Treatment of atopic dermatitis with upadacitinib: adcare single center experience.

Introduction: The role of upadacitinib in the management of moderate to severe atopic dermatitis seems promising, but more data on its efficacy and safety are needed. This study endeavors to assess the practical impact and safety of upadacitinib in patients with moderate to severe atopic dermatitis. The study aims to evaluate the efficacy and safety of upadacitinib in the treatment of moderate to severe atopic dermatitis, focusing on analyzing patient responses to the treatment. Methods: In this study, adult patients diagnosed with moderate to severe atopic dermatitis received upadacitinib at daily doses of 15 mg or 30 mg, as prescribed by their attending physicians. The therapeutic efficacy of upadacitinib was meticulously assessed using established clinical metrics. Simultaneously, a comprehensive safety assessment was conducted through monthly monitoring, including the evaluation of potential effects of upadacitinib intake on hepatic function, lipid profile, and hematopoiesis using the pertinent laboratory tests. Results: Sixteen participants were enrolled in the study. At 1month follow-up, there was a significant reduction in the mean Eczema Area and Severity Index (EASI) score to 18.8 points, which further increased to 24 points at the 4-month mark. Additionally, 9 participants (56%) demonstrated an EASI-50 response after 1 month of treatment, with this response increasing to 9 participants (90%) after 4 months. Furthermore, enhanced therapeutic responses were observed at 4 months, with 6 patients (38%) achieving an EASI-75 response at 1month and 8 patients (80%) achieving this milestone at the 4-month follow-up. This study highlights the potential of upadacitinib as an effective treatment option for moderate to severe atopic dermatitis. While it demonstrates improved symptom management, close monitoring for potential adverse events, particularly infections and the known risks of Janus kinase inhibitors, is essential. Further research is essential to determine the long-term safety and efficacy of upadacitinib.

Cytokine gene expression in the skin and peripheral blood of atopic dermatitis patients and healthy individuals.

OBJECTIVES: Atopic dermatitis (AD) is an increasingly common, chronic, relapsing, inflammatory skin disease characterized by impaired epidermal barrier function and cutaneous inflammation. The prevalence of AD has steadily increased during the past few decades. The aim of this study was to comparatively investigate cytokine gene expression in the skin and peripheral blood of atopic dermatitis patients and healthy individuals. RESULTS: In the skin of patients with AD, a significant increase of the level of gene expression was observed for interleukin (IL)-2r (p < 0.0023), IL-5 (p = 0.002), IL-6 (p < 0.0023), IL-8 (p = 0.01), IL-12B (p < 0.0023), IL-10 (p < 0.0023), IL-23 (p = 0.002), IL-29 (p < 0.0023), and transforming growth factor beta (tGFbeta) (p < 0.0023) as compared to healthy individuals. In contrast, no difference between AD patients and healthy donors was detected with respect to cytokine gene expression in the peripheral blood. METHODS: Samples of skin and peripheral blood from 48 severe AD patients (SCORAD = 78.5 [57;89], IGA = 4.2 [3,9;4,7]) at the age of 17 to 45 years and 20 healthy donors aged from 19 to 32 years were analyzed for gene expression of cytokines using real-time reverse transcription polymerase chain reaction (RT-PCR). CONCLUSIONS: Activity of markers of chronic inflammation and Th1 immune response in severe AD, namely IL-2r, IL-8, IL-12B, IL-23, IL-29 and TGFbeta, as well as activity of anti-inflammatory IL-5 were predominant in the skin but not in the blood of AD patients.

Muropeptides trigger distinct activation profiles in macrophages and dendritic cells.

Bacterial peptidoglycan and its muropeptide derivatives potently activate mammalian innate immune system and are promising immunomodulators and vaccine adjuvants. However, their effects on human antigen-presenting cells, such as dendritic cells (DCs) and Mphi, are not fully understood. Lysozyme treatment of PG from Salmonella typhi yielded three muropeptides, GlcNAc-MurNAc-L-Ala-D-isoGlu-meso-DAP (GM-3P), GlcNAc-MurNAc-L-Ala-D-isoGlu-meso-DAP-D-Ala (GM-4P), and a dimer (GM-4P)(2), in which two GM-4P monomers are linked through their peptidic moieties. All three muropeptides induced TNF-alpha and IL-6 production by Mphi (GM-3P>GM-4P>>(GM-4P)(2)), but failed to trigger TNF-alpha, IL-6 and IL-12p70 production by immature DCs. At the same time, muropeptide-stimulated DCs abundantly produced inflammatory chemokines IL-8, MIP-1 alpha and MIP-1 beta, as well as displayed signs of phenotypic and functional maturation. Thus, muropeptide-dependent pro-inflammatory cytokine production is repressed in DCs. While this defect may be partly compensated in vivo by muropeptide-activated Mphi, neither Mphi nor DCs produce Th1- or Th17-polarizing cytokines upon muropeptide stimulation, which may contribute to the preferential induction of Th2 responses by muropeptides and should be taken into account when designing muropeptide-based immunomodulators and adjuvants.