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Avacopan, a C5a receptor (C5aR) inhibitor, has emerged as a novel treatment for antineutrophil cytoplasmic antibody-associated vasculitis (AAV), providing an alternative to glucocorticoids (GCs).1 Despite its promising potential, severe liver dysfunction associated with avacopan has been reported in Japan.2,3.
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OBJECTIVES: To investigate the appropriate timing, useful findings and combination of magnetic resonance imaging (MRI) and ultrasound (US) for predicting the radiographic progression in early rheumatoid arthritis (RA). METHODS: Forty-four active RA patients, who examined by both of MRI and US in the symptomatic wrist and finger joints, were recruited in Nagasaki University Hospital from 2010 to 2017 and treated by the treat-to-target therapeutic strategy for 1 year. MRI was evaluated by RA MRI scoring and US by Outcomes Measures in Rheumatology Clinical Trial, respectively. Plain radiographs were assessed by the Genant-modified Sharp score for the symptomatic side in the same manner as MRI and US. Radiographic progression was defined as an annual increase ≥0.75 at 1 year. Factors associated with radiographic progression were analysed. Also, the optimal combination of MRI and US at each timepoint was considered. RESULTS: Logistic regression model revealed that MRI-proven bone marrow oedema at baseline and 6 months and joint counts of power-Doppler grade ≥2 articular synovitis at 3 or 6 months were significantly associated with radiographic progression at 1 year. CONCLUSION: This study may suggest the favourable timing and combination of MRI and US at each point to predict radiographic progression in patients with early-stage RA.
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Artritis Reumatoide , Enfermedades de la Médula Ósea , Sinovitis , Humanos , Médula Ósea , Progresión de la Enfermedad , Imagen por Resonancia Magnética/métodos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Sinovitis/diagnóstico por imagen , Sinovitis/etiología , Enfermedades de la Médula Ósea/etiología , Enfermedades de la Médula Ósea/complicaciones , Articulaciones de los Dedos/diagnóstico por imagen , Articulaciones de los Dedos/patología , Articulación de la Muñeca/diagnóstico por imagen , Articulación de la Muñeca/patología , Edema/diagnóstico por imagen , Edema/etiologíaRESUMEN
OBJECTIVE: We aimed to compare life prognosis and renal relapse after induction therapy in proliferative (PLN) and pure membranous LN (MLN). METHODS: We retrospectively analysed the cases of 140 of 172 patients with LN who underwent a renal biopsy at our hospital or community hospitals from 1993 to 2016. We determined the complete response (CR) rate at 12 months after the patients had started induction therapy, and we evaluated the predictive factors for CR, life prognosis and renal relapse in PLN and pure MLN. We defined PLN as International Society of Neurology and the Renal Pathology Society (ISN/RPS) Class III or IV and MLN as ISN/RPS Class V. RESULTS: The renal pathology of 99 (70.7%) patients was classified as PLN, and that of the other 41 (29.3%) patients as MLN. Fifty patients (50.5%) with PLN and 22 patients (53.7%) with MLN achieved a CR at 12 months. A multivariate analysis showed that a lower index of chronicity in PLN and a higher total haemolytic complement (CH50) level in MLN were predictive factors for achieving a CR at 12 months. A Kaplan-Meier analysis showed that the life prognosis (P = 0.93) and renal relapse (P = 0.52) were not significantly different between PLN and MLN. CONCLUSIONS: The predictive factors for a CR at 12 months post-induction therapy were index of chronicity in PLN and CH50 level in MLN. There were no significant differences in life prognosis or renal relapse between PLN and MLN in the achievement of a CR at 12 months post-induction therapy.
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Glomerulonefritis Membranosa/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Quimioterapia de Inducción , Nefritis Lúpica/tratamiento farmacológico , Adulto , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Estudios RetrospectivosRESUMEN
OBJECTIVES: To investigate the utility of 18F-FDG PET/CT in the diagnostic procedure of IgG4-related disease (IgG4-RD), we analysed the association between quantitative method of 18F-FDG PET/CT and histological findings. METHODS: Twenty-one patients with IgG4-RD in whom 18F-FDG PET/CT was performed at the time of diagnosis were enrolled. Tissue biopsy was performed at 24 sites in 21 patients. To perform quantitative analysis of 18F-FDG PET/CT imaging, the highest standardised uptake value (SUV) of the pixels (SUVmax) and the average SUV (SUVmean) within the biopsied lesion were measured. The SUVmean of the liver was also measured as a reference. RESULTS: The mean age at diagnosis was 64.6±11.9 years, and the median serum IgG4 level was 650 mg/dl. Histological findings were consistent with IgG4-RD (histopathology-positive) at 19 out of 24 sites. Although there was no significant difference in the values of SUVmax between histopathology-positive and histopathology-negative tissues, the values of SUVmean were significantly higher in the histopathology-positive tissue (4.98 and 3.54, respectively p<0.05). The values of SUVmean/liver were also higher in the histopathology-positive tissue (2.17 and 1.52, respectively p<0.05). To establish a cut-off value of SUVmean to determine which of multiple lesions should be biopsied, a ROC curve was constructed. ROC curve analysis indicated SUVmean=4.07 or SUVmean/liver=1.66 as a cut-off value. CONCLUSIONS: Our present study suggested that quantitative analysis of 18F-FDG-PET/CT imaging might be useful for selecting the biopsy site in IgG4-RD. The calculation of SUVmean, not of SUVmax, is important for evaluating IgG4-RD-related lesions in 18F-FDG PET/CT imaging.
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Fluorodesoxiglucosa F18 , Enfermedad Relacionada con Inmunoglobulina G4 , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , RadiofármacosRESUMEN
BACKGROUND: To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept. METHODS: We enrolled 59 RA patients treated with abatacept from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients' clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. 'Power Doppler (PD) responder' was defined as a patient whose Δtotal PD score over 6 months was greater than the median change. RESULTS: Abatacept significantly improved the clinical disease activity and MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the abatacept introduction (p = 0.016). The ΔSOST and ΔOPG were significantly greater in the PD responders versus the non-PD responders (p = 0.0041 and 0.0073, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) vs. the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, 95% confidence interval [CI] 0.23-0.91, p = 0.043) was an independent predictor of PD responder status. CONCLUSION: Serum levels of bone biomarkers may be useful for predicting RA patients' therapeutic responses to abatacept. TRIAL REGISTRATION: Name of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort study Trial registration number: UMIN000012524 Date of registration: 12/9/2013 URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657.
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Antirreumáticos , Artritis Reumatoide , Abatacept/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores , Estudios de Cohortes , Humanos , Japón , Estudios Prospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: To determine whether specific parameters contribute to clinical outcomes at 1 year post-diagnosis in early rheumatoid arthritis (RA) patients under the 'treat-to-target' strategy in clinical practice. METHODS: We retrospectively analyzed 125 RA patients selected according to the following criteria; the patients' symptom duration was ≤6 months, and none had experience with DMARDs. We evaluated the patients' clinical disease activity at baseline and 1 year of treatment and the musculoskeletal ultrasound (MSUS)-detected synovitis activity at baseline. We performed an analysis to identify parameters that contribute to SDAI remission and the use of biologic/targeted synthetic (b/ts) DMARDs at 1 year post-diagnosis. RESULTS: Forty-seven patients received b/tsDMARDs therapy, and 58 patients achieved SDAI remission at 1 year post-diagnosis. Rheumatoid factor positivity, low patient's/evaluator's global assessment at baseline, and methotrexate use at 1 year post-diagnosis were associated with SDAI remission. The baseline clinical disease activity and MSUS scores were not associated with SDAI remission. Anti-cyclic citrullinated peptide antibody positivity/high titer and high swollen joint counts or the presence of severe synovial hypertrophy at baseline were associated with the use of b/tsDMARDs therapy. CONCLUSION: The value of the expected poor-prognosis factors may be diminished by intensive therapy within the 'windows of opportunity'.
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Artritis Reumatoide/tratamiento farmacológico , Sinovitis/tratamiento farmacológico , Adulto , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/patología , Progresión de la Enfermedad , Femenino , Humanos , Articulaciones/diagnóstico por imagen , Articulaciones/patología , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Factor Reumatoide/análisis , Sinovitis/diagnóstico por imagen , Sinovitis/patologíaRESUMEN
We examined the efficacy and safety of denosumab as treatment for glucocorticoid-induced osteoporosis (GIOP) patients complicated with rheumatic diseases, by measuring patients' lumber bone mineral density (BMD) and bone turnover markers. A total of 66 consecutive patients for whom denosumab was initiated between July 2013 and August 2016 were enrolled and evaluated for 12 months. All of the patients were treated with glucocorticoids for underlying rheumatic diseases. The clinical assessment included measurements of the BMD of the lumbar spine (L2-L4) by a dual-energy X-ray absorptiometry technique and the bone turnover markers N-terminal telopeptide of type 1 collagen (NTX) in urine, serum intact procollagen type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatase (BAP) at baseline, 6 months and 12 months after the start of denosumab treatment. Adverse events (AEs) until 12 months were also analyzed. The mean percentage changes in BMD from baseline to 6 and 12 months were significant (2.85% increase, p < 0.0001 and 4.40% increase, p < 0.0001, respectively) regardless of the prior anti-osteoporotic drugs treatment (16 no transition from anti-osteoporotic drugs, 27 transition from bisphosphonate, 23 transition from teriparatide). The decreases in NTX, P1NP and BAP at 6 and 12 months were also significant. No serious AEs were noted. A multivariable logistic analysis showed that the prednisolone dose at baseline was associated with the clinical response to denosumab. In a real-world setting, denosumab was effective and safe for treating GIOP patients complicated with rheumatic diseases regardless of prior anti-osteoporotic drug treatment.
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Conservadores de la Densidad Ósea/uso terapéutico , Denosumab/uso terapéutico , Glucocorticoides/efectos adversos , Osteoporosis/inducido químicamente , Osteoporosis/tratamiento farmacológico , Enfermedades Reumáticas/complicaciones , Anciano , Fosfatasa Alcalina/sangre , Biomarcadores/metabolismo , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/efectos adversos , Conservadores de la Densidad Ósea/farmacología , Remodelación Ósea/efectos de los fármacos , Denosumab/efectos adversos , Denosumab/farmacología , Difosfonatos/farmacología , Difosfonatos/uso terapéutico , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Osteoporosis/sangre , Osteoporosis/complicaciones , Fracturas Osteoporóticas/epidemiología , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Análisis de Regresión , Enfermedades Reumáticas/tratamiento farmacológico , Resultado del TratamientoAsunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Linfocitos Intraepiteliales/patología , Leucemia Linfocítica Granular Grande/etiología , Lupus Eritematoso Sistémico/complicaciones , Anticuerpos Antivirales/sangre , Enfermedad Crónica , Ciclosporina/uso terapéutico , ADN Viral/sangre , Diverticulitis/complicaciones , Drenaje , Femenino , Reordenamiento Génico de Linfocito T , Herpesvirus Humano 4/inmunología , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Linfocitos Intraepiteliales/virología , Leucemia Linfocítica Granular Grande/patología , Leucemia Linfocítica Granular Grande/virología , Leucopenia/tratamiento farmacológico , Leucopenia/etiología , Vértebras Lumbares , Recuento de Linfocitos , Persona de Mediana Edad , Prednisolona/efectos adversos , Prednisolona/uso terapéutico , Aplasia Pura de Células Rojas/complicaciones , Enfermedades Cutáneas Infecciosas/complicaciones , Espondilitis/complicaciones , Espondilitis/cirugíaRESUMEN
The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1(+/-) mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a(-/-) mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1(+/-) mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring.
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Cicatriz/patología , Factores de Transcripción Forkhead/metabolismo , Queloide/patología , Cicatrización de Heridas/fisiología , Animales , Western Blotting , Cicatriz/metabolismo , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Proteína Forkhead Box O1 , Humanos , Queloide/metabolismo , Macrófagos/inmunología , Ratones , Ratones Noqueados , Microscopía Electrónica de Transmisión , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaAsunto(s)
Azatioprina/efectos adversos , Inmunosupresores/efectos adversos , Leucopenia/inducido químicamente , Leucopenia/genética , Lupus Eritematoso Sistémico/tratamiento farmacológico , Pirofosfatasas/genética , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Variantes FarmacogenómicasRESUMEN
BACKGROUND: Previous studies have shown conflicting evidence regarding the incidence of cancer in patients with systemic lupus erythematosus (SLE) compared with that in healthy individuals. Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus have been widely used to treat SLE; however, their effects on cancer risk remain unclear. We aimed to investigate the incidence of cancer in patients with SLE and determine the potential association between CNI use and cancer risk. METHODS: The standardized incidence ratio (SIR) of cancer among patients with lupus in the Lupus Registry of Nationwide Institutions (LUNA) was calculated based on the age-standardized incidence rate of cancer reported by Japan's Ministry of Health, Labour and Welfare. We also examined the association between CNI exposure and cancer risk, while considering potential confounding factors. The analysis accounted for confounding variables such as age, sex, smoking history, maximum glucocorticoid dose, treatment history with cyclophosphamide, ongoing hydroxychloroquine, Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) value (excluding cancer occurrence), comorbidity of diabetes mellitus, and smoking history. RESULTS: The study included 704 patients with SLE (625 females; 88.8%) with a median age of 44 years [interquartile range (IQR) = 34-55] years. The median past maximum glucocorticoid dose was 40 mg/day [IQR = 30-60 mg/day], and the SDI at registration was 1 [IQR = 0-2]. Among the patients, 246 (35.1%) had smoking histories, and 38 (5.4%) experienced cancer complications. Gynecological malignancies accounted for 63.2% of all cancers. The SIR of cancer in the LUNA cohort was 1.08 (95% confidence interval [CI] = 0.74-1.43). No statistically significant risks of cancer were found in relation to CNI treatment history; the odds ratio using multiple logistic regression was 1.12 (95% CI = 0.42-3.00), the risk ratio using standardization was 1.18 (95% CI = 0.47-2.16), and the risk ratio using inverse probability weighting was 1.8 (95% CI = 0.41-4.66). CONCLUSIONS: The incidence of cancer in patients with SLE in the LUNA cohort did not significantly differ from that in the general population. These findings suggest that CNI treatment in this cohort did not pose a risk factor for cancer development.
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Lupus Eritematoso Sistémico , Neoplasias , Femenino , Humanos , Adulto , Persona de Mediana Edad , Estudios de Cohortes , Inhibidores de la Calcineurina/efectos adversos , Glucocorticoides/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Factores de Riesgo , Sistema de Registros , Neoplasias/inducido químicamente , Neoplasias/epidemiología , Índice de Severidad de la EnfermedadRESUMEN
Activated macrophages at wound sites release many cytokines which positively affect skin wound healing. However, the molecular mechanisms controlling cytokine secretion from macrophages have not been elucidated. In the present study, we performed an RT-PCR analysis and found that 19 small GTPase Rab isoforms were expressed at skin wound sites, with six of them (i.e. Rab3B, Rab27B, Rab30, Rab33A, Rab37, and Rab40C) being upregulated during the inflammation and proliferation/migration phase of skin repair. We also found that gene expression of Rab37 in murine primary and RAW264.7 macrophages was significantly induced after stimulation with LPS. Overexpression of wild type and constitutively active Rab37 in RAW264.7 cells significantly increased TNF-α secretion, whereas knockdown of Rab37 by siRNA significantly decreased it. We also identified 29 putative Rab37-interacting proteins, including the membrane fusion regulating Munc13-1, using liquid chromatography/linear ion trap mass spectrometry (LC-MS/MS). Immunocytochemical analysis further revealed that TNF-α-containing vesicles were colocalized with both Rab37 and Munc13-1 in activated macrophages. Knockdown of Munc13-1 by siRNA significantly decreased TNF-α secretion. Taken together, these findings demonstrate that Rab37 interacts with Munc13-1 to control TNF-α secretion from activated macrophages.
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Macrófagos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Cicatrización de Heridas/inmunología , Proteínas de Unión al GTP rab/metabolismo , Animales , Inmunohistoquímica , Activación de Macrófagos/inmunología , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos ICR , Proteínas del Tejido Nervioso/inmunología , Isoformas de Proteínas/inmunología , ARN Interferente Pequeño , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/inmunología , Proteínas de Unión al GTP rab/inmunologíaRESUMEN
OBJECTIVE: To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting. METHODS: A total of 242 patients with RA who were treated with tofacitinib (n = 161) or baricitinib (n = 81) were enrolled. We evaluated efficacy and safety between tofacitinib and baricitinib using multivariable analyses to avoid confounding. Their clinical disease activity and AEs were evaluated for 24 weeks. RESULTS: The mean (SD) DAS28-ESR change from baseline to 24 weeks was 1.57 (1.55) (tofacitinib) and 1.46 (1.36) (baricitinib). There was no significant difference in the clinical response between the two groups (adjusted mean difference, 0.04; 95% CI, -0.35 to 0.28). The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in the tofacitinib group, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was associated. CONCLUSIONS: Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, there is a possibility that the influence of clinical characteristics on the treatment response differs. The comparison provides useful information to the optimal use of JAK inhibitors in real-world settings.
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Antirreumáticos , Artritis Reumatoide , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Azetidinas , Humanos , Piperidinas/efectos adversos , Purinas , Pirazoles , Pirimidinas/efectos adversos , Pirroles/efectos adversos , Sulfonamidas , Resultado del TratamientoRESUMEN
ABSTRACT: We evaluated the effect of abatacept treatment on osteoclast-related biomarkers and explored whether the biomarkers are associated with the therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept.We enrolled 44 RA patients treated with abatacept from a multicenter prospective ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug therapy. We evaluated the disease activity score (DAS) 28-CRP (C-reactive protein), musculoskeletal ultrasound scores including the total grayscale score (GS)/power Doppler (PD) score and the serum concentrations of isoform 5b of tartrate-resistant acid phosphate (TRACP-5b) and soluble receptor activator of nuclear factor-κB ligand (sRANKL) at baseline and at 3 and 6âmonths of treatment. "PD responder" was defined as a patient whose Δtotal PD score over 6âmonths was greater than the median change of that.Abatacept significantly improved DAS28-CRP as well as the total GS/PD score over 6âmonths. Serum TRACP-5b was significantly elevated and serum sRANKL was significantly decreased at 6âmonths (Pâ<â.0001 and Pâ<â.01, respectively). At 6âmonths, serum sRANKL was significantly decreased in the patients who achieved DAS28-CRP remission and the PD responders but not in those who did not. However, serum TRACP-5b rose regardless of the therapeutic response.Among RA patients treated with abatacept, serum sRANKL decreased in the patients with a good therapeutic response, but serum TRACP-5b elevated paradoxically regardless of the therapeutic response.
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Abatacept/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Osteoclastos/efectos de los fármacos , Abatacept/farmacología , Anciano , Anciano de 80 o más Años , Antirreumáticos/farmacología , Biomarcadores , Proteína C-Reactiva/análisis , Femenino , Humanos , Japón , Masculino , Metotrexato/uso terapéutico , Estudios Prospectivos , Ligando RANK/biosíntesis , Inducción de Remisión , Índice de Severidad de la Enfermedad , Fosfatasa Ácida Tartratorresistente/biosíntesisRESUMEN
ABSTRACT: We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs.
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Artritis Reumatoide/clasificación , Artritis Reumatoide/diagnóstico por imagen , Ultrasonografía/métodos , Anciano , Artritis Reumatoide/tratamiento farmacológico , Estudios de Cohortes , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Ultrasonografía/normasRESUMEN
To compare therapeutic efficacy of tumour necrosis factor inhibitor (TNFi) cyclers and non-TNFi switchers in patients with rheumatoid arthritis (RA) having inadequate response to previous TNFis (TNF-IR patients) using composite measures including imaging assessment with power Doppler ultrasonography (PDUS). Patients with RA who had inadequate response to one or more previous TNFi agents with moderate or higher disease activity were enrolled. The outcomes of 56 TNF-IR patients were analysed. Patients were divided into 19 TNFi cyclers and 37 non-TNFi switchers (16 abatacept [ABT] and 21 tocilizumab [TCZ] switchers). Retention ratio at 6 months was significantly higher in non-TNFi switchers than in TNFi cyclers (p < .05). Although there was no significant difference, non-TNFi switchers tended to have a larger decrease than TNFi cyclers in efficacy indicators based on clinical disease activity index and PDUS. Multivariate logistic regression analysis identified a following independent factor associated with both EULAR good response and retention of a biologic agent: non-TNFi switch (p < .05 for both). Non-TNFi switchers were shown to have significantly higher percentage of EULAR good response and higher retention than TNFi cyclers. A non-TNFi biologic agent may hence be a preferential next-line treatment for TNF-IR patients.
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Abatacept/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antirreumáticos/administración & dosificación , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Sustitución de Medicamentos , Inhibidores del Factor de Necrosis Tumoral/administración & dosificación , Ultrasonografía , Abatacept/efectos adversos , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Estudios de Cohortes , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/efectos adversosRESUMEN
RATIONALE: Mucormycosis is a rare opportunistic fungal infection with poor prognosis. The incidence of mucormycosis has been increasing, and it is a threat to immunocompromised hosts. We present a case of gastric mucormycosis complicated by a gastropleural fistula during immunosuppressive treatment for adult-onset Still disease (AOSD). PATIENT CONCERNS: An 82-year-old woman diagnosed with AOSD who developed gastric ulcers during the administration of an immunosuppressive therapy with corticosteroids, cyclosporine, and tocilizumab complained of melena and epigastralgia. Esophagogastroduodenoscopy showed multiple ulcers covered with grayish or greenish exudates. DIAGNOSES: The patient diagnosed with mucormycosis based on culture and biopsy of the ulcers, which showed nonseptate hyphae branching at wide angles. Mucor indicus was identified using polymerase chain reaction. INTERVENTIONS AND OUTCOMES: Although liposomal amphotericin B was administered, gastric mucormycosis was found to be complicated by a gastropleural fistula. The patient died because of pneumonia due to cytomegalovirus infection, and autopsy revealed the presence of Mucorales around the fistula connecting the stomach and diaphragm. LESSONS: Gastric mucormycosis is refractory to treatment and fatal. Surgical resection, if possible, along with antifungal drugs can result in better outcomes.
Asunto(s)
Fístula Gástrica/microbiología , Mucormicosis/complicaciones , Infecciones Oportunistas/complicaciones , Fístula del Sistema Respiratorio/microbiología , Úlcera Gástrica/microbiología , Anciano de 80 o más Años , Femenino , Fístula Gástrica/inducido químicamente , Humanos , Inmunosupresores/efectos adversos , Mucormicosis/inducido químicamente , Mucormicosis/microbiología , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/microbiología , Pleura/microbiología , Fístula del Sistema Respiratorio/inducido químicamente , Enfermedad de Still del Adulto/tratamiento farmacológico , Úlcera Gástrica/inducido químicamenteRESUMEN
A 44-year-old female with rheumatoid arthritis treated with methotrexate (MTX) and tocilizumab (TCZ) was admitted to our hospital with nasal pain. Nasal fiberscopy revealed septum perforation, while a membrane biopsy indicated granuloma and fibrinoid necrosis of the small artery. The patient was treated with prednisolone 30 mg/day after discontinuation of MTX and TCZ. Inguinal lymph node biopsy revealed diffuse infiltrations of atypical T-cells and Epstein-Barr virus-positive B cells. The patient was diagnosed with peripheral T-cell lymphoma due to MTX-associated lymphoproliferative disorder (MTX-LPD). We herein describe the case of a patient with nasal septum perforation due to MTX-LPD mimicking granulomatosis with polyangiitis.
Asunto(s)
Antirreumáticos/efectos adversos , Artritis Reumatoide/complicaciones , Trastornos Linfoproliferativos/inducido químicamente , Metotrexato/efectos adversos , Perforación del Tabique Nasal/etiología , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Biopsia , Diagnóstico Diferencial , Quimioterapia Combinada , Femenino , Humanos , Ganglios Linfáticos/patología , Trastornos Linfoproliferativos/complicaciones , Metotrexato/uso terapéutico , Tabique Nasal/patologíaRESUMEN
RATIONALE: Rare cases of reactive arthritis induced by active extra-articular tuberculosis (Poncet disease) have been reported. Complete response to antitubercular treatment and evidence of active extra-articular tuberculosis are the most important clinical features of Poncet disease. We report the case of successfully treated a patient with reactive arthritis induced by active extra-articular tuberculosis with a TNF inhibitor after sufficient antitubercular treatment. PATIENT CONCERNS: A 56-year-old Japanese man was admitted to our department with polyarthralgia, low back pain, and high fever. The results of rheumatoid factor, anti-citrullinated protein antibody, human leukocyte antigen B27, and the assays for the detection of infections (with an exception of T-SPOT.TB) were all negative. Fluoro-deoxy-D-glucose-positron emission tomography with CT (PET/CT) showed moderate uptake in the right cervical, right supraclavicular, mediastinal, and abdominal lymph nodes. As magnetic resonance imaging and power Doppler ultrasonography showed peripheral inflammation (tendinitis, tenosynovitis, ligamentitis, and enthesitis in the limbs). DIAGNOSIS: A diagnosis of tuberculous lymphadenitis was eventually established on the basis of lymph node biopsy results. There was no evidence of a bacterial infection including acid-fast bacteria in his joints, and the symptoms of polyarthralgia and low back pain were improved but not completely resolved with NSAID therapy; in addition, a diagnosis of reactive arthritis induced by active extraarticular tuberculosis was made. INTERVENTIONS: The patient experienced persistent peripheral inflammation despite antitubercular treatment for more than nine months and was then successfully treated with a tumor necrosis factor inhibitor (adalimumab 40 mg every 2 weeks). OUTCOMES: Finally, the patient responded to the treatment and has been in remission for over 4 months as of this writing. LESSONS: In patients who present with symptoms associated with spondyloarthritis, it is important to distinguish between classic reactive arthritis and reactive arthritis induced by extra-articular tuberculosis infection. Introduction of biological agents should be carefully considered in settings where reactive arthritis induced by active extra-articular tuberculosis shows progression to chronicity despite sufficient antitubercular treatment.
Asunto(s)
Antituberculosos/uso terapéutico , Artritis Reactiva/etiología , Tuberculosis Ganglionar/complicaciones , Tuberculosis Ganglionar/tratamiento farmacológico , Artritis Reactiva/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Tuberculosis Ganglionar/diagnósticoRESUMEN
RATIONALE: Severe fever with thrombocytopenia syndrome (SFTS) is a recently recognized fatal infectious disease caused by the SFTS virus, and severe cases are complicated by the presence of hemophagocytic lymphohistiocytosis (HLH) associated with a cytokine storm. Herein, we report on serial changes of serum cytokine levels and viral load in a severe case of SFTS. PATIENT CONCERNS: A 63-year-old Japanese woman presented with high-grade fever, abdominal pain, diarrhea, impaired consciousness, leukocytopenia, and thrombocytopenia. DIAGNOSIS: SFTS was diagnosed based on a positive serum test for SFTS virus RNA and electroencephalogram (EEG) findings of encephalopathy. INTERVENTIONS: The patient was treated with supportive therapy, including steroid pulse therapy (intravenous methylprednisolone 1âg/d for 3 days) for HLH and intravenous recombinant thrombomodulin 19200âU/d for 7 days for disseminated intravascular coagulation. OUTCOMES: Treatment for 7 days improved both symptoms and abnormal EEG findings, and SFTS virus RNA disappeared from the serum at day 10 from the onset of symptoms. The serum cytokines and chemokines analysis during the clinical course revealed 2 distinct phases: the acute phase and the recovery phase. The cytokines and chemokines elevated in the acute phase included interleukin (IL)-6, IL-10, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, interferon-γ-induced protein-10, and fractalkine, while the IL-1ß, IL-12p40, IL-17, and vascular endothelial growth factor levels were higher in the recovery phase. CONCLUSION: These observations suggest that the cytokines and chemokines elevated in the acute phase may reflect the disease severity resulted in a cytokine storm, while those in the recovery phase may be attributed to T-cell activation and differentiation.