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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 For those patients who maintained clinically inactive disease over the 6 months, anti-TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare.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.
J Rheumatol ; 45(12): 1680-1688, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30219769

RESUMO

OBJECTIVE: To identify clinical features that define disease activity in pediatric localized scleroderma (LS), and determine their specificity and importance. METHODS: We conducted a multicenter prospective study of patients with active and inactive LS skin lesions. A standardized evaluation of a single designated study lesion per subject was performed at 3 visits. We evaluated the pattern and correlation between assessed features and physician's global assessments of activity (PGA-A). RESULTS: Ninety of 103 subjects had evaluable data; 66 had active and 24 inactive disease. Subjects had similar age of onset, sex, and disease patterns. Linear scleroderma was the most common subtype. Features specific for active disease included erythema, violaceous color, tactile warmth, abnormal skin texture, and disease extension. Scores for these variables changed over time and correlated with PGA-A of the lesion. Active and inactive lesions could not be distinguished by the presence or level of skin thickening, either of lesion edge or center. However, in active lesions, skin thickening scores did correlate with PGA-A scores. Regression analysis identified the combination of erythema, disease extension, violaceous color, skin thickening, and abnormal texture as predictive of PGA-A at study entry. Damage features were common irrespective of activity status. CONCLUSION: We identified variables strongly associated with disease activity, expanding upon those used in current measures, and determined their relative importance in physician activity scoring. Skin thickening was found to lack specificity for disease activity. These results will help guide development of a sensitive, responsive activity tool to improve care of patients with LS.


Assuntos
Esclerodermia Localizada/diagnóstico , Pele/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Esclerodermia Localizada/patologia , Índice de Gravidade de Doença , Avaliação de Sintomas/métodos
3.
Pediatr Clin North Am ; 65(4): 623-638, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30031490

RESUMO

This article focuses on creating an orderly approach to history taking, examination, and ordering appropriate investigations when caring for a child with joint complaints. It classifies complaints as those with and without pain, swelling, or fever and of short or long duration. It recommends an approach to the physical examination and both suggests and discourages various laboratory and imaging studies.


Assuntos
Artralgia/etiologia , Artrite/diagnóstico , Adolescente , Artralgia/diagnóstico , Artralgia/diagnóstico por imagem , Artralgia/terapia , Artrite/complicações , Criança , Pré-Escolar , Diagnóstico Diferencial , Humanos , Anamnese , Medição da Dor , Febre Reumática/complicações , Febre Reumática/diagnóstico , Índice de Gravidade de Doença
4.
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
5.
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
6.
J Rheumatol ; 44(10): 1484-1486, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28765255

RESUMO

OBJECTIVE: To determine cancer incidence in a large pediatric-onset systemic lupus erythematosus (SLE) population. METHODS: Data were examined from 12 pediatric SLE registries in North America. Patients were linked to their regional cancer registries to detect cancers observed after cohort entry, defined as date first seen in the clinic. The expected number of malignancies was obtained by multiplying the person-years in the cohort (defined from cohort entry to end of followup) by the geographically matched age-, sex-, and calendar year-specific cancer rates. The standardized incidence ratio (SIR; ratio of cancers observed to expected) was generated, with 95% CI. RESULTS: A total of 1168 patients were identified from the registries. The mean age at cohort entry was 13 years (SD 3.3), and 83.7% of the subjects were female. The mean duration of followup was 7.6 years, resulting in a total observation period of 8839 years spanning the calendar period 1974-2009. During followup, fourteen invasive cancers occurred (1.6 cancers per 1000 person-yrs, SIR 4.13, 95% CI 2.26-6.93). Three of these were hematologic (all lymphomas), resulting in an SIR for hematologic cancers of 4.68 (95% CI 0.96-13.67). SIR were increased for both male and female patients, and across age groups. CONCLUSION: Although cancer remains a relatively rare outcome in pediatric-onset SLE, our data do suggest an increase in cancer for patients followed an average of 7.6 years. About one-fifth of the cancers were hematologic. Longer followup, and study of drug effects and disease activity, is warranted.


Assuntos
Lúpus Eritematoso Sistêmico/epidemiologia , Neoplasias/epidemiologia , Adolescente , Criança , Comorbidade , Feminino , Seguimentos , Humanos , Incidência , Masculino , Sistema de Registros , Fatores Sexuais
7.
Pediatr Rheumatol Online J ; 13: 36, 2015 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-26310855

RESUMO

BACKGROUND: Intra-articular corticosteroid injections (IACI) are routinely used by pediatric rheumatologists in the treatment of chronic arthritis. Frequently, topical anesthetics are used to control procedural pain, but their relative efficacy has not been reported. In this study, we evaluated the level of pain associated with different anesthetic methods, Numby® 900 Iontophoretic Drug Delivery System, or EMLA® cream, with or without subcutaneous buffered lidocaine (SQBL), during IACI of the knee in children with arthritis. METHODS: We conducted a prospective study of patients, ages 4 to 21 years old, followed at three pediatric rheumatology centers who were undergoing IACI of a knee joint. Patients were randomized into two treatment groups: 1) topical anesthetic only (EMLA® or Numby® (E/N)), or 2) topical anesthetic (E/N) and SQBL. Pain was assessed at baseline, during topical anesthetic placement, and following the IACI (post-procedure). The Faces Pain Scale-Revised (FPS-R), the Face, Leg, Activity, Cry, Consolability (FLACC) behavioral scale and the parental global assessment (PGA) (0 = best experience, 10 = worst experience) were determined. RESULTS: Sixty-three patients (44 females) with a median [IQR] age of 10.8 [IQR = (8.2-14.4)] years (range 4.7-20 years) with active knee arthritis were consented. FPS-R post-procedure (P = 0.03), FLACC (P = 0.02) and PGA (P = 0.01) scores were significantly lower in females treated with E/N plus SQBL compared to patients treated with E/N only. Females in the E/N only group had a significant worsening of their baseline pain (p < 0.0004) and a greater magnitude of change in their baseline FPS-R scores (p < 0.001) from the procedure compared to females in the E/N plus SQBL group who had no worsening of their baseline pain. No significant change in pain level or PGA score was found among males in either treatment group. Pain scores overall were similar to the oligoarthritis patients, a more homogeneous group of patients. Both EMLA® (n = 33) and Numby® (n = 29) were equally well tolerated with no significant difference in median FPS-R administration scores overall. CONCLUSION: Our results suggest that a topical anesthetic plus SQBL is more effective for injection pain control than topical anesthesia only. Further studies addressing pain and anxiety will help determine the optimal method of pain control for IACI.


Assuntos
Corticosteroides/administração & dosagem , Anestesia Local/métodos , Artrite Juvenil/tratamento farmacológico , Injeções Intra-Articulares , Manejo da Dor/métodos , Adolescente , Corticosteroides/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Injeções Intra-Articulares/métodos , Iontoforese/métodos , Masculino , Medição da Dor , Adulto Jovem
8.
Arthritis Res Ther ; 15(6): R198, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24267155

RESUMO

INTRODUCTION: The aim of this study was to assess cancer incidence in childhood-onset systemic lupus erythematosus (SLE). METHODS: We ascertained cancers within SLE registries at 10 pediatric centers. Subjects were linked to cancer registries for the observational interval, spanning 1974 to 2009. The ratio of observed to expected cancers represents the standardized incidence ratio (SIR) or relative cancer risk in childhood-onset SLE, versus the general population. RESULTS: There were 1020 patients aged <18 at cohort entry. Most (82%) were female and Caucasian; mean age at cohort entry was 12.6 years (standard deviation (SD) = 3.6). Subjects were observed for a total of 7,986 (average 7.8) patient-years. Within this interval, only three invasive cancers were expected. However, 14 invasive cancers occurred with an SIR of 4.7, 95% confidence interval (CI) 2.6 to 7.8. Three hematologic cancers were found (two non-Hodgkin's lymphoma, one leukemia), for an SIR of 5.2 (95% CI 1.1 to 15.2). The SIRs stratified by age group and sex, were similar across these strata. There was a trend for highest cancer occurrence 10 to 19 years after SLE diagnosis. CONCLUSIONS: These results suggest an increased cancer risk in pediatric onset SLE versus the general population. In absolute terms, this represents relatively few events. Of note, risk may be highest only after patients have transferred to adult care.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Neoplasias/complicações , Neoplasias/epidemiologia , Adolescente , Idade de Início , Criança , Feminino , Humanos , Incidência , Masculino , Sistema de Registros , Fatores de Risco
9.
J Rheumatol ; 37(1): 175-81, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19918041

RESUMO

OBJECTIVE: We surveyed pediatric rheumatologists (PR) in North America to learn how they treat pediatric localized scleroderma (LS), a disease associated with significant morbidity for the growing child. METHODS: A Web-based survey was sent to the 195 PR members of the pediatric rheumatology research alliance CARRA (Childhood Arthritis and Rheumatology Research Alliance). Members were asked which medications they use to treat LS and which factors modify their treatment strategies. Clinical vignettes were provided to learn the specific treatment regimens used. RESULTS: A total of 158 PR from over 70 clinical centers in the United States and Canada participated in the survey, representing 81% of the CARRA membership. These PR saw over 650 patients with LS in the prior year. Nearly all respondents treated LS with methotrexate (MTX) and corticosteroids; most of them intensify treatment for lesions located on the face or near a joint, and about half intensify treatment for recent disease onset (< 6 months). Most PR reserve topical medications for limited treatment situations. Clinical vignettes showed that PR use a broad range of treatment doses and durations for MTX and corticosteroids. CONCLUSION: Most PR in North America treat localized scleroderma with a combination of MTX and corticosteroids. However, there is no consensus on specific treatment regimens. There is a need for controlled treatment trials to better determine optimal therapy for this potentially disabling disease.


Assuntos
Antirreumáticos/uso terapêutico , Pediatria/estatística & dados numéricos , Reumatologia/estatística & dados numéricos , Esclerodermia Localizada/tratamento farmacológico , Adolescente , Corticosteroides/uso terapêutico , Adulto , Criança , Pré-Escolar , Coleta de Dados , Humanos , Metotrexato/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Esclerodermia Localizada/patologia , Resultado do Tratamento
10.
Arthritis Rheum ; 60(9): 2772-81, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19714584

RESUMO

OBJECTIVE: To determine whether neutrophil gelatinase-associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood-onset systemic lupus erythematosus (SLE). METHODS: One hundred eleven patients with childhood-onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physician's assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme-linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed-effect models. RESULTS: Significant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score. CONCLUSION: Serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhood-onset SLE disease activity.


Assuntos
Proteínas da Fase Aguda/urina , Nefropatias/diagnóstico , Nefropatias/metabolismo , Lipocalinas/sangue , Lipocalinas/urina , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/metabolismo , Proteínas Proto-Oncogênicas/sangue , Proteínas Proto-Oncogênicas/urina , Índice de Gravidade de Doença , Adolescente , Biomarcadores/sangue , Biomarcadores/urina , Criança , Creatinina/urina , Progressão da Doença , Feminino , Humanos , Nefropatias/complicações , Lipocalina-2 , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/complicações , Masculino , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos
11.
Pediatr Nephrol ; 23(3): 403-12, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18202859

RESUMO

We hypothesized that neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of disease activity in lupus nephritis. NGAL in serial plasma (PNGAL) and urine (UNGAL) samples was measured by enzyme-linked immunosorbent assay (ELISA) in 85 participants with pediatric systemic lupus erythematosus (pSLE), healthy children (n = 50), and children with juvenile idiopathic arthritis (JIA) (n = 30). Disease activity was measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Plasma and urinary NGAL were significantly increased in subjects with pSLE compared with those with JIA or with healthy controls (all p < 0.03), and unrelated to subjects' age, weight, or height. Plasma and urinary NGAL were stable in pSLE subjects with unchanged disease activity. The pSLE subjects with worsening global or renal disease activity had a mean +/- standard error (SE) increase of UNGAL (in ng/ml) of 11.5 +/- 6.4 or 36.6 +/- 12.1 (p < 0.01), corresponding to a 156% or 380% increase, respectively. PNGAL increased with worsening disease but to a much lesser degree than UNGAL [global disease activity (mean +/- SE): 7.3 +/- 6.2 or 21%; renal disease activity: 20.2 +/- 6.0 or 51%; both p = not significant]. In conclusion, NGAL in urine but not in plasma represents a novel biomarker for renal disease activity in pSLE.


Assuntos
Proteínas da Fase Aguda/urina , Lipocalinas/sangue , Lipocalinas/urina , Nefrite Lúpica/sangue , Nefrite Lúpica/urina , Proteínas Proto-Oncogênicas/sangue , Proteínas Proto-Oncogênicas/urina , Adolescente , Biomarcadores/sangue , Criança , Feminino , Humanos , Lipocalina-2 , Masculino
12.
Bull NYU Hosp Jt Dis ; 65(3): 205-11, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17922671

RESUMO

Juvenile idiopathic arthritis (JIA) is an umbrella term for seven or more clinical patterns of arthritis of unknown cause in children. Until the mid-1980s, therapy for children, with what was then called juvenile rheumatoid arthritis in the United States and juvenile chronic arthritis (JRA) elsewhere, consisted primarily of a small repertoire of antiinflammatory drugs and corticosteroids. However, only a small percentage of children respond to NSAIDs (nonsteroidal antiinflammatory drugs) alone; almost all will respond to corticosteroids, but with the cost of unacceptable toxicities. Juvenile arthritis was often a crippling disease. The controlled trial that demonstrated methotrexate therapy was safe and effective in children was the major advance of that decade. With the burgeoning understanding of the immune system and the advent of biologic agents in the 21st century, pediatric rheumatologists now have many more therapies to offer patients, with the expectation that their disease will be controlled. This review will discuss current therapy and the approach to treatment of JIA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Abatacepte , Corticosteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Artrite Juvenil/classificação , Artrite Juvenil/imunologia , Criança , Etanercepte , Humanos , Imunoconjugados/uso terapêutico , Imunoglobulina G/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Metotrexato/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico
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