In Hashimoto’s thyroiditis (HT), oxidative stress (OS) is driven by Th1 cytokines’ response interfering with the normal function of thyrocytes. OS results from an imbalance between an excessive production of reactive oxygen species (ROS) and a lowering of antioxidant production. Moreover, OS has been shown to inhibit Sirtuin 1 (SIRT1), which is able to prevent hypoxia-inducible factor (HIF)-1α stabilization. The aims of this study were to determine the involvement of NADPH-oxidases (NOX), SIRT1, and HIF-1α in HT pathophysiology as well as the status of antioxidant proteins such as peroxiredoxin 1 (PRDX1), catalase, and superoxide dismutase 1 (SOD1). The protein expressions of NOX2, NOX4, antioxidant enzymes, SIRT1, and HIF-1α, as well as glucose transporter-1 (GLUT-1) and vascular endothelial growth factor A (VEGF-A), were analyzed by Western blot in primary cultures of human thyrocytes that were or were not incubated with Th1 cytokines. The same proteins were also analyzed by immunohistochemistry in thyroid samples from control and HT patients. In human thyrocytes incubated with Th1 cytokines, NOX4 expression was increased whereas antioxidants, such as PRDX1, catalase, and SOD1, were reduced. Th1 cytokines also induced a significant decrease of SIRT1 protein expression associated with an upregulation of HIF-1α, GLUT-1, and VEGF-A proteins. With the exception of PRDX1 and SOD1, similar results were obtained in HT thyroids. OS due to an increase of ROS produced by NOX4 and a loss of antioxidant defenses (PRDX1, catalase, SOD1) correlates to a reduction of SIRT1 and an upregulation of HIF 1α, GLUT-1, and VEGF-A. Our study placed SIRT1 as a key regulator of OS and we, therefore, believe it could be considered as a potential therapeutic target in HT.

Background Tralokinumab, the first fully human monoclonal antibody that binds specifically to interleukin-13, was safe and effective for treating atopic dermatitis (AD) in clinical trials, but real-life experience is still limited. Objectives The objective of this study was to evaluate the effectiveness and safety of tralokinumab in severe AD in a reallife multicenter prospective cohort. Methods Adult patients with severe AD were enrolled between January 2022 and July 2022 and received tralokinumab subcutaneously for 16 weeks. Objective and subjective scores were collected at baseline, weeks 6 and 16. Adverse events were reported throughout the study. Results Twenty-one patients were included. An improvement of at least 75% on the Eczema Area and Severity Index (EASI 75) was achieved in 66.7% of patients at week 16. The median objective and subjective scores at week 16 were significantly (p < 0.001) lower than those at baseline. Combination with cyclosporine was sometimes necessary at the beginning of treatment, and addition of upadacitinib was required for some patients with very severe disease during the treatment. The most frequent adverse events were flares of eczema (23.8%) and reactions at injection site (19.0%). No cases of conjunctivitis were reported. Four patients (19.0%) discontinued treatment. Conclusions Tralokinumab is an effective first-line biotherapy for severe AD. However, therapeutic response may be progressive. Safety data were reassuring. Atopic dermatitis flares or reactions at the injection site may lead to discontinuation of treatment. A history of conjunctivitis on dupilumab is not a contraindication to the initiation of tralokinumab. Key PointsTralokinumab, a monoclonal antibody anti-interleukin-13 approved for the treatment of severe atopic dermatitis in adult patients, was effective and safe in clinical trials, but real-world data are limited.

Introduction:The efficacy and safety of upadacitinib in atopic dermatitis have been defined in clinical trials, but long-term real-life experience, essential for clinical decision-making, is still limited. We aimed to assess the effectiveness and tolerance of upadacitinib in a real-life cohort of adults and adolescents with severe atopic dermatitis in whom previous systemic therapies largely failed. Methods: Retrospective cohort study collecting data from adults and adolescents treated with upadacitinib 15 or 30 mg per day between July 2021 to August 2022. The outcomes for effectiveness were evaluated by the percentage of patients who achieved a validated Investigator's Global Assessment for atopic dermatitis (vIGA-AD) of 0 (clear) or 1 (almost clear) and/or an improvement of at least 75% on the Eczema Area and Severity Index (EASI 75) at the end of the follow-up. All treatment-emergent adverse events were collected. Results: A total of 29 patients were included (22 adults and 7 adolescents), with a median follow-up of 54.4 weeks. At the end of the follow-up, 23 patients (79.3%) reached a vIGA-AD of 0/1, and 24 patients (82.7%) achieved EASI 75. Among patients treated with upadacitinib after initial failure of first-and/or secondline treatment with biologics or baricitinib, 5/7 patients (71.4%) reached a vIGA-AD score of 0/1. Disease control was slightly better in adults than in adolescents (81.8% vs 71.4% reached the efficacy endpoint, respectively). Response rate in patients with upadacitinib 15 mg seemed better than in clinical trials or network metaanalysis. Safety data were reassuring; lipid changes were the most frequent adverse event. Conclusion: This real-life study confirms the effectiveness of upadacitinib, particularly for the treatment of atopic dermatitis recalcitrant to conventional systemic agents, biologics or baricitinib. Induced lipid changes require close follow-up.

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This case report will present the case of an 11 years old child diagnosed with childhood-onset systemic lupus erythematosus (cSLE) during the coronavirus Covid-19 pandemic. Her initial symptoms were compatible with a Covid-19 infection but repeated PCR on naso-pharyngeal swabs were negative. Two serological assays were carried out but only one showed doubtful IgG results.Considering that viral infection could be responsible for autoimmune disease outbreaks and with increasing evidences of SARS Cov 2 actions on human inflammatory and immune systems; we discuss here a potential cSLE diagnosis triggered by Covid-19 infection.

Pyoderma gangrenosum (PG) is one of the neutrophilic dermatosis, a heterogenous group of rare inflammatory diseases affecting the skin. It is often associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis or hematological malignancies. Classical PG is characterized by painful ulcers with violaceous, undermined border, often developing at sites of injury because of the typical pathergy phenomenon. Because of its polymorphic presentation, misdiagnosis and delayed diagnosis are common. We present a case of PG occurring after transcutaneous electrical nerve stimulation (TENS) in a young female patient with ulcerative colitis. Although electric current has previously been incriminated as a trigger for PG, to the best of our knowledge this is the first case precipitated by TENS. We report a typical case of PG occurring after an unusual stimulus and highlight the challenges that the diagnosis of this relatively rare pathology poses to the clinician.

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