological, and serological criteria. DIF of perilesional mucosal biopsies showed linear deposits of IgG, IgA, IgM, C3, and fibrinogen along the basement membrane zone (BMZ). Diagnostic efficacy was assessed via ROC curve analysis. RESULTS: 55 cases were confirmed. Histopathology demonstrated subepithelial blisters in 51, with 100% specificity, 92.73% sensitivity (AUC = 0.964, p < 0.05). DIF identified 47 cases, with C3 (63.64%) and IgG (60.00%) most common, showing 85.45% sensitivity, 100% specificity, and 97.87% concordance with histopathology. Disease duration independently predicted positive IgM (p = 0.023). STUDY LIMITATIONS: This study is a single-center retrospective study with a limited sample size, which has certain limitations. CONCLUSION: DIF, 100% specific, aids histopathology in MMP diagnosis, especially with C3/IgG linear BMZ deposition. Notably, IgM positivity correlates with prolonged disease duration, suggesting DIF efficiency may link to disease stage.
Fonseca JTD, Figueiredo JP, Neves LVBT
… +4 more, Oliveira JCS, Oliveira JS, Figueiredo VR, Campos RA
An Bras Dermatol
· 2026 · PMID 41579768
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BACKGROUND: Chronic urticaria (CU) compromises quality of life, requiring escalated treatment with second-generation H1 antihistamines, omalizumab, and, in refractory cases, cyclosporine. Predictors of therapeutic respon...BACKGROUND: Chronic urticaria (CU) compromises quality of life, requiring escalated treatment with second-generation H1 antihistamines, omalizumab, and, in refractory cases, cyclosporine. Predictors of therapeutic response are not yet well established. OBJECTIVE: To evaluate clinical and laboratory factors associated with treatment response in patients with CU. METHODS: Cross-sectional study of 175 patients with CU followed at the Urticaria Reference Center (UCARE) of Complexo Hospitalar Universitário Professor Edgard Santos (HUPES/UFBA) between 2023 and 2024. Sociodemographic, clinical, and laboratory data were analyzed. Treatment response was assessed using the Urticaria Control Test (UCT), with responders being those with a score ≥12 or Angioedema Control Test (AECT) ≥10. RESULTS: Most patients were female (80.6%), with a mean age of 45.3 years. Chronic spontaneous urticaria (CSU) was predominant (86.3%). Higher body mass index (BMI), early onset, longer disease duration, and psychiatric disorders were associated with poorer response to second-generation H1 antihistamines. Responders to these drugs had shorter disease duration and a lower proportion of women compared to those requiring omalizumab. In omalizumab users, mental disorders remained associated with refractoriness. Total IgE, eosinophils, CRP, ESR, D-dimer, and anti-TPO did not correlate with therapeutic response. STUDY LIMITATIONS: Cross-sectional study and reliance on clinical records, information bias, and selection bias. CONCLUSIONS: High BMI, female gender, early symptom onset, prolonged disease duration, and mental disorders were associated with poorer response to CU treatment. The evaluated laboratory tests did not demonstrate predictive value for treatment response.
Xavier-Júnior JCC, de Paula Alves Coelho KM, de Macedo MP
… +4 more, Lellis RF, de Freitas Pinheiro Junior N, Rocha RF, Comitê de Dermatopatologia da Sociedade Brasileira de Patologia
An Bras Dermatol
· 2026 · PMID 41558423
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