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1.
Artigo em Inglês | MEDLINE | ID: mdl-38885408

RESUMO

OBJECTIVES: The predictive validity of disease-specific quality of life (QOL) remains unknown in patients with systemic lupus erythematosus (SLE), although disease-specific measures are equally or more responsive to changes than generic QOL. We aimed to examine the predictive validity of the Lupus patient-reported outcome (PRO) for damage accrual. METHODS: Patients with SLE and ≥2 measurements over time were included in Japanese nationwide multicentre registry (LUNA). The Lupus PRO questionnaire contains both health-related (HR) and non-HR-QOL measures. Damage accrual was evaluated using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We examined the association between the Lupus-PRO score at baseline and longitudinal SDI scores using mixed-effects models adjusted for prognostic factors. RESULTS: Among 1295 patients, those with higher HR-QOL of Lupus PRO at baseline demonstrated a significantly lower increase in SDI (-0.005/year, 95% confidence interval [CI]: -0.007 to - 0.004, p < 0.001). According to the categorisation of HR-QOL based on tertile, a similar dose-dependent effect of HR-QOL on longitudinal SDI was identified (second vs first tertile category: -0.101/year, 95% CI: -0.172 to - 0.030; third tertile category: -0.211/year, 95% CI: -0.281 to - 0.142). Non-HR-QOL was not significantly associated with the SDI scores. Among the HR-QOL domains, cognition, procreation, and physical health were significantly associated with the total SDI scores over time. HR-QOL was associated with corticosteroid-dependent and -independent SDI scores. CONCLUSION: A higher HR-QOL of Lupus PRO was associated with a lower increase in SDI scores. Our findings imply the importance of disease-specific HR-QOL measurements in assessing prognosis.

2.
Mod Rheumatol ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38482606

RESUMO

OBJECTIVES: Specific HLA haplotypes are associated with Behçet's disease (BD). Because the effects of HLA-A26 and its combination with HLA-B51 on organ involvement in BD have not been well demonstrated, we aimed to examine them. METHODS: This multicenter, cross-sectional, observational study enrolled patients with BD who visited Kyoto University Hospital between 2018 and 2021 or Kurashiki Central Hospital between 2006 and 2016 (n = 200). Disease severity was evaluated using the Krause score. RESULTS: Uveitis and gastrointestinal involvement were observed in 95/196 and 57/167 patients, respectively. The HLA alleles identified were HLA-B51 (n = 52/106), HLA-A26 (n = 25/88), and HLA-B51 and HLA-A26 (n = 6/88). In patients harboring HLA-B51, the presence of HLA-A26 was associated with higher frequencies of uveitis (p = 0.03) and coexistence of uveitis and gastrointestinal involvement (p = 0.002), and higher Krause scores (p = 0.02). Furthermore, the presence of HLA-A26 was associated with a higher frequency of uveitis in patients with gastrointestinal involvement (p = 0.001) and gastrointestinal involvement in patients with uveitis (p = 0.001). CONCLUSIONS: Since specific HLA haplotypes and their combinations are associated with organ involvement, both HLA-A and HLA-B haplotypes should be confirmed when screening for affected organs.

3.
Mod Rheumatol ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38564330

RESUMO

OBJECTIVE: Infections are a critical concern for patients with microscopic polyangiitis (MPA). This study aimed to identify the risk factors associated with serious infections (SIs) and infection-related mortality in patients with MPA, as well as the effect of glucocorticoid (GC) dose tapering on these outcomes. METHODS: This multicentre, retrospective, and observational study utilised data from a cohort of patients with MPA in Japan [Registry of Vasculitis Patients to Establish REAL World Evidence (REVEAL) cohort]. Patients were categorised based on the occurrence of SIs or infection-related deaths, and various characteristics were compared among the groups. RESULTS: Among 182 patients, 66 (36.2%) experienced 129 SIs and 27 (14.8%) developed infection-related deaths. Advanced age, elevated C-reactive protein (CRP) levels, and higher ratio of the GC dose at 3 months to the initial dose were identified as independent risk factors for SIs. Older age was also associated with infection-related deaths. Furthermore, the cumulative incidence of infection-related deaths was significantly higher in patients with a higher ratio of the GC dose at 24 months to the initial dose. CONCLUSION: Older age, elevated CRP levels, and slower GC dose tapering predispose patients to SIs and infection-related deaths. Strategies, such as rapid GC dose tapering, are anticipated to mitigate the risk of infections.

4.
Mod Rheumatol ; 34(3): 523-529, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37300805

RESUMO

OBJECTIVES: Decreased sialylation of IgG-Fc glycans has been reported in autoimmune diseases, but its role in systemic lupus erythematosus (SLE) is not fully understood. In this study, we examined the pathogenicity of IgG desialylation and its association with Th17 in SLE using an animal model. METHODS: B6SKG mice, which develop lupus-like systemic autoimmunity due to the ZAP70 mutation, were used to investigate the pathogenicity of IgG desialylation. The proportion of sialylated IgG was compared between B6SKG and wild-type mice with or without ß-glucan treatment-induced Th17 expansion. Anti-interleukin (IL)-23 and anti-IL-17 antibodies were used to examine the role of Th17 cells in IgG glycosylation. Activation-induced cytidine deaminase-specific St6gal1 conditionally knockout (cKO) mice were generated to examine the direct effect of IgG desialylation. RESULTS: The proportions of sialylated IgG were similar between B6SKG and wild-type mice in the steady state. However, IgG desialylation was observed after ß-glucan-induced Th17 expansion, and nephropathy also worsened in B6SKG mice. Anti-IL-23/17 treatment suppressed IgG desialylation and nephropathy. Glomerular atrophy was observed in the cKO mice, suggesting that IgG desialylation is directly involved in disease exacerbation. CONCLUSIONS: IgG desialylation contributes to the progression of nephropathy, which is ameliorated by blocking IL-17A or IL-23 in an SLE mouse model.


Assuntos
Lúpus Eritematoso Sistêmico , beta-Glucanas , Camundongos , Animais , Células Th17 , Virulência , Lúpus Eritematoso Sistêmico/genética , Modelos Animais de Doenças , Imunoglobulina G
5.
Rheumatology (Oxford) ; 62(9): 3151-3155, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36645239

RESUMO

OBJECTIVE: We previously reported that RF recognized the IgG heavy chain (IgGH)/RA-susceptible HLA class II molecule complex. In the present study, we investigated the molecular mechanisms underlying HLA binding to and the RF recognition of IgGH. METHODS: We synthesized various types of IgGH segments, including VH, CH1, CH2 and CH3, and transfected them with or without HLA class II molecules into the Human Embryonic Kidney 293T cell line. IgGH single domains linked with the HLA-Cw3 peptide, which binds to the binding groove of the HLA class II molecule, were also synthesized. The expression of IgGH domains on the cell surface and their recognition by RF were examined using flow cytometry. RESULTS: Flag-tagged IgGH segments containing CH1 (CH1, VH-CH1, CH1-CH2, VH-CH1-CH2, CH1-CH2-CH3 and VH-CH1-CH2-CH3) were clearly presented on the cell surface by HLA-DR4, while segments without the CH1 domain were expressed at a low level, and the CH3 single domain was only weakly detected on the cell surface, even with HLA-DR4. We then transfected IgGH single domains linked to the Cw3 peptide together with HLA-DR4 and showed that RF-containing sera from RA patients only recognized the CH3 domain and none of the other single domains. When various segments without the Cw3 peptide were transfected with HLA-DR4, only the CH1-CH2-CH3 segment and full-length IgGH were detected by the sera of RA patients. CONCLUSION: The CH1 domain of IgGH binds to the RA-susceptible HLA-DR molecule and is expressed on the cell surface. RF specifically recognizes the CH3 domain of the IgGH/HLA-DR4 complex.


Assuntos
Artrite Reumatoide , Fator Reumatoide , Humanos , Antígenos de Histocompatibilidade Classe II , Antígeno HLA-DR4 , Imunoglobulina G , Peptídeos
6.
Rheumatology (Oxford) ; 62(12): 3909-3915, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36943365

RESUMO

OBJECTIVES: Although the SLE Disease Activity Score (SLE-DAS) and its definitions to classify disease activity have been recently developed to overcome the drawbacks of the SLE Disease Activity Index 2000 (SLEDAI-2K), the performance of the SLE-DAS for patient-reported outcomes (PROs) has not been fully examined. We aimed to compare SLE-DAS with SLEDAI-2K and validate the classifications of disease activity based on SLE-DAS in terms of PROs. METHODS: We assessed generic quality of life (QoL) using the Medical Outcome Survey 36-Item Short-Form Health Survey (SF-36), disease-specific QoL using the lupus patient-reported outcome tool (LupusPRO), burden of symptoms using the SLE Symptom Checklist (SSC), patient global assessment (PtGA) and physician global assessment (PhGA). RESULTS: Of the 335 patients with SLE, the magnitudes of the mean absolute error, root mean square error, Akaike information criterion, and Bayesian information criterion were comparable for most PROs between the SLE-DAS and SLEDAI-2K. In contrast, SLEDAI-2K had a higher predictive value for health-related QoL of LupusPRO and PtGA than SLE-DAS. Low disease activity, Boolean and index-based remission and categories of disease activity (remission, mild and moderate/severe activity) were significantly associated with health-related QoL in LupusPRO, SSC and PhGA, but not SF-36 or PtGA. CONCLUSION: No clear differences were identified in the use of the SLE-DAS over the SLEDAI-2K in assessing PROs in patients with SLE. The classification of disease activity based on the SLE-DAS was validated against several PROs. SLE-DAS and its categories of disease activity effectively explain some of the PROs.


Assuntos
Lúpus Eritematoso Sistêmico , Qualidade de Vida , Humanos , Teorema de Bayes , Índice de Gravidade de Doença , Reprodutibilidade dos Testes , Medidas de Resultados Relatados pelo Paciente
7.
Mod Rheumatol ; 33(5): 911-917, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36069659

RESUMO

OBJECTIVES: We aimed to determine the clinical impact of plasma homocysteine levels on disease activity and clinical remission in patients with rheumatoid arthritis (RA). METHODS: A cross-sectional study was conducted using KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. We enrolled 291 female patients, who were treated in a treat-to-target manner. We measured plasma total homocysteine using a liquid chromatography-tandem mass spectrometry system and collected clinical data including a 28-joint RA disease activity score-erythrocyte sedimentation rate (DAS28-ESR). Clinical remission of disease activity was defined as a DAS28-ESR < 2.6. RESULTS: In a univariable analysis, the plasma homocysteine concentration was significantly and positively associated with DAS-28-ESR and was higher in the non-remission group than in the remission group. The cutoff value of the plasma homocysteine level was calculated to be 7.9 nmol/mL by the test of the receiver operating characteristic curve analysis. In a multivariable analysis, after adjusting for clinically relevant variables, the high homocysteine level remained a significant positive association for DAS28-ESR (estimate 0.27, P = .0019) and a positive factor for the presence of RA non-remission (odds ratio 2.39, P = .0071). CONCLUSIONS: Increased plasma homocysteine levels showed a significant positive association with current disease activity and the non-remission state in female patients with RA under treat-to-target treatment. The findings suggest the potential utility of plasma homocysteine as a disease state marker reflecting conditions that are treatment failure and difficult to remission and may provide clinical evidence on the interplay between homocysteine and inflammatory activation in RA.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Feminino , Estudos Transversais , Prevalência , Indução de Remissão , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Curva ROC , Índice de Gravidade de Doença , Antirreumáticos/uso terapêutico
8.
Mod Rheumatol ; 34(1): 113-121, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36680424

RESUMO

OBJECTIVES: Osteoporosis and compression fractures of the lumbar spine are some of the major adverse effects of glucocorticoid therapy in patients with systemic lupus erythematosus (SLE). This study examined the association between bone mineral density, bone turnover markers, presence of vertebral fractures, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in SLE patients. METHODS: This was a cross-sectional study of 246 outpatients with SLE at the Kyoto University Hospital. Lumbar and femoral bone mineral density was measured with dual-energy X-ray absorptiometry, and the presence of vertebral fractures was determined using X-ray, computed tomography, or magnetic resonance imaging. RESULTS: On multiple regression analysis, both high lumbar and femoral T-scores were associated with the concomitant use of hydroxychloroquine (P = .018 and P = .037, respectively), no use of bisphosphonate or denosumab (P = .004 and P = .038, respectively), high body mass index (P < .001), and low bone-specific alkaline phosphatase level (P = .014 and P = .002, respectively). Vertebral fractures showed a significant association with Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score (P < .001) and femoral T-score (P < .001). CONCLUSION: Vertebral fracture was associated with SLE-associated organ damage, and serum bone-specific alkaline phosphatase level is a potentially useful marker for osteoporosis monitoring in SLE patients.


Assuntos
Fraturas Ósseas , Lúpus Eritematoso Sistêmico , Osteoporose , Fraturas da Coluna Vertebral , Humanos , Estudos Transversais , Fosfatase Alcalina , Osteoporose/etiologia , Osteoporose/complicações , Densidade Óssea , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/patologia
9.
J Autoimmun ; 126: 102774, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896887

RESUMO

Intracellular proteins are often targeted by autoantibodies in autoimmune diseases; however, the mechanism through which intracellular molecules are targeted remains unknown. We previously found that several intracellular misfolded proteins are transported to the cell surface by HLA class II molecules and are recognized by autoantibodies in some autoimmune diseases, such as rheumatoid arthritis, antiphospholipid syndrome, and microscopic polyangiitis. Ro52 is an intracellular Fc receptor that is a target antigen for myositis-associated autoantibodies. We analyzed the role of HLA class II molecules in the autoantibody recognition of Ro52. Ro52 alone was not transported to the cell surface by HLA class II molecules; however, it was transported to the cell surface in the presence of both IgG heavy chain and HLA class II molecules to form a Ro52/IgG/HLA-DR complex. The Ro52/IgG/HLA-DR complex was specifically recognized by autoantibodies from some patients with inflammatory myopathies. We then evaluated 120 patients with inflammatory myopathies with four types of myositis-specific antibodies and analyzed the autoantibodies against the Ro52/IgG/HLA-DR complex. The specific antibodies against the Ro52/IgG/HLA-DR complex were detected in 90% and 93% of patients who were positive for anti-MDA5 and anti-ARS antibodies, respectively. In individual patients with these two inflammatory myopathies, changes in serum titers of anti-Ro52/IgG/HLA-DR-specific antibodies were correlated with the levels of KL-6 (R = 0.51 in anti-MDA5 antibody-positive DM patients, R = 0.67 in anti-ARS antibody-positive PM/DM patients with respiratory symptoms) and CK (R = 0.63 in anti-ARS antibody-positive PM/DM patients with muscle symptoms) over time. These results suggest that antibodies against Ro52/IgG/HLA-DR expressed on the cell surface could be involved in the pathogenesis of inflammatory myopathy subgroups.


Assuntos
Doenças Autoimunes , Miosite , Ribonucleoproteínas/imunologia , Autoanticorpos , Antígenos HLA-DR , Humanos , Imunoglobulina G
10.
Rheumatology (Oxford) ; 61(10): 4130-4135, 2022 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-35078211

RESUMO

OBJECTIVE: The aim of this study was to investigate association of autoantibodies with scleroderma renal crisis (SRC) among Japanese patients. METHODS: The clinical characteristics and mortality of 330 patients with sytemic screlosis (SSc) at Kyoto University Hospital were retrospectively analysed, focusing on possible association with anti-topoisomerase I (anti-topo I), anti-centromere (ACA), anti-RNA polymerase III (RNAPIII) and/or anti-U1-RNP. Logistic regression analyses were performed to reveal any association of these autoantibodies with the development and mortality of SRC. RESULTS: SRC was observed in 24 out of 330 SSc patients, including patients with anti-topo I (n = 12/24, 50%), anti-RNAPIII (n = 7/24, 29%), anti-U1-RNP (n = 5/24, 21%) and ACA (n = 3/24, 13%). Anti-U1-RNP [odds ratio (95% CI), 3.63 (1.11, 10.2)], anti-topo I [3.22 (1.37, 7.57)] and anti-RNAPIII (3.29 [1.16, 8.70]) were associated with the development of SRC. Furthermore, anti-topo I [6.00 (1.11, 41.1)] was associated with 1-year mortality of SRC. The 1-year survival rate after the onset of SRC among all patients and among those positive for anti-topo I was 54% and 33%, respectively. In contrast, the survival rate in patients negative for anti-topo I was 75%, of which the survival rate of patients positive for anti-RNAPIII and ACA was 83% and 100%, respectively. CONCLUSION: Specific SSc-related autoantibodies were associated with the morbidity and mortality of SRC.


Assuntos
Autoanticorpos , Escleroderma Sistêmico , Anticorpos Antinucleares , Humanos , Morbidade , RNA Polimerase III , Estudos Retrospectivos , Escleroderma Sistêmico/complicações
11.
Mod Rheumatol ; 32(1): 127-135, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33851898

RESUMO

OBJECTIVES: We aimed to clarify the clinical implication of ultrasound (US)-detected foot joint inflammation in tightly controlled patients with rheumatoid arthritis (RA). METHODS: We evaluated bilateral foot joints (second to fifth metatarsophalangeal joints of forefoot; tarsometatarsal, cuneonavicular and midtarsal joints of midfoot) of 430 RA patients for synovitis using Power Doppler (PD) imaging by US. We made a cross-sectional and a 3-year longitudinal analysis about the associations of US-detected synovitis with clinical, laboratory and radiographic data as well as foot-specific outcomes using a self-administered foot evaluation questionnaire (SAFE-Q). RESULTS: The US-detected foot synovitis was seen in 28% of patients. The US-detected synovitis was closely related to 28 joint-disease activity score (DAS28) more in the forefoot than in the midfoot, while related to joint destruction in both. Multiple regression analyses showed significant associations between midfoot PD positivity and SAFE-Q in the remission group. SAFE-Q was worsened after the 3-year interval, but PD positivity at baseline did not contribute to the changes. On the other hand, destruction of the joints with US-detected synovitis significantly progressed in 3 years than with not. CONCLUSIONS: US-detected synovitis on foot joints were related to systemic inflammation, clinical symptoms, and future joint destruction with region specificity.


Assuntos
Artrite Reumatoide , Sinovite , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Estudos Transversais , Humanos , Inflamação , Índice de Gravidade de Doença , Sinovite/complicações , Sinovite/diagnóstico por imagem , Ultrassonografia , Ultrassonografia Doppler/métodos
12.
Mod Rheumatol ; 32(3): 571-576, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-34894258

RESUMO

OBJECTIVES: The present study aimed to clarify comprehensive relationships among the clinical variables of systemic lupus erythematosus (SLE). METHODS: We retrospectively surveyed 32 clinical variables in 581 patients and conducted comprehensive association studies among SLE clinical phenotypes. A univariate analysis of all possible combinations was performed, and the results of phenotypic correlations were reduced into two dimensions. We also created a regression formula using L1 regularisation (LASSO) to calculate the probability of exhibiting each phenotype. RESULTS: The univariate analysis identified 26 correlations, including multiple phenotypes with low complement. Some unpredicted correlations were identified, including fever and the anti-Sm antibody (odds ratio; OR = 2.3, p = 1.6 × 10-5) or thrombocytopenia and psychosis (OR = 3.7, p = 3.2 × 10-5). The multivariate analysis accurately estimated the probability of exhibiting each phenotype (area under the curve > 0.7) in 10 out of 20 phenotypes. CONCLUSIONS: The present results show the phenotypic architecture of SLE and represent a model for estimating the probability of exhibiting each phenotype. They also offer insights into the pathology of SLE and estimating the probability of the onset of new phenotypes in clinical practice.


Assuntos
Lúpus Eritematoso Sistêmico , Anticorpos Antinucleares , Estudos de Coortes , Humanos , Fenótipo , Estudos Retrospectivos
13.
Lupus ; 30(10): 1577-1585, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34121502

RESUMO

OBJECTIVES: It is important to clarify the relationship between irreversible organ damage and the quality of life (QOL) by considering the unique factors of patients with systemic lupus erythematosus (SLE). We aimed to clarify their correlation using SLE-specific QOL assessment tools. We also aimed to identify which type of organ damage is adversely correlated with the QOL. METHODS: We conducted a questionnaire-based survey of outpatients with SLE at Kyoto University Hospital and evaluated irreversible organ damage using the SLICC/ACR damage index (SDI). LupusPRO and the SLE symptom checklist (SSC) were employed as SLE-specific QOL tools, and the SF-36v2 was used as a conventional QOL tool. Multiple linear regression analyses were performed to examine the correlations between the total SDI score and each QOL score, and between each SDI item/system score and each QOL score. RESULTS: We analyzed the data of 265 patients. The total SDI score was significantly correlated with physical (PCS) and role/social component summary (RCS) of the SF-36v2, health-related QOL (HRQOL) of LupusPRO, and SSC (p < 0.001). Among the SDI items, atrophy/weakness and osteoporosis with fracture/vertebral collapse were negatively correlated with PCS (ß = -0.40, p < 0.001/ß = -0.28, p < 0.001), RCS (ß = -0.30, p < 0.001/ß = -0.35, p < 0.001), and HRQOL (ß = -0.34, p < 0.001/ß = -0.31, p < 0.001), respectively. Among the SDI systems, musculoskeletal damage had higher negative correlations with PCS (ß = -0.51, p < 0.001), RCS (ß = -0.29, p < 0.001), and HRQOL (ß = -0.40, p < 0.001). CONCLUSION: We demonstrated the QOL of patients with SLE is negatively correlated with irreversible organ damage. We also revealed musculoskeletal damage is adversely correlated with the health-related QOL, especially the physical and role/social QOL.


Assuntos
Lúpus Eritematoso Discoide , Lúpus Eritematoso Sistêmico , Humanos , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários
14.
Mod Rheumatol ; 31(2): 334-342, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32243209

RESUMO

OBJECTIVE: Although recent clinical trials showed that ultrasound (US) remission is not required to achieve good outcomes at the group level, it currently remains unclear whether the prognosis of individual patients in clinical remission, but not US remission, i.e. those with subclinical sonographic synovitis (SSS), is favorable. However, it is no longer acceptable to perform US on all patients in order to identify those with SSS. Therefore, the present study was initiated to elucidate the conditions under which SSS is frequently detected. METHODS: In total, 563 consecutive RA patients were recruited. Bilateral 2-5 MCP, wrist, ankle, and 2-5 MTP joints were scanned by US, and Gray scale and Power Doppler (PD) images were scored semi-quantitatively. Clinical data were obtained by physicians who were blind to US results. Changes in the modified Total Sharp Score (mTSS) of tocilizumab (TCZ) users were calculated. RESULTS: A total of 402 patients were included. SSS was more frequently detected in patients with more severe joint deformity, even if they were in remission. In contrast, a high Patient Global Assessment of Disease (PtGA) did not reflect SSS. Furthermore, the relationship between PtGA and PD scores was weak. Although the frequency of SSS was high in TCZ user, the presence of SSS in TCZ users not always results in the progression of mTSS. CONCLUSIONS: While remission is overestimated in patients with severe joint deformity, underestimations may occur in those who do not fulfill remission criteria because of a high PtGA.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Sinovite/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Adulto , Idoso , Articulação do Tornozelo/diagnóstico por imagem , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Sinovite/tratamento farmacológico , Sinovite/patologia , Ultrassonografia Doppler/normas , Articulação do Punho/diagnóstico por imagem
15.
Rheumatology (Oxford) ; 59(11): 3284-3292, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32276271

RESUMO

OBJECTIVES: Rapidly progressive interstitial lung disease (RP-ILD) with poor prognosis often accompanies anti-melanoma differentiation-associated gene 5 (MDA5)-positive DM. Combined immunosuppressive therapy, including glucocorticoids, calcineurin inhibitors and intravenous cyclophosphamide (IVCY) is reportedly effective in DM with RP-ILD, but some patients remain resistant to therapy. We examined the utility of plasma exchange (PE) in such intractable cases and investigated the prognostic factors of the disease. METHODS: Thirty-eight anti-MDA5-positive DM-ILD patients who received the combined immunosuppressive therapy were retrospectively reviewed. Their serum cytokines were evaluated by multiplex assay before treatment. The patients were divided into two groups: those who achieved remission without exacerbation of respiratory dysfunction (n = 25, group A) and those who progressed to hypoxemia during the treatment (n = 13, group B). RESULTS: PE was carried out in eight group B patients, but none of group A. Five of the eight treated with PE survived, while the five untreated patients died (P =0.04). Higher neutrophil lymphocyte ratio, higher serum ferritin, hypoxemia, high-resolution computed tomography (HRCT) score before treatment and increase of Krebs von Lungen-6 (KL-6) in the first 4 weeks of the treatment were the prognostic factors for disease progression. Serum cytokines such as IL-1, IL-6, IL-8, IL-10, IL-12p70, IL-18 and sCD163 levels were higher in group B than group A. CONCLUSION: PE should be an effective adjuvant treatment in anti-MDA5-positive DM with RP-ILD. Assessment of basal laboratory tests or monocyte/macrophage-derived cytokines and the increase of KL-6, HRCT score and hypoxemia may help us to predict intractable cases and to make early treatment decisions regarding PE in anti-MDA5-positive DM.


Assuntos
Dermatomiosite/terapia , Imunossupressores/uso terapêutico , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/terapia , Troca Plasmática , Adulto , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Autoanticorpos/sangue , Ciclosporina/uso terapêutico , Dermatomiosite/sangue , Dermatomiosite/mortalidade , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Interferons/sangue , Interleucinas/sangue , Japão , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular/sangue , Tacrolimo/uso terapêutico
16.
Mod Rheumatol ; 30(4): 640-647, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31393192

RESUMO

Objectives: To determine the clinical characteristics of rheumatoid arthritis (RA) patients with low serum triiodothyronine (T3) levels.Methods: We evaluated serum free T3 (fT3), free T4, and thyroid-stimulating hormone (TSH) levels in 338 RA patients. After excluding patients taking anti-thyroid drugs or having anti-thyroid antibodies, we compared the clinical characteristics of the RA patients with low fT3 to those with normal/high fT3, before and after RA treatment.Results: Six percent of RA patients had low fT3 levels. Patients with low fT3 were older and had higher disease activity scores (DAS28), higher Steinbrocker stage, higher health assessment questionnaire scores, lower body mass index, and lower hemoglobin and albumin levels compared with normal/high-fT3 patients. After RA treatment, fT3 levels normalized in half of the low-fT3 patients and remained low in the other half. Although DAS28 scores were similarly improved in both subgroups of the low-fT3 patients, anemia and hypoalbuminemia did not normalize in the persistently low-fT3 subgroup.Conclusion: Low serum fT3 levels represent the profound wasting seen in RA patients that is characterized by anemia and hypoalbuminemia and that cannot be evaluated by DAS28 scores alone.


Assuntos
Anemia/sangue , Artrite Reumatoide/sangue , Hipoalbuminemia/sangue , Tri-Iodotironina/sangue , Adulto , Idoso , Anemia/epidemiologia , Artrite Reumatoide/complicações , Feminino , Humanos , Hipoalbuminemia/epidemiologia , Masculino , Pessoa de Meia-Idade
19.
Mod Rheumatol ; 27(1): 155-161, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25159158

RESUMO

We report on a 30-year-old Japanese woman with granulomatosis with polyangiitis (GPA) complicated by pituitary diabetes insipidus and multiple lung granulomas. The granulomas disappeared with prednisolone (50 mg/day) and rituximab, although continuous nasal desmopressin was needed to control diabetes insipidus after immunosuppressive therapies. At the time of presentation, the patient had abdominal pain and disseminated intravascular coagulation but no rash. She died of continuous hemorrhage from her skin of neck, mucosa of her pharynx, and small intestine. At autopsy, varicella zoster virus (VZV)-DNA detected in serum and VZV antigens detected in tissues of her pharynx, esophagus, and liver led to a diagnosis of visceral disseminated VZV infection (VD-VZV). She also complicated cytomegalovirus infection in her stomach and ovaries. Her posterior pituitary gland had been replaced by foamy macrophages. In 38 reported cases of VD-VZV, rash appeared following the onset of abdominal pain (mean interval, 6.5 days) but was lacking in 11% of cases. The mortality rate associated with VD-VZV was as high as 29% and survived cases were treated with antivirals earlier than mortal cases. A quick diagnosis with detection of VZV-DNA or VZV antigens in sera or tissues using PCR or immunohistochemistry examination and early empirical treatment with antivirals are important.


Assuntos
Granulomatose com Poliangiite/tratamento farmacológico , Herpes Zoster/etiologia , Fatores Imunológicos/efeitos adversos , Rituximab/efeitos adversos , Adulto , Quimioterapia Combinada , Evolução Fatal , Feminino , Herpesvirus Humano 3/isolamento & purificação , Humanos , Fatores Imunológicos/uso terapêutico , Prednisolona/uso terapêutico , Rituximab/uso terapêutico
20.
Clin Calcium ; 25(12): 1835-42, 2015 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-26608859

RESUMO

There had been proved the efficacy of preventing bone destruction by using disease modifying anti-rheumatic drugs (DMARDS) such as methotrexate(MTX). A certain combination of DMARDS is more effective than treated alone. But the data about DMARDS combination therapy or DMARDS used mainly in Japan is not abundant, and there needed to establish the evidences of them.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Doenças Ósseas/tratamento farmacológico , Doenças das Cartilagens/tratamento farmacológico , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Humanos
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