RESUMO
OBJECTIVES: We aimed to assess the clinical features of human T-cell leukaemia virus type 1 (HTLV-1)-positive rheumatoid arthritis (RA) patients. Furthermore, we investigated the impact of HTLV-1 infection on incidences of serious infections requiring hospitalisation (SIH) and malignancies. METHODS: A total of 150 sex- and age-matched HTLV-1-negative and 50 HTLV-1-positive RA patients were enrolled from the HTLV-1 RA Miyazaki Cohort Study. Clinical and laboratory data were collected from this cohort database. The incidence rate (IR) for SIH and malignancies from 2015 to 2020 was analysed. RESULTS: The median age and female ratio in the study population were 70 years old and 80%, respectively. Although no differences were found in inflammatory marker values between the two groups, the patient global assessment and Health Assessment Questionnaire scores were higher in HTLV-1-positive RA patients. In HTLV-1-negative RA patients, the IR for SIH was 6.37/100 person-years (PY) and 1.32/100 PY for malignancies. In HTLV-1-positive RA patients, SIH occurred in 11.1/100 PY and malignancies in 2.46/100 PY. The crude IR ratio comparing SIH between two groups was 1.74 (95% confidence interval, 1.04-2.84), which was a significant increase. CONCLUSIONS: HTLV-1-positive RA patients may worsen RA symptoms. HTLV-1 may be a risk factor for SIH.
Assuntos
Artrite Reumatoide , Vírus Linfotrópico T Tipo 1 Humano , Leucemia de Células T , Idoso , Artrite Reumatoide/epidemiologia , Estudos de Coortes , Feminino , Hospitalização , Humanos , IncidênciaRESUMO
BACKGROUND: Aripiprazole is regarded as the first-line antipsychotic medication. Long-term aripiprazole therapy can cause hypoprolactinemia, which may result from its activity as a dopamine agonist. However, there is little information on hypoprolactinemia and steady-state aripiprazole concentrations. METHODS: The subjects included 66 male and 177 female patients diagnosed with schizophrenia who were treated with aripiprazole. The plasma concentrations of aripiprazole and dehydroaripiprazole and the plasma concentration of prolactin were measured using high-performance liquid chromatography and enzyme immunoassay, respectively. A prolactin concentration of <5 ng/mL was defined as hypoprolactinemia. RESULTS: Fifty-two of the 66 male patients (79%) and 58 of the 177 female patients (33%) had hypoprolactinemia. There were significant inverse correlations between plasma prolactin levels and plasma concentrations of aripiprazole (rs = -0.447, P < 0.001) and the active moiety (aripiprazole plus dehydroaripiprazole) (rs = -0.429, P < 0.001) in men. In women, significant inverse correlations were also found between plasma prolactin levels and plasma concentrations of aripiprazole (rs = -0.273, P < 0.01) and the active moiety (rs = -0.275, P < 0.01). CONCLUSIONS: These findings suggest that lower prolactin levels are, to some extent, associated with higher plasma drug concentrations in male and female patients with schizophrenia treated with aripiprazole.
Assuntos
Antipsicóticos , Aripiprazol/farmacocinética , Prolactina/sangue , Esquizofrenia , Antipsicóticos/sangue , Antipsicóticos/farmacocinética , Aripiprazol/sangue , Feminino , Humanos , Masculino , Esquizofrenia/tratamento farmacológicoRESUMO
BACKGROUND: CD4-positive T cells are the main target of human T-cell leukemia virus type 1 (HTLV-1). Interferon-γ release assays rely on the fact that T-lymphocytes release this cytokine when exposed to tuberculosis-specific antigens and are useful in testing for latent tuberculosis infection before initiating biologic therapy, such as anti-tumor necrosis factor agents. However, the reliability of interferon-γ release assays in detecting tuberculosis infection among HTLV-1-positive patients with rheumatoid arthritis (RA) remains unclear. The present study aimed to evaluate the use of the T-SPOT.TB assay in HTLV-1-positive RA patients. METHODS: Overall, 29 HTLV-1-positive RA patients and 87 age- and sex-matched HTLV-1-negative RA patients (controls) were included from the HTLV-1 RA Miyazaki Cohort Study. Results of the T-SPOT.TB assay for latent tuberculosis infection screening were collected from medical records of patients. RESULTS: Approximately 55% of the HTLV-1-positive RA patients showed invalid T-SPOT.TB assay results (odds ratio: 108, 95% confidence interval: 13.1-890, p < 0.0001) owing to a spot count of >10 in the negative controls. HTLV-1 proviral load values were significantly higher in patients with invalid results compared with those without invalid results (p = 0.003). CONCLUSION: HTLV-1 infection affects T-SPOT.TB assay results in RA patients. Assay results in HTLV-1 endemic regions should be interpreted with caution when screening for latent tuberculosis infection before initiation of biologic therapy.
Assuntos
Artrite Reumatoide/imunologia , Linfócitos T CD4-Positivos/imunologia , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Testes de Liberação de Interferon-gama , Tuberculose/imunologia , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/microbiologia , Artrite Reumatoide/patologia , Artrite Reumatoide/virologia , Linfócitos T CD4-Positivos/patologia , Feminino , Infecções por HTLV-I/microbiologia , Infecções por HTLV-I/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Tuberculose/microbiologia , Tuberculose/patologia , Tuberculose/virologiaRESUMO
Objective: This study aimed to investigate the time-sequential changes of risk factors for adult T-cell leukemia (ATL) development in human T-cell leukemia virus type 1 (HTLV-1)-positive rheumatoid arthritis (RA) patients. Methods: HTLV-1 infection was screened using particle agglutination assay and confirmed via western blotting in 365 RA patients. Twenty-three HTLV-1-positive RA patients were included in the study cohort. Blood samples were obtained from these patients at each observation time point. The values of HTLV-1 proviral load (PVL) and serum soluble IL-2 receptor (sIL2-R), which are risk factors for ATL development, were measured using real-time PCR and enzyme immunoassay, respectively. Results: The study cohort comprised 79 person-years. The median HTLV-1 PVL and sIL2-R values of the HTLV-1-positive RA patients were 0.44 copies per 100 white blood cells (WBCs) and 406 U/mL, respectively. Three HTLV-1-positive RA patients showed a high PVL value. No remarkable changes were observed in the PVL and sIL2-R values during the observation period. However, one elderly HTLV-1-positive RA patient who had a high PVL value developed ATL during treatment with methotrexate and infliximab. Conclusion: A thorough clinical assessment of the risk factors for ATL development may be necessary in daily clinical practice for RA patients in HTLV-1-endemic areas in Japan.
Assuntos
Artrite Reumatoide/epidemiologia , Infecções por HTLV-I/epidemiologia , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Adulto , Idoso , Artrite Reumatoide/complicações , Feminino , Infecções por HTLV-I/complicações , Humanos , Japão , Masculino , Pessoa de Meia-IdadeRESUMO
In this article, we discussed leukocytapheresis (LCAP) for rheumatoid arthritis (RA). Recently, a simple and practical on-line continuous LACP system has been developed. It is equipped with a direct hemoperfusion column (Cellsorba®, Asahikasei Medical Co., Ltd.) packed with fine-diameter polyester fibers, which are commonly used to adsorb white blood cells to prevent a graft-versus-host reaction during blood transfusion. Clinical trials revealed that LCAP is a effective and safe therapy for patients with drug-resistant RA or RA complicated with vasculitis. Because the procedure is simple and requires no plasma substitutes and the volume needed for extracorporeal circulation is less than that for other plasmapheresis, LCAP might be accepted as an optional therapeutic modality for active RA that was refractory to conventional drug therapy including biological agents. The mechanism of the efficiency of LCAP on RA is unclear. LCAP may cause a reduction of activated T cells from affected joints, down-regulation of Pgp on helper T cells and restoration of Treg function, and that may modify the abnormal cytokine balance. These findings may explain some of the mechanisms by which the articular symptoms are improved by LCAP.
Assuntos
Artrite Reumatoide/terapia , Leucaférese/métodos , Artrite Reumatoide/sangue , HumanosRESUMO
BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) has been recognized as a cause of adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis, and HTLV-1-associated uveitis. HTLV-1 infection is normally detected by screening for HTLV-1 antibodies, and positive samples are confirmed by Western blot (WB). However, WB fails to confirm some samples that were positive for HTLV-1 antibodies on screening. Line immunoassay (LIA) is commonly used in Europe and Brazil, but not in Japan. Therefore, we evaluated the performance of LIA as a method of confirming HTLV-1 antibodies using samples in Japan. METHODS: LIA was compared with polymerase chain reaction (PCR) and WB using 50 negative and 70 positive samples tested by chemiluminescent enzyme immunoassay (CLEIA) in Miyazaki, Japan, an HTLV-1 endemic area. LIA (INNO-LIA HTLVI/II Score) and WB (Problot HTLV-I) were performed according to the manufacturer's instructions. Real-time PCR for HTLV-1 pX region was performed using DNA derived from white blood cells. The samples that tested negative by real-time PCR were further tested by nested PCR. RESULTS: All 50 CLEIA negative samples were determined to be negative by LIA and PCR. Of the 70 positive samples, 66 tested positive by both of LIA and PCR. Three samples tested negative by LIA and PCR, and the remaining sample (PCR negative) showed non-specific staining in LIA and WB. WB showed more indeterminate results than LIA. Gp21 antibody in LIA demonstrated a high ability to discriminate between positive and negative PCR results. Furthermore, the degree of gp21 antibody reaction by LIA showed correlation with HTLV-1 proviral loads (PVLs). CONCLUSIONS: Our results indicate that LIA performs well in confirming HTLV-1 seropositivity by showing a low incidence of indeterminate results and good agreement with PCR using samples in Japan, although the number of samples tested was small. In addition, semi-quantitative antibody titer to gp21 correlated well with HTLV-1 PVLs. Further study including larger samples is necessary to determine the positioning of LIA for HTLV-1 detection in Japan.
Assuntos
Anticorpos Antivirais/sangue , Western Blotting , Doenças Endêmicas , Infecções por HTLV-I/diagnóstico , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Técnicas Imunoenzimáticas , Reação em Cadeia da Polimerase em Tempo Real , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Biomarcadores/sangue , DNA Viral/sangue , DNA Viral/genética , Infecções por HTLV-I/sangue , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Japão/epidemiologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Testes Sorológicos , Carga ViralRESUMO
A 60-year-old woman experienced fever, headache, rash, and altered vision after returning to Japan from India. Testing detected elevated antibody titers to spotted fever group rickettsia; PCR on blood yielded positive results for the rickettsial outer membrane protein A gene. We isolated a unique rickettsial agent and performed a full-genome analysis.
Assuntos
Doenças Transmissíveis Importadas/diagnóstico , Doenças Transmissíveis Importadas/microbiologia , Rickettsia/genética , Rickettsiose do Grupo da Febre Maculosa/diagnóstico , Rickettsiose do Grupo da Febre Maculosa/microbiologia , Doença Relacionada a Viagens , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Biomarcadores , Biópsia , Doenças Transmissíveis Importadas/transmissão , Exantema/etiologia , Exantema/patologia , Feminino , Genes Bacterianos , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Índia , Japão , Pessoa de Meia-Idade , Filogenia , Rickettsia/imunologia , Rickettsiose do Grupo da Febre Maculosa/transmissãoRESUMO
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China, Korea and Japan caused by a novel bunyavirus, SFTS virus (SFTSV). Although central nervous system manifestations are common in SFTS patients, the pathogenesis has not been elucidated; and there are few reports of myocardial dysfunction. Here we report an elderly Japanese patient with reversible myocardial dysfunction and encephalopathy. A previously healthy 65-year-old male engaged in forestry got a tick bite and developed fever and fatigue in 3 days. Three days after onset, he presented to a local hospital where the diagnosis of SFTS with hemophagocytotic syndrome was made. The blood test showed leukopenia and thrombocytopenia as well as elevated levels of alanine aminotransferase and aspartate aminotransferase. Marked hemophagocytosis was found on bone marrow smear. Peripheral blood was positive for SFTSV gene by reverse-transcription polymerase chain reaction. On day 7, the patient was transferred to our hospital. We observed disturbance of consciousness, Kernig sign and myoclonus to face and limbs. Decreased blood flow of whole cerebral cortex was detected by single photon emission computed tomography (SPECT). Chest X-ray revealed cardiomegaly and electrocardiography (ECG) showed abnormal T waves. These data suggested acute encephalopathy and myocardial dysfunction. We treated him with corticosteroid and blood transfusion, which resulted in the complete recovery of the above abnormal symptoms and laboratory data including the findings in SPECT and ECG in about a month. This case demonstrated transient myocardial dysfunction and encephalopathy can occur in addition to typical clinical manifestation of SFTS.
Assuntos
Encefalopatias/virologia , Infecções por Bunyaviridae/complicações , Febre/virologia , Phlebovirus/isolamento & purificação , Trombocitopenia/etiologia , Trombocitopenia/virologia , Idoso , Encefalopatias/diagnóstico por imagem , Infecções por Bunyaviridae/diagnóstico , Infecções por Bunyaviridae/virologia , Cardiomiopatias/etiologia , Doenças Transmissíveis Emergentes , Humanos , Japão , Masculino , Radiografia , Picadas de Carrapatos , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Anti-tumor necrosis factor (anti-TNF) biologics are effective in the treatment of rheumatoid arthritis (RA); however, it is still not clear whether this treatment promotes the development of malignancies such as lymphoma. Human T-lymphotropic virus type 1 (HTLV-1), which is a causative agent of adult T-cell lymphoma (ATL), is prevalent in Japan. Many HTLV-1-positive patients with RA are assumed to exist; however, there have thus far been no reports on the effect of anti-TNF biologics on HTLV-1-positive patients. We analyzed the response to treatment with anti-TNF biologics and change of HTLV-1 markers in two cases of RA. The two cases showed no response based on the European League Against of Rheumatism response criteria 60-96 weeks after administration of anti-TNF biologics (infliximab and etanercept). No signs of ATL were observed and HTLV-1 markers, such as proviral load and clonality of HTLV-1-infected cells, showed no significant change in either of two cases. Therefore, treatment with anti-TNF biologics did not induce activation of HTLV-1, although the effect on RA was not as effective as in HTLV-1-negative patients in this limited study. Further long-term study with a greater number of patients is necessary to clarify the safety and efficacy of anti-TNF biologics in HTLV-1-positive patients with RA.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Etanercepte/uso terapêutico , Infecções por HTLV-I/diagnóstico , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Infliximab/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Antirreumáticos/uso terapêutico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/virologia , Produtos Biológicos , Biomarcadores/sangue , Feminino , Infecções por HTLV-I/metabolismo , Infecções por HTLV-I/virologia , Humanos , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
A 63-year-old woman presented to our hospital with fever, purpura and pain in both legs and died 4 days after admission. Her blood smear and skin biopsy showed cylinder-like bodies (20×120 µm). She was diagnosed to have monoclonal gammopathy (IgG, lambda type). An autopsy revealed cylinder-like bodies in the vasculature of various organs. We noted a proliferation of atypical plasma cells in her bone marrow, suggesting pre-existing myeloma. Crystalglobulinemia is a rare manifestation of hypergammaglobulinemia that can cause multiple embolisms of the small vessels, and this resulted in the patient's fulminant course. The identification of cylinder-like bodies in the peripheral blood may help in reaching a diagnosis in such cases.
Assuntos
Hipergamaglobulinemia/sangue , Hipergamaglobulinemia/patologia , Cadeias lambda de Imunoglobulina/sangue , Biópsia , Medula Óssea/patologia , Cristalização , Evolução Fatal , Feminino , Testes Hematológicos , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/patologia , Plasmócitos/patologia , Pele/irrigação sanguínea , Pele/patologiaRESUMO
OBJECTIVE: To investigate the response to and safety of antitumor necrosis factor (anti-TNF) therapy in human T lymphotropic virus type I (HTLV-I)positive patients with rheumatoid arthritis (RA). METHODS: Therapeutic response was evaluated in 10 HTLV-Ipositive and 20 HTLV-Inegative patients with RA (sex and age matched) at 3 months after the beginning of anti-TNF therapy using the European League Against Rheumatism improvement criteria. As secondary end points, the discontinuation rate of anti-TNF therapy and its safety, especially the development of adult T cell leukemia (ATL), were evaluated over a 2-year period. RESULTS: Significantly higher baseline levels of C-reactive protein (CRP) were observed in HTLV-Ipositive patients than in HTLV-Inegative patients (P = 0.0003). The response rate to anti-TNF therapy was lower in HTLV-Ipositive patients than in HTLV-Inegative patients. The median CRP level, erythrocyte sedimentation rate, and Disease Activity Score in 28 joints at 3 months after anti-TNF treatment in HTLV-Ipositive patients were significantly higher than in HTLV-I negative patients (P = 0.003, P = 0.03, and P = 0.003, respectively). The discontinuation rate due to insufficient response was significantly higher in HTLV-Ipositive patients than in HTLV-Inegative patients (P = 0.013). During the 2-year observation period, no patients developed ATL. CONCLUSION: These data suggest that HTLV-Ipositive patients with RA had higher inflammation and greater resistance to anti-TNF treatment than HTLV-Inegative patients. Further study is necessary to determine whether HTLV-I infection should be measured when anti-TNF agents are administered to patients with RA, especially in areas were HTLV-I is endemic.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Infecções por HTLV-I/tratamento farmacológico , Vírus Linfotrópico T Tipo 1 Humano , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Fatores Biológicos/farmacologia , Feminino , Infecções por HTLV-I/sangue , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/metabolismo , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A 36-year-old woman was given a diagnosis of hemophagocytic syndrome associated with systemic lupus erythematosus, and was treated with high-dose methylprednisolone and etoposide. She needed endotracheal intubation for mechanical ventilation because of respiratory failure. She developed hoarseness and stridor 69 days after extubation. A pedunculated mass under her glottis was observed by the laryngoscopy. Development of a laryngeal granuloma due to long-term contact with the endotracheal tube was considered, although she was continuously given oral prednisolone (22.5 mg/day) even after extubation. She was treated with inhalation of fluticasone propionate and her symptoms, e.g. hoarseness, decreased. Disappearance of the polypoid lesion was seen on day 26. A laryngeal granuloma due to intubation developed, even with the systemic administration of steroids; but it was successfully treated with steroid inhalation.
Assuntos
Androstadienos/administração & dosagem , Granuloma/tratamento farmacológico , Granuloma/etiologia , Intubação Intratraqueal/efeitos adversos , Doenças da Laringe/tratamento farmacológico , Doenças da Laringe/etiologia , Esteroides/administração & dosagem , Administração por Inalação , Adulto , Feminino , Fluticasona , Humanos , Lúpus Eritematoso Sistêmico/terapia , Prednisolona/administração & dosagemRESUMO
A 25-year-old man undergoing splenectomy at 3 years of age to treat idiopathic thrombocytopenic purpura but no history of Streptococcus pneumonia vaccination, and reporting high fever, nausea, and headache developed purpura, confusion, and hypotension the next day and was admitted. Detailed examination showed disseminated intravascular coagulation and multiple-organ dysfunction. Chest X-ray and computed tomography (CT) showed pneumonia and pleural effusion. Blood culture was positive for S. pneumoniae. Gram staining of sputa yielded numerous white blood cells and gram-negative rods, and sputa culture was positive for Pasteurella multocida and Haemophilus influenzae. The medical history and presence of these organisms yielded a diagnosis of overwhelming postsplenectomy infection (OPSI), and the patient responded to treatment with a combination of benzylpenicillin, cefotaxime, and meropenem. This case suggests that patients with a history of splenectomy may benefit from vaccination for S. pneumoniae and adequate education on OPSI.