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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.
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OBJECTIVES: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomised into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day, and IVMP 1.0 g/day. The primary outcome was all-cause death, and the secondary outcomes were composite all-cause death and kidney failure, severe relapse, and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. RESULTS: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (2.8%) died, 4 (2.0%) had kidney failure, 11 (5.3%) had severe relapse, and 40 (19.8%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause death = 0.46 (95% confidence interval [95%CI]: 0.07-2.81) and 0.07 (95%CI: 0.01-0.41); all-cause death/kidney failure = 1.18 (95%CI: 0.26-5.31) and 0.59 (95%CI: 0.08-4.52); subdistribution HRs for severe relapse = 1.26 (95%CI: 0.12-13.70) and 3.36 (95%CI: 0.49-23.29); and serious infection = 1.88 (95%CI: 0.76-4.65) and 0.94 (95%CI: 0.28-3.13). CONCLUSIONS: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.
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OBJECTIVES: To update an evidence base informing the 2024 Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis (RA) in older adults. METHODS: Four clinical questions (CQs) regarding efficacy and safety of drug treatment were evaluated, with CQ1 addressing methotrexate (MTX), CQ2 biological disease-modifying antirheumatic drugs, CQ3 Janus kinase (JAK) inhibitors, and CQ4 glucocorticoids (GCs). Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS: Observational studies confirmed a pivotal role of methotrexate in the treatment of older RA patients. The meta-analysis showed that tumour necrosis factor inhibitors and JAK inhibitors were unequivocally effective in older RA patients. No data indicated that biological disease-modifying antirheumatic drugs were unsafe for older patients. No safety data for JAK inhibitor use in older patients were available. One randomized controlled trial demonstrated that long-term treatment with low-dose GCs increased risks of GC-associated adverse events. The certainty of overall evidence was very low for all CQs. CONCLUSIONS: This systematic review provides the necessary evidence for developing 2024 Japan College of Rheumatology clinical practice guidelines for managing older patients with RA. Continued updates on the evidence of JAK inhibitors and GC are desired.
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Antirreumáticos , Artrite Reumatoide , Guias de Prática Clínica como Assunto , Reumatologia , Humanos , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/uso terapêutico , Japão , Idoso , Reumatologia/normas , Metotrexato/uso terapêutico , Glucocorticoides/uso terapêutico , Inibidores de Janus Quinases/uso terapêuticoRESUMO
OBJECTIVE: The European League Against Rheumatism recommends that the disease activity of systemic lupus erythematosus should be stable before pregnancy because complications and disease flares increase if pregnancy occurs while disease activity is high. However, some patients have ongoing serological activity even after treatment. Herein, we investigated how physicians decide on the acceptability of pregnancy in patients showing only serological activity. METHODS: A questionnaire was administered from December 2020 to January 2021. It included the characteristics of physicians, facilities, and the allowance for pregnancies of patients using vignette scenarios. RESULTS: The questionnaire was distributed to 4946 physicians, and 9.4% responded. The median age of respondents was 46 years, and 85% were rheumatologists. Pregnancy allowance was significantly affected by the duration of the stable period and status of serological activity [duration: proportion difference 11.8 percentage points (p.p.), P < .001; mild activity: proportion difference -25.8 p.p., P < .001; high activity: proportion difference -65.6 p.p., P < .001]. For patients with high-level serological activity, 20.5% of physicians allowed pregnancy if there were no clinical symptoms for 6 months. CONCLUSIONS: Serological activity had a significant effect on the acceptability of pregnancy. However, some physicians allowed patients with serological activity alone to become pregnant. Further observational studies are required to clarify such prognoses.
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Lúpus Eritematoso Sistêmico , Médicos , Complicações na Gravidez , Gravidez , Feminino , Humanos , Pessoa de Meia-Idade , Complicações na Gravidez/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Resultado da Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVES: A quality indicator for the treatment of systemic lupus erythematosus during pregnancy and childbirth that is useful for sharing standard treatment policies has not yet been developed. This study aimed to develop a quality indicator for systemic lupus erythematosus associated with pregnancy and childbirth. METHODS: To identify candidate quality indicators, we conducted a systematic literature review on the development of quality indicators for systemic lupus erythematosus related to pregnancy and childbirth and on clinical practice guidelines. Candidate quality indicator items were extracted from the final selected articles, and a first evaluation, panel meeting, and second evaluation were conducted to determine whether the candidate items were appropriate as quality indicators. Items for which all panel members reached a consensus were designated pregnancy and childbirth-related systemic lupus erythematosus quality indicators. RESULTS: Four articles on systemic lupus erythematosus-quality indicator development and 28 practice guidelines were listed through abstract/text screening. Based on these studies, 52 candidate quality indicators were extracted that were limited to items related to pregnancy and childbirth, and 41 items were selected on which all panel members agreed. CONCLUSION: We developed pregnancy-related systemic lupus erythematosus quality indicators using the RAND/UCLA method and selected 41 items, which could be used clinically.
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OBJECTIVES: To update evidence on the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) and provide information to the taskforce for the 2024 update of the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA). METHODS: We searched various databases for randomised controlled trials on RA published until June 2022, with no language restriction. For each of the 15 clinical questions, 2 independent reviewers screened the articles, evaluated the core outcomes, and performed meta-analyses. RESULTS: Subcutaneous injection of methotrexate (MTX) showed similar efficacy to oral MTX in MTX-naïve RA patients. Ozoralizumab combined with MTX improved drug efficacy compared to the placebo in RA patients with inadequate response (IR) to csDMARD. Rituximab with and without concomitant csDMARDs showed similar efficacy to other bDMARDs in bDMARD-IR RA patients. Combined Janus kinase inhibitors and MTX achieved similar clinical responses and equal safety during a 4-year period compared to tumour necrosis factor inhibitors in MTX-IR RA patients. Biosimilars showed efficacy equivalent to that of the original bDMARDs in csDMARD-IR and bDMARD-IR RA patients. CONCLUSION: This systematic review provides latest evidence for the 2024 update of the JCR CPG for RA management.
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OBJECTIVES: To investigate the association between decreased serum IgG levels caused by remission-induction immunosuppressive therapy of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the development of severe infections. METHODS: We conducted a retrospective cohort study of patients with new-onset or severe relapsing AAV enrolled in the J-CANVAS registry, which was established at 24 referral sites in Japan. The minimum serum IgG levels up to 24 weeks and the incidence of severe infection up to 48 weeks after treatment initiation were evaluated. After multiple imputations for all explanatory variables, we performed the multivariate analysis using a Fine-Gray model to assess the association between low IgG (the minimum IgG levels <500 mg/dl) and severe infections. In addition, the association was expressed as a restricted cubic spline (RCS) and analysed by treatment subgroups. RESULTS: Of 657 included patients (microscopic polyangiitis, 392; granulomatosis with polyangiitis, 139; eosinophilic granulomatosis with polyangiitis, 126), 111 (16.9%) developed severe infections. The minimum serum IgG levels were measured in 510 patients, of whom 77 (15.1%) had low IgG. After multiple imputations, the confounder-adjusted hazard ratio of low IgG for the incidence of severe infections was 1.75 (95% confidence interval: 1.03-3.00). The RCS revealed a U-shaped association between serum IgG levels and the incidence of severe infection with serum IgG 946 mg/dl as the lowest point. Subgroup analysis showed no obvious heterogeneity between treatment regimens. CONCLUSION: Regardless of treatment regimens, low IgG after remission-induction treatment was associated with the development of severe infections up to 48 weeks after treatment initiation.
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Agamaglobulinemia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Granulomatose com Poliangiite/tratamento farmacológico , Estudos Retrospectivos , Agamaglobulinemia/induzido quimicamente , Quimioterapia de Indução , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Poliangiite Microscópica/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Anticorpos Anticitoplasma de NeutrófilosRESUMO
BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis characterized by eosinophil-rich granulomatous inflammation and small-to-medium vessel vasculitis associated with asthma, rhinosinusitis, and eosinophilia. EGPA is often difficult to distinguish from severe asthma and eosinophilic chronic rhinosinusitis (ECRS) in cases when there are no findings that suggest vasculitis. Dupilumab, an anti-IL-4Rα monoclonal antibody, is expected to be effective in eosinophilic airway inflammatory diseases, such as refractory asthma and chronic rhinosinusitis (CRS). Although transient eosinophilia and eosinophilic pneumoniae have been reported in patients with refractory asthma and CRS associated with dupilumab, few studies have examined the development of EGPA. CASE PRESENTATION: We report a case of a 61-year-old woman treated with dupilumab for refractory ECRS and eosinophilic otitis media (EOM) complicated by severe asthma. Although she had a previous history of eosinophilic pneumoniae and myeloperoxidase (MPO) ANCA positivity, there were no apparent findings of vasculitis before the initiation of dupilumab. After the second administration of dupilumab, several adverse events developed, including worsening of ECRS, EOM and asthma, and neuropathy. A blood test showed an eosoinophilia and re-elevation of MPO-ANCA levels after the administration of dupilumab. Therefore, dupilumab was discontinued owing to the development of EGPA, and prednisolone and azathioprine administration was initiated for a remission induction therapy. CONCLUSION: To the best of our knowledge, this is the first case report that suggests that dupilumab may directly trigger the manifestation of vasculitis in patients who were previously MPO-ANCA-positive. Although the precise mechanism of how dupilumab could trigger the development of EGPA requires further elucidation, measuring MPO-ANCA in patients with multiple eosinophilic disorders before the initiation of dupilumab might be helpful when considering the possibility of a latent EGPA. When administering dupilumab to patients with a previous history of MPO-ANCA positivity, clinicians must carefully monitor and collaborate with other specialists in the pertinent fields of study for appropriate usage.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Asma , Síndrome de Churg-Strauss , Eosinofilia , Granulomatose com Poliangiite , Feminino , Humanos , Pessoa de Meia-Idade , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Síndrome de Churg-Strauss/induzido quimicamente , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Eosinofilia/induzido quimicamente , Eosinofilia/complicações , Asma/complicações , Asma/tratamento farmacológicoRESUMO
Objectives This cross-sectional study aimed to determine the relationship between falls and use of psychotropic medications in patients with rheumatoid arthritis. Methods The psychotropic medication group included patients with rheumatoid arthritis prescribed psychotropic medications (hypnotics/sedatives, antidepressants, antipsychotics, and anxiolytic [benzodiazepines] drugs). Poisson regression with robust variance was performed to investigate the relationship between falls and the use of psychotropic medications, with adjustment for age, sex, rheumatoid arthritis disease activity, stroke, dementia, diabetes mellitus, and osteoarthritis. Results Of the 307 patients enrolled, 49 (16.0%) used psychotropic medications, and 70 (22.8%) experienced at least one fall per year. Nineteen of the 49 patients (38.8%) taking psychotropic medications and 51 of 258 (19.8%) not taking psychotropic medications experienced at least one fall per year. Falls were significantly more frequent in the group with psychotropic medications than in the group without psychotropic medications (adjusted incidence rate ratio, 1.63; 95% confidence interval; 1.08-2.48, p = 0.02). No relationship was found between the number of falls and the use of psychotropic medications (adjusted incidence rate ratio, 1.16; 95% confidence interval; 0.39-3.44, p = 0.78). Conclusions There may be a relationship between psychotropic medication use and falls in patients with rheumatoid arthritis.
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OBJECTIVES: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We retrospectively assessed patients with AAV who received IVCY every 2-3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5-12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes were also evaluated. RESULTS: Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94-19.8) for VLD and 5.1 (95% CI 1.21-21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly. CONCLUSION: Low-dose IVCY (7.5-12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg).
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OBJECTIVE: This study aimed to assess the prevalence and actual treatment conditions for hypertension and dyslipidaemia complicated with systemic lupus erythematosus (SLE). METHODS: This was a cross-sectional study. We established the lupus registry of nationwide institutions (LUNA), a multi-centre cohort of SLE patients in Japan. From February 2016 to July 2018, 597 SLE patients were registered in the LUNA. We evaluated the incidence of hypertension and dyslipidaemia and analysed the risk factors for hypertension and dyslipidaemia by logistic regression analysis. RESULTS: Overall, 597 patients were enrolled in the study. The median age was 44 years, and 88.0% of the patients were female. Among all the patients, 92.9% used prednisolone. The prevalence of hypertension and dyslipidaemia was 43.9% and 54.7%, respectively. Among the patients receiving medication for hypertension, 24.7% exhibited insufficient control (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg), and among those receiving medication for hyperlipidaemia, 48.1% showed insufficient control (low-density lipoprotein cholesterol >140 mg/dL or triglyceride >150 mg/dL). The risk factors for hypertension were age, body mass index (BMI), disease duration, past maximum dose of prednisolone, and renal involvement, whereas those for dyslipidaemia were age and BMI. CONCLUSION: About half of the patients had hypertension or dyslipidaemia, and a considerable number of cases were poorly controlled despite medication. Our data suggest that physicians should treat SLE activity as well as its complications, especially the common risk factors for atherosclerosis.
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Dislipidemias/epidemiologia , Hipertensão/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Adulto , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Estudos de Coortes , Estudos Transversais , Dislipidemias/tratamento farmacológico , Feminino , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Incidência , Japão/epidemiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Prevalência , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Hemotropic mycoplasmas are common pathogens in animals, but it remains unclear what role these pathogens play in human infections. We report clinical and biologic characterization of Candidatus Mycoplasma haemohominis infection in a 42-year-old man in Japan. The patient had severe hemophagocytic syndrome 1 month after an accidental needlestick injury. Metagenomic deep sequencing identified Candidatus M. haemohominis and determined its draft genome for an isolate from serum of the patient. A high copy number of the Candidatus M. haemohominis genome was detected in serum and bone marrow samples. Electron microscopy examination showed morphologic characteristics of Candidatus M. haemohominis. Levofloxacin monotherapy induced resistance caused by a gyrase A gene mutation in the quinolone resistance-determining region, but a combination treatment with moxifloxacin and minocycline was effective. We identified Candidatus M. haemohominis in a patient who had life-threatening symptoms related to multiple organ infection. Human infection with this mycoplasma might occur more frequently than has been generally recognized.
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Infecções por Mycoplasma/microbiologia , Mycoplasma , Adulto , Eritema/microbiologia , Eritema/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Japão/epidemiologia , Masculino , Microscopia Eletrônica , Mycoplasma/genética , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/patologia , Prurido/microbiologia , Prurido/patologia , Pele/patologiaRESUMO
A 68-year-old Japanese male presented with atrophic erythematous white lesions with peripheral dark reddish rims on his back. Multiple ulcers were detected from his stomach to his large intestine using endoscopy. Although the patient was given high doses of a steroid, aspirin, dipyridamole, and intravenous immunoglobulin therapy, he died of gastrointestinal hemorrhage, perforation and septic shock. An autopsy examination revealed pauci-inflammatory thrombotic microangiopathy with endothelial cell injury, fibrous occlusive arteriopathy, and vascular C5b-9 deposition in the wall of the gastrointestinal tract from the esophagus to the large intestine as well as in the dermis of the skin.
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Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Trato Gastrointestinal/patologia , Papulose Atrófica Maligna/diagnóstico , Pele/patologia , Idoso , Evolução Fatal , Trato Gastrointestinal/metabolismo , Humanos , Masculino , Papulose Atrófica Maligna/metabolismo , Papulose Atrófica Maligna/patologia , Pele/metabolismoRESUMO
To examine the relationship between serum cytokine levels and response to tocilizumab in patients with RA. The disease status of 21 RA patients was assessed at baseline and after 12 weeks of tocilizumab treatment, using the clinical disease activity index (CDAI). Clinical response to tocilizumab was defined as an improvement of >50% from the baseline CDAI. Serum cytokine levels were quantified using double-ligand ELISA for TNF-α, IL-6, CCL2, CCL3, CXCL8, CXCL10, CX3CL1, and macrophage migration inhibitory factor (MIF). After 12 weeks of tocilizumab treatment, there was a significant overall reduction in RA disease activity (CDAI), from 22.4 ± 11.3 to 9.2 ± 6.6 (p < 0.0001), across the entire patient group. After 12 weeks of tocilizumab treatment, 14 patients achieved a >50% improvement (the responder group), but there were no significant responses in the other 7 patients (the non-responder group). The erythrocyte sedimentation rate levels, the positive % of anti-cyclic citrullinated protein antibody and patients (%) receiving methotrexate in combination with tocilizumab were significantly higher in the responder group than in the non-responder group. Although serum baseline levels of CCL2 and CXCL8 were higher in the responder group than in the non-responder group, there were no significant changes in these chemokine levels after treatment. The serum MIF levels, but not the levels of other cytokines, in the responder group were significantly decreased after tocilizumab treatment. Our results suggest that tocilizumab differentially regulates serum cytokine profiles in patients with RA, and MIF regulation in patients with active RA may be sensitive to anti-IL-6 therapy.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Fatores Inibidores da Migração de Macrófagos/sangue , Adulto , Idoso , Anticorpos Anti-Idiotípicos/sangue , Anticorpos Monoclonais Humanizados/imunologia , Sedimentação Sanguínea , Citocinas/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/imunologia , Receptores de Interleucina-6/imunologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody-positive dermatomyositis is associated with rapidly progressive interstitial lung disease (RP-ILD). We encountered a man in his 40s who presented with a history of a fever and dry cough. Based on laboratory tests and computed tomography scans of his chest, he was diagnosed with anti-MDA5 antibody-positive dermatomyositis with RP-ILD refractory to antimicrobial agents. Although the patient was treated with glucocorticoids, calcineurin inhibitors, intravenous cyclophosphamide, and plasma exchange, ventilatory management was still required. The patient survived additional therapy with tofacitinib; however, he developed a catheter-related pulmonary embolism as a complication.
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We aimed to clarify the long-term safety and efficacy of rituximab (RTX) as a remission induction therapy following severe relapse in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We retrospectively collected the data of patients with severely relapsed AAV from a Japanese multicentre cohort. The primary exposure was RTX use; the primary outcome was complete remission (CR) proportions at week 24. Baseline characteristics were compared between the RTX and non-RTX groups. We performed multivariate logistic regression analysis and one-to-one propensity score matching analysis as a sensitivity analysis. Totally, 100 patients were enrolled: 52 in the RTX group and 48 in the non-RTX group. Baseline characteristics were comparable between the two groups, except for age, AAV subtype and ANCA serotype. The median age was 71 vs. 75 years, and the PR3-ANCA positivity rate was 44.2% vs. 18.8% in the RTX and non-RTX groups, respectively. No significant difference was observed in CR proportions at week 24 between the two groups (79.2% vs. 68.1%, p = 0.321), with an adjusted odds ratio of 1.27 (95% confidence interval [CI] 0.47-3.51). At week 48, CR proportions were significantly higher in the RTX group (91.7% vs. 64.9%, p = 0.005), with an adjusted odds ratio of 2.95 (95% CI 0.97-9.91). Serious infection rates were lower in the RTX group than in the non-RTX group, with no statistically significant difference. RTX was not superior to conventional immunosuppressive therapies at week 24 but showed significantly favourable results at week 48 for severely relapsed AAV.
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Cardiovascular disease in patients with systemic lupus erythematosus (SLE) remains one of the most common causes of death and is caused by several factors, including both traditional and disease-specific risk factors. We aimed to systematically appraise the evidence of cardiovascular disease risk factors focusing on the SLE population. The protocol for this umbrella review is registered in PROSPERO (registration no. CRD42020206858). A systematic literature search was conducted in PubMed, Embase, and the Cochrane Library from database inception to June 22, 2022, for systematic reviews and meta-analyzes that examined cardiovascular disease risk factors in patients with SLE. Two reviewers independently extracted data and assessed the quality of the included studies using the "Assessing the Methodological Quality of Systematic Reviews 2 (AMSTER 2)" tool. Of the 102 identified articles, nine systematic reviews were included in this umbrella review. All included systematic reviews were assessed as critically low quality according to the AMSTER 2 tool. The traditional risk factors identified in this study were older age, male sex, hypertension, dyslipidemia, smoking, and a family history of cardiovascular disease. SLE-specific risk factors were long-term disease duration, lupus nephritis, neurological disorders, high disease activity, organ damage, use of glucocorticoids, azathioprine, and antiphospholipid antibodies, including anticardiolipin antibodies and lupus anticoagulant. This umbrella review identified some cardiovascular disease risk factors in patients with SLE; however, the study quality of all included systematic reviews was critically low. Key Points ⢠We examined the evidence of cardiovascular disease risk factors focusing on patients with systemic lupus erythematosus. ⢠We found that long-term disease duration, lupus nephritis, neurological disorders, high disease activity, organ damage, use of glucocorticoids, azathioprine, and antiphospholipid antibodies, including anticardiolipin antibodies and lupus anticoagulant, were cardiovascular disease risk factors among patients with systemic lupus erythematosus. ⢠The review indicates the need for well-validated and high-quality future reviews that assess major adverse cardiovascular events as an outcome in patients with systemic lupus erythematosus.
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Síndrome Antifosfolipídica , Doenças Cardiovasculares , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Doenças do Sistema Nervoso , Humanos , Masculino , Doenças Cardiovasculares/epidemiologia , Inibidor de Coagulação do Lúpus , Anticorpos Anticardiolipina , Azatioprina , Revisões Sistemáticas como Assunto , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Anticorpos Antifosfolipídeos , Fatores de RiscoRESUMO
INTRODUCTION: Patients with systemic lupus erythematosus (SLE) frequently change attending physicians. The number of changes in attending physicians is related to the accumulated organ damage in patients with diabetes mellitus and inflammatory bowel disease, although similar results are not known for patients with SLE. This study investigated whether the number of attending physicians after the onset of SLE is associated with organ damage. METHODS: Patients with SLE were enrolled in a multicenter registry of 14 institutions (the Lupus Registry of Nationwide Institutions). Patients with a disease duration of 6 months to 10 years were included. Exposure was defined as the number of attending physicians. The primary outcome was the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). The secondary outcomes were corticosteroid- and non-corticosteroid-related damage. Multiple logistic regression analysis was used to estimate the association between the number of attending physicians and SDI, adjusting for potential confounders, including age, sex, disease duration, number of hospitalizations due to SLE, disease activity at diagnosis, and emotional health. RESULTS: Of the 702 patients, 86.5% were women (median age 46 years, interquartile range 35-58). The disease duration was 7.3 years (4.3-11.3), the number of hospitalizations due to SLE was 1 (1-3), the number of attending physicians was 3 (2-4), and SDI was 0 points (0-1). The number of attending physicians was significantly associated with SDI [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.03-1.26]. In the secondary outcome, the number of attending physicians was significantly associated with corticosteroid-related damage (OR 1.22, 95% CI 1.09-1.38). The number of attending physicians was not significantly associated with non-corticosteroid-related damage (OR 1.08, 95% CI 0.99-1.19). CONCLUSIONS: This study showed that SDI could increase as the number of attending physicians increases. The impact of changing attending physicians warrants greater attention for SLE and other diseases.
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OBJECTIVE: To clarify seasonal and other environmental effects on the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We enrolled patients with new-onset eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and granulomatosis with polyangiitis (GPA) registered in the database of a Japanese multicenter cohort study. We investigated the relationship between environmental factors and clinical characteristics. Seasons were divided into 4 (spring, summer, autumn, and winter), and the seasonal differences in AAV onset were analyzed using Pearson chi-square test, with an expected probability of 25% for each season. RESULTS: A total of 454 patients were enrolled, with a mean age of 70.9 years and a female proportion of 55.5%. Overall, 74, 291, and 89 patients were classified as having EGPA, MPA, and GPA, respectively. Positivity for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA was observed in 355 and 46 patients, respectively. Overall, the seasonality of AAV onset significantly deviated from the expected 25% for each season (P = 0.001), and its onset was less frequently observed in autumn. In ANCA serotypes, seasonality was significant in patients with MPO-ANCA (P < 0.001), but not in those with PR3-ANCA (P = 0.97). Additionally, rural residency of patients with AAV was associated with PR3-ANCA positivity and biopsy-proven pulmonary vasculitis. CONCLUSION: The onset of AAV was influenced by seasonal variations and was less frequently observed in autumn. In contrast, the occurrence of PR3-ANCA was triggered, not by season, but by rural residency.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Feminino , Idoso , Granulomatose com Poliangiite/complicações , Anticorpos Anticitoplasma de Neutrófilos , Estações do Ano , Síndrome de Churg-Strauss/complicações , Estudos Retrospectivos , Estudos de Coortes , Japão/epidemiologia , Mieloblastina , Poliangiite Microscópica/complicações , PeroxidaseRESUMO
The role of antidepressants in relieving pain and depression in rheumatic diseases are not clear. Specifically, higher depression has been shown to be related to higher pain, higher fatigue, and reduced quality of life for persons with rheumatic disease. At first, treat steroid, immunosuppressive agent and disease modifying anti-rheumatoid drug for rheumatic disease. When depression state does not improve even it, psychotropic drug (e.g., antidepressant drug, anti-anxiety agent, sleeping drug, etc) is used if necessary.