RESUMO
Lupus erythematosus panniculitis (LEP) is a chronic inflammatory skin disease with a significant impact on the overall well-being of patients. The safety and efficacy of oral baricitinib for the treatment of LEP have not been studied. This study aimed to explore the efficacy of oral baricitinib in patients with LEP who are recalcitrant or intolerant to conventional therapies. Patients (aged ≥18 years) with active LEP (with a revised cutaneous lupus erythematosus disease area and severity index [RCLASI]-active score ≥4] were randomly assigned 2:1 to baricitinib (4 mg) or placebo (once daily for 20 weeks). The placebo group was switched to baricitinib (4 mg) at week 13, and the final evaluation was conducted at week 24. The primary endpoint was the proportion of patients with an RCLASI-A score decreased by 20% at week 12. The secondary endpoints included the changes in the Cutaneous Lupus Erythematosus Disease Area and Severity Index active-(CLASI-A) score, the Dermatology Life Quality Index (DLQI), the Physician's Global Assessment (PGA) score, and safety. Five patients were enrolled. Three patients received baricitinib (4 mg), and two patients were treated with placebo. Two patients in the baricitinib treatment group showed a significant RCLASI-A decrease at week 12 and week 24. Two patients in the placebo group had no change in RCLASI-A at week 12 and a significant decrease at week 24. No new safety events were observed. Treatment with baricitinib was effective and well tolerated in patients with LEP.
RESUMO
BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe cutaneous adverse reaction to drugs with considerable morbidity and mortality. Immunomodulators for SJS/TEN including systemic corticosteroids and intravenous immunoglobulin (IVIG) have been widely used in clinical practice. Emerging evidence suggested the therapeutic effects of tumor necrosis factor-α antagonists on SJS/TEN. OBJECTIVE: To compare the efficacy and safety of IVIG and systemic steroids in conjunction with or without etanercept, a tumor necrosis factor-α inhibitor, for patients with SJS/TEN. METHODS: We undertook a retrospective review of 41 patients with SJS/TEN admitted to our institution from 2015 to February 2021. A total of 25 patients with integrated data were involved in this study, of which 14 patients were treated with IVIG and corticosteroids and 11 were in addition given etanercept. The clinical characteristics, duration of hospitalization, exposure time to high-dose steroids, and the total amount of systemic steroids were analyzed. RESULTS: In comparison to conventional therapy, conjunction with etanercept reduced the duration of hospitalization (13.5 vs 19.0 days; P = .01), the exposure time of high-dose steroids (7.1 vs 14.9 days; P = .01), and the overall amount of systemic steroid (925 mg vs 1412.5 mg; P = .03) in patients with SJS/TEN. No pronounced adverse effects were observed within 6 months of follow-up after the treatment. CONCLUSION: The add-in of etanercept at the time of initiating conventional therapy could be a superior option to accelerate disease recovery and reduce the high dose and total amount of systemic steroids without pronounced adverse events in patients with SJS/TEN.
Assuntos
Etanercepte , Síndrome de Stevens-Johnson , Corticosteroides/uso terapêutico , Etanercepte/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Estudos Retrospectivos , Esteroides/uso terapêutico , Síndrome de Stevens-Johnson/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
Artesunate (ART), a derivative of artemisinin, is a medication to treat malaria. Beyond that, the anti-inflammatory and immunoregulatory activities of ART have been identified in autoimmune diseases. However, whether ART functions in psoriasis-like dermatitis induced by imiquimod (IMQ, a TLR7/8 agonist) is currently unkown. There, we found that the cumulative score, epidermal thickening and expression of Ki-67 of ART-treated BALB/c mice were significantly lower than those in the IMQ psoriatic model group. In addition, ART treatment ameliorated mice from systemic inflammation. Mechanistically, ART reduced γδ T cells in draining lymph nodes, which might be benefit the improvement of dermatitis. These findings suggested that ART could be a promising drug of psoriasis in clinic.
Assuntos
Anti-Inflamatórios/uso terapêutico , Artesunato/uso terapêutico , Dermatite/tratamento farmacológico , Psoríase/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Artesunato/farmacologia , Dermatite/imunologia , Dermatite/patologia , Imiquimode , Linfócitos Intraepiteliais/efeitos dos fármacos , Linfócitos Intraepiteliais/imunologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Masculino , Camundongos Endogâmicos BALB C , Psoríase/imunologia , Psoríase/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Células Th17/efeitos dos fármacos , Células Th17/imunologiaRESUMO
OBJECTIVE: The specific autoantibodies and antigens that mediate systemic lupus erythematosus (SLE)-related organ injuries remain largely unknown. This study was undertaken to investigate the antibody-mediated immune response that leads to SLE skin lesions. METHODS: The study included 85 SLE patients with lupus-specific skin lesions and 31 without skin lesions. The reactivity of serum antibody with skin antigens was determined by immunoblotting using human foreskin as the substrate. Skin antigens were identified using mass spectrometry. Serum antibody was isolated by affinity purification and was injected intracutaneously into mouse skin to determine pathogenicity. Serum antibody levels were monitored by enzyme-linked immunosorbent assay. RESULTS: We determined that 78% of the patients with skin lesions had serum antibodies reactive with 35-kd and/or 25-kd skin antigens, which was significantly higher than the percentage of patients without skin lesions (P < 0.0001), suggesting a correlation between immune response and skin lesions. Acidic ribosomal protein P0 (RPLP0) and galectin 3 were 2 target antigens identified from 35-kd and 25-kd proteins, respectively. Purified serum anti-RPLP0 and anti-galectin 3 antibodies induced lupus-like histologic changes after intracutaneous injection. Anti-RPLP0 and anti-galectin 3 antibody levels were significantly higher in SLE patients than in healthy controls and decreased with skin recovery. Anti-galectin 3 antibody levels were not significantly higher in SLE patients than in patients with dermatomyositis or scleroderma, but strongly related to lupus cutaneous vasculitis. Additionally, levels of the 2 antibodies were positively correlated with leukopenia and C3 deficiency, and the anti-RPLP0 antibody level was also positively correlated with arthritis and SLE disease activity. CONCLUSION: Our findings indicate that the immune response mediated by serum anti-RPLP0 and anti-galectin 3 antibodies plays a key role in the pathogenesis of SLE skin lesions. These findings provide new insights into the mechanism of SLE-related organ disorders.
Assuntos
Anticorpos Anti-Idiotípicos/fisiologia , Galectina 3/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Proteínas Ribossômicas/imunologia , Dermatopatias/imunologia , Adolescente , Adulto , Animais , Anticorpos Anti-Idiotípicos/imunologia , Estudos de Casos e Controles , Dermatomiosite/imunologia , Dermatomiosite/patologia , Dermatomiosite/fisiopatologia , Feminino , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Modelos Animais , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/fisiopatologia , Índice de Gravidade de Doença , Pele/metabolismo , Pele/patologia , Pele/fisiopatologia , Dermatopatias/patologia , Dermatopatias/fisiopatologia , Vasculite/imunologia , Vasculite/patologia , Vasculite/fisiopatologia , Adulto JovemRESUMO
Cutaneous mucormycosis, an uncommon disease caused by Mucorales, predominantly occurs in immunocompromised host. The present case is a primary cutaneous mucormycosis due to Mucor indicus in an immunocompetent individual. It is with the features of necrotizing fasciitis over the right pretibial area. We are presenting this case owing to its rarity and the successful treatment with amphotericin B and skin grafting.
Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Fasciite Necrosante/tratamento farmacológico , Mucor/efeitos dos fármacos , Mucormicose/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Transplante de Pele/efeitos adversos , Fasciite Necrosante/etiologia , Fasciite Necrosante/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucor/isolamento & purificação , Mucormicose/etiologia , Mucormicose/microbiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/microbiologiaRESUMO
Detection of immunoreactants including IgG, IgM, IgA, and C3 by direct immunofluorescence (DIF) from skin is useful for distinguishing lupus lesions from other skin disorders. Despite their diagnostic value, the type and number of cutaneous immunoreactants as they relate to serological disorders and disease severity has been poorly studied. We examined 36 patients with systemic lupus erythematosis (SLE) with positive DIF (DIF+) and 28 patients with negative DIF (DIF-) tests performed on lesional skin. Among DIF+ patients, the most frequent patterns of immunoreactants were IgM alone (36%) and the coexistence of IgM with C3 (28%). IgM was the highest detected individual immunoreactant (86%). As classified by number, 17 of 36 DIF+ patients had one immunoreactant (= 1), while the remaining patients had two to four immunoreactants (>1). Compared with DIF- patients, DIF+ patients were more likely to have severe disease as indicated by lower serum C3 levels and a higher SLE disease activity index (SLEDAI). The coexistence of IgM with any other immunoreactants indicated a more severe disease than that present in the DIF- group, whereas the IgM-alone group was comparable with the DIF- group in both serum C3 levels and SLEDAI. These findings were also applicable in the comparison of patients with more than one (>1) immunoreactant and patients with no (DIF-) and one ( = 1) immunoreactant. Collectively, the presence of multiple immunoreactants in lesional skin implies a more severe disease activity of SLE, while a single immunoreactant may be equal to the absence of immunoreactants (DIF-) in terms of predicting disease activity.
Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Pele/metabolismo , Adolescente , Adulto , Complemento C3/metabolismo , Feminino , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Pele/imunologia , Pele/patologia , Adulto JovemRESUMO
BACKGROUND/AIM: The abnormal activation of the AKT/GSK3ß signal pathway in lymphocytes from systemic lupus erythematosus (SLE) patients plays an important role in the pathogenesis of the disease. Recently Hydrogen sulfide (H2S) has been recognized as a crucial gaseous signaling molecule, involved in regulation of cell proliferation. However, the role of H2S in regulating the abnormal activation of lymphocytes from SLE patients has not been established. This study was conducted to investigate the effect of H2S on lymphocytes and to explore the mechanisms involved. METHODS: The lymphocytes were isolated from SLE patients with or without renal disease and healthy controls. The cells were treated as indicated in each experiment. Cell viability was analyzed by CCK-8. Cell cycle distribution was determined by flow cytometry. Western blot was used to detect the expression of phosphorylated AKT (ser473), GSK3ß (ser9) and CDK2, p27(Kip1) and p21(WAF1/CIP1). RESULTS: Our findings showed that proliferation of lymphocytes was stimulated following treatment with NaHS (a H2S donor) at low NaHS concentrations (<1mM) but inhibited at high NaHS concentrations (>2mM). Similar results were observed using GYY4137, which is a slow-releasing H2S donor. Pretreatment of lymphocytes from SLE patients with NaHS at high concentrations prior to exposure to phytohemagglutinin (PHA) significantly attenuated proliferation, evidenced by decrease in cell viability and S phase distribution of cell cycle. Pretreatment with NaHS decreased PHA-induced expression of CDK2, phosphorylation levels of AKT (ser473) and GSK3ß (ser9) and increased the expression of p27(Kip1) and p21(WAF1/CIP1). Moreover, pretreatment with NaHS blunted the stimulation of SLE lymphocyte proliferation by GSK3ß inhibitor lithium chloride. CONCLUSION: These results demonstrate that H2S inhibits the abnormal activation of lymphocytes from SLE patients throuqh the AKT/GSK3ß signal pathway.
Assuntos
Quinase 3 da Glicogênio Sintase/metabolismo , Sulfeto de Hidrogênio/farmacologia , Linfócitos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quinase 2 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta , Humanos , Cloreto de Lítio/farmacologia , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Linfócitos/citologia , Linfócitos/metabolismo , Morfolinas/farmacologia , Compostos Organotiofosforados/farmacologia , Fosforilação , Fito-Hemaglutininas/farmacologia , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by activation and proliferation of autoreactive T cells and B cells. We examined changes in cell cycle progression of T cells from MRL/lpr mice with or without allogenic bone marrow mesenchymal stem cells (BMMSCs) treatment and analyzed the expression of cell cycle associated proteins. In addition, the Akt/GSK3ß protein kinase cascade was studied. We demonstrated that high-dose MSCs transplantation effectively ameliorated disease activity in MRL/lpr mice. BMMSCs treatment inhibited G1/S transition of the abnormal lupus T lymphocytes. Moreover, it increased the expression of p21(WAF1/CIP1) and p27(Kip1) and decreased the expression of CDK2. Furthermore, high-dose MSCs inhibited abnormal activation of the Akt/GSK3ß signaling pathway of T cells from MRL/lpr mice. Our results suggest that high-dose BMMSCs transplantation successfully treated MRL/lpr lupus mice by inhibiting abnormal activation of Akt/GSK3ß signaling pathway of T cells.
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Quinase 3 da Glicogênio Sintase/metabolismo , Lúpus Eritematoso Sistêmico/enzimologia , Transplante de Células-Tronco Mesenquimais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Linfócitos T/enzimologia , Animais , Ciclo Celular , Quinases Ciclina-Dependentes/metabolismo , Modelos Animais de Doenças , Ativação Enzimática , Glicogênio Sintase Quinase 3 beta , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Endogâmicos C57BL , FosforilaçãoRESUMO
BACKGROUND: Interstitial lung disease (ILD) is a serious lung complication in polymyositis (PM) and dermatomyositis (DM) which affects prognosis and requires a more aggressive approach in therapy. This study investigated the prevalence, characteristics, predictive factors and unfavourable prognostic factors of ILD in newly diagnosed PM, DM and amyopathic DM (ADM). METHODS: From January 2000 to December 2008, the medical records of 197 consecutive PM and DM patients at the Second Affiliated Hospital of Sun Yat-Sen University were reviewed excluding overlapping, juvenile, and malignancy-associated cases. The patients were assigned to an ILD (69 patients) and a non-ILD group (128 patients). The clinical features, laboratory findings, and prognosis were compared. RESULTS: The multivariate analysis indicated that older age at onset (OR 1.033, 95%CI 1.009 - 1.058, P = 0.007), fever (OR 4.109, 95%CI 1.926 - 8.767, P < 0.001) and arthritis/arthralgia (OR 2.274, 95%CI 1.101 - 4.695, P = 0.026) were the independent predictive factors for developing ILD in PM/DM after excluding anti-Jo-1. Regarding anti-Jo-1, fever (OR 4.912, 95%CI 2.121 - 11.376, P < 0.001) was associated with ILD. Poor survival in ILD patients was associated with ILD clinical subset (RR 0.122, 95%CI 0.049 - 0.399, P < 0.001), ADM/DM/PM-ILD (RR 0.140, 95%CI 0.031 - 0.476, P = 0.002), cardiac involvement (RR 4.654, 95%CI 1.391 - 15.577, P = 0.013) and serum albumin level (RR 0.910, 95%CI 0.831 - 0.997, P = 0.042). CONCLUSIONS: Patients who presented with fever tended to have a higher frequency of PM/DM-associated ILD. A Hamman-Rich-like presentation, ADM-ILD, cardiac involvement and hypoalbuminemia were poor prognostic factors in ILD-PM/DM.