Hydroxychloroquine exacerbates imiquimod-induced psoriasis-like dermatitis through stimulating overexpression of IL-6 in keratinocytes.

OBJECTIVE: Hydroxychloroquine (HCQ) is a US Food and Drug Administration (FDA)-approved treatment for systemic lupus erythematosus (SLE) through inhibition of antigen presentation and subsequent reduction in T cell activation. Psoriasis relapse after antimalarial therapy have been reported in up to 18% of patients with psoriasis. Here, we explored the role of HCQ on exacerbating dermatitis utilizing an imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model. METHODS: Thirty-six C57BL/6 female mice were divided into six groups: wild-type control, IMQ-Only, pre-treat HCQ (30 mg/kg and 60 mg/kg HCQ), and co-treat HCQ with IMQ (30 mg/kg and 60 mg/kg HCQ). Besides control, all were topically treated with IMQ for 5 days. Pharmacological effects and mechanisms of HCQ were assessed by clinical severity of dermatitis, histopathology, and flow cytometry. HaCaT cells were co-treated with both HCQ and recombinant IL-17A, followed by the detection of proinflammatory cytokine expression and gene profiles through enzyme-linked immunosorbent assay and next-generation sequencing. RESULTS: In the pre-treated and co-treated HCQ groups, skin redness and scaling were significantly increased compared to the IMQ-Only group, and Th17 cell expression was also upregulated. Acanthosis and CD11b+IL23+ dendritic cell (DC) infiltration were observed in the HCQ treatment group. IL-6 overexpression was detected in both the HaCaT cells and skin from the experimental mice. Psoriasis-related genes were regulated after being co-treated with HCQ and recombinant IL-17A in HaCaT cells. CONCLUSIONS: HCQ exacerbates psoriasis-like skin inflammation by increasing the expression of IL-6, stimulating DC infiltration, and promoting Th17 expression in the microenvironment of the skin. KEY MESSAGES: This study provided possible mechanisms for inducing psoriasis during HCQ treatment through an animal model.

Inhibition of NLRP3 Inflammasome Activation by 3H-1,2-Dithiole-3-Thione: A Potential Therapeutic Approach for Psoriasis Treatment.

Psoriasis is a chronic autoimmune skin disease with a significant impact on quality of life and potential for severe comorbidities. Inflammation in the skin is induced by immune cells that overexpress pro-inflammatory cytokines, with the Th17 cell playing a crucial role. NLRP3 inflammasome activation is associated with inflammatory diseases and abnormal T cell differentiation. 3H-1,2-dithiole-3-thione (D3T), isolated from cruciferous vegetables, has anti-inflammatory effects and inhibits Th17 differentiation. This study aimed to investigate how D3T reduces skin inflammation and modulates Th17 cell differentiation by inhibiting NLRP3 inflammasome activation. In an imiquimod-induced psoriasis mouse model, D3T treatment demonstrated significant reductions in ear thickness, skin redness, and scaling compared to a control group. Our study also observed decreased expression of ki-67, NLRP3 inflammasome, and cleaved caspase-1 in skin samples, reduced levels of IL-6 and IL-17A in serum samples, and inhibition of Th17 differentiation after D3T application. D3T could also inhibit the expression of NLRP3, caspase-1, and IL-1ß in TNF-α stimulated HaCaT cells. The mechanical study also revealed that D3T could inhibit NLRP3 inflammasome activation by inhibiting the JNK pathway in HaCaT cells. These results indicate that targeting NLRP3 inflammasome activation is a promising strategy in the treatment of psoriasis.

Forsythoside A Alleviates Imiquimod-Induced Psoriasis-like Dermatitis in Mice by Regulating Th17 Cells and IL-17A Expression.

Psoriasis is a recurrent inflammatory skin disease characterized by redness and scaly skin lesions with itchy or painful sensations. Forsythoside A, one of the main active compounds isolated from the fruit of Forsythia suspensa, has been widely applied to treat inflammatory diseases in the clinical use of traditional oriental medicine. However, the effect of forsythoside A on psoriasis remains unclear. This study aimed to explore the therapeutic effects and immune regulation of forsythoside A on psoriasis. C57BL/6 mice were divided into six groups and treated with imiquimod cream on their shaved back skin to induce psoriasis-like dermatitis. Different doses of forsythoside A (5 mg/kg, 10 mg/kg, or 20 mg/kg) were administered to the respective treatment groups. Skin redness, scaling, and ear thickness were measured; keratinocyte proliferation and inflammatory cytokine expression were detected by hematoxylin-eosin and immunohistochemical staining. Th17 cells in the inguinal lymph nodes were detected by flow cytometric analysis. IL-17A levels were measured using ELISA. The results showed that forsythoside A relieved psoriatic skin symptoms such as skin redness, thickness, scaling, and reduced epidermal thickening. The expression of IL-6, IL-17, and Ki-67 was downregulated in the forsythoside-A-treated groups. Th17 cell expression in inguinal lymph nodes and IL-17A secretion was suppressed by forsythoside A. In conclusion, forsythoside A was found to alleviate imiquimod-induced psoriasis-like dermatitis in mice by suppressing Th17 development and IL-17A secretion. These findings demonstrate the feasibility of forsythoside A in treating human psoriasis.

Brevilin A Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis and Reduces Th17 Differentiation in Psoriasis Patients.

Psoriasis is a predominantly Th17 cell-driven chronic autoinflammatory skin disorder. Brevilin A, a natural sesquiterpene lactone extracted from Centipeda minima, has been used as a traditional oriental medicine for allergic diseases for centuries. However, the effects of brevilin A on psoriasis have yet to be established. In this study, we investigated brevilin A to elucidate its potential effects on T cell activities in psoriasis, in animal models and patients. An imiquimod (IMQ)-induced psoriasis-like dermatitis murine model was utilized. Experimental mice were administered different doses of brevilin A (5, 10, 20 mg/kg respectively) for a duration of 5 days. Cutaneous manifestations were measured daily. Under hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC), acanthosis and proinflammatory cytokine expression in the dorsal skin of mice were detected. Enzyme-linked immunosorbent assay (ELISA) was used for the measurement of IL-17A levels in serum samples. Naïve CD4+ T cells, isolated from mice spleen and lymph nodes and from peripheral blood mononuclear cells (PBMCs) of psoriatic patients, were used to evaluate the effects of brevilin A on Th17 differentiation. In brevilin A-treated mice, brevilin A significantly reduced skin redness and scaling; acanthosis as well as IL-6, IL-17A, and ki-67 expressions were downregulated in the dorsal skin, and serum levels of IL-17A were lowered. Brevilin A also inhibited Th17 differentiation. In conclusion, brevilin A demonstrated significant capability in ameliorating skin inflammation in IMQ-induced psoriasis-like dermatitis and could modulate Th17 differentiation. Therefore, brevilin A is potentially pharmacologically effective in the treatment of psoriasis.

The impact of systemic lupus erythematosus on women's sexual functioning.

INTRODUCTION: The effect of systemic lupus erythematosus (SLE) on women's sexual functioning has been rarely assessed. AIM: The aim of this study is to evaluate the impact of SLE on women's sexual functioning. METHODS: A total of 302 consecutive female outpatients with SLE were provided with a questionnaire composed of the Female Sexual Function Index (FSFI), questions for sociodemographic characteristics and comorbidities. Similarly, 2,159 hospital female employees were assessed as the control group. In patients, data of SLE duration and Sjögren's syndrome were derived from the chart records and the disease activity was assessed using the SLE Disease Activity Index 2000. MAIN OUTCOME MEASURES: The FSFI scores were compared between the patients and the controls. Correlates of the FSFI scores were determined in the patients. RESULTS: Of 302 eligible patients, 92.4% (279/302) responded, in addition to 73.2% (1,580/2,159) of controls. Ninety-five percent (255/268) of the respondent patients were in no-to-mild SLE disease activity. Among the respondents, 171 (61.3%) patients and 930 (58.9%) controls were sexually active in the previous month, P = 0.446. Of the sexually active patients, 52.5% (85/162) had impaired sexual function (the FSFI total score < 26.55) and so did 47.1% (408/867) of the sexually active controls, P = 0.206. With adjustment of age group, marital status and education level, patients had lower FSFI scores than controls only in the domains of lubrication and pain. Significant risk factors for lower FSFI scores in the patients included persistent activity or flare of SLE, menstrual cycle disturbances, and vascular disease. With further adjustment of other risk factors, only vascular disease remained significant as a risk factor for impaired sexual function (odds ratio = 5.7; 95% confidence interval 1.6-20.1). CONCLUSION: When not in an exacerbation period, the impact of SLE on women's sexual functioning is not great and is related to vascular factors.

Myelodysplasia followed by Good's Syndrome: a unique manifestation associated with thymoma.

Good's syndrome, also known as thymoma with combined immunodeficiency, is rare. The immunodeficiency may precede, arise concurrently with or follow the diagnosis of thymoma. In addition to myasthenia gravis and Good's syndrome, paraneoplastic syndromes associated with thymoma can also be manifested with hematological disorders, such as pure red cell aplasia, aplastic anemia, agranulocytosis, hemolytic anemia, pernicious anemia, and paroxysmal nocturnal hemoglobinuria. Myelodysplastic syndrome is a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more lineages, ineffective hematopoiesis, and potential precursors of acute leukemia. One proposed pathogenesis of myelodysplasia is autoantibodies that directly reject against hematopoietic cells, but this situation is rare in thymoma. Herein, we report a thymoma patient with unique paraneoplastic syndromes who developed myelodysplasia prior to Good's syndrome. Early and accurate diagnosis of myelodysplastic syndrome is important for disease management, especially in patients whose myelodysplastic syndrome is possibly derived from autoimmunity. For thymoma patients with recurrent infections, comprehensive immunologic studies to exclude the possibility of Good's syndrome and prophylactic intravenous immunoglobulin infusion in suitable candidates are warranted.

Diagnostic pitfalls of nonsecretory myeloma manifesting as multiple foci of periosseous plasmacytomas.

Nonsecretory myeloma, which comprises 1-5% of all myelomas, is a variant of plasma cell myeloma. It is defined as symptomatic myeloma without detectable monoclonal immunoglobulin levels on serum or urine immunofixation electrophoresis. Here, we report two cases of nonsecretory plasma cell myeloma that manifested as multi-foci periosseous plasmacytomas. Due to the inability to detect monoclonal immunoglobulin on serum or urine immunofixation electrophoresis and the lack of evidence of clonal plasma cells in the bone marrow, it was difficult to establish an early, accurate diagnosis. Misdiagnosing or mislabeling symptomatic myeloma patients with plasmacytoma results in the delay of their systemic treatment. Therefore, comprehensive imaging studies, the detection of free light chains, and histopathological confirmation from different sites and time points are necessary.