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OBJECTIVE: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). METHODS: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models. RESULTS: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens. CONCLUSION: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset.
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Antirreumáticos , Artritis Reumatoide , Trastornos Linfoproliferativos , Metotrexato , Inhibidores del Factor de Necrosis Tumoral , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Trastornos Linfoproliferativos/inducido químicamente , Masculino , Femenino , Persona de Mediana Edad , Metotrexato/uso terapéutico , Anciano , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Japón , Tacrolimus/uso terapéutico , Tacrolimus/efectos adversos , Quimioterapia Combinada , Infecciones por Virus de Epstein-Barr/complicaciones , AdultoRESUMEN
Gigantomastia is characterised by excessive breast growth and can occur as a rare, drug-induced adverse event. D-penicillamine is the most frequent cause of drug-induced gigantomastia. Only one case of gigantomastia due to bucillamine, an analogue of D-penicillamine, has been reported so far. We herein report a case of bucillamine-induced gigantomastia presenting with acute enlargement of the bilateral breasts and accessory breast tissue in the axillae 7 months after the start of bucillamine therapy. Awareness about this rare adverse event is important since bucillamine is still widely used in Japan and Korea.
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Antiinflamatorios no Esteroideos/efectos adversos , Mama/anomalías , Cisteína/análogos & derivados , Galactorrea/metabolismo , Hiperprolactinemia/metabolismo , Hipertrofia/diagnóstico , Hipertrofia/etiología , Mama/metabolismo , Cisteína/efectos adversos , Susceptibilidad a Enfermedades , Femenino , Humanos , Hiperprolactinemia/diagnóstico , Hipertrofia/metabolismo , Japón , República de CoreaRESUMEN
This study aimed to describe the utility of the neutrophil-to-lymphocyte ratio (NLR) for predicting bacterial infections in patients with rheumatoid arthritis (RA) treated with Tocilizumab (TCZ). We extracted RA patients treated with TCZ in whom an infection developed between April 2008 and March 2018 from our hospital database. We divided these patients into the bacterial infection and non-bacterial infection groups and compared their background, C-reactive protein (CRP) values, white blood cell count (WBC), the NLR at the time of infection diagnosis, and the ratio of the NLR at the time of infection diagnosis (post-NLR) to the NLR at baseline (pre-NLR). Of the 196 patients who received TCZ, 21 experienced a bacterial infection and 20 had a non-bacterial infection. The median CRP level, WBC count, post-NLR, and post-NLR/pre-NLR ratio in the bacterial infection group were significantly higher than in the non-bacterial infection group. In receiver operating characteristics (ROC) curve analysis for predicting bacterial infection, the area under the curve (AUC) for CRP, WBC, NLR, and the post-NLR/pre-NLR ratio were 0.787, 0.857, 0.887, and 0.975, respectively. The cut-off value of 2.25 for the post-NLR/pre-NLR ratio showed the greatest sensitivity (90.5%) and specificity (100%). The post-NLR/pre-NLR ratio may be a useful surrogate marker for predicting bacterial infections in patients with RA treated with TCZ.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Infecciones Bacterianas/sangre , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/farmacología , Antirreumáticos/efectos adversos , Antirreumáticos/farmacología , Artritis Reumatoide/complicaciones , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/diagnóstico , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Femenino , Humanos , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: Susceptibility genes that can account for characteristic features of SSc such as fibrosis, vasculopathy and autoimmunity remain to be determined. In mice, deficiency of Friend leukaemia integration 1 transcription factor (Fli1) causes SSc-like disease with these features. The human FLI1 gene contains (GA)n microsatellite, which has been shown to be associated with expression level. Because microsatellite polymorphisms are difficult to capture by genome-wide association studies, we directly genotyped FLI1 (GA)n microsatellite and examined its association with SSc. METHODS: Genomic DNA from 639 Japanese SSc patients and 851 healthy controls was genotyped for (GA)n microsatellite using the fragment assay. The cut-off repeat number for susceptibility to SSc was determined by receiver operating characteristics (ROC) analysis. Association with susceptibility and clinical characteristics was examined using logistic regression analysis. FLI1 mRNA levels were determined using quantitative RT-PCR. RESULTS: Based on the ROC analysis, (GA)n alleles with ≥22 repeats were collectively defined as L alleles and alleles with ≤21 repeats as S alleles. (GA)n L alleles were significantly associated with susceptibility to SSc (P = 5.0e-04, odds ratio 1.34, additive model). Significant association was observed both in diffuse cutaneous and limited cutaneous SSc. Among the SSc, (GA)n L alleles were significantly enriched in the patients with a modified Rodnan total skin thickness score ≥10 compared with those with a score <10. FLI1 mRNA levels were significantly decreased in healthy controls carrying (GA)n L alleles as compared with non-carriers. CONCLUSION: Extended repeat alleles of FLI1 (GA)n microsatellite may be associated with lower FLI1 mRNA levels and susceptibility to human SSc.
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Repeticiones de Microsatélite/genética , Proteína Proto-Oncogénica c-fli-1/genética , ARN Mensajero/metabolismo , Esclerodermia Sistémica/genética , Adulto , Anciano , Femenino , Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genética , Proteína Proto-Oncogénica c-fli-1/metabolismo , Esclerodermia Sistémica/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: We aimed to standardize the definition of low disease activity in rheumatoid arthritis (RA) using the Outcome Measures in Rheumatology (OMERACT) group's proposed definition of minimal disease activity. METHOD: Based on a nationwide RA database, we proposed new Boolean low disease activity criteria using OMERACT's core set definition of minimal disease activity that requires the fulfillment of at least five of the following seven core set measures: a pain score of 2 or less, a swollen joint count (SJC28) of 1 or fewer, a tender joint count of 1 or fewer, a Health Assessment Questionnaire score of 0.5 or less, a Physician's Global Assessment score of 1.5 or less, a Patient's Global Assessment score of 2 or less, and an erythrocyte sedimentation rate (ESR) of 20 mm/h or less. Using receiver operating characteristic analysis, we determined the cutoffs for the Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Routine Assessment of Patient Index Data 3 (RAPID3), and the Disease Activity Score in 28 joints (DAS28)-ESR. RESULTS: Of 8298 patients, 56.2% met the proposed Boolean low disease activity criteria. We determined an SDAI score of 5.5 or less and a CDAI score of 5 or less to be the new cutoffs, and we chose a DAS28 of 2.85 or less (the original cutoff for DAS-based minimal disease activity) and a RAPID3 score of 6 or less (the original cutoff for RAPID3-based low disease activity) with or without a swollen joint count (SJC) (SJC of 2 or fewer) as the cutoffs for DAS28 and RAPID3. The agreement between the new cutoffs for DAS28 of 2.85 or less vs. CDAI score of 5 or less, CDAI score of 5 or less vs. RAPID3 score of 6 or less (with SJC of 2 or fewer), and DAS28 of 2.85 or less vs. RAPID3 score of 6 or less (with SJC of 2 or fewer), was 0.619, 0.612 (0.702), and 0.474 (0.531), respectively. CONCLUSION: OMERACT's minimal disease activity definition may be used to standardize the criteria for low disease activity.
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Objective: The human leukocyte antigen (HLA) is the strongest genetic risk factor for idiopathic inflammatory myopathy (IIM), and different HLA alleles have been reported to be associated with IIM susceptibility among different ethnic groups. In this study, we have investigated HLA alleles associated with IIM in Japanese patients.Methods: Genotyping of HLA-DRB1 and DPB1 were performed in 252 Japanese IIM patients (166 dermatomyositis [DM] and 86 polymyositis [PM] patients) and the association was analyzed with comparison to controls (n = 1026 for DRB1 and n = 413 for DPB1).Results: DRB1*08:03 was associated with IIM (p = 1.60 × 10-5, pc = .0005, odds ratio [OR] 2.11, 95% confidence interval [CI] 1.52-2.92) and DM (p = .0004, pc = .0128, OR 2.06, 95%CI 1.40-3.02). DPB1*05:01 was also associated with IIM (p = .0001, pc = .0021, OR 1.96, 95%CI 1.38-2.77) and DM (p = .0005, pc = .0075, OR 2.05, 95%CI 1.37-3.08). DRB1*09:01 (p = .0012, pc = .0368, OR 0.35, 95% CI 0.18-0.69) and DPB1*04:01(p = .0004, pc = .0057, OR 0.05, 95% CI 0.00-0.85) were protectively associated with PM. Two locus analyses suggested that DRB1*09:01 and DPB1*04:01 were independently associated with PM.Conclusion: Protective associations of HLA were detected in Japanese PM patients.
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Alelos , Cadenas beta de HLA-DP/genética , Cadenas HLA-DRB1/genética , Miositis/genética , Adulto , Femenino , Predisposición Genética a la Enfermedad , Humanos , Japón , Masculino , Persona de Mediana EdadRESUMEN
Genome-wide association studies of systemic lupus erythematosus (SLE) in Chinese and Korean populations demonstrated strong association of single nucleotide polymorphisms (SNPs) located in the GTF2I-NCF1 region, rs73366469 (GTF2I), rs117026326 (GTF2I), rs80346167(GTF2IRD1) and rs201802880 (NCF1). This region has also been associated with susceptibility to Sjögren syndrome and rheumatoid arthritis; however, association studies with systemic sclerosis (SSc) and ANCA-associated vasculitis (AAV) have not been reported. Here we made an attempt to confirm their associations with SLE in the Japanese population, to find the primarily associated SNP, and to investigate whether these SNPs are also associated with susceptibility to SSc and AAV. By genotyping these four SNPs on 842 SLE, 467 SSc, 477 AAV patients and 934 healthy controls, striking association was confirmed in Japanese SLE. In addition, these SNPs were significantly associated with susceptibility to SSc, but not with AAV. Conditional logistic regression analysis revealed that the association of NCF1 rs201802880, a missense SNP encoding p.Arg90His, can account for the association of other SNPs by linkage disequilibrium. These results suggested that GTF2I-NCF1 region is associated with susceptibility to multiple autoimmune rheumatic diseases but not with AAV, and the primarily associated variant may be the missense SNP in NCF1.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Pueblo Asiatico/genética , Lupus Eritematoso Sistémico/epidemiología , NADPH Oxidasas/genética , Polimorfismo de Nucleótido Simple , Esclerodermia Sistémica/epidemiología , Adulto , Edad de Inicio , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Japón/epidemiología , Desequilibrio de Ligamiento , Lupus Eritematoso Sistémico/genética , Masculino , Prevalencia , Esclerodermia Sistémica/genética , Adulto JovenRESUMEN
This study aimed to examine the characteristics of patients with systemic lupus erythematosus (SLE) visiting the emergency department (ED) and the risk factors of an ED visit by these patients. This 4-year retrospective study was performed at a tertiary care center in Japan. We included all 205 patients with SLE who were treated in our outpatient clinic between April 1, 2008 and March 31, 2012 and divided them into two groups: those who visited the ED (the ED-user group) and those who did not (the ED-non-user group). We statistically compared the patient backgrounds and characteristics of the groups and identified the risk factors of an ED visit. Of all the patients, 118 visited the ED during study period and 87 did not. In total, 269 events were identified in the ED-user group. Of these, 91 (33.8%) were cases of infection, 32 (11.9%) were orthopedic problems, 32 (11.9%) were cases of gastrointestinal disease, 31 (11.5%) were cases of neurological disease, and 25 (9.3%) were cardiovascular events. Twenty-four events (8.9%) were due to SLE flares, of which ten (41.7%) were cases of neuropsychiatric lupus (NPSLE). The glucocorticoid dosage and the presence of a psychiatric illness, NPSLE, and lupus nephritis were higher among the ED-user group. Multivariate logistic regression analysis demonstrated high glucocorticoid dosage to be a risk factor of an ED visit. Among SLE patients, infections were the principal reason for visiting the ED. The most common reasons for an ED visit were common diseases rather than flares.
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Servicio de Urgencia en Hospital , Glucocorticoides/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adulto , Anciano , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/terapia , Progresión de la Enfermedad , Femenino , Glucocorticoides/administración & dosificación , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Nefritis Lúpica/epidemiología , Nefritis Lúpica/terapia , Vasculitis por Lupus del Sistema Nervioso Central/epidemiología , Vasculitis por Lupus del Sistema Nervioso Central/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Centros de Atención Terciaria , Tokio/epidemiologíaRESUMEN
OBJECTIVE: To evaluate the effect of sulfasalazine (SSZ) on the presence of Pneumocystis jirovecii (P. jirovecii) in the lungs of rheumatoid arthritis (RA) patients. METHODS: We retrospectively studied episodes of suspected P. jirovecii pneumonia (PJP) which were examined for P. jirovecii with polymerase chain reaction (PCR). We employed a test negative design case-control study; the cases were episodes of suspected PJP that were positive for PCR, and the controls were episodes of suspected PJP that were negative for PCR. The odds ratio for the positive PCR result associated with SSZ use was estimated by Firth's logistic regression. RESULTS: Between 2003 and 2017, 36 cases and 83 controls were identified. While none of the cases received SSZ before the episode, 18 of the controls received the drug. In the primary analysis involving all the episodes, SSZ use was negatively associated with PCR positivity (adjusted odds ratio, 0.087; confidence interval, <0.001-0.789). The sensitivity analysis, excluding those who received PJP prophylaxis, showed the same association as the primary analysis (adjusted odds ratio 0.085, 95% CI <0.001-0.790). CONCLUSION: This study demonstrated that SSZ use is associated with the absence of P. jirovecii in the lung, suggesting the preventive efficacy of the drug against PJP.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Neumonía por Pneumocystis/epidemiología , Sulfasalazina/uso terapéutico , Adulto , Anciano , Antirreumáticos/farmacología , Femenino , Humanos , Pulmón/microbiología , Masculino , Persona de Mediana Edad , Pneumocystis carinii/efectos de los fármacos , Pneumocystis carinii/patogenicidad , Sulfasalazina/farmacologíaRESUMEN
Objective: To examine the clinical characteristics and severity of community-acquired pneumonia (CAP) between patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ) and those treated with TNF inhibitors. Methods: We extracted RA patients treated with biological DMARDs who developed CAP between 2003 and 2015 from our hospital database. We compared the patient backgrounds, duration from the onset of symptoms to diagnosis, and the severity of CAP between patients who developed CAP after treatment with TCZ or tumor necrosis factor (TNF) inhibitor. Results: Of 98 patients who received TCZ, seven developed CAP (IL-6 inhibitor group). Of 560 patients who received TNF inhibitors, 27 developed CAP (TNF inhibitor group). Between the two groups, there was no difference in the duration from the onset of symptoms to diagnosis (7 [4-21], 7 days [1-15]). The IL-6 inhibitor group had a lower body temperature (36.5 °C [36.4-36.8], 37.8 °C [35.9-40.5]) and CRP level (0.09 mg/dL [0.02-2.5], 6.76 mg/dL [0.63-15.2]) at diagnosis than the TNF inhibitor group. The CURB-65 score did not differ significantly between groups. Conclusion: There were no delays in the diagnosis of CAP or any difference in the severity of CAP between patients with RA treated with TCZ and those treated with TNF-inhibitors.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/epidemiología , Neumonía/epidemiología , Adulto , Artritis Reumatoide/complicaciones , Infecciones Comunitarias Adquiridas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía/patología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
OBJECTIVES: To evaluate the prophylactic effect of sulfasalazine against Pneumocystis jirovecii pneumonia (PJP) among rheumatoid arthritis (RA) patients. METHODS: We used a nationwide Japanese multicenter RA database to extract data from 2005 and 2014. To identify PJP cases, we selected patients hospitalized for PJP and verified their diagnosis. Two control groups, one unmatched and the other matched for age, sex, glucocorticoid, methotrexate, and tacrolimus dosage, and the use (and type, if used) of biological disease-modifying antirheumatic drug were selected by incidence-density sampling. The odds ratios for PJP associated with sulfasalazine use and other clinical factors were estimated by exact and standard conditional logistic regression. RESULTS: From 18,668 participants, 60 cases, 356 unmatched controls, and 337 matched controls were selected. None of the cases received sulfasalazine before PJP onset. A comparison of the cases with the unmatched controls showed that sulfasalazine use carried a decreased risk of PJP (adjusted odds ratio 0.18, 95% confidence interval 0.00-0.92). A comparison of the cases and matched controls also showed that sulfasalazine use had a decreased risk of PJP (0.08, 0.00-0.36). In an analysis of the cases and unmatched controls who did not receive sulfasalazine, an increased risk of PJP was associated with lung disease (3.88, 1.89-7.95) and the use of glucocorticoid (5.71, 2.68-12.19), methotrexate (5.25, 2.01-13.74), and tumor necrosis factor inhibitors (2.32, 1.10-4.93). CONCLUSIONS: The results of this nested case-control study demonstrated the preventive effect of sulfasalazine against PJP. The results await confirmation by future prospective studies.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Neumonía por Pneumocystis/prevención & control , Sulfasalazina/uso terapéutico , Anciano , Estudios de Casos y Controles , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Japón , Masculino , Persona de Mediana Edad , Neumonía por Pneumocystis/epidemiología , RiesgoRESUMEN
OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized with joint destructions; environmental and genetic factors were thought to be involved in the etiology of RA. The production of anti-citrullinated peptide antibodies (ACPA) is specifically associated with RA. DRB1 is associated with the susceptibility of RA, especially ACPA-positive RA [ACPA(+)RA]. However, a few studies reported on the independent associations of DPB1 alleles with RA susceptibility. Thus, we investigated the independent association of DPB1 alleles with RA in Japanese populations. METHODS: Association analyses of DPB1 were conducted by logistic regression analysis in 1667 RA patients and 413 controls. RESULTS: In unconditioned analysis, DPB1*04:02 was nominally associated with the susceptibility of ACPA(+)RA (P = 0.0021, corrected P (Pc) = 0.0275, odds ratio [OR] 1.52, 95% confidence interval [CI] 1.16-1.99). A significant association of DPB1*02:01 with the susceptibility of ACPA(+)RA was observed, when conditioned on DRB1 (Padjusted = 0.0003, Pcadjusted = 0.0040, ORadjusted 1.47, 95%CI 1.19-1.81). DPB1*05:01 was tended to be associated with the protection against ACPA(+)RA, when conditioned on DRB1 (Padjusted = 0.0091, Pcadjusted = 0.1184, ORadjusted 0.78, 95%CI 0.65-0.94). When conditioned on DRB1, the association of DPB1*04:02 with ACPA(+)RA was disappeared. No association of DPB1 alleles with ACPA-negative RA was detected. CONCLUSION: The independent association of DPB1*02:01 with Japanese ACPA(+)RA was identified.
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Artritis Reumatoide/genética , Cadenas beta de HLA-DP/genética , Adulto , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Japón , Masculino , Persona de Mediana EdadRESUMEN
To compare Pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA) with PCP in patients with non-RA connective tissue diseases (CTDs) in order to clarify the characteristics of the former. We extracted consecutive patients satisfying the following criteria for "clinical PCP": (1) positive plasma ß-D-glucan, (2) PCP-compatible computed tomography findings of the lung, and (3) successful treatment with antipneumocystic antibiotics. Patients who underwent methylprednisolone "pulse" therapy or sufficient antibiotics to cure bacterial pneumonia were excluded. We used the t test, U test, or Fischer's exact probability test to compare the two groups and Jonckheere-Terpstra's test and Ryan's procedure for the trend test. Thirty-five cases were extracted. The underlying rheumatic diseases were RA in 25 and non-RA CTDs in ten. At the onset of clinical PCP, the lymphocyte counts were 884 vs 357/mm3 (p < 0.001), PC-PCR positivity 64% vs 100% (p = 0.029), glucocorticoid dose 4.0 vs 17.5 mg PSL/day (p < 0.001), and methotrexate dose 8 vs 0 mg/week (p = 0.003). The PC-PCR-negative patients, observed only in the RA group, were all receiving methotrexate (MTX) therapy except one patient who was receiving high-dose prednisolone alone. All PC-PCR-positive patients were receiving glucocorticoid, TNF inhibitor, or a non-MTX immunosuppressant. No patient with MTX alone had positive PC-PCR results. Clinical PCP in RA patients differed from that in non-RA CTD patients and may be understood as only a part of the rheumatoid-specific interstitial lung injury spectrum influenced by multiple, synergistic factors including MTX, Pneumocystis, and RA itself.
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Artritis Reumatoide/complicaciones , Enfermedades del Tejido Conjuntivo/complicaciones , Inmunosupresores/administración & dosificación , Enfermedades Pulmonares Intersticiales/complicaciones , Neumonía por Pneumocystis/tratamiento farmacológico , Anciano , Antibacterianos/uso terapéutico , Artritis Reumatoide/microbiología , Enfermedades del Tejido Conjuntivo/microbiología , Femenino , Glucocorticoides/administración & dosificación , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Neumonía por Pneumocystis/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , beta-Glucanos/sangreRESUMEN
No studies have yet reported the influence of swelling in individual joints on serum C-reactive protein and erythrocyte sedimentation rate. To examine this association, we used data from the NinJa registry, the largest registry of rheumatoid arthritis patients in Japan. Sixty-six palpable joints were categorized by size into three groups (small, medium-sized, and knees) with surface area cutoffs of 10 and 100 cm2. Of 10,720 cases registered in NinJa in 2012, 8444 cases with either no swollen joints or swelling limited to one joint-size category were analyzed. Groups with larger numbers of swollen joints showed higher levels of both markers in each joint-size category. Groups with larger swollen joints had higher levels of both markers compared with groups with the same number of (smaller) swollen joints. Linear regression revealed that the increments of C-reactive protein (mg/dL/joint) and erythrocyte sedimentation rate (mm/1 h/joint) were 0.056 and 0.89, 0.24 and 5.0, and 0.46 and 8.9 for small and medium-sized joints and knee joints, respectively. The levels of systemic inflammation markers increased with the involvement of larger and/or more joints. These results were successfully illustrated by the use of large-scale data, which eliminated wide intragroup scattering of the marker values.
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Artritis Reumatoide/sangre , Sedimentación Sanguínea , Proteína C-Reactiva/química , Articulaciones/fisiopatología , Anciano , Estudios Transversales , Femenino , Marcadores Genéticos , Humanos , Inflamación , Japón , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Análisis de Regresión , Sinovitis/sangreRESUMEN
HLA-G plays a role in fetal-maternal tolerance as well as immunoregulation, and has been suggested to be involved in autoimmune diseases and cancers. HLA-G encodes two potentially functional polymorphisms in the 3' untranslated region, 14bp insertion/deletion (14bp indel, rs371194629) and a single nucleotide polymorphism rs1063320, previously reported to affect HLA-G expression level or splicing isoform and to be associated with susceptibility to systemic lupus erythematosus (SLE). However, the results of SLE association studies are inconsistent, probably due to the small sample size of each study and lack of consideration of linkage disequilibrium (LD) with HLA-class II haplotypes in each population. In this study, we performed association studies of these polymorphisms on 843 patients with SLE and 778 healthy controls in a Japanese population, in many of whom HLA-DRB1 alleles have been genotyped at the four-digit level. LD was detected between DRB1*13:02, protective against multiple autoimmune diseases in the Japanese, and the rs1063320 G (D' = 0.86, r2 = 0.02) and with 14bp del (D' = 0.62, r2 = 0.01), but not between SLE-susceptible DRB1*15:01 and HLA-G. Although significant association with overall SLE was not detected, 14bp ins allele was significantly associated with SLE with the age of onset <20 years, when compared with healthy controls (P = 0.0067, PFDR = 0.039, OR 1.44, additive model) or with SLE patients with the age of onset ≥20 (P = 0.033, PFDR = 0.0495, OR 2.09, additive model). This association remained significant after conditioning on DRB1*13:02 or DRB1*15:01. On the other hand, significant association was detected between rs1063320 C and anti-RNP antibody and anti-Sm antibody positive SLE, which was dependent on negative LD with DRB1*13:02. eQTL analysis showed reduced HLA-G mRNA level in 14bp ins/ins individuals. In conclusion, our observations showed that HLA-G 14bp ins allele represents a genetic contribution on early-onset SLE independent of DRB1.
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Regiones no Traducidas 3'/genética , Pueblo Asiatico/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Antígenos HLA-G/genética , Lupus Eritematoso Sistémico/genética , Polimorfismo Genético , Polimorfismo de Nucleótido Simple/genética , Edad de Inicio , Emparejamiento Base/genética , Estudios de Casos y Controles , Cadenas HLA-DRB1/genética , Haplotipos/genética , Humanos , Mutación INDEL/genética , Desequilibrio de Ligamiento/genética , Modelos Logísticos , Sitios de Carácter Cuantitativo/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
OBJECTIVES: Chronic lung diseases including interstitial lung disease and airway disease (AD) occur in RA patients. Interstitial lung disease and AD in RA are extra-articular manifestations that influence the prognosis quoad vitam of RA. Studies on associations of HLA alleles with RA have been carried out, and shared epitopes of several alleles are reported to be associated with RA susceptibility. Few association studies in RA subpopulations with chronic lung diseases have been conducted. The aim of the study was to identify HLA alleles predisposing to RA phenotypes including the presence of AD. METHODS: Associations of HLA-DRB1 and DQB1 alleles with chronic lung diseases in RA were analysed. RESULTS: A positive association was found between the DR4 serological group and resistance to usual interstitial pneumonia [P = 0.0250, odds ratio (OR) 0.62, 95% CI: 0.41, 0.93]. The DR2 serological group was associated with susceptibility to usual interstitial pneumonia (P = 0.0036, OR = 1.86, 95% CI: 1.23, 2.81). An association was found for shared epitopes alleles with bronchiolitic AD (P = 0.0040, OR = 2.06, 95% CI: 1.24, 3.41). DQB1*03:01 was associated with bronchiectatic AD (P = 0.0021, corrected P-value (Pc) = 0.0315, OR = 1.99, 95% CI: 1.30, 3.06), as well as with emphysema (P = 0.0007, Pc = 0.0104, OR = 2.43, 95% CI: 1.49, 3.95). In combined analysis, a predisposing association of DQB1*03:01 (P = 1.94 ×10(-5), Pc = 0.0003, OR = 2.16, 95% CI: 1.53, 3.06) and a negative association of DQB1*03:02 (P = 0.0008, Pc = 0.0117, OR = 0.33, 95% CI: 0.17, 0.67) with bronchiectatic AD or emphysema were observed in RA. CONCLUSION: The present study identified an association of HLA-DQB1*03:01 with predisposition to, and DQB1*03:02 with resistance to, bronchiectatic AD or emphysema in RA.
Asunto(s)
Artritis Reumatoide/complicaciones , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Enfermedades Pulmonares Intersticiales/genética , Enfisema Pulmonar/genética , Anciano , Alelos , Artritis Reumatoide/genética , Epítopos , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , FenotipoRESUMEN
OBJECTIVE: Several studies on associations between human leukocyte antigen (HLA) allele frequencies and susceptibility to systemic sclerosis (SSc) have been reported. Anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies (ATA) are found in SSc patients. Here, we sought to identify HLA alleles associated with SSc in Japanese, and explored their associations with SSc phenotypes including the presence of autoantibodies. METHODS: Associations of HLA-DRB1, DQB1, and DPB1 were analyzed in 463 Japanese SSc patients and 413 controls. RESULTS: We found that DRB1*13:02 (P = 0.0011, Pc = 0.0319, odds ratio [OR] 0.46, 95% confidence interval [CI] 0.29-0.73), DRB1*14:06 (P = 6.60X10-5, Pc = 0.0020, OR 0.05, 95%CI 0.01-0.41), DQB1*03:01 (P = 0.0009, Pc = 0.0150, OR 0.56, 95%CI 0.40-0.79), and DPB1*02:01 (P = 5.16X10-6, Pc = 8.77X10-5, OR 0.52, 95%CI 0.39-0.69) were protectively associated with SSc. In addition, these four alleles seemed to be independently associated with the protection against the susceptibility of SSc. On the other hand, we could not find predisposing alleles for overall SSc. With respect to SSc subsets, a tendency for these four alleles to be protectively associated was observed. However, there was a significant association between DRB1*01:01, DRB1*10:01, DQB1*05:01, and DPB1*04:02 and the susceptibility to SSc with ACA. On the other hand, the presence of DRB1*15:02, DQB1*06:01, DPB1*03:01, and DPB1*09:01 was associated with SSc with ATA. CONCLUSION: Thus, the present study has identified protective associations of the four HLA class II alleles with overall Japanese SSc and predisposing associations of HLA class II alleles with Japanese SSc subsets.
Asunto(s)
Cadenas beta de HLA-DP/genética , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Esclerodermia Sistémica/genética , Adulto , Alelos , Pueblo Asiatico/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Factores Protectores , Esclerodermia Sistémica/epidemiologíaRESUMEN
Thrombocytopenia due to antitumor necrosis factorα agents is very rare. A 68-year-old woman with rheumatoid arthritis on methotorexate received infliximab (IFX). Three days after the first IFX infusion, she developed gingival bleeding, petechia, and gross hematuria. Her platelet count fell to 2000/µL. We administered a platelet transfusion and intravenous methylprednisolone. Three days after admission, her platelet count was 7000/µL and her bleeding persisted. After double filtration plasmapheresis, her bleeding stopped and her platelet count recovered over 2 weeks. Thrombocytopenia is a rare but severe complication of IFX. Double filtration plasmapheresis may be useful for removing IFX or possible antibodies against platelets when IFX remaining in the patient's blood interferes with improvement of the patient's condition.
Asunto(s)
Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Infliximab/efectos adversos , Trombocitopenia/inducido químicamente , Administración Intravenosa , Anciano , Femenino , Hemorragia Gingival/etiología , Glucocorticoides/uso terapéutico , Hematuria/etiología , Humanos , Metilprednisolona/uso terapéutico , Plasmaféresis , Transfusión de Plaquetas , Púrpura/etiología , Índice de Severidad de la Enfermedad , Trombocitopenia/complicaciones , Trombocitopenia/terapiaRESUMEN
OBJECTIVE: We sought to identify clinical features at diagnosis that can distinguish isolated polymyalgia rheumatica (PMR) without giant cell arteritis (GCA) from PMR with GCA, and clinical features at diagnosis of isolated PMR that can predict subsequent relapse and corticosteroid discontinuation. METHODS: A retrospective study of 115 patients with isolated PMR and 29 patients with GCA was performed. A comparison between isolated PMR patients, GCA patients (with or without PMR), and PMR with GCA patients was performed. Predictors of relapse and corticosteroid discontinuation were identified using a logistic regression in the patients with isolated PMR. RESULTS: Matrix metalloproteinase-3 (MMP-3) level was significantly different among the patient groups. MMP-3: 230.5 ± 201.5 ng/mL in isolated PMR, 80.5 ± 47.5 ng/mL in GCA (p < 0.01), and 96.8 ± 54.8 ng/mL in PMR with GCA (p = 0.03). In the patients with isolated PMR, female gender (odds ratio [OR], 2.73; 95% confidence interval [CI], 1.16-6.41; p < 0.05) and creatinine (Cr) < 50 µmol/L (OR, 2.48; 95% CI, 1.02-5.99; p < 0.05) were significant prognostic factors that predicted relapse. CONCLUSION: A low level of MMP-3 is an excellent positive predictor for PMR with GCA. Among patients with isolated PMR, female gender and Cr < 50 µmol/L were significant prognostic factors that predicted relapse.
Asunto(s)
Arteritis de Células Gigantes/diagnóstico , Metaloproteinasa 3 de la Matriz/sangre , Polimialgia Reumática/diagnóstico , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Diagnóstico Diferencial , Femenino , Arteritis de Células Gigantes/sangre , Arteritis de Células Gigantes/complicaciones , Humanos , Japón , Masculino , Polimialgia Reumática/sangre , Polimialgia Reumática/complicaciones , Pronóstico , Recurrencia , Estudios Retrospectivos , Factores SexualesRESUMEN
Medical management of systemic sclerosis (SSc)-associated chronic intestinal pseudo- obstruction (CIPO) has often proved inadequate. Percutaneous endoscopic colostomy (PEC) has been proposed as a method of treatment, but it is associated with a relatively high incidence of serious complications. We report herein a very severe case of SSc-associated CIPO in which complications were successfully controlled by long tube placement via a gastrostomy. Transgastric long tube placement may offer a relatively safe alternative to PEC in treating severe SSc-associated CIPO.