RESUMO
OBJECTIVES: To determine prognostic factors for the Health Assessment Questionnaire-Disability Index (HAQ-DI) progression in patients with rheumatoid arthritis (RA) in clinical practice. METHODS: We evaluated 388 biological disease-modifying anti-rheumatic drug (bDMARD)-naïve Japanese patients with RA with moderate to high disease activity at study entry after being treated with conventional synthetic DMARDs. These patients were treated according to a treat-to-target (T2T) strategy for one year. The Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) and the HAQ-DI were assessed every three months. We also evaluated joint destruction using a modified total Sharp score at baseline and at one year. HAQ-DI progression was defined as the yearly progression of HAQ-DI >0.1. We performed a multiple logistic regression analysis to explore the factors predicting HAQ-DI progression at one year. RESULTS: HAQ-DI progression was observed in 18% of the patients. The multiple logistic regression analysis revealed the independent variables associated with HAQ-DI progression were: DAS28-ESR >5.1 at baseline (odds ratio [OR] 0.31, 95% con dence interval [CI] 0.13-0.74, p=0.0083); HAQ-DI score at baseline <0.5 (OR 2.27, 95% CI 1.22-4.26, p=0.0102); and achievement of low disease activity at 12 weeks (OR 0.42, 95% CI 0.21-0.82, p=0.0112). CONCLUSIONS: Our data suggest that maintaining clinical improvement according to T2T and initiating the treatment at an early stage are important for functional improvement after one year and that patients with low baseline HAQ scores have a higher risk of HAQ disability progression.
Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Avaliação da Deficiência , Progressão da Doença , Humanos , Japão/epidemiologia , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: We investigated clinical outcomes in patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. METHODS: This is a retrospective multicenter study conducted in Nagasaki, Japan. We consecutively diagnosed a total of 41 patients with RS3PE syndrome between October 2003 and September 2012 and evaluated their outcomes from medical records from the first year of follow-up. RESULTS: Although an excellent initial response to corticosteroids was noted in all 41 patients, 34 (82.9%) were still receiving corticosteroids and 13 (31.7%) showed elevated C-reactive protein (CRP) at one year. Multivariate analysis demonstrated that male gender and high CRP level at entry were independent variables associated with patients' one-year CRP level being ≥0.5 mg/dL. Odds ratios were 17.05 ([95% CI 2.41-370.12], p < 0.026) and 12.99 ([95% CI 1.78-269.62], p < 0.0096), respectively. Twenty-four patients (58.5%) were still receiving prednisolone (PSL) ≥ 5 mg/day at one year. Disease-modifying anti-rheumatic drugs including methotrexate were required in three patients (10.3%). Neoplasms were found in 14 patients (34.1%) and 1 of these had died due to lung cancer at one year. CONCLUSIONS: RS3PE syndrome initially responds well to corticosteroids with remission of symptoms. However, outcomes of RS3PE syndrome appear to be worse than expected, and may be influenced by gender and initial CRP level.
Assuntos
Antirreumáticos/uso terapêutico , Edema/tratamento farmacológico , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêutico , Sinovite/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Edema/sangue , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Síndrome , Sinovite/sangue , Resultado do TratamentoRESUMO
OBJECTIVE: Although glucocorticoids are effective for patients with IgG4-related disease, the treatment has not yet been standardized. Therefore, the treatment strategy should be established. PATIENTS AND METHODS: Patients who fulfilled the comprehensive diagnostic criteria for definite IgG4-related disease were started on prednisolone (0.6 mg/kg body weight) with the dose reduced every two weeks. The subsequent maintenance dose and need for prednisolone were determined for individual patients. The primary endpoint was the complete remission (CR) rate at one year. Secondary endpoints included overall response rate (ORR), the maintenance dose, the relapse rate, and adverse events. RESULTS: This study enrolled 61 patients. After clinicopathological review, three patients were excluded, and one, 13, and 44 patients were diagnosed with probable, possible, and definite IgG4-related disease, respectively. Of the 44 patients with definite IgG4-RD, 29 (65.9%) achieved CR, and the ORR was 93.2%. No patient was refractory to primary treatment. The most frequent adverse events were glucose intolerance. Six patients relapsed. CONCLUSIONS: Glucocorticoid treatment is usually effective for patients with IgG4-RD, and we should examine the possibility of other disorders when a patient is glucocorticoid refractory. Some patients are misdiagnosed, making central clinicopathological review of diagnosis very important in conducting clinical studies.
Assuntos
Hipergamaglobulinemia , Imunoglobulina G/imunologia , Prednisolona , Adulto , Idoso , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Hipergamaglobulinemia/sangue , Hipergamaglobulinemia/diagnóstico , Hipergamaglobulinemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Estudos Prospectivos , Indução de Remissão/métodos , Resultado do TratamentoRESUMO
Polymyositis (PM) is an inflammatory muscle disease characterized by chronic inflammation in skeletal muscle. Although most patients with PM respond to corticosteroids, some cases show an unsatisfactory response and other therapeutic options must be considered. Furthermore, glucocorticosteroid (GC) toxicity leads to a significant disability known as steroid myopathy, particularly in elderly patients. Here we report two patients with refractory PM. Combined treatment with high-dose GCs, tacrolimus, and intravenous immunoglobulin resulted in beneficial effects against myositis. However, muscle weakness and the disability progressed due to steroid myopathy, and subsequent oral intake became impossible because of swallowing disturbance in these two patients. Nutritional intervention, including branched-chain amino acids (BCAAs) and rehabilitation, was undertaken in addition to treatment against myositis. These treatments finally improved the muscle weakness and activities of daily living, and the two patients were discharged after recovery. The high-dose GC treatment caused elevation of serum levels of amino acids, including BCAAs, but these amino acids subsequently declined during BCAA replacement therapy. These findings suggest that the catabolic effects of the glucocorticoid treatment impair the balance of amino acids, including BCAAs, within the muscle, leading to steroid myopathy.
Assuntos
Glucocorticoides/efeitos adversos , Debilidade Muscular/induzido quimicamente , Polimiosite/tratamento farmacológico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Pessoa de Meia-Idade , Debilidade Muscular/tratamento farmacológico , Músculo Esquelético/efeitos dos fármacos , Tacrolimo/uso terapêutico , Resultado do TratamentoRESUMO
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that affects women of childbearing years. Pregnancy with SLE is associated with an increase risk of adverse maternal and fetal outcomes. Recently, tacrolimus has been used for steroid-resistant SLE. However, because of limited information regarding the use of immunosuppressants during pregnancy, many SLE patients give up pregnancy. We report two SLE patients receiving tacrolimus who hoped to become pregnant. Patient 1 was a 31-year-old woman diagnosed with SLE 6 years earlier and treated with tacrolimus for 3 years because her symptoms were not controlled with other immunosuppressants. Patient 2 was a 28-year-old woman diagnosed with SLE 13 years earlier and treated with tacrolimus for 3 years because her symptoms were not controlled with prednisolone alone. The medical ethics board in our hospital approved the use of tacrolimus during pregnancy and lactation, and informed consent was obtained from the patients. Both patients were well controlled during pregnancy with prednisolone (Patient 1: 12 mg/day and Patient 2: 10 mg/day) and tacrolimus therapy (3 mg/day). They had healthy newborns and continued breastfeeding with tacrolimus therapy. The blood concentrations of tacrolimus 12 hours after taking tacrolimus was 3.0 ng/ml in Patient 1 and 2.9 ng/ml in Patient 2, and their newborns' blood concentrations of tacrolimus 1 hour after breastfeeding were 0.2 ng/ml and 0.5 ng/ml, respectively. Both newborns are healthy for at least 3 years after birth. This is the first report on the safety of tacrolimus for pregnancy and lactation in patients with SLE.
Assuntos
Imunossupressores/uso terapêutico , Lactação/fisiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Tacrolimo/uso terapêutico , Adulto , Feminino , Humanos , Japão , Prednisolona/uso terapêutico , Gravidez , Resultado da Gravidez , Tacrolimo/sangue , Resultado do TratamentoRESUMO
We describe herein a patient who presented with immunoglobulin G4-related disease (IgG4-RD) involving the testis and prostate as well as the submandibular glands. Massive infiltration of IgG4-expressing plasma cells was observed in testis and prostate tissues. Serum concentrations of B cell activating factor belonging to the tumor necrosis factor family (BAFF) were elevated in parallel with serum IgG4 concentrations, and infiltration of BAFF-receptor (BAFF-R)-expressing B cells and BAFF-expressing lymphoid cells was observed around the ectopic lymphoid foci in the affected urogenital tissues. To date, testicular involvement in a patient diagnosed with IgG4-RD had not been reported, making this the first reported case of IgG4-related epididymo-orchitis. These findings suggest that the immune mechanism underlying ectopic lymphoneogenesis in IgG4-RD may involve enhanced BAFF/BAFF-R interactions among lymphoid cells.
Assuntos
Doenças Autoimunes/complicações , Imunoglobulina G/imunologia , Orquite/complicações , Neoplasias da Bexiga Urinária/complicações , Idoso , Doenças Autoimunes/imunologia , Receptor do Fator Ativador de Células B , Humanos , Masculino , Orquite/imunologia , Próstata/imunologia , Testículo/imunologia , Neoplasias da Bexiga Urinária/imunologiaRESUMO
Familial Mediterranean fever (FMF) is an autoinflammatory disorder characterized by recurrent febrile polyserositis and arthritis. Although accompanying seronegative spondyloarthropathy has been reported in FMF, coexistence with rheumatoid arthritis (RA) is very rare. This case report describes a Japanese female RA patient who presented with periodic fever. Genetic analysis revealed compound heterozygous mutations in exon 2 and 3 of the MEFV gene (E148Q/G304R/P369S/R408Q). The patient was successfully treated with colchicine with 3-year follow-up.
Assuntos
Artrite Reumatoide/complicações , Febre Familiar do Mediterrâneo/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Colchicina/uso terapêutico , Proteínas do Citoesqueleto/genética , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Pirina , Resultado do TratamentoRESUMO
We report a case of a 60-year-old female with cutaneous polyarteritis nodosa (CPN) of the left ankle, accompanied by elevated serum interleukin (IL)-6 levels. Computed tomographic angiography revealed severe narrowing of medium-sized arteries in her left leg. Destructive arthropathy in the left ankle was identified by X-ray and magnetic resonance imaging. This is the first Japanese case of severe CPN complicated by destructive arthropathy. Quantification of serum IL-6 might be useful in diagnosis and evaluation of CPN.
Assuntos
Articulação do Tornozelo/diagnóstico por imagem , Tornozelo/diagnóstico por imagem , Arteriosclerose/complicações , Interleucina-6/sangue , Poliarterite Nodosa/complicações , Pele/patologia , Tornozelo/patologia , Articulação do Tornozelo/patologia , Arteriosclerose/sangue , Arteriosclerose/diagnóstico por imagem , Arteriosclerose/patologia , Constrição Patológica/sangue , Constrição Patológica/complicações , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/patologia , Feminino , Humanos , Perna (Membro)/diagnóstico por imagem , Perna (Membro)/patologia , Pessoa de Meia-Idade , Poliarterite Nodosa/sangue , Poliarterite Nodosa/diagnóstico por imagem , Poliarterite Nodosa/patologia , RadiografiaRESUMO
OBJECTIVES: IgG4-related Mikulicz's disease (IgG4-MD) has been recently established as a subtype of IgG4-related diseases involving the salivary and lacrimal glands, and the diseased glands are characteristically and highly responsive to corticosteroid therapy. We retrospectively evaluated ultrasonography (US) of the salivary and lacrimal glands for monitoring the efficacy of corticosteroid treatment in patients with IgG4-MD. METHODS: US features of the salivary and lacrimal glands were assessed and compared with the serum IgG4 levels in 8 patients with IgG4-MD before and at various stages after initiation of oral corticosteroids. RESULTS: US features of the lacrimal and salivary glands of patients with IgG4-MD were characterised by multiple hypoechoic areas in enlarged glands. The submandibular glands were most frequently involved by the disease, and bilateral glands of the same type were similarly affected exhibiting the same hypoechoic pattern. Alleviations of abnormal gland architecture and size in response to corticosteroid therapy were effectively detected with US. The US findings of the involved glands were proportional to the serum IgG4 level before and during the corticosteroid therapy. CONCLUSIONS: US helps monitor the efficacy of corticosteroid treatment in patients with IgG4-MD.
Assuntos
Corticosteroides/uso terapêutico , Monitoramento de Medicamentos/métodos , Imunoglobulina G/sangue , Aparelho Lacrimal/efeitos dos fármacos , Aparelho Lacrimal/diagnóstico por imagem , Doença de Mikulicz/diagnóstico por imagem , Doença de Mikulicz/tratamento farmacológico , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/diagnóstico por imagem , Administração Oral , Corticosteroides/administração & dosagem , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença de Mikulicz/sangue , Doença de Mikulicz/imunologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , UltrassonografiaRESUMO
A case of apoplectic lymphocytic hypophysitis complicated by polymyalgia rheumatica (PMA) is described. A 72-year-old man was admitted to our hospital due to severe headache. Two months prior to admission, the patients had exhibited recent-onset stiffness and myalgia of shoulder and pelvic girdle that was compatible with PMR. Magnetic resonance imaging revealed a mass lesion in the pituitary fossa with focal hemorrhage. Endocrinologic studies demonstrated hypopituitarism. The headache and myalgia were improving with corticosteroid treatment; however, a trans-sphenoidal surgery was performed due to visual field loss. A white-colored mass was resected, and histologic examination showed diffuse infiltration of lymphocytes and plasma cells consistent with lymphocytic hypophysitis. Post-operatively, the headache and visual field loss resolved completely. This is the first documented case of apoplectic lymphocytic hypophysitis complicating PMR, and a possible mechanism for this rare association was discussed.
Assuntos
Hipopituitarismo/complicações , Linfócitos/patologia , Apoplexia Hipofisária/complicações , Polimialgia Reumática/complicações , Idoso , Glucocorticoides/uso terapêutico , Humanos , Hipofisectomia , Hipopituitarismo/diagnóstico , Hipopituitarismo/terapia , Inflamação/complicações , Inflamação/patologia , Inflamação/terapia , Imageamento por Ressonância Magnética , Masculino , Apoplexia Hipofisária/patologia , Apoplexia Hipofisária/terapia , Hipófise/patologia , Hipófise/cirurgia , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/terapia , Resultado do TratamentoRESUMO
Patients with rheumatoid arthritis (RA), especially those treated with methotrexate (MTX), might have an increased risk of lymphoproliferative disorders that are associated with Epstein-Barr virus (EBV). We describe a case of EBV-associated central nervous system (CNS) lymphoma (diffuse large B-cell lymphoma) in a patient with RA on a short course of MTX treatment. The neoplastic cells express the B-cell surface markers (CD20, Pax-5 and CD30), and EBV-encoded RNA was demonstrated by in situ hybridization. The patient's lymphoma did not recur for the 8-year follow-up period after the tumor resection and cessation of MTX. MTX may promote EBV-positive CNS lymphoma in RA patient due to its immunosuppressive properties as well as reactivating latent EBV infection.
Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/complicações , Neoplasias Encefálicas/induzido quimicamente , Infecções por Vírus Epstein-Barr/complicações , Linfoma Difuso de Grandes Células B/induzido quimicamente , Metotrexato/efeitos adversos , Abatacepte , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/virologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/virologia , Feminino , Humanos , Imunoconjugados/uso terapêutico , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/virologia , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Retratamento , Resultado do TratamentoRESUMO
OBJECTIVE: Pentraxin 3 (PTX3) is an acute-phase reactant that is involved in amplification of the inflammatory response and innate immunity. In the present study, we evaluated the relationship between PTX3 and serum amyloid A (SAA), another acute-phase reactant, in rheumatoid synoviocytes. METHODS: PTX3 mRNA expression was examined by reverse transcription polymerase chain reaction, and PTX3 protein was measured by enzyme-linked immunosorbent assay. RESULTS: SAA induced PTX3 mRNA and PTX3 protein expression in rheumatoid synoviocytes. SAA-induced PTX3 expression was attenuated when rheumatoid synoviocytes were nucleofected with N-formyl peptide receptor ligand-1 (FPRL-1)-specific siRNA, suggesting the involvement of FPRL-1. Furthermore, SAA-induced PTX3 expression was inhibited by NF-κB or mitogen-activated protein kinase-specific inhibitors. Neither soluble TNF receptor (etanercept) nor recombinant IL-1 receptor antagonist affected PTX3 production by SAA-stimulated synoviocytes, suggesting that SAA directly induces PTX3. CONCLUSION: Our data suggest that SAA plays a role in the proinflammatory and immune responses in rheumatoid synovium by inducing PTX3. We provide the first evidence that the acute-phase reactant SAA, which is produced systemically by hepatocytes, perpetuates the rheumatoid inflammatory processes by inducing another proinflammatory molecule, PTX3, locally in rheumatoid synovial tissues.
Assuntos
Artrite Reumatoide/metabolismo , Proteína C-Reativa/metabolismo , Osteoartrite/metabolismo , Proteína Amiloide A Sérica/farmacologia , Componente Amiloide P Sérico/metabolismo , Membrana Sinovial/efeitos dos fármacos , Artrite Reumatoide/patologia , Proteína C-Reativa/antagonistas & inibidores , Proteína C-Reativa/genética , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Osteoartrite/patologia , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologia , Receptores de Formil Peptídeo/genética , Receptores de Formil Peptídeo/metabolismo , Receptores de Lipoxinas/genética , Receptores de Lipoxinas/metabolismo , Proteínas Recombinantes , Componente Amiloide P Sérico/antagonistas & inibidores , Componente Amiloide P Sérico/genética , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , TransfecçãoRESUMO
Familial Mediterranean fever (FMF) is an autosomal recessive disease affecting populations surrounding the Mediterranean area. In this case report, we report a Japanese female patient with polymyositis (PM) who presented with periodic fever. Genetic analysis revealed that she had compound heterozygous mutations in exon 2 of the MEFV gene (L110P/E148Q/R202Q). Treatment with colchicines (1.0 mg/day) successfully eliminated febrile attack and normalized the elevated levels of neutrophil CD64 expression, leading to the diagnosis of FMF. The association of FMF and PM has not previously been reported, so we discuss this rare association.
Assuntos
Febre Familiar do Mediterrâneo/complicações , Polimiosite/complicações , Adulto , Colchicina/uso terapêutico , Proteínas do Citoesqueleto/genética , Análise Mutacional de DNA , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/genética , Feminino , Heterozigoto , Humanos , Mutação , Polimiosite/tratamento farmacológico , Polimiosite/genética , Pirina , Resultado do TratamentoRESUMO
This is the first report on the efficacy of leukocytapheresis (LCAP) in a patient with refractory systemic-type adult-onset Still's disease (AOSD). A 17-year-old Japanese woman with AOSD who had been treated with prednisolone and cyclosporine A presented with relapse of typical systemic AOSD, including high fever, rash, and liver dysfunction. Steroid pulse therapy (methylprednisolone 500 mg/day) was performed, which failed to stabilize the disease. Therefore, LCAP (twice/week for a total of five courses) was introduced in combination with high-dose steroids plus cyclosporin A. Elevated levels of serum ferritin and transaminases and neutrophil CD64 expression normalized after the patient's disease was successfully controlled by the induction of LCAP. In this case, elevated levels of interleukin (IL)-1ß and IL-18 were normalized after LCAP induction, suggesting that LCAP treatment modulates the deregulated cytokine-mediated inflammatory responses observed in AOSD. Our clinical observations suggest that LCAP may be beneficial for flare-up of systemic manifestations of AOSD refractory to conventional treatment, including high-dose steroids and immunosuppressants.
Assuntos
Leucaférese , Doença de Still de Início Tardio/terapia , Adolescente , Antirreumáticos/uso terapêutico , Ciclosporina/uso terapêutico , Feminino , Ferritinas/sangue , Humanos , Neutrófilos/metabolismo , Prednisolona/uso terapêutico , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/tratamento farmacológico , Transaminases/sangue , Resultado do TratamentoRESUMO
Recently, it was reported that remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome could be complicated with solid tumors. In a retrospective, multicenter study between October, 2003 and September, 2010, we investigated the characteristics of patients with paraneoplastic RS3PE syndrome who fulfilled following criteria: (1) bilateral pitting edema of hands or feet or both, (2) sudden onset of polyarthritis, and (3) age >50 years, (4) seronegativity for rheumatoid factor (RF). A total of 33 cases fulfilled the above criteria. Eight patients (seven men and one woman) developed cancer within 2 years of RS3PE syndrome onset. There was no significant difference between the neoplastic and nonneoplastic groups in the proportions of patients with fever, symmetrical polyarthritis, pitting edema, and good response to corticosteroids. Serum matrix metalloproteinase 3 (MMP-3) level (median 437.3 ng/ml) in the paraneoplastic RS3PE patients was significantly higher than that in patients without neoplasia (median 114.7 ng/ml) (p < 0.05). We found that high serum MMP-3 is characteristic of patients with paraneoplastic RS3PE syndrome.
Assuntos
Edema/sangue , Metaloproteinase 3 da Matriz/sangue , Síndromes Paraneoplásicas/sangue , Sinovite/sangue , Idoso , Idoso de 80 Anos ou mais , Artrite/sangue , Artrite/complicações , Artrite/diagnóstico , Biomarcadores/sangue , Edema/complicações , Edema/diagnóstico , Extremidades , Feminino , Humanos , Masculino , Síndromes Paraneoplásicas/complicações , Síndromes Paraneoplásicas/diagnóstico , Estudos Retrospectivos , Fator Reumatoide/sangue , Testes Sorológicos , Sinovite/complicações , Sinovite/diagnósticoRESUMO
Remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE), a rheumatic disease affecting the elderly, responds well to corticosteroids; however, our RS3PE patients' corticosteroid therapy is longer than expected. Elderly-onset rheumatoid arthritis (EORA) patients are reported to be at a significantly increased risk for steroid-related side effects including cardiovascular diseases (CVDs). To clarify the complications during a 1-year follow-up in corticosteroid-treated RS3PE patients compared to EORA patients. We retrospectively analyzed the records of 47 RS3PE patients (28 men, 19 women, age 78.4 ± 7.5 years) and 46 EORA patients (10 men, 36 women; 77.0 ± 6.8 yrs) to compare the complications over a 1-year follow-up. The RS3PE and EORA groups' average initial PSL doses were 16.5 ± 7.2 mg/day and 7.3 ± 4.6 mg/day, respectively. During the 1-year follow-up after treatment, there was no significant increase in CVDs in both groups. However, infections occurred in nine RS3PE patients, which is a significantly higher incidence compared to the EORA patients with infections (n = 3). The initial PSL dose was the independent variable associated with the incidence of infection. Infections were significantly increased during elderly RS3PE patients' steroid therapy. The initial corticosteroid dose was an infection-risk factor.Key messagesInfections are increased during steroid therapy in elderly patients with RS3PE syndrome.The initial dose of corticosteroids was one of the risk factors for infections.
Assuntos
Artrite Reumatoide , Sinovite , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Edema/tratamento farmacológico , Edema/etiologia , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Síndrome , Sinovite/tratamento farmacológicoRESUMO
BACKGROUND: The new JAK3 inhibitor, CP690,550, has shown efficacy in the treatment of rheumatoid arthritis. The present study was undertaken to assess the effects of CP690,550 on cytokine production and cellular signaling in human CD4(+) T cells. RESULTS: CD4(+) T cells produced IL-2, IL-4, IL-17, IL-22 and IFN-γ in following stimulation with a CD3 antibody. At the optimal concentration, CP690,550 almost completely inhibited the production of IL-4, IL-17, IL-22 and IFN-γ from these activated CD4(+) T cells, but only had marginal effects on IL-2 production. Moreover CP690,550 inhibited anti-CD3-induced phosphorylation of STAT1, STAT3, STAT4, STAT5, and STAT6, but not the TCR-associated phosphorylation of ZAP-70. CONCLUSIONS: Therefore, CP690,550-mediated modification of the JAK/STAT pathway may be a new immunosuppressive strategy in the treatment of autoimmune diseases.
Assuntos
Artrite Reumatoide/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Janus Quinase 3/antagonistas & inibidores , Pirimidinas/farmacologia , Pirróis/farmacologia , Fatores de Transcrição STAT/metabolismo , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/metabolismo , Artrite Reumatoide/tratamento farmacológico , Complexo CD3/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Células Cultivadas , Citocinas/metabolismo , Humanos , Terapia de Imunossupressão , Ativação Linfocitária/efeitos dos fármacos , Fosforilação , Piperidinas , Receptores de Antígenos de Linfócitos T/metabolismo , Fatores de Transcrição STAT/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologiaRESUMO
IgG4-related sclerosing disease (IgG4-RSD) is an inflammatory and fibrosing disorder characterized by lymphoplasmacytic inflammation with infiltration of various organs, including the pancreas, bile ducts, lung, kidney, and retroperitoneum. As for malignancy in IgG4-RSD, only limited literature is available. We report here a case of thyroid papillary carcinoma showing unique morphology in IgG4-RSD. Solid tumor nests were surrounded by dense IgG4-positive plasma cells and fibrosis at both the primary site and metastatic lymph nodes. In contrast the background thyroid showed focal lymphocytic thyroiditis. IgG4-related sclerosing sialadenitis and autoimmune pancreatitis were also diagnosed, and prednisolone treatment improved symptoms and serum IgG4 abnormality. To the best of our knowledge, this is the first documentation of a malignancy of the thyroid gland occurring in a background of IgG4-RSD. A brief review of the literature on the relationship between IgG4 and malignancy is included.
Assuntos
Doenças Autoimunes/patologia , Carcinoma Papilar/secundário , Imunoglobulina G/sangue , Linfonodos/patologia , Neoplasias da Glândula Tireoide/patologia , Idoso , Doenças Autoimunes/complicações , Carcinoma Papilar/imunologia , Fibrose/patologia , Humanos , Linfonodos/imunologia , Masculino , Plasmócitos/patologia , Esclerose , Neoplasias da Glândula Tireoide/imunologiaRESUMO
Pancreatitis is a relatively rare complication in systemic lupus erythematosus (SLE). Herein we report a case of SLE with the initial development of acute pancreatitis, subsequently complicated by bleeding pseudoaneurysms. A 55-year-old Japanese woman was admitted to our hospital for the treatment of SLE. During the course of treatment, she complained of upper abdominal pain. An abdominal computed tomography (CT) scan showed that the pancreas was diffusely enlarged, and she was diagnosed with acute pancreatitis. Her pancreatitis was resistant to glucocorticoid therapy and was subsequently associated with pancreatic pseudocysts and recurrent rupture of the pseudoaneurysms. After surgical drainage of the hemorrhagic pseudocysts, the patient's clinical condition gradually improved with intensive therapies. Our case indicates that lupus pancreatitis can be associated with the potentially fatal complication of recurrent bleeding of pseudoaneurysms.
Assuntos
Falso Aneurisma/etiologia , Aneurisma Roto/etiologia , Lúpus Eritematoso Sistêmico/complicações , Pancreatite/etiologia , Artéria Esplênica , Falso Aneurisma/diagnóstico , Falso Aneurisma/terapia , Aneurisma Roto/diagnóstico , Aneurisma Roto/terapia , Angiografia , Antibacterianos/uso terapêutico , Embolização Terapêutica , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Pancreatite/tratamento farmacológico , Prednisolona/administração & dosagem , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) achieving remission or low disease activity (LDA) in clinical practice. METHODS: Using data from a nationwide, multicenter, prospective study in Japan, we evaluated 198 biological disease-modifying antirheumatic drug (bDMARD)-naïve RA patients who were in remission or had LDA at study entry after being treated with conventional synthetic DMARDs (csDMARDs). CRRP was defined as the yearly progression of modified total Sharp score (mTSS) >3.0 U. We performed a multiple logistic regression analysis to explore the factors to predict CRRP at 1 year. We used receiver operating characteristic (ROC) curve to estimate the performance of relevant variables for predicting CRRP. RESULTS: The mean Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) was 2.32 ± 0.58 at study entry. During the 1-year observation, remission or LDA persisted in 72% of the patients. CRRP was observed in 7.6% of the patients. The multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: anti-citrullinated peptide antibodies (ACPA) positivity at baseline (OR = 15.2, 95%CI 2.64-299), time-integrated DAS28-ESR during the 1 year post-baseline (7.85-unit increase, OR = 1.83, 95%CI 1.03-3.45), and the mTSS at baseline (13-unit increase, OR = 1.22, 95%CI 1.06-1.42). CONCLUSIONS: ACPA positivity was the strongest independent predictor of CRRP in patients with RA in remission or LDA. Physicians should recognize ACPA as a poor-prognosis factor regarding the radiographic outcome of RA, even among patients showing a clinically favorable response to DMARDs.