FIRST REPORT ON OTOTOXICITY OF MEGLUMINE ANTIMONIATE

Pentavalent antimonials are the first drug of choice in the treatment of tegumentary leishmaniasis. Data on ototoxicity related with such drugs is scarcely available in literature, leading us to develop a study on cochleovestibular functions. Case Report: A case of a tegumentary leishmaniasis patient, a 78-year-old man who presented a substantial increase in auditory threshold with tinnitus and severe rotatory dizziness during the treatment with meglumine antimoniate, is reported. These symptoms worsened in two weeks after treatment was interrupted. Conclusion: Dizziness and tinnitus had already been related to meglumine antimoniate. However, this is the first well documented case of cochlear-vestibular toxicity related to meglumine antimoniate

Lúpus eritematoso sistêmico bolhoso: diagnóstico diferencial com dermatite herpetiforme

O lúpus eritematoso sistêmico bolhoso é um subtipo raro do lúpus eritematoso sistêmico, que ocorre ainda de forma mais incomum nos pacientes pediátricos. Relatamos o caso de uma adolescente de 12 anos, apresentando lesões vésico-bolhosas em face, pescoço, tronco, mucosas oral e genital, anemia, leucocitúria estéril, FAN: 1/1280 padrão nuclear pontilhado grosso, Anti-Sm e Anti-RNP positivos. O estudo anatomopatológico sugere dermatite herpetiforme e a imunofluorescência direta revela IgG, IgA e fibrina ao longo da zona de membrana basal. Apresentamos um caso típico de lúpus eritematoso sistêmico bolhoso e enfatizamos a importância do diagnóstico diferencial com a dermatite herpetiforme<br>Bullous systemic lupus erythematosus is a rare subset of systemic lupus erythematosus that is even rarer in pediatric patients. We report a case of a 12-year-old girl who presented with a vesiculobullous eruption on her face, neck, trunk and genital and oral mucosa, as well as anemia, sterile pyuria, ANA (1:1280, speckled pattern) and positive anti-Sm and anti-RNP. Pathological examination suggested dermatitis herpetiformis, and direct immunofluorescence revealed IgG, IgA and fibrin in the epithelial basement membrane zone. We present a typical case of bullous systemic lupus erythematosus and emphasize the importance of clinical and histopathological differential diagnosis with dermatitis herpetiformi

Sarcoidose pulmonar: achados na tomografia computadorizada de alta resolução Pulmonary sarcoidosis: high-resolution computed tomography findings

A sarcoidose é uma doença sistêmica de causa indeterminada, caracterizada por granulomas não-caseosos. Embora possa afetar qualquer órgão, esta doença tem sua morbi-mortalidade relacionada principalmente ao acometimento pulmonar, presente em 80% a 90% dos pacientes. Este artigo ilustra as principais manifestações pulmonares da sarcoidose na tomografia computadorizada de alta resolução, incluindo as formas típicas e atípicas.<br>Sarcoidosis is a systemic disease of unknown etiology, characterized by noncaseating granulomas. Although it may affect any organ, morbidity and mortality are most commonly related to pulmonary involvement, which is found in 80-90% of patients. This study illustrates the principal manifestations of sarcoidosis seen in high-resolution computed tomography scans, including typical as well as atypical forms

Safety and efficacy of subcutaneous iscalimab (CFZ533) in two distinct populations of patients with Sj\uf6gren\u27s disease (TWINSS): week 24 results of a randomised, double-blind, placebo-controlled, phase 2b dose-ranging study

\ua9 2024 Elsevier LtdBackground: Sj\uf6gren\u27s disease is a chronic autoimmune disease with an unmet need for targeted therapies. The aim of the TWINSS study is to evaluate the safety and efficacy of iscalimab, a monoclonal antibody against CD40, in patients with active Sj\uf6gren\u27s disease. Methods: This randomised, double-blind, placebo-controlled, phase 2b study, conducted at 71 sites in 23 countries, enrolled patients aged 18 years or older fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) 2016 criteria. In the dose-ranging cohort 1, patients with a EULAR Sj\uf6gren\u27s Syndrome Disease Activity Index (ESSDAI) score of 5 or higher and a EULAR Sj\uf6gren\u27s Syndrome Patient Reported Index (ESSPRI) score of 5 or higher were randomly assigned (1:1:1:1) to subcutaneous iscalimab 150 mg, 300 mg, 600 mg, or placebo. In the proof-of-concept cohort 2, patients with an ESSDAI score of less than 5, ESSPRI (dryness or fatigue) score of 5 or higher, and Impact of Dry Eye on Everyday Life score of 30 or higher were randomly assigned (1:1) to iscalimab 600 mg or placebo. The sponsor, investigator, site personnel, and patients were masked to the treatment assignment. The primary objectives were to demonstrate a dose–response relationship of iscalimab based on the change in ESSDAI from baseline to week 24 in cohort 1 by Multiple Comparison Procedure—Modelling (MCP-Mod), and to assess the effect of iscalimab 600 mg on ESSPRI at week 24 in cohort 2. All the efficacy analyses included all patients who were randomly assigned, and safety analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03905525), and is complete. Findings: Between Oct 1, 2019, and Feb 28, 2022, 460 patients were screened; 173 patients were assigned to cohort 1 (44 to iscalimab 150 mg, 43 to 300 mg, 43 to 600 mg, and 43 to placebo) and 100 to cohort 2 (50 to each group). In cohort 1, the MCP step showed a significant dose–response relationship for placebo-adjusted ESSDAI change from baseline in one of four models (Linlog model, one-sided p=0\ub70041). ESSDAI decreased from baseline to week 24 with all three doses of iscalimab; 150 mg and 600 mg doses showed statistically significant improvement (placebo-adjusted least squares [LS] mean difference –3\ub70 [95% CI –4\ub79 to –1\ub71]; p=0\ub70025 for 150 mg and –2\ub79 [–4\ub79 to –1\ub70]; p=0\ub70037 for 600 mg). In cohort 2, ESSPRI showed a trend towards improvement with iscalimab 600 mg (placebo-adjusted LS mean change from baseline –0\ub757 points [95% CI –1\ub730 to 0\ub715]; p=0\ub712). Serious adverse events were reported in nine patients in cohort 1 (one [2%] of 43 in the placebo group, one [2%] of 44 in the iscalimab 150 mg group, three [7%] of 42 in the 300 mg group, four [9%] of 44 in the 600 mg group) and four patients in cohort 2 (two [4%] of 50 in each group). No deaths occurred over the 24-week period. Interpretation: The study met the primary objective of demonstrating a significant dose–response relationship with iscalimab in terms of disease activity at week 24. Iscalimab was well tolerated and showed initial clinical benefit over placebo in two distinct populations of patients with Sj\uf6gren\u27s disease, to be confirmed in larger trials. Funding: Novartis Pharma