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1.
Arthritis Rheumatol ; 71(3): 451-459, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30225949

RESUMO

OBJECTIVE: To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti-tumor necrosis factor (anti-TNF) therapy and the occurrence of disease flare following withdrawal of anti-TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA). METHODS: In this prospective, multicenter study, 137 patients with polyarticular-course JIA whose disease was clinically inactive while receiving anti-TNF therapy were enrolled. Patients were observed for an initial 6-month phase during which anti-TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti-TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti-TNF withdrawal. Spearman's rank correlation test, Mann-Whitney U test, Kruskal-Wallis test, receiver operating characteristic (ROC) curve, and Kaplan-Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti-TNF withdrawal. RESULTS: Over the 6-month initial phase with anti-TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular-course JIA; following anti-TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti-TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti-TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti-TNF withdrawal were inversely correlated with the time to disease flare (r = -0.36). CONCLUSION: Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular-course JIA, and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/sangue , Artrite Juvenil/tratamento farmacológico , Calgranulina A/sangue , Calgranulina B/sangue , Proteína S100A12/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Humanos , Quimioterapia de Manutenção/métodos , Masculino , Exacerbação dos Sintomas , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Suspensão de Tratamento
2.
Eye (Lond) ; 33(4): 629-639, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30487588

RESUMO

AIMS: Methotrexate (MTX) is standard treatment in pediatric chronic anterior uveitis (CAU). Addition of tumor necrosis factor-α inhibitors (TNFi) is often needed. We describe the timing and risk factors for TNFi use in children with CAU on MTX. METHODS: In this retrospective study, we reviewed 51 records, and 46 met inclusion criteria. Primary outcome was the addition of TNFi due to active CAU per Standardization of Uveitis Nomenclature criteria. Time to TNFi and factors associated with their addition were assessed using survival analysis models. RESULTS: Of 46 children treated with MTX for uveitis (36 juvenile idiopathic arthritis-associated uveitis, 10 idiopathic CAU), 72% had ocular complications. MTX was started a median of 5.0 months, and TNFi 43 months from uveitis diagnosis. Kaplan-Meier estimates suggest that cumulatively, 12% (95% CI: 4-23%) start TNFi within 6 months of MTX, 21% (12-37%) within 1 year, and 39% (24-54%) within 2 years. On Cox Proportional Hazard regression analysis, children with idiopathic CAU required TNFi earlier in their uveitis course (at 3 months (Hazard Ratio 6.06; 95% confidence interval (1.25-29.41))). Females appeared less likely to require TNFi early. Children treated in 2012 and later were more likely to receive TNFi earlier than those treated before 2012. CONCLUSION: Little is known about optimal time to initiate treatment or factors associated with the need to add TNFi in children on MTX. Children with idiopathic CAU and males required TNFi earlier in their course. Factors associated with these potential risk factors for TNFi warrant further investigation.


Assuntos
Adalimumab/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Infliximab/uso terapêutico , Metotrexato/uso terapêutico , Uveíte/tratamento farmacológico , Adolescente , Artrite Juvenil , Criança , Doença Crônica , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fator de Necrose Tumoral alfa/antagonistas & inibidores
3.
Pediatr Nephrol ; 34(1): 117-128, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30159624

RESUMO

OBJECTIVES: To delineate urine biomarkers that reflect kidney structural damage and predict renal functional decline in pediatric lupus nephritis (LN). METHODS: In this prospective study, we evaluated kidney biopsies and urine samples of 89 patients with pediatric LN. Urinary levels of 10 biomarkers [adiponectin, ceruloplasmin, kidney injury molecule-1, monocyte chemotactic protein-1, neutrophil gelatinase-associated lipocalin, osteopontin, transforming growth factor-ß (TGFß), vitamin-D binding protein, liver fatty acid binding protein (LFABP), and transferrin] were measured. Regression analysis was used to identify individual and combinations of biomarkers that determine LN damage status [NIH-chronicity index (NIH-CI) score ≤ 1 vs. ≥ 2] both individually and in combination, and biomarker levels were compared for patients with vs. without renal functional decline, i.e., a 20% reduction of the glomerular filtration rate (GFR) within 12 months of a kidney biopsy. RESULTS: Adiponectin, LFABP, and osteopontin levels differed significantly with select histological damage features considered in the NIH-CI. The GFR was associated with NIH-CI scores [Pearson correlation coefficient (r) = - 0.49; p < 0.0001] but not proteinuria (r = 0.20; p > 0.05). Similar to the GFR [area under the ROC curve (AUC) = 0.72; p < 0.01], combinations of osteopontin and adiponectin levels showed moderate accuracy [AUC = 0.75; p = 0.003] in discriminating patients by LN damage status. Renal functional decline occurred more commonly with continuously higher levels of the biomarkers, especially of TGFß, transferrin, and LFABP. CONCLUSION: In combination, urinary levels of adiponectin and osteopontin predict chronic LN damage with similar accuracy as the GFR. Ongoing LN activity as reflected by high levels of LN activity biomarkers heralds renal functional decline. KEY MESSAGES: • Levels of osteopontin and adiponectin measured at the time of kidney biopsy are good predictors of histological damage with lupus nephritis. • Only about 20% of children with substantial kidney damage from lupus nephritis will have an abnormally low urine creatinine clearance. • Continuously high levels of biomarkers reflecting lupus nephritis activity are risk factors of declining renal function.

4.
J Ophthalmic Inflamm Infect ; 8(1): 17, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30327966

RESUMO

BACKGROUND: Biomarkers in easily obtained specimens that accurately predict uveitis in children with juvenile idiopathic arthritis (JIA) are needed. Aqueous humor has been studied for biomarkers, but is not routinely available. We evaluated tears from children with chronic anterior uveitis (CAU) for biomarkers reported in aqueous humor. In this pilot study, we used Schirmer strips to collect tears from seven children (nine eyes); three children had JIA- associated uveitis (JIA-U) and four had idiopathic disease (I-CAU). Liquid chromatography-tandem mass spectrometry was used to identify and quantify tear proteins. The Mann-Whitney U test identified differential tear protein expression between children with JIA-U and those with I-CAU. RESULTS: S100A9, LAP3, TTR, MIF, sCD14, S100A8, and SAA1 were detected in tears of all children; the same cytokines have been reported in aqueous humor of children with JIA-U. Tears from children with JIA-U had higher expression of proteins associated with inflammatory arthritis (SEMA3G, TIMP1, HEXB, ERN1, and SAA1) than tears from those with I-CAU. In addition, we found higher expression of sCD14, S100A8, and SAA1, but lower expression of S100A9, LAP3, TTR, and MIF, in tears from children with JIA-U compared to tears from those with I-CAU. CONCLUSIONS: Tears contain similar cytokine profiles to aqueous humor in children with CAU and may be a clinically useful source of disease biomarkers. Tears from children with JIA-U also contain cytokines associated with inflammatory arthritis; furthermore, differential expression of other tear proteins as well may provide clues to intrinsic differences between JIA-U and I-CAU, despite their similar clinical phenotypes.

5.
Arthritis Rheumatol ; 70(9): 1508-1518, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29604189

RESUMO

OBJECTIVE: To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease. METHODS: In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare. RESULTS: Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05). CONCLUSION: Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/patologia , Quimioterapia de Indução/estatística & dados numéricos , Suspensão de Tratamento/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Lactente , Tábuas de Vida , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Exacerbação dos Sintomas , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
6.
Arthritis Care Res (Hoboken) ; 70(8): 1228-1237, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29112802

RESUMO

OBJECTIVE: To develop standardized treatment regimens for chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), to enable comparative effectiveness treatment studies. METHODS: Virtual and face-to-face discussions and meetings were held within the CNO/CRMO subgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). A literature search was conducted, and CARRA membership was surveyed to evaluate available treatment data and identify current treatment practices. Nominal group technique was used to achieve consensus on treatment plans for CNO refractory to nonsteroidal antiinflammatory drug (NSAID) monotherapy and/or with active spinal lesions. RESULTS: Three consensus treatment plans (CTPs) were developed for the first 12 months of therapy for CNO patients refractory to NSAID monotherapy and/or with active spinal lesions. The 3 CTPs are methotrexate or sulfasalazine, tumor necrosis factor inhibitors with optional methotrexate, and bisphosphonates. Short courses of glucocorticoids and continuation of NSAIDs are permitted for all regimens. Consensus was achieved on these CTPs among CARRA members. Consensus was also reached on subject eligibility criteria, initial evaluations that should be conducted prior to the initiation of CTPs, and data items to collect to assess treatment response. CONCLUSION: Three consensus treatment plans were developed for pediatric patients with CNO refractory to NSAIDs and/or with active spinal lesions. Use of these CTPs will provide additional information on efficacy and will generate meaningful data for comparative effectiveness research in CNO.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Osteomielite/tratamento farmacológico , Planejamento de Assistência ao Paciente/normas , Doenças da Coluna Vertebral/tratamento farmacológico , Adolescente , Criança , Consenso , Feminino , Humanos , Masculino , Osteomielite/diagnóstico , Prognóstico , Retratamento/métodos , Medição de Risco , Índice de Gravidade de Doença , Doenças da Coluna Vertebral/diagnóstico , Falha de Tratamento
7.
J Rheumatol ; 44(8): 1239-1248, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28620062

RESUMO

OBJECTIVE: To delineate urine biomarkers that forecast response to therapy of lupus nephritis (LN). METHODS: Starting from the time of kidney biopsy, patients with childhood-onset systemic lupus erythematosus who were diagnosed with LN were studied serially. Levels of 15 biomarkers were measured in random spot urine samples, including adiponectin, α-1-acid glycoprotein (AGP), ceruloplasmin, hemopexin, hepcidin, kidney injury molecule 1, monocyte chemotactic protein-1, lipocalin-like prostaglandin D synthase (LPGDS), transforming growth factor-ß (TGF-ß), transferrin, and vitamin D binding protein (VDBP). RESULTS: Among 87 patients (mean age 15.6 yrs) with LN, there were 37 treatment responders and 50 nonresponders based on the American College of Rheumatology criteria. At the time of kidney biopsy, levels of TGF-ß (p < 0.0001) and ceruloplasmin (p = 0.006) were significantly lower among responders than nonresponders; less pronounced differences were present for AGP, hepcidin, LPGDS, transferrin, and VDBP (all p < 0.05). By Month 3, responders experienced marked decreases of adiponectin, AGP, transferrin, and VDBP (all p < 0.01) and mean levels of these biomarkers were all outstanding (area under the receiver-operating characteristic curve ≥ 0.9) for discriminating responders from nonresponders. Patient demographics and extrarenal disease did not influence differences in biomarker levels between response groups. CONCLUSION: Low urine levels of TGF-ß and ceruloplasmin at baseline and marked reduction of AGP, LPGDS, transferrin, or VDBP and combinations of other select biomarkers by Month 3 are outstanding predictors for achieving remission of LN. If confirmed, these results can be used to help personalize LN therapy.


Assuntos
Biomarcadores/urina , Ceruloplasmina/urina , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/urina , Fator de Crescimento Transformador beta/urina , Adolescente , Quimiocina CCL2/urina , Criança , Feminino , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Humanos , Oxirredutases Intramoleculares/urina , Lipocalinas/urina , Masculino , Orosomucoide/urina , Transferrina/urina , Resultado do Tratamento , Proteína de Ligação a Vitamina D/urina
8.
Pediatr Rheumatol Online J ; 14(1): 14, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26965173

RESUMO

BACKGROUND: Clinically distinct autoimmune phenotypes share genetic susceptibility factors. We investigated the prevalence of familial autoimmunity among subjects with juvenile idiopathic arthritis (JIA), childhood systemic lupus erythematosus (cSLE) and juvenile dermatomyositis (JDM) in the CARRA Registry, the largest multicenter observational Registry for pediatric rheumatic disease. METHODS: Children with JIA, cSLE and JDM enrolled in the CARRA Registry between May 2010 and May 2012 were investigated for differences in proportion of subjects who had first-degree relatives (FDR) with autoimmunity. If a significant difference was detected, pairwise comparisons, adjusted for multiple comparisons, were made. RESULTS: There were 4677 JIA, 639 cSLE and 440 JDM subjects. The proportion of subjects having FDR with any autoimmune disease in the JDM group (20.5 %) was less compared to subjects with JIA (31.8 %, p < 0.001) or SLE (31.9 %; p < 0.001). Significantly greater proportion of JIA cases had FDR with inflammatory arthritis (13 %) compared to cSLE (9.2 %, p = 0.007) or JDM (4.3 %, p <0.001). Significantly greater proportion of cSLE cases had FDR with SLE (11.1 % vs. 1.7 % for JIA and 1.1 % for JDM p < 0.001) or type-I diabetes (7.4 % for cSLE vs. 3.1 % for JIA and 3.0 % for JDM p < 0.001). CONCLUSION: Higher proportions of subjects with JIA and cSLE have FDR with autoimmunity compared to those of JDM. Relatives of cSLE cases had an increased prevalence of SLE, and relatives of JIA cases were enriched for inflammatory arthropathies demonstrating distinct patterns of familial autoimmunity among these phenotypes.


Assuntos
Artrite Juvenil/epidemiologia , Autoimunidade , Pesquisa Biomédica , Sistema de Registros , Reumatologia/estatística & dados numéricos , Artrite Juvenil/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Prevalência , Estudos Retrospectivos , Estados Unidos/epidemiologia
9.
Pediatr Rheumatol Online J ; 14(1): 8, 2016 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-26861944

RESUMO

BACKGROUND: The association between rheumatoid arthritis (RA) and periodontitis is well established. Some children with juvenile idiopathic arthritis (JIA) phenotypically resemble adults with RA, characterized by the presence of anti-cyclic citrullinated peptide (CCP) antibodies. We sought to investigate an association between CCP-positive JIA and symptoms of periodontitis and antibodies to oral microbiota. METHODS: Antibodies to oral pathogens Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum were measured using ELISA in 71 children with CCP-positive JIA and 74 children with CCP-negative JIA. Oral health history was collected from 37 children with CCP-positive JIA and 121 children with CCP-negative JIA. T-tests, Chi-square tests, Mann-Whitney U tests, and multivariable regression were used to compare the groups. RESULTS: Compared to those with CCP-negative JIA, children with CCP-positive JIA were more likely to be female, older and non-Caucasian. Anti-P. gingivalis (p <0.003) and anti-P. intermedia (p <0.008) IgG antibody titers were higher in the CCP-positive cohort. Differences in P. gingivalis antibody titers remained significant after adjusting for age (p = 0.007). Children with CCP-positive JIA more likely reported tender/bleeding gums (43 % vs. 24 %, p < 0.02) compared to children with CCP-negative JIA. After controlling for age at collection, the odds of having tender/bleeding gums were 2.2 times higher in the CCP-positive group compared (95 % CI 0.98 - 4.83; p = 0.056). CONCLUSIONS: Children with CCP-positive JIA have higher antibody titers to P. gingivalis and more symptoms of poor oral health, supporting a possible role for periodontitis in the etiology of CCP-positive JIA.


Assuntos
Anticorpos Antibacterianos/imunologia , Artrite Juvenil/complicações , Autoanticorpos/imunologia , Periodontite/microbiologia , Porphyromonas gingivalis/imunologia , Adolescente , Formação de Anticorpos , Artrite Juvenil/imunologia , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Periodontite/etiologia , Periodontite/imunologia , Porphyromonas gingivalis/isolamento & purificação
10.
Arthritis Care Res (Hoboken) ; 68(7): 1003-11, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26473509

RESUMO

OBJECTIVE: Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histologic LN activity. METHODS: We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n = 47) at the time of kidney biopsy. Histologic LN activity was measured by the National Institutes of Health activity index (NIH-AI) and the tubulointerstitial activity index (TIAI). High LN-activity status (versus moderate/low) was defined as NIH-AI scores >10 (versus ≤10) or TIAI scores >5 (versus ≤5). RAIL algorithms that predicted LN-activity status for both NIH-AI and TIAI were derived by stepwise multivariate logistic regression, considering traditional biomarkers and UBMs as candidate components. The accuracy of the RAIL for discriminating by LN-activity status was determined. RESULTS: The differential excretion of 6 UBMs (neutrophil gelatinase-associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin, and kidney injury molecule 1) standardized by urine creatinine was considered in the RAIL. These UBMs predicted LN-activity (NIH-AI) status with >92% accuracy and LN-activity (TIAI) status with >80% accuracy. RAIL accuracy was minimally influenced by concomitant LN damage. Accuracies between 71% and 85% were achieved without standardization of the UBMs. The strength of these UBMs to reflect LN-activity status was confirmed by principal component and linear discriminant analyses. CONCLUSION: The RAIL is a robust and highly accurate noninvasive measure of LN activity. The measurement properties of the RAIL, which reflect the degree of inflammatory changes as seen on kidney biopsy, will require independent validation.


Assuntos
Biomarcadores/urina , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/urina , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Adulto Jovem
11.
Arthritis Care Res (Hoboken) ; 66(5): 649-57, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24756998

RESUMO

OBJECTIVE: To create a pediatric rheumatology Top 5 list as part of the American Board of Internal Medicine Foundation's Choosing Wisely campaign. METHODS: Delphi surveys of a core group of representative pediatric rheumatology providers from across North America generated candidate Top 5 items. Items with high content agreement and perceived to be of prevalent use and of high impact were included in a survey of all American College of Rheumatology (ACR) members who identified themselves as providing care to pediatric patients. Items with the highest ratings were subjected to literature review and further evaluation. RESULTS: A total of 121 candidate items were proposed in the initial Delphi survey and were reduced to 28 items in subsequent surveys. These 28 items were sent to 1,198 rheumatology providers who care for pediatric patients, and 397 (33%) responded. Based upon survey data and literature review, the Top 5 items were identified. These items focused on testing for antinuclear antibodies, autoantibody panels, Lyme disease, methotrexate toxicity monitoring, and use of routine radiographs. CONCLUSION: The ACR pediatric rheumatology Top 5 is one of the first pediatric subspecialty-specific Choosing Wisely Top 5 lists and provides an opportunity for patients and providers to discuss appropriate use of health care in pediatric rheumatology.


Assuntos
Comportamento de Escolha , Pesquisas sobre Serviços de Saúde/métodos , Pediatria/normas , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/terapia , Reumatologia/normas , Sociedades Médicas/normas , Antirreumáticos/uso terapêutico , Criança , Humanos , Pediatria/métodos , Reumatologia/métodos , Estados Unidos
12.
J Rheumatol ; 41(3): 547-53, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24488421

RESUMO

OBJECTIVE: Rheumatoid factor-positive polyarthritis (RF+ poly) is the juvenile idiopathic arthritis (JIA) category that resembles adult seropositive rheumatoid arthritis (RA). We studied children with RF+ and/or anticyclic citrullinated peptide antibody (anti-CCP)+ JIA to determine what proportion of those children meet International League of Associations for Rheumatology (ILAR) criteria for RF+ poly JIA and to assess for significant differences between children who meet RF+ poly criteria and those who are classified in other categories. METHODS: Charts of children with JIA who were RF+ and/or anti-CCP+ were reviewed. Children with RF+ poly JIA were compared to children in other categories. Statistical analysis was performed using chi-square, Fisher's exact test, and the Student's t-test. RESULTS: Of 56 children with RF+ and/or anti-CCP+ JIA, 34 (61%) met ILAR criteria for RF+ poly JIA. Twelve children had RF-/anti-CCP+ JIA with low anti-CCP titers. When these 12 children were excluded, there were few significant differences between children who met criteria for RF+ poly and those who were classified in other categories. The American College of Rheumatology/European League Against Rheumatism criteria for RA identified more RF+ children than did the ILAR RF+ poly classification (100% vs 77%). CONCLUSION: A number of children with RF+ arthritis were excluded from the RF+ poly JIA classification, though many demographic features and disease measures were similar to those of children who met criteria for RF+ poly JIA. We propose prioritization of RF/anti-CCP positivity over specific exclusions, along with inclusion of anti-CCP, in future revisions of the JIA classification criteria, to improve the sensitivity of diagnosing childhood-onset RA.


Assuntos
Artrite Juvenil/classificação , Adolescente , Artrite Juvenil/diagnóstico , Artrite Juvenil/imunologia , Autoanticorpos/sangue , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Peptídeos Cíclicos/imunologia , Fator Reumatoide/sangue
13.
Arthritis Care Res (Hoboken) ; 66(5): 783-7, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24127327

RESUMO

OBJECTIVE: To evaluate the efficacy of etanercept in patients with juvenile dermatomyositis (DM) refractory to standard treatment. METHODS: Nine patients with juvenile DM prospectively received etanercept 0.4 mg/kg subcutaneous twice weekly concurrently with baseline medications for 12 weeks. Patients were reevaluated 12 weeks (week 24) after stopping etanercept. Outcome measures included a validated Disease Activity Score (DAS), serum muscle enzymes, Childhood Myositis Assessment Scale (CMAS), and nailfold capillaroscopy (NFC). RESULTS: Six patients completed all visits; 2 patients completed through week 12 and 1 patient stopped after the fifth etanercept dose due to marked worsening of a rash. At week 12, 7 patients had a mild decrease in DAS and 1 patient noted worsening of the DAS. At week 24, 1 patient remained stable, 2 patients had worsening of the DAS, and 3 patients had improvement of the DAS (1 patient with inactive disease), including the patient who worsened while receiving etanercept. This patient and the patient who stopped (worsening rash) both had the tumor necrosis factor α (TNFα) 308A allele. There was a trend of worsening NFC at week 12, while at week 24 improvement of NFC was noted. There was no appreciable change in serum muscle enzymes or CMAS throughout the study. CONCLUSION: In this trial of patients with refractory juvenile DM, etanercept did not demonstrate appreciable improvement and some patients noted worsening of disease. Caution should be taken when recommending TNF receptor inhibitors to patients with active symptoms of juvenile DM, and close followup is warranted. Further investigation of the interaction of the TNFα-308A polymorphism and type I interferon is needed to define the mechanism of TNF blockade in juvenile DM.


Assuntos
Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Imunossupressores/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Adolescente , Adulto , Criança , Etanercepte , Feminino , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos
14.
Arthritis Care Res (Hoboken) ; 62(10): 1446-51, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20521307

RESUMO

OBJECTIVE: To determine if mycophenolate mofetil (MMF) diminishes skin and muscle disease activity in children with juvenile dermatomyositis (DM), thereby permitting a decrease in corticosteroid dose. METHODS: A retrospective data review for 50 children with juvenile DM (mean ± SD age 12.2 ± 5.0 years) who had received MMF for 12 months identified the following characteristics: 38 (76%) were girls, 39 (78%) were white, 10 (20%) were Hispanic, and 1 (2%) was African American. The MMF dose and frequency, type of infection, white blood cell (WBC) count, corticosteroid dose, and the validated disease activity score (DAS) subscores for skin (DAS-S) and muscle (DAS-M) were obtained. RESULTS: Twelve months after the start of MMF, the mean ± SD DAS-S decreased from 5.24 ± 0.29 to 3.72 ± 0.29 (P = 0.001), and the mean ± SD DAS-M decreased from 2.44 ± 0.39 to 1.17 ± 0.28 (P = 0.002). The mean ± SD prednisone dosage decreased from 0.39 ± 0.06 to 0.23 ± 0.02 mg/kg/day (P = 0.0001), with resumption of linear growth (P = 0.008). The WBC/lymphocyte count was unchanged over the 12 months on MMF. The infection rate was assessed in a subset of 26 children with juvenile DM who were observed for 12 months before the start of MMF and then compared with the ensuing 12 months of MMF therapy. There was no significant difference between the pretreatment period and the first 6 months of MMF therapy (P = 0.44), but the infection rate decreased in months 7-12 (P = 0.001). CONCLUSION: MMF appears to be worthy of consideration as an additional therapeutic modality for treatment of children with juvenile DM. These data suggest that the use of MMF decreases skin and muscle disease activity and is steroid sparing. MMF appears to be well tolerated, but patients should be monitored for infection.


Assuntos
Dermatomiosite/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Adolescente , Fatores Etários , Criança , Pré-Escolar , Dermatomiosite/epidemiologia , Dermatomiosite/patologia , Feminino , Seguimentos , Humanos , Masculino , Ácido Micofenólico/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
15.
Curr Opin Rheumatol ; 22(2): 213-7, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20010296

RESUMO

PURPOSE OF REVIEW: The current review summarizes the existing knowledge about exercise therapy in the management of juvenile idiopathic arthritis (JIA) along with activity level, functional abilities and exercise capacity of this population. RECENT FINDINGS: Current studies show that children with JIA are considerably less active than their peers. They have significantly impaired aerobic and anaerobic exercise capacity. The inactivity, decreased exercise capacity and disease course lead to deconditioning and disability. Adolescent girls with polyarticular rheumatoid factor-positive subtype appear to be most vulnerable to disability. Recent trials suggest that structured aerobic training or low-intensity programs do not exacerbate arthritis and can lead to improved physical fitness, quality of life and functional abilities in children and adolescents with JIA. SUMMARY: Inactivity in pediatric patients with JIA leads to deconditioning and disability and decreased bone mass, reduced quality of life and possibly increased mortality in adulthood. Although advances in pharmacology have improved the lives of children with JIA, management should also include a moderate, consistent exercise program or more active lifestyle. Physical activity may improve exercise capacity, decrease disability in adulthood, improve quality of life and, in some patients, decrease disease parameters. Further studies are needed to assess practicality of various programs and long-term effects of exercise in children and adolescents with JIA.


Assuntos
Artrite Juvenil/terapia , Terapia por Exercício , Adolescente , Criança , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Satisfação do Paciente , Qualidade de Vida
16.
J Rheumatol ; 35(5): 927-9, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18322984

RESUMO

Anti-signal recognition particle (anti-SRP) is a myositis-specific autoantibody that is linked to a severe polymyositis (PM) associated with interstitial lung disease (ILD) and esophageal dysmotility in adults. We describe 3 African American adolescent girls with anti-SRP juvenile PM. One child required aggressive treatment to control her disease and 2 were refractory to multiple immunosuppressants. Patient 1 developed ILD and cardiac disease; Patient 2 developed ILD; Patient 3 developed esophageal dysmotility and cardiac disease. Organ system involvement was comparable to that seen in adults. We conclude that testing for anti-SRP in children with PM may facilitate diagnosis and management.


Assuntos
Afro-Americanos , Autoanticorpos/imunologia , Polimiosite/diagnóstico , Polimiosite/imunologia , Partícula de Reconhecimento de Sinal/imunologia , Adolescente , Afro-Americanos/etnologia , Autoanticorpos/sangue , Criança , Feminino , Humanos , Imunossupressores/uso terapêutico , Polimiosite/etnologia , Prognóstico
17.
Arthritis Rheum ; 59(2): 222-6, 2008 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-18240180

RESUMO

OBJECTIVE: To determine areas under the curve (AUCs) of oral prednisolone (OP) and intravenous methylprednisolone (IVMP) in patients with juvenile dermatomyositis (DM) and assess the association with nailfold end-row loops (ERLs). Patients with active disease have fewer ERLs that possibly occur in the gastrointestinal tract, impairing absorption of oral medications. METHODS: Six patients with juvenile DM received 50 mg/m(2) of OP (day 1) and IVMP (day 2). Blood was drawn at baseline and at 5, 15, 30, 45, 60, and 90 minutes, and hourly (hours 2-8) after each dose. Samples were analyzed by reverse-phase high-performance liquid chromatography for levels of prednisolone and methylprednisolone. AUCs of OP and IVMP were determined by the trapezoid method; pharmacokinetic parameters were obtained using noncompartmental and compartmental analysis. ERLs were determined from freeze-frame video microscopy and nailfold capillaroscopy. RESULTS: There was a trend toward significance in difference in mean AUC of IVMP (116.72 microg x ml/hour) compared with OP (65.16 microg x ml/hour; P = 0.059). Mean peak concentration was higher for IVMP (34.49 microg/ml) than OP (7.08 microg/ml); mean half-life was shorter for IVMP (1.90 hours) than OP (2.36 hours). There was an inverse association between DeltaAUCs (IVMP AUC - OP AUC) and ERLs (R = -0.68, P = 0.044). CONCLUSION: Patients with juvenile DM and ERL loss may have decreased bioavailability of OP compared with IVMP. This can provide the rationale for greater efficacy of IVMP in patients with active vasculopathy of juvenile DM. Further studies investigating the pharmacokinetics and pharmacodynamics of high-dose IVMP need to be performed in patients with juvenile DM.


Assuntos
Anti-Inflamatórios/farmacocinética , Dermatomiosite/tratamento farmacológico , Metilprednisolona/farmacocinética , Prednisolona/farmacocinética , Administração Oral , Adolescente , Adulto , Anti-Inflamatórios/administração & dosagem , Capilares , Criança , Feminino , Humanos , Injeções Intravenosas , Masculino , Metilprednisolona/administração & dosagem , Prednisolona/administração & dosagem
18.
Arthritis Rheum ; 56(3): 977-83, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17328075

RESUMO

OBJECTIVE: To determine bone mineral density (BMD) in patients at the time of diagnosis of juvenile dermatomyositis (DM), to compare the RANKL:osteoprotegerin (OPG) ratio in patients with juvenile DM with that in healthy control subjects, and to evaluate whether BMD is associated with the RANKL:OPG ratio and the duration of untreated disease. METHODS: Thirty-seven children with juvenile DM were enrolled. Dual x-ray absorptiometry (DXA) was performed before treatment, and Z scores for the lumbar spine (L1-L4) were determined. The duration of untreated disease was defined as the period of time from the onset of rash or weakness to the time at which DXA was performed. Serum specimens obtained at the time of DXA were analyzed for concentrations of RANKL and OPG, using enzyme-linked immunosorbent assay. The RANKL:OPG ratio was also determined in 44 age-matched healthy control subjects. RESULTS: At the time of diagnosis of juvenile DM, patients had a significantly increased RANKL:OPG ratio compared with that in healthy children (mean +/- SD 2.19 +/- 3.03 and 0.13 +/- 0.17, respectively; P < 0.0001). In patients with a lumbar spine BMD Z score of -1.5 or lower, the RANKL:OPG ratio was significantly higher than that in patients with a lumbar spine BMD Z score higher than -1.5 (P = 0.038). Lumbar spine BMD Z scores (mean +/- SD -0.13 +/- 1.19 [range -2.10 to 2.85]) were inversely associated with the duration of untreated disease (R = -0.50, P = 0.003). CONCLUSION: Children with juvenile DM have an elevated RANKL:OPG ratio at the time of diagnosis, resulting in expansion of the number of osteoclasts and activation of the bone resorptive function. This may lead to a lack of normal bone mineral accretion and a subsequent reduction in the lumbar spine BMD Z score. Patients with a longer duration of untreated juvenile DM have reduced lumbar spine BMD Z scores. These data suggest that early diagnosis could reduce the likelihood of reduced lumbar spine BMD in these patients by prompting intervention strategies at an early stage.


Assuntos
Densidade Óssea/fisiologia , Dermatomiosite/sangue , Dermatomiosite/fisiopatologia , Osteoprotegerina/sangue , Ligante RANK/sangue , Absorciometria de Fóton , Reabsorção Óssea/fisiopatologia , Estudos de Casos e Controles , Proliferação de Células , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Osteoclastos/patologia
19.
Pediatr Emerg Care ; 23(1): 38-46, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17228221

RESUMO

Juvenile rheumatoid arthritis is a chronic condition. The goal of therapy is to control pain, preserve joint range of motion and function, minimize systemic complications, and assist in normal growth and development. Recent advances in understanding the pathophysiology of arthritis have expanded the treatment of this chronic condition. Many medications including nonsteroidal anti-inflammatory agents, disease-modifying antirheumatic drugs, biologic agents, and cytotoxic agents are available for treating juvenile rheumatoid arthritis. Emergency medicine physicians should be familiar with the different classes and adverse effects of these drugs.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Antirreumáticos/efeitos adversos , Criança , Medicina Baseada em Evidências , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico
20.
Curr Opin Pediatr ; 17(6): 703-8, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16282774

RESUMO

PURPOSE OF REVIEW: Children with chronic rheumatic disease have decreased bone mass. In adults, lowered bone mineral density is associated with increased fracture risk. This morbidity is undetermined in pediatric rheumatic disease as osteoporosis has not been well-defined in children. This review compares methods for determining bone mass in children, examines insights into molecular mechanisms of bone metabolism, and discusses the prevention and treatment of decreased bone mass in children. RECENT FINDINGS: Peak bone mass, attained during adolescence and early adulthood, is critical in determining fracture risk. Studies of children with chronic rheumatic disease demonstrate decreased bone mineral density, and potentially lowered peak bone mass. Dual energy x-ray absorptiometry is the most commonly used technique for monitoring bone mineral density and should be interpreted utilizing age-appropriate Z-scores. Recent studies suggest quantitative ultrasound may be as reliable as dual energy x-ray absorptiometry and lacks radiation exposure. The molecular mechanisms by which inflammation alters bone mineral density involve receptor activator of nuclear factor kappaB ligand (RANKL)/osteoprotegerin, tumor necrosis factor-alpha, and interleukin-1. Limited data on the use of bisphosphonates and calcitonin in children suggest they are safe and effective, but should be used cautiously. SUMMARY: Children with chronic rheumatic disease should have bone mass monitored by dual energy x-ray absorptiometry Z-scores. Targeting the RANKL/osteoprotegerin pathway may lead to therapies that improve bone health in this population. More studies on the role of bisphosphonates and calcitonin must be pursued to establish guidelines for use in pediatric patients with chronic rheumatic disease. For now, supplemental calcium and vitamin D should be implemented in these children.


Assuntos
Osso e Ossos/patologia , Doenças Reumáticas/diagnóstico , Absorciometria de Fóton , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/metabolismo , Cálcio/uso terapêutico , Criança , Humanos , Osteoporose/diagnóstico , Osteoporose/etiologia , Osteoporose/prevenção & controle , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológico , Vitamina D/uso terapêutico
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