RESUMO
OBJECTIVES: The aim is to evaluate the prevention and development of cervical cancer in systemic lupus erythematosus (SLE) patients in Japan and its background based on a questionnaire survey. METHODS: The questionnaire was handed to 460 adult female SLE patients at 12 medical institutions. The participants were grouped by age, and data related to their human papillomavirus vaccination status, age at first coitus, cervical cancer screening, and diagnosis of cervical cancer were analysed. RESULTS: A total of 320 responses were received. Patients aged 35-54 years included a higher proportion of patients whose age at first coitus was <20 years. This group also showed a higher rate of cervical cancer/dysplasia. Only nine patients had a human papillomavirus vaccination history. Adequate frequency of cervical cancer screening was slightly higher (52.1%) among SLE patients than in the Japanese general population. However, 23% of the patients had never undergone examination, primarily because of a feeling of troublesome. The incidence of cervical cancer was significantly higher among SLE patients. One reason for this may be associated with the use of immunosuppressants, although the difference was not significant. CONCLUSIONS: SLE patients are at a higher risk of cervical cancer and dysplasia. Rheumatologists should proactively recommend vaccination and screening examinations for SLE female patients.
Assuntos
Lúpus Eritematoso Sistêmico , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adulto , Feminino , Humanos , Detecção Precoce de Câncer , Japão/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Inquéritos e Questionários , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To revise the 2017 clinical practice guidelines (CPG) for the management of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) to reflect advancements in the field. METHODS: Similar to the 2017 CPG, the Grading of Recommendations, Assessment, Development, and Evaluation system was adopted for this revision. The intended users of this CPG include patients diagnosed with MPA or GPA in Japan and their families and healthcare professionals, including specialists and non-specialists. Based on a scoping review, four clinical questions (CQs) of the 2017 guidelines were modified, and six new CQs were added. RESULTS: We suggest a combination of glucocorticoid and cyclophosphamide or rituximab for remission induction therapy. In cases where cyclophosphamide or rituximab is used, we suggest the use of avacopan over high-dose glucocorticoid. Furthermore, we suggest against the use of plasma exchange in addition to the standard treatment in severe cases of MPA/GPA. Finally, we suggest the use of glucocorticoid and rituximab over glucocorticoid and azathioprine for remission maintenance therapy. CONCLUSIONS: The recommendations have been updated based on patient preference, certainty of evidence, benefit and risk balance, and cost.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos , Ciclofosfamida/uso terapêutico , Glucocorticoides/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/diagnóstico , Imunossupressores/uso terapêutico , Japão , Poliangiite Microscópica/tratamento farmacológico , Rituximab/uso terapêuticoRESUMO
INTRODUCTION: The introduction of biologic therapies and a treat-to-target approach has transformed the management of rheumatoid arthritis (RA), which has led to improved outcomes for women with RA who wish to become pregnant. However, guidelines for the management of reproductive health in female patients with RA are still lacking. AREAS COVERED: A task force (Women of Childbearing Age [WoCBA]-Rheumatoid Arthritis in Japan) comprising 10 experts in the fields of rheumatology, obstetrics and orthopedic surgery developed 10 clinical questions (CQ) related to the management of WoCBA with RA. For each CQ, a systematic literature review was conducted to identify relevant evidence. Based on this evidence, a set of recommendations for each CQ were drafted and evaluated using the modified Delphi method. This article describes the agreed recommendations along with the supporting evidence. EXPERT OPINION: There are many ongoing challenges associated with the provision of reproductive healthcare in WoCBA with RA. It is hoped that the consensus-based recommendations provided here can be implemented in clinical practice in order to increase collaboration between rheumatologists and obstetricians/gynecologists and to improve reproductive health outcomes for WoCBA with RA.
Assuntos
Artrite Reumatoide , Reumatologia , Gravidez , Humanos , Feminino , Medicina Baseada em Evidências , Artrite Reumatoide/tratamento farmacológico , Reumatologia/métodos , Consenso , JapãoRESUMO
OBJECTIVES: The aim of this article is to evaluate the effectiveness and safety of rituximab (RTX) for microscopic polyangiitis and granulomatosis with polyangiitis in Japan. METHODS: In this prospective observational study, all patients with microscopic polyangiitis and granulomatosis with polyangiitis administered RTX were enrolled at each institution. During the observation period of 2 years, data up to 6 months were analysed. Cox proportional hazards analysis was used to assess the factors associated with an outcome. RESULTS: Of the 75 patients who received RTX for remission induction therapy, 53 achieved remission by the sixth month and 50 were in remission at the sixth month. During therapy, 38 serious adverse events were observed in 24 patients, 21 serious infections in 16 patients, and 9 patients died. No factors were associated with remission; however, there was a significant difference between patients with and without remission in serious adverse events (22.6% vs. 54.5%), serious infections (11.3% vs. 45.4%), and death (1.9% vs. 36.4%). The hazard ratio (95% confidence interval) for serious infection was 3.49 (1.29-9.74) for patients aged ≥ 75 years and 3.53 (1.31-9.53) for pulmonary complications. Four patients maintained remission for 6 months. CONCLUSIONS: The effectiveness and safety of RTX for microscopic polyangiitis and granulomatosis with polyangiitis for up to 6 months was demonstrated.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Rituximab/efeitos adversos , Anticorpos Anticitoplasma de Neutrófilos , Estudos de Coortes , População do Leste Asiático , Resultado do Tratamento , Indução de RemissãoRESUMO
Acute fibrinous and organizing pneumonia (AFOP) is rare in patients with systemic lupus erythematosus (SLE). We herein report a case of AFOP with SLE and hemophagocytic syndrome. Early-phase high-resolution computed tomography showed a fine granular lung pattern. A pathological examination revealed AFOP. An immunohistological examination revealed numerous CD163+ and fewer CD68+ macrophages present in the lung tissue and in alveolar spaces as well, including fibrin balls, the interstitium, and bronchial walls. Pneumonia and thrombocytopenia worsened during high-dose steroid therapy, plasma exchange, and intravenous immunoglobulin administration. The addition of intravenous cyclophosphamide successfully ameliorated the symptoms and radiographic lesions. Therefore, this therapy may be useful for treating severe AFOP.
Assuntos
Lúpus Eritematoso Sistêmico , Linfo-Histiocitose Hemofagocítica , Pneumonia , Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Macrófagos/patologia , Pneumonia/complicações , Receptores de Superfície CelularRESUMO
OBJECTIVES: To determine the clinical characteristics of methotrexate-associated lymphoproliferative disorder (MTX-LPD). METHODS: In this study, 12 RA patients who developed MTX-LPD were assessed. The peripheral blood lymphocyte (PBL) count at the onset of MTX-LPD was compared to that 6 months before the onset, in Epstein-Barr virus-encoded RNA (EBER)-positive and -negative subgroups. We examined the change in the PBL count after MTX withdrawal. In patients with relapsed LPD, changes in the PBL count before relapse were also examined. RESULTS: Regression of LPD after MTX withdrawal was noted in eight patients. In these patients, the PBL count was decreased at the onset of MTX-LPD compared to 6 months before the onset; the decrease was significantly more prominent in EBER-positive patients. In cases of spontaneous regression of LPD, the PBL count recovered quickly after MTX withdrawal. Four of eight patients showed a recurrence of LPD after they improved following MTX withdrawal. These patients also exhibited a decreased PBL count at recurrence compared to 6 months before recurrence. CONCLUSION: A decrease in the PBL count might be involved in the pathogenesis of MTX-LPD, especially in EBER-positive cases and in patients with LPD relapse after MTX withdrawal following initial improvement.
Assuntos
Artrite Reumatoide , Contagem de Linfócitos/métodos , Linfócitos , Transtornos Linfoproliferativos , Metotrexato , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Japão/epidemiologia , Linfócitos/imunologia , Linfócitos/patologia , Transtornos Linfoproliferativos/sangue , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/diagnóstico , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Avaliação de Resultados em Cuidados de Saúde , Recidiva , Suspensão de Tratamento/estatística & dados numéricosRESUMO
Sporadic cases of rheumatoid nodules (RNs) in the lung during treatment with tumour necrosis factor (TNF) inhibitors have been reported, but no treatment has been established. Here, we report a case of symptomatic lung RNs refractory to abatacept (ABT) and intravenous cyclophosphamide (IVCY) that improved with tofacitinib (TOF) treatment. A 75-year-old Japanese woman with a 10-year history of rheumatoid arthritis (RA) presented with a cough and haemoptysis during treatment with etanercept (ETN). Radiographic examinations revealed multiple nodules that were diagnosed as lung RNs via biopsy. The ETN was discontinued and ABT followed by IVCY was introduced; however, neither was sufficiently effective against the lung RNs. Thereafter, TOF was started and the lung RNs improved rapidly. The precise mechanisms that induce RNs during treatment with TNF inhibitors are unknown. Cytokines (IL-23 and IL-6) are suspected to be involved. TOF may be a reasonable strategy for treating symptomatic lung RNs.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Pneumopatias/patologia , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Nódulo Reumatoide/tratamento farmacológico , Idoso , Artrite Reumatoide/complicações , Etanercepte/uso terapêutico , Feminino , Humanos , Pneumopatias/etiologia , Nódulo Reumatoide/etiologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Inibidores do Fator de Necrose TumoralRESUMO
BACKGROUND: Relapses frequently occur in giant cell arteritis (GCA), and long-term glucocorticoid therapy is required. The identification of associated factors with poor treatment outcomes is important to decide the treatment algorithm of GCA. METHODS: We enrolled 139 newly diagnosed GCA patients treated with glucocorticoids between 2007 and 2014 in a retrospective, multi-center registry. Patients were diagnosed with temporal artery biopsy, 1990 American College of Rheumatology classification criteria, or large vessel lesions (LVLs) detected by imaging based on the modified classification criteria. Poor treatment outcomes (non-achievement of clinical remission by week 24 or relapse during 52 weeks) were evaluated. Clinical remission was defined as the absence of clinical signs and symptoms in cranial and large vessel areas, polymyalgia rheumatica (PMR), and elevation of C-reactive protein (CRP) levels. A patient was determined to have a relapse if he/she had either one of the signs and symptoms that newly appeared or worsened after achieving clinical remission. Re-elevation of CRP without clinical manifestations was considered as a relapse if other causes such as infection were excluded and the treatment was intensified. Associated factors with poor treatment outcomes were analyzed by using the Cox proportional hazard model. RESULTS: Cranial lesions, PMR, and LVLs were detected in 77.7%, 41.7%, and 52.5% of the enrolled patients, respectively. Treatment outcomes were evaluated in 119 newly diagnosed patients who were observed for 24 weeks or longer. The mean initial dose of prednisolone was 0.76 mg/kg/day, and 29.4% received any concomitant immunosuppressive drugs at baseline. Overall, 41 (34.5%) of the 119 patients had poor treatment outcomes; 13 did not achieve clinical remission by week 24, and 28 had a relapse after achieving clinical remission. Cumulative rates of the events of poor treatment outcomes in patients with and without LVLs were 47.5% and 17.7%, respectively. A multivariable model showed the presence of LVLs at baseline was significantly associated with poor treatment outcomes (adjusted hazard ratio [HR] 3.54, 95% CI 1.52-8.24, p = 0.003). Cranial lesions and PMR did not increase the risk of poor treatment outcomes. CONCLUSION: The initial treatment intensity in the treatment algorithm of GCA could be determined based upon the presence or absence of LVLs detected by imaging at baseline.
Assuntos
Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Feminino , Arterite de Células Gigantes/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde/métodos , Modelos de Riscos Proporcionais , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de RiscoRESUMO
We herein report two cases of eosinophilic granulomatosis with polyangiitis (EGPA) initially diagnosed as eosinophilic gastroenteritis (EGE) based solely on endoscopic biopsy results. One year after the EGE diagnosis, one patient presented with multiple purpura, and skin biopsy findings resulted in a change of the diagnosis to EGPA. In another patient, multiple skin and colonic ulcerations emerged eight years after the diagnosis of EGE, at which time histological examinations of endoscopic biopsy specimens revealed vasculitis, and the diagnosis was changed to EGPA. Physicians should be aware of the possible existence of EGPA in cases diagnosed as EGE.
Assuntos
Eosinofilia/diagnóstico , Eosinofilia/patologia , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/patologia , Adulto , Biópsia , Síndrome de Churg-Strauss/diagnóstico , Enterite/diagnóstico , Feminino , Gastrite/diagnóstico , Humanos , Pessoa de Meia-Idade , Pele/patologiaRESUMO
OBJECTIVE: The Japan Research Committee for Intractable Vasculitis has fully revised the clinical practice guidelines (CPG) for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) to improve and standardize the medical treatment of the disease in Japan. METHODS: The previous CPG was published in a classical review style in Japanese in 2011 and 2014. We adopted the Grading of Recommendations Assessment, Development and Evaluation system for this revision, and various stakeholders, including patients, participated in it. The expected users of this CPG are AAV patients in Japan and their families and healthcare professionals, including both AAV specialists and non-specialists. We set clinical questions concerning the three important clinical topics of remission induction therapy, plasma exchange, remission maintenance therapy, and developed eight recommendation statements. RESULTS: For remission induction therapy for newly developed AAV, we weakly recommend glucocorticoid (GC) plus intravenous cyclophosphamide pulse (IVCY) or oral cyclophosphamide (POCY) rather than GC alone, and IVCY rather than POCY. We also weakly recommend CY rather than rituximab. In the case of AAV with severe renal impairment, we weakly recommend plasma exchange as a conjunction therapy. We weakly recommend azathioprine for remission maintenance therapy. CONCLUSION: The revised CPG has demonstrated evidence-based treatment recommendations for AAV.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Azatioprina/administração & dosagem , Ciclofosfamida/administração & dosagem , Glucocorticoides/administração & dosagem , Troca Plasmática/métodos , Plasmaferese/métodos , Rituximab/administração & dosagem , Azatioprina/uso terapêutico , Vias de Administração de Medicamentos , Esquema de Medicação , Quimioterapia Combinada/métodos , Humanos , Imunossupressores/administração & dosagem , Japão , Quimioterapia de Manutenção/métodos , Indução de Remissão/métodosRESUMO
OBJECTIVE: An aberrant production of inflammatory cytokines, with resultant febrile response, is a cardinal finding of hemophagocytic syndrome. A role of inflammatory cytokines on phagocytosis and clearance of apoptotic cells or particles has been shown, but effects of cytokines or hyperthermia on phagocytosis of viable blood cells were not fully understood. We examined effects of cytokines and hyperthermia on phagocytosis, and externalization of phosphatidylserine on the surface of phagocytosed blood cells, to clarify the pathophysiology of hemophagocytic syndrome. METHODS: THP-1 macrophage cells were incubated with non-opsonized and opsonized sheep erythrocytes (SE) in the presence of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), macrophage-colony stimulating factor (M-CSF), interleukin (IL)-6, IL-10 or IL-18, and phagocytic activity was analyzed. Co-operative effect between cytokines was also examined. In addition, SE were incubated at 37 or 39°C, and phagocytic activity was analyzed. After treatment of SE with cytokine or hyperthermia, phosphatidylserine expression of the cell surface was analyzed by detecting Annexin V-positive cells. RESULTS: IL-6, IL-10 and IL-18 significantly increased phagocytosis of non-opsonized SE, but IFN-γ suppressed it. Phagocytosis of opsonized SE was significantly increased by any of the cytokines. IFN-γ suppressed and IL-10 enhanced phagocytic activity induced by other cytokines in non-opsonized SE, while in opsonized SE, both cytokines co-operated with other cytokines to enhance phagocytosis. Incubation of SE at a high temperature (39°C) resulted in increased phagocytic activity, as compared to SE incubated at 37°C. Cytokines and a high temperature did not increase the number of Annexin V-positive SE. CONCLUSIONS: IL-6, IL-10 and IL-18 can augment phagocytosis of viable blood cells, whether cells are opsonized or not. Hyperthermia also enhances phagocytosis. These in vitro data suggest that therapy for targeting cytokine (IL-6, IL-10 or IL-18) by using biologics or small molecule drugs may be beneficial for the treatment of hemophagocytic syndrome. Unlike the case of apoptotic cells, phagocytosis of viable blood cells seems to be mediated via phosphatidylserine-independent manner.
Assuntos
Citocinas/farmacologia , Eritrócitos/patologia , Hipertermia Induzida/efeitos adversos , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Fagocitose/fisiologia , Fosfatidilserinas/metabolismo , Animais , Células Cultivadas , Eritrócitos/efeitos dos fármacos , Humanos , Linfo-Histiocitose Hemofagocítica/etiologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Fagocitose/efeitos dos fármacos , OvinosRESUMO
Previously, female RA patients wishing to become pregnant were treated with only glucocorticoid, NSAIDs and sulfasalazine. However, these limited therapy sometimes fail to sustain RA remission, though pregnancy in most cases is associated with improving RA activity. High RA activity and relative high dose of glucocorticoid also involved poor fertility. Recently, a variety of medications are available to treat patients with RA. This article reviewed the safety or not safety of these medications during prior to conception, pregnancy and post-partum period. Accumulating experience with TNF blockade provide the useful insights for the treatment of RA patients during pre-conception, pregnancy or lactation.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Lactação/fisiologia , Complicações na Gravidez , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/etiologia , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Feminino , Fertilidade/efeitos dos fármacos , Fertilização/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Masculino , Terapia de Alvo Molecular , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Gravidez , Resultado da Gravidez , Fatores de Necrose TumoralRESUMO
INTRODUCTION: This study aims to elucidate the prognosis and the effectiveness of current treatments for Japanese patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: Patients with newly diagnosed MPA and GPA were enrolled in a nationwide, prospective, inception cohort study from 22 tertiary Japanese institutions, and treatment patterns and responses were evaluated for 24 months. Primary outcome measures were rates of remission (Birmingham Vasculitis Activity Score, 0) and remission with low-dose glucocorticoids (GC) (prednisolone ≤ 10 mg) (GC remission). RESULTS: Of 156 enrolled patients, 78 MPA patients and 33 GPA patients were included. Concomitant cyclophosphamide (CY) was used in 24 MPA (31 %) and 20 GPA (60 %) patients during the initial 3 weeks of treatment. After 6 months, remission was achieved in 66 MPA (85 %) and 29 GPA (87 %) patients, while GC remission was obtained in only 31 MPA (40 %) and 13 GPA (39 %) patients. During the 24-month period, 14 MPA patients and 2 GPA patients died; end stage renal disease (ESRD) was noted in 13 MPA patients but no GPA patients. Patients with severe disease, according to the European Vasculitis Study Group (EUVAS) classification, showed poorer ESRD-free and overall survival rates than those with generalized disease (p < 0.0001). There were no differences in relapse-free survival rates between GPA and MPA, among EUVAS-defined disease severity categories, and between anti-neutrophil cytoplasmic antibody subspecialties. CONCLUSIONS: The majority of Japanese patients with MPA and GPA received treatment with high-dose GC and limited CY use, and showed high remission and relapse-free survival rates but low GC remission rates in clinical practice. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000001648 . Registered 28 February 2009.
Assuntos
Granulomatose com Poliangiite/tratamento farmacológico , Poliangiite Microscópica/tratamento farmacológico , Prednisolona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Azatioprina/uso terapêutico , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Quimioterapia Combinada , Feminino , Glucocorticoides/uso terapêutico , Granulomatose com Poliangiite/classificação , Granulomatose com Poliangiite/patologia , Humanos , Imunossupressores/uso terapêutico , Japão , Falência Renal Crônica/diagnóstico , Masculino , Poliangiite Microscópica/classificação , Poliangiite Microscópica/patologia , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Indução de Remissão , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: To better define the clinical characteristics and treatment outcomes of autoimmune-associated hemophagocytic syndrome (AAHS) in adults. METHODS: Adults with AAHS (defined as pathologic evidence of hemophagocytosis without any obvious cause other than an autoimmune disease) were identified through a review of the literature. RESULTS: Among 116 patients identified, underlying diseases included systemic lupus erythematosus (SLE) in 52.3%, adult-onset Still's disease (AOSD) in 26.7%, and dermatomyositis in 6.9%. Fever, lymphadenopathy, hepatomegaly, and splenomegaly were found in 86.8%, 41.0%, 41.8%, and 45.5% of patients, respectively. Cytopenia, liver dysfunction, and hyperferritinemia developed frequently, and coagulopathy was seen in 50.6% of patients. Normal or low C-reactive protein levels were characteristic of patients with underlying SLE. The most commonly used therapy was corticosteroids, which were initially administered in 95.7% of patients, with 57.7% responding. Patients with corticosteroid-refractory disease were usually treated with cyclosporine, intravenous cyclophosphamide (IV CYC), or intravenous immunoglobulin (IVIG), with IV CYC being highly effective. Treatment with biologic agents resulted in favorable effects in the majority of patients. The mortality rate was 12.9%. Male sex (odds ratio [OR] 6.47, 95% confidence interval [95% CI] 2.06-30.39, P < 0.01), dermatomyositis (OR 5.57, 95% CI 1.08-28.65, P < 0.05), and anemia (hemoglobin <8 gm/dl; OR 3.74, 95% CI 1.02-13.8, P < 0.05) were identified as factors associated with mortality. CONCLUSION: AAHS is potentially fatal. Corticosteroids are a mainstay of initial treatment. For corticosteroid-refractory disease, IV CYC may be beneficial as compared with cyclosporine or IVIG. Treatment that proceeds directly from corticosteroids to biologic agents is promising.
Assuntos
Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/imunologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Takayasu's arteritis (TA) and Crohn's disease (CD) are chronic inflammatory diseases of uncertain etiology. Although co-existence of these rare diseases is estimated to occur in 1 in 10 billion individuals, a theoretically unexpected association has been reported in several patients and it is suggested that those associations may have been more than an unusual coincidence. Herein, we report a case of TA associated with clinically inactive CD. A Japanese woman was diagnosed with colonic CD at the age of 15, developed aortic valve regurgitation at 19, and then presented with general fatigue, low grade fever, and painful sensations in her left arm at 25. She was diagnosed with TA based on computed tomography scanning and magnetic resonance angiography findings, and treatments with prednisolone and cyclosporine were started. Thereafter, valve replacement and right coronary artery bypass graft surgery were performed. The possible pathophysiological mechanism responsible for concurrent existence of TA and CD may be associated with immune disorders. Early diagnosis of vascular lesions for patients with inflammatory bowel disease is highly encouraged.
Assuntos
Doença de Crohn/complicações , Arterite de Takayasu/complicações , Adolescente , Adulto , Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/cirurgia , Aspirina/administração & dosagem , Ponte de Artéria Coronária , Doença de Crohn/diagnóstico , Ciclosporina/administração & dosagem , Quimioterapia Combinada , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Angiografia por Ressonância Magnética , Prednisolona/administração & dosagem , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/tratamento farmacológico , Arterite de Takayasu/cirurgia , Tomografia Computadorizada por Raios X , Varfarina/administração & dosagem , Adulto JovemRESUMO
We investigated the expression of hepatocyte growth factor (HGF), which has mitogenic and anti-fibrotic activities, in muscle tissue of polymyositis/dermatomyositis (PM/DM) patients, as well as its functional roles in cultured myoblasts. Immunohistochemistry in muscle from PM/DM patients revealed that HGF was expressed predominantly on infiltrating mononuclear cells and that muscle cells expressed the receptor c-met. Cultured myoblasts produced HGF; which was increased by IL-1alpha but suppressed by TGF-beta and dexamethasone. Exogenous HGF induced myoblast proliferation and reduced procollagen type I production. Furthermore, HGF enhanced the gene expression of muscle regulatory factors MyoD and Myf5, while suppressing expression of fibrosis-related genes, connective tissue growth factor and alpha-smooth muscle actin. Although dexamethasone showed contrasting effects to HGF on the expression of these genes, co-treatment with HGF ameliorated the effects of dexamethasone. Taking the beneficial roles of HGF into consideration, administration of HGF might contribute to muscle regeneration in PM/DM especially under corticosteroid treatment.
Assuntos
Dermatomiosite/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Polimiosite/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Actinas/genética , Antígeno CD56/metabolismo , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/biossíntese , Fator de Crescimento do Tecido Conjuntivo/genética , Dexametasona/farmacologia , Expressão Gênica/efeitos dos fármacos , Fator de Crescimento de Hepatócito/farmacologia , Humanos , Imuno-Histoquímica , Proteína MyoD/genética , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/efeitos dos fármacos , Mioblastos Esqueléticos/metabolismo , Fator Regulador Miogênico 5/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/farmacologia , Regeneração/efeitos dos fármacos , Regeneração/genética , Regeneração/fisiologia , c-Mer Tirosina QuinaseRESUMO
Within the lesions of inflammatory myopathies, muscle fibres and invading mononuclear cells express Fas and Fas ligand (FasL), respectively. However, the roles of the Fas/FasL interaction in the pathogenesis of inflammatory myopathies are not fully understood. In the present study, we investigated the roles of proinflammatory cytokines and the Fas/FasL system in the pathogenesis of inflammatory myopathies. In vitro culturing of muscle cells with the proinflammatory cytokines interferon-gamma, tumour necrosis factor-alpha, and interleukin (IL)-1beta synergistically increased Fas expression, susceptibility to Fas-mediated apoptosis, and the expression of cytoplasmic caspases 8 and 3. In addition, culturing of muscle cells with activated CD4(+) T cells induced muscle cell apoptosis, which was partially inhibited by anti-FasL antibody. We also tested the possibility that T helper (Th) 17, which is an IL-17-producing helper T-cell subset that plays crucial roles in autoimmune and inflammatory responses, participates in the pathogenesis of inflammatory myopathies. Interestingly, in vitro culturing of dendritic cells with anti-Fas immunoglobulin M (IgM) or activated CD4(+) T cells induced the expression of mRNA for IL-23p19, but not for IL-12p35, in addition to proinflammatory cytokines. Furthermore, IL-23p19 and IL-17 mRNAs were detected in the majority of biopsy samples from patients with inflammatory myopathies. Taken together, these results suggest that proinflammatory cytokines enhance Fas-mediated apoptosis of muscle cells, and that the Fas/FasL interaction between invading dendritic cells and CD4(+) T cells induces local production of IL-23 and proinflammatory cytokines, which can promote the proliferation of Th17 cells and enhance Fas-mediated apoptosis of muscle cells, respectively.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Proteína Ligante Fas/imunologia , Células Musculares/imunologia , Miosite/imunologia , Receptor fas/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Caspase 3/efeitos dos fármacos , Caspase 3/imunologia , Caspase 8/efeitos dos fármacos , Caspase 8/metabolismo , Linhagem Celular , Células Cultivadas , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Proteína Ligante Fas/metabolismo , Humanos , Interferon gama/farmacologia , Subunidade p35 da Interleucina-12/metabolismo , Interleucina-17/metabolismo , Interleucina-1beta/farmacologia , Interleucina-23/imunologia , Interleucina-23/metabolismo , Subunidade p19 da Interleucina-23/metabolismo , Células Musculares/efeitos dos fármacos , Miosite/patologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia , Fator de Necrose Tumoral alfa/farmacologia , Receptor fas/agonistasRESUMO
BACKGROUND & AIMS: Aceruloplasminemia is a novel hereditary iron overload disease caused by a mutation in the ceruloplasmin gene and characterized by a complete deficiency of serum ceruloplasmin and iron accumulation in the liver and brain. METHODS: We herein studied a novel clinical type of aceruloplasminemia in which a low amount of ceruloplasmin was detected in the serum of a patient. The patient presented with an asymptomatic hepatic iron overload, retinal degeneration, and diabetes mellitus. Magnetic resonance imaging of the liver and basal ganglia showed T2-hypointensity signals associated with parenchymal iron accumulation because of an absence of the ferroxidase activity in ceruloplasmin. RESULTS: A gene analysis showed a novel G969S mutation in the ceruloplasmin gene. A biochemical analysis of the patients' serum and a biogenesis study of G969S mutant ceruloplasmin using mammalian cell culture system resulted in the synthesis and secretion of only apoceruloplasmin without any ferroxidase activity. CONCLUSIONS: This novel clinical type of aceruloplasminemia should therefore be considered in the differential diagnosis of unexplained hemochromatosis, which is associated with a decrease in the serum ceruloplasmin level.
Assuntos
Ceruloplasmina/deficiência , Sobrecarga de Ferro/metabolismo , Fígado/metabolismo , Idoso , Células Cultivadas , Ceruloplasmina/genética , DNA/genética , Feminino , Humanos , Sobrecarga de Ferro/diagnóstico , Fígado/patologia , Imageamento por Ressonância Magnética , Mutação de Sentido Incorreto , Reação em Cadeia da PolimeraseRESUMO
Hemophagocytic syndrome (HPS) is a clinicopathological condition characterized by the activation of histiocytes with prominent hemophagocytosis in bone marrow and other reticuloendothelial systems. The occurrence of HPS is usually associated with underlying disorders such as infection and lymphoma. Recently, we described patients with autoimmune disease who developed HPS. In these cases there was no evidence of underlying infection and malignancy, and the occurrences of HPS were associated with active autoimmune disease. Based on these observations, we described autoimmune-associated hemophagocytic syndrome (AAHS). This disease entity is becoming better known, and case reports presenting features compatible with clinical AAHS are increasing. Here, we review the clinical aspects, mechanisms, diagnosis, and treatment of AAHS according to our data and that in the literature.