A Case Report of JAK Inhibitors Therapy for Adult-Onset Still's Disease with Persistent Pruritic Lesions.

BACKGROUND AND OBJECTIVE: Adult-onset Still's disease (AOSD) is a recognized autoinflammatory disorder of unknown etiology. The standard initial management for AOSD includes conventional corticosteroids and disease-modifying antirheumatic drugs. In cases that are resistant to these treatments, additional therapeutic options such as immunosuppressants, biologics, and other alternative treatments may be considered. Yet, a significant proportion of patients remain unresponsive to these therapeutic interventions. Herein, a case is reported involving a patient with AOSD who had persistent pruritic lesions that did not respond to conventional therapy, but were alleviated with Janus kinase inhibitors (JAKi), namely baricitinib and upadacitinib. The objective is to expand the number of refractory AOSD cases treated with JAKi in clinical practice. Another aim is to offer potentially effective therapeutic options for AOSD patients who experience persistent pruritus. METHODS: A case was reported involving AOSD characterized by persistent pruritic lesions that failed to respond to conventional treatment, but showed favorable outcomes with JAKi therapy. An analysis of the PubMed literature was performed to assess the medication's efficacy and explore possible mechanisms. RESULTS: The present case study is one of the few documented instances exploring the use of JAKi for treating AOSD, aligning with previously published research. After initiating JAKi therapy, the patient exhibited significant improvement in symptoms, most notably a reduction in persistent pruritus. Additionally, there was a substantial decrease in the patient's glucocorticoid dosage. Aside from minor renal function anomalies, no adverse reactions were observed. CONCLUSIONS: The present case illustrates that JAKi can provide rapid and sustained clinical improvement in patients with AOSD, especially those who have not responded to conventional treatment, and they have the ability to alleviate persistent itching. Further investigation is needed to ascertain the precise mechanism.

Long-Noncoding RNA ANCR Activates the Hedgehog Signaling Pathway to Promote Basal Cell Carcinoma Progression by Binding to PTCH.

Purpose: The long non-coding RNA (lncRNA) anti-differentiation noncoding RNA (ANCR) is closely related to the occurrence and development of various malignancies. However, its expression and potential role in basal cell carcinoma (BCC) have not been established. In this study, we characterized the effects of ANCR in BCC and its underlying mechanism. Methods: The expression of ANCR in BCC tissues and cells was detected by qRT-PCR. Proliferation, invasion, migration and apoptosis of ANCR overexpressed or knock down TE354.T and A431 cells were examined by CCK8, transwell assay, wound healing assay and flow cytometry analysis, respectively. Western blot was performed to measure the expression of apoptosis-related proteins (BAX, BCL2 and Cleaved-caspase3), epithelial-mesenchymal transformation-related proteins (E-cadherin, N-cadherin, vimentin and ß-catenin), and Hedgehog-pathway-related proteins (PTCH, GLI1 and SMO). RNA pull-down assay was used to analyze the relationship between ANCR and PTCH. The effect of ANCR on BCC growth in vivo was analyzed using xenograft model. TUNEL assay was used to determine the cell apoptosis. Results: ANCR and Hedgehog pathway were more highly expressed in BCC tissues than in adjacent normal tissues. ANCR overexpression substantially promoted BCC cell proliferation, invasion, and migration, inhibited apoptosis, and up-regulated BCL2 and decreased the expression of BAX and Cleaved-caspase3 proteins. Additionally, the upregulation of N-cadherin, vimentin, ß-catenin, PTCH, GLI1, and SMO expression, and downregulation of E-cadherin expression were observed after ANCR overexpression. Moreover, ANCR knockdown had the opposite effects. An RNA pull-down assay further revealed that ANCR is specifically bound to PTCH. In vivo experiments also showed that ANCR overexpression significantly increased tumor growth and decreased apoptosis, which was reversed by cyclopamine, a specific inhibitor of the Hedgehog signaling pathway. Conclusion: ANCR activates the Hedgehog signaling pathway by binding to PTCH, thereby promoting BCC progression; accordingly, ANCR could be a candidate therapeutic target in BCC.