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1.
J Rheumatol ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262295

RESUMO

OBJECTIVE: Macrophage activation syndrome (MAS), a life-threatening inflammatory complication, is increasingly recognized in childhood-onset SLE (cSLE). It can be a challenge to differentiate active cSLE from MAS. We generated decision rules for discriminating MAS from active cSLE in newly diagnosed patients. METHODS: We conducted a retrospective cohort study of consecutive, newly diagnosed, active cSLE patients with fever, requiring hospital admission to SickKids from January 2003 - December 2007 (cohort 1), and January 2008 - December 2013 (Cohort 2). All patients met ≥4 ACR or SLICC criteria, were steroid naïve and infection free. MAS was diagnosed based on expert opinion. Recursive partitioning was applied to each cohort to derive a decision rule based on clinical and laboratory features, distinguishing MAS from non-MAS cSLE. Each decision rule was applied to the alternate, independent cohort. Sensitivity and specificity of these decision rules were compared to existing criteria. RESULTS: Cohort 1 (n=34) and cohort 2 (n=41) each had 10 MAS patients. Recursive partitioning in cohort 1 identified ferritin ≥699 µg/L, as the sole best discriminator between MAS and non- MAS patients (R2=0.48) and in cohort 2 ferritin ≥1107 µg/L, followed by lymphocytes < 0.72 x103/mm3 were the best discriminators for MAS (R2=0.52). Cross-validation of our decision rules maintained 90-100% sensitivity and 65-85% specificity. CONCLUSION: Our decision rule demonstrated improved performance compared to preliminary guidelines for MAS in cSLE from the Lupus Working Group of the Paediatric Rheumatology European Society, and familial Hemophagocytic Lymphohistiocytosis diagnostic criteria. Validation in independent cohorts is required.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32976694

RESUMO

OBJECTIVE: The aim of this study was to examine the impact of timing of childhood-onset systemic lupus erythematosus (cSLE) diagnosis relative to menarchal status, on final height, accounting for and disease associated factors. METHODS: A cohort study of female cSLE patients <18 years of age at diagnosis, followed at a tertiary care, pediatric center from July 1982 to March 2016, restricted to patients with documented age of menarche and final height. We compared final height between patients diagnosed pre- and post-menarche. We tested the association of timing of cSLE diagnosis with final height, adjusted for ethnicity, in linear regression models. We performed subgroup analyses of patients with growth during follow-up, additionally adjusting for average daily corticosteroid dose and disease activity. RESULTS: Of 401 female cSLE patients in the study, 115 patients (29%) were diagnosed pre-menarche and 286 (71%) post-menarche. Patients diagnosed pre-menarche were older at menarche compared with patients diagnosed post-menarche (13.5 ± 1.4 vs. 12.5 ± 1.3 years; p < 0.001). The mean final height for females diagnosed post-menarche (161.4 cm [SD 6.9 cm]) was greater than those diagnosed pre-menarche (158.8 cm [SD 7.3 cm], P=0.001). In regression analysis, those diagnosed post-menarche were significantly taller than those diagnosed pre-menarche, adjusted for ethnicity, and disease severity (Beta=2.6cm, [SD 0.7cm], P=0.0006). CONCLUSION: In this large cohort study of females with cSLE, patients diagnosed post-menarche achieved a taller final height than those diagnosed pre-menarche even after accounting for ethnicity and disease severity.

3.
Arthritis Rheumatol ; 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32951358

RESUMO

OBJECTIVE: Report the 2-year efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). METHODS: Patients 2 to 17 years of age with active pcJIA whose treatment with methotrexate failed received 16 weeks of open-label intravenous tocilizumab in part 1 (every 4 weeks: 8 mg/kg or 10 mg/kg for body weight [BW] <30 kg; 8 mg/kg for BW ≥30 kg). Patients with ≥JIA-ACR30 response at week 16 were randomly assigned (1:1) to receive tocilizumab or placebo in part 2. Patients remained in part 2 until week 40 or occurrence of JIA flare. On starting part 3, all patients received open-label tocilizumab. At week 104 of the study, efficacy was assessed using JIA-ACR50/70/90 response rates, achievement of inactive disease, and Juvenile Arthritis Disease Activity Score-71 (JADAS-71). Safety was assessed in the all-exposure population per 100 patient-years (PY) of exposure. RESULTS: Overall, 188 patients entered part 1, 166 part 2, and 160 part 3. At week 104, among 188 patients in the modified-intent-to-treat group who received tocilizumab, JIA-ACR50/70/90 response rates were 80.3%/77.1%/59.6%; median JADAS-71 decreased from 3.6 at week 40 to 0.7 at week 104; 51.1% of patients achieved inactive disease; and 31 of 66 patients who were receiving glucocorticoids discontinued them. Adverse event (AE) and serious AE rates were 406.5/100PY and 11.1/100PY. Infections rates were 151.4/100PY and serious infections rates were 5.2/100PY. CONCLUSION: Patients treated with tocilizumab for pcJIA showed high-level disease control for up to 2 years. The tocilizumab safety profile was consistent with that previously reported.

4.
BMJ Case Rep ; 13(1)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31919069

RESUMO

A 16-year-old previously well girl presented with bilateral painful lower leg swelling and non-pruritic blanching rash across her torso and upper and lower limbs. These symptoms started after commencing amoxicillin for presumed tonsillitis. She was diagnosed with serum sickness-like illness and started on non-steroidal agents. The rash and painful leg swelling improved over the next 48 hours. However, she subsequently developed fevers, cough and new-onset haemoptysis.She continued to deteriorate with increasing amounts of haemoptysis, work of breathing and escalating respiratory support requirements. Serial chest radiographs showed worsening lung consolidation and enlarging pleural effusion. A CT chest revealed extensive bilateral lung consolidation, most likely pulmonary haemorrhage. Subsequent investigations showed positive classic antineutrophil cytoplasmic antibody, confirming the diagnosis of granulomatosis with polyangiitis.


Assuntos
Granulomatose com Poliangiite/terapia , Hemoptise/terapia , Doença Aguda , Adolescente , Anticorpos Anticitoplasma de Neutrófilos/sangue , Terapia Combinada , Diagnóstico Diferencial , Edema/diagnóstico , Edema/terapia , Exantema/diagnóstico , Exantema/terapia , Feminino , Granulomatose com Poliangiite/diagnóstico por imagem , Hemoptise/diagnóstico por imagem , Humanos , Imunoglobulinas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Troca Plasmática , Rituximab/uso terapêutico , Esteroides/uso terapêutico , Tomografia Computadorizada por Raios X
5.
Rheumatology (Oxford) ; 59(1): 90-98, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31236574

RESUMO

OBJECTIVE: LN is one of the most common and severe manifestations of SLE. Our aim was to test the association of SLE risk loci with LN risk in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE). METHODS: Two Toronto-based tertiary care SLE cohorts included cSLE (diagnosed <18 years) and aSLE patients (diagnosed ⩾18 years). Patients met ACR and/or SLICC SLE criteria and were genotyped on the Illumina Multi-Ethnic Global Array or Omni1-Quad arrays. We identified those with and without biopsy-confirmed LN. HLA and non-HLA additive SLE risk-weighted genetic risk scores (GRSs) were tested for association with LN risk in logistic models, stratified by cSLE/aSLE and ancestry. Stratified effect estimates were meta-analysed. RESULTS: Of 1237 participants, 572 had cSLE (41% with LN) and 665 had aSLE (30% with LN). Increasing non-HLA GRS was significantly associated with increased LN risk [odds ratio (OR) = 1.26; 95% CI 1.09, 1.46; P = 0.0006], as was increasing HLA GRS in Europeans (OR = 1.55; 95% CI 1.07, 2.25; P = 0.03). There was a trend for stronger associations between both GRSs and LN risk in Europeans with cSLE compared with aSLE. When restricting cases to proliferative LN, the magnitude of these associations increased for both the non-HLA (OR = 1.30; 95% CI 1.10, 1.52; P = 0.002) and HLA GRS (OR = 1.99; 95% CI 1.29, 3.08; P = 0.002). CONCLUSION: We observed an association between known SLE risk loci and LN risk in children and adults with SLE, with the strongest effect observed among Europeans with cSLE. Future studies will include SLE-risk single nucleotide polymorphisms specific to non-European ancestral groups and validate findings in an independent cohort.


Assuntos
Idade de Início , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Adolescente , Adulto , Criança , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/etnologia , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Adulto Jovem
6.
J Rheumatol ; 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31154408

RESUMO

The 73rd Annual Meeting of The Canadian Rheumatology Association was held at the Fairmont The Queen Elizabeth, Montreal, Quebec, Canada February 27 - March 2, 2019. The program consisted of presentations covering original research, symposia, awards, and lectures. Highlights of the meeting include the following 2019 Award Winners: Distinguished Rheumatologist, Edward Keystone; Distinguished Investigator, Diane Lacaille; Teacher-Educator, Shirley Tse; Emerging Investigator, Glen Hazlewood; Best Abstract on SLE Research by a Trainee - Ian Watson Award, Alexandra Legge; Best Abstract on Clinical or Epidemiology Research by a Trainee - Phil Rosen Award, Lauren King; Best Abstract on Basic Science Research by a Trainee, Remy Pollock; Best Abstract for Research by an Undergraduate Student, Andrea Carboni-Jimènez; Best Abstract on Research by a Rheumatology Resident, May Choi; Best Abstract by a Medical Student, Leonardo Calderon; Best Abstract by a Post-Graduate Research Trainee, Carolina Munoz-Grajales; Best Abstract by a Rheumatology Post-Graduate Research Trainee, Andre Luquini; Best Abstract on Quality Care Initiatives in Rheumatology, Cheryl Barnabe and Ines Colmegna; Best Abstract on Research by Young Faculty, Bindee Kuriya; Practice Reflection Award, Gold, Jason Kur; Practice Reflection Award, Silver, May Choi. Lectures and other events included Keynote Lecture by Andre Picard: Quirky Past, Uncertain Future: The State of Medicare in Canada; Keynote Address by Diane Lacaille, Distinguished Investigator Awardee: Time to Re-Label Comorbidities in RA - Coexisting or Complications; State of the Art Lecture by Mark Roberts: Myositis and its Mimics; Dunlop-Dottridge Lecture by Gilles Boire: The 4-H of Biomarkers in Arthritis: A lot of Help, Potential Harm, Some Hype, Increasing Hope; and the Great Debate: Be it Resolved that Competency-based Medical Education will Result in Improved Quality of Care for Patients vs the "Old Way" of Training Rheumatologists. Arguing for: Mercedes Chan and Marie-Paule Morin, and against: Beth Hazel and Heather McDonald-Blumer. Topics including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, psoriatic arthritis, spondyloarthritis, vasculitis, osteoarthritis, fibromyalgia, and their respective diagnoses, treatments, and outcomes are reflected in the abstracts, which we are pleased to publish in this issue of The Journal.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30805629

RESUMO

OBJECTIVE: Childhood-onset SLE (cSLE) manifests differently than adult-onset SLE (aSLE). This study determined whether ethnic differences contribute to the differences in clinical presentation between the two groups. METHODS: This cross-sectional study used data from a multi-centred registry from eight adult and four paediatric Canadian centres gathered at study entry. We compared the frequency of clinical manifestations and autoantibodies between aSLE and cSLE. For those with a significant difference, a multivariable logistic regression was performed, adjusting for ethnicity, SLE onset (cSLE vs aSLE), disease duration and centre. Disease activity and damage between aSLE and cSLE were compared after stratifying by disease duration. RESULTS: Of 552 aSLE subjects, 502 (90.9%) were female and 381 (69.0%) were Caucasian. Mean age at diagnosis was 37.0 ± 13.6 years and disease duration 10.9 ± 9.6 years. Of 276 cSLE subjects, 231 (83.7%) were female and 101 (36.6%) were Caucasian. Mean age at diagnosis was 12.7 ± 3.3 years and disease duration 5.6 ± 8.2 years. In multivariable regression analysis, aSLE was associated with decreased odds of having a neurologic disorder (odds ratio = 0.49) and increased odds of having aCL antibodies (odds ratio = 1.85). Disease activity and damage accrual scores were higher in aSLE than cSLE within the same disease duration strata, although the differences were not clinically significant. Ethnicity was not associated with any differences in clinical manifestations or autoantibody frequency between aSLE and cSLE. CONCLUSIONS: Although a crude comparison of aSLE and cSLE yielded several differences in clinical symptoms and autoantibodies, this difference was not attributable to ethnic differences between aSLE and cSLE.

8.
J Rheumatol ; 46(7): 731-738, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30770510

RESUMO

OBJECTIVE: Currently there are 2 different classification criteria for systemic lupus erythematosus (SLE): American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC). The aim of this study was to compare the sensitivities of ACR and SLICC criteria in childhood-onset SLE (cSLE) using a large, multiethnic cohort. METHODS: We conducted a retrospective study of 722 patients diagnosed with cSLE at The Hospital for Sick Children (SickKids). Prospectively collected data from SickKids' Lupus Database were reviewed/validated against medical records prior to ACR and SLICC scoring based on cumulative symptoms up to the last visit. Sensitivities were compared using McNemar's test. Descriptive statistics were used to identify SLE features unique to each set of criteria and autoantibodies not included in either. RESULTS: ACR and SLICC sensitivities were as follows: 92.4% and 96.3% overall (p = 0.001); 82.5% and 91.3% (p = 0.01) in those scored ≤ 1 year from diagnosis; 92.7% and 97.9% (p = 0.02) in those scored 2-3 years from diagnosis. Forty-eight of 55 (87.3%) patients who did not meet ACR criteria met SLICC criteria through SLICC-specific criterion or renal biopsy. Twenty of 27 (74.1%) patients who did not meet SLICC criteria met ACR criteria as a result of photosensitivity (73.9%) and ACR lymphopenia criteria (26.1%). Six of 7 patients (85.7%) who were clinically diagnosed with cSLE but did not meet either SLICC or ACR criteria had anti-Ro antibodies. CONCLUSION: SLICC criteria were significantly more sensitive than ACR criteria in cSLE classification, especially early in the disease course. Because of the extreme rarity of primary Sjögren syndrome in children, one may consider adding anti-Ro antibodies to the classification criteria for cSLE because they are present in ∼40% of patents with cSLE.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/imunologia , Projetos de Pesquisa , Adolescente , Anticorpos Antinucleares/sangue , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Cooperação Internacional , Rim/patologia , Leucopenia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Linfopenia , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade , Estados Unidos
9.
Ann Rheum Dis ; 77(12): 1742-1749, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30297329

RESUMO

OBJECTIVE: Cutaneous neonatal lupus (cNL) occurs in possibly 5%-16% of anti-Ro±anti-La antibody-exposed infants. Data suggest in utero exposure to hydroxychloroquine (HCQ) may prevent cardiac NL. The aim was to assess whether in utero exposure to HCQ decreases the risk of cNL and/or delays onset. METHODS: A multicentre case-control study was performed with 122 cNL cases and 434 controls born to women with a rheumatological disease who had documentation of maternal anti-Ro±anti-La antibodies at pregnancy and confirmation of medication use and the child's outcome. A secondary analysis was performed on 262 cNL cases, irrespective of maternal diagnosis, to determine if HCQ delayed time to cNL onset. RESULTS: Twenty (16%) cNL cases were exposed to HCQ compared with 146 (34%) controls (OR 0.4 (95% CI 0.2 to 0.6); p<0.01). Exposure to HCQ was associated with a reduced risk of cNL; exposure to anti-La antibody and female gender were associated with an increased risk of cNL. Exposure to HCQ remained significantly associated with a reduced cNL risk in the analyses limited to mothers with systemic lupus erythematosus and those who developed rash ≤1 month. When analysing all 262 cNL cases, HCQ-exposed infants were older (6.0 (95% CI 5.7 to 6.3) weeks) at cNL onset versus HCQ-non-exposed infants (4.4 (95% CI 3.9 to 5.0) weeks), but the difference was not statistically significant (p=0.21). CONCLUSION: Exposure to HCQ was associated with a reduced risk of cNL. Among cNL cases, those exposed to HCQ tend to have later onset of rash. Both findings suggest a protective effect of HCQ on cNL.


Assuntos
Antirreumáticos/uso terapêutico , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/congênito , Complicações na Gravidez/tratamento farmacológico , Doenças Autoimunes/tratamento farmacológico , Estudos de Casos e Controles , Feminino , Humanos , Lactente , Recém-Nascido , Lúpus Eritematoso Cutâneo/etiologia , Lúpus Eritematoso Sistêmico/etiologia , Masculino , Gravidez , Estudos Retrospectivos , Doenças Reumáticas/tratamento farmacológico
10.
Arthritis Rheumatol ; 70(4): 616-624, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29342508

RESUMO

OBJECTIVE: To describe the features and treatment of macrophage activation syndrome (MAS) in a single-center cohort of patients with childhood-onset systemic lupus erythematosus (SLE), and to compare childhood-onset SLE manifestations and outcomes between those with and those without MAS. METHODS: We included all patients with childhood-onset SLE followed up at The Hospital for Sick Children from 2002 to 2012, and identified those also diagnosed as having MAS. Demographic, clinical, and laboratory features of MAS and SLE, medication use, hospital and pediatric intensive care unit (PICU) admissions, as well as damage indices and mortality data were extracted from the Lupus database. Student's t-tests and Fisher's exact tests were used to compare continuous and categorical variables, respectively. We calculated incidence rate ratios of hospital and PICU admissions comparing patients with and those without MAS, using Poisson models. Kaplan-Meier survival analysis was used to examine the time to disease damage accrual. RESULTS: Of the 403 patients with childhood-onset SLE, 38 (9%) had MAS. The majority (68%) had concomitant MAS and SLE diagnoses. Fever was the most common MAS clinical feature. The frequency of renal and central nervous system disease, hospital admissions, the average daily dose of steroids, and time to disease damage were similar between those with and those without MAS. We observed a higher mortality rate among those with MAS (5%) than those without MAS (0.2%) (P = 0.02). CONCLUSION: MAS was most likely to develop concomitantly with childhood-onset SLE diagnosis. The majority of the MAS patients were successfully treated with corticosteroids with no MAS relapses. Although the numbers were small, there was a higher risk of death associated with MAS compared to SLE without MAS.


Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Síndrome de Ativação Macrofágica/mortalidade , Adolescente , Corticosteroides/uso terapêutico , Idade de Início , Criança , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Estimativa de Kaplan-Meier , Síndrome de Ativação Macrofágica/tratamento farmacológico , Síndrome de Ativação Macrofágica/imunologia , Masculino , Estudos Prospectivos
11.
Arthritis Care Res (Hoboken) ; 70(5): 750-757, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28704581

RESUMO

OBJECTIVE: No previous study has studied the longitudinal disease course of childhood-onset systemic lupus erythematosus (cSLE). Our objectives are to assess distinguishable differences in disease activity trajectories in cSLE patients, determine baseline factors predictive of disease trajectory membership, and assess if the different disease activity trajectories are associated with different damage trajectories. METHODS: This is a retrospective, longitudinal inception cohort of cSLE patients. Patients were followed from diagnosis as children, until they were adults. SLE disease activity was modeled as a latent characteristic, jointly using the Systemic Lupus Erythematosus Disease Activity Index 2000 and prednisone in a Bayesian growth mixture model. Baseline factors were tested for membership prediction of the latent classes of disease trajectories. Differences in damage trajectories by disease activity classes were tested using a mixed model. RESULTS: A total of 473 patients (82% females), with median age at diagnosis of 14.1 years, were studied. We studied 11,992 visits (2,666 patient-years). We identified 5 classes of disease activity trajectories. Baseline major organ involvement, number of American College of Rheumatology criteria, and age at diagnosis predicted memberships into different classes. A higher proportion of Asians was in class 2 compared to class 5. Class 1 was associated with the most accrual of damage, while class 5 was associated with no significant damage accrual, even after 10 years. CONCLUSION: There are 5 distinct latent classes of disease trajectory in patients with cSLE. Membership within disease trajectories is predicted by baseline clinical and demographic factors. Membership in different disease activity trajectory classes is associated with different damage trajectories.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Adolescente , Criança , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Modelos Estatísticos , Ontário/epidemiologia
12.
Ann Rheum Dis ; 77(1): 21-29, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28507219

RESUMO

OBJECTIVE: This report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA). METHODS: In this three-part randomised double-blinded placebo-controlled withdrawal trial, all patients received open-label golimumab (30 mg/m2 of body surface area; maximum: 50 mg/dose) every 4 weeks together with weekly methotrexate during Part 1 (weeks 0-16). Patients with at least 30% improvement per American College of Rheumatology Criteria for JIA (JIA ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16-48) after 1:1 randomisation to continue golimumab or start placebo. In Part 3, golimumab was continued or could be restarted as in Part 1. The primary outcome was JIA flares in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical remission, PK and safety. RESULTS: Among 173 patients with polyJIA enrolled, 89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41% vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event rates were similar in the treatment groups during Part 2. Injection site reactions occurred with <1% of all injections. PK analysis confirmed adequate golimumab dosing for polyJIA. CONCLUSION: Although the primary endpoint was not met, golimumab resulted in rapid, clinically meaningful, improvement in children with active polyJIA. Golimumab was well tolerated, and no unexpected safety events occurred. CLINICAL TRIAL REGISTRATION: NCT01230827; Results.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Juvenil/tratamento farmacológico , Artrite/tratamento farmacológico , Metotrexato/administração & dosagem , Adolescente , Artrite/patologia , Artrite Juvenil/patologia , Criança , Pré-Escolar , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Injeções Subcutâneas , Masculino , Indução de Remissão , Exacerbação dos Sintomas , Resultado do Tratamento
13.
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
14.
Rheum Dis Clin North Am ; 43(3): 415-434, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28711143

RESUMO

Systemic lupus erythematosus (SLE) is a systemic, autoimmune, multisystem disease with a heterogeneous clinical phenotype. Genome-wide association studies have identified multiple susceptibility loci, but these explain a fraction of the estimated heritability. This is partly because within the broad spectrum of SLE are monogenic diseases that tend to cluster in patients with young age of onset, and in families. This article highlights insights into the pathogenesis of SLE provided by these monogenic diseases. It examines genetic causes of complement deficiency, abnormal interferon production, and abnormalities of tolerance, resulting in monogenic SLE with overlapping clinical features, autoantibodies, and shared inflammatory pathways.


Assuntos
Lúpus Eritematoso Sistêmico/genética , Autoanticorpos/genética , Doenças Autoimunes/imunologia , Predisposição Genética para Doença , Genômica , Humanos , Lúpus Eritematoso Sistêmico/imunologia
15.
Rheumatology (Oxford) ; 56(9): 1552-1559, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28595349

RESUMO

Objective: Recent studies have suggested that prenatal exposure to HCQ reduces the risk of cardiac neonatal lupus. The aim of this study is to assess if maternal intake of antimalarials (AMs) throughout pregnancy lowered the risk of cardiac and non-cardiac neonatal lupus. Methods: Consecutive children seen between 1 January 1984 to 1 October 2013 born to women with a CTD and positive anti-Ro and/or anti-La antibodies were eligible for this single-centre retrospective cohort study. A total of 315 individuals were screened and 268 participants were included. Exposure to AMs was defined as HCQ or chloroquine throughout pregnancy. Outcomes were cardiac and non-cardiac neonatal lupus. Frequentist and Bayesian analyses were performed. We hypothesized that prenatal AM exposure would decrease the risk of cardiac but not non-cardiac neonatal lupus. Results: A total of 268 pregnancies were included; 73 were exposed to AMs throughout pregnancy. Ninety-nine children developed neonatal lupus, 117 remained unaffected and 52 children did not develop cardiac neonatal lupus but could not be categorized as unaffected since their full non-cardiac neonatal lupus status was unknown. Logistic regression suggested a protective effect of AM on cardiac neonatal lupus, but results were not statistically significant [odds ratio (OR) 0.21; P = 0.07]. Bayesian analysis showed that the probability of obtaining a protective effect (OR < 1.0) for cardiac neonatal lupus was significant (98.7%). The effect of AMs on non-cardiac neonatal lupus was not significant (OR 0.78; P = 0.21). Conclusion: In this large single-centre cohort study, exposure to AMs throughout pregnancy was associated with a decreased probability of developing cardiac but not non-cardiac neonatal lupus.


Assuntos
Antimaláricos/uso terapêutico , Doenças do Tecido Conjuntivo/tratamento farmacológico , Bloqueio Cardíaco/congênito , Lúpus Eritematoso Sistêmico/congênito , Complicações na Gravidez/tratamento farmacológico , Adulto , Teorema de Bayes , Feminino , Bloqueio Cardíaco/prevenção & controle , Humanos , Recém-Nascido , Lúpus Eritematoso Sistêmico/prevenção & controle , Masculino , Troca Materno-Fetal , Gravidez , Resultado da Gravidez , Cuidado Pré-Natal/métodos , Efeitos Tardios da Exposição Pré-Natal , Estudos Retrospectivos
16.
J Rheumatol ; 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28461649

RESUMO

The 72nd Annual Meeting of The Canadian Rheumatology Association (CRA) was held at The Westin Ottawa, Ottawa, Ontario, Canada, February 8-11, 2017. The program consisted of presentations covering original research, symposia, awards, and lectures. Highlights of the meeting include the following 2017 award winners: Dr. Vinod Chandran, Young Investigator; Dr. Jacques P. Brown, Distinguished Investigator; Dr. David Robinson, Teacher-Educator; Dr. Michel Zummer, Distinguished Rheumatologist; Ms. Rebecca Gole, Best Abstract on SLE Research by a Trainee - Ian Watson Award; Ms. Bailey Russell, Best Abstract on Clinical or Epidemiology Research by a Trainee - Phil Rosen Award; Dr. Sahil Koppikar and Dr. Henry Averns, Practice Reflection Award; Dr. Shirine Usmani, Best Abstract on Basic Science Research by a Trainee; Ms. Carol Dou, Best Abstract for Research by an Undergraduate Student; Dr. Dania Basodan, Best Abstract on Research by a Rheumatology Resident; Dr. Claire Barber, Best Abstract on Adult Research by Young Faculty; Ms. Audrea Chen, Best Abstract by a Medical Student; Dr. Kun Huang, Best Abstract by a Post-Graduate Resident; and Dr. Ryan Lewinson, Best Abstract by a Post-Graduate Research Trainee. Lectures and other events included a Keynote Lecture by Jonathon Fowles: Exercise is Medicine: Is Exercise a Good or Bad Thing for People with Arthritis?; State of the Art Lecture by Matthew Warman: Insights into Bone Biology and Therapeutics Gleaned from the Sustained Investigation of Rare Diseases; Dunlop-Dottridge Lecture by Allen Steere: Lyme Disease: A New Problem for Rheumatologists in Canada; and the Great Debate: Be it Resolved that the Least Expensive Treatment Should be Chosen. Switch, Switch, Switch! Arguing for: Jonathan Chan and Antonio Avina, and against: Marinka Twilt and Glen Hazlewood. Topics such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, psoriatic arthritis, spondyloarthritis, vasculitis, osteoarthritis, fibromyalgia, pediatric rheumatology, and their respective diagnoses, treatments, and outcomes are reflected in the abstracts, which we are pleased to publish in this issue of The Journal.

17.
Pediatr Rheumatol Online J ; 15(1): 18, 2017 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-28356102

RESUMO

Most outcome studies of rheumatic diseases report outcomes ascertained on a single occasion. While single assessments are sufficient for terminal or irreversible outcomes, they may not be sufficiently informative if outcomes change or fluctuate over time. Consequently, longitudinal studies that measure non-terminal outcomes repeatedly afford a better understanding of disease evolution.Longitudinal studies require special analytic methods. Newer longitudinal analytic methods have evolved tremendously to deal with common challenges in longitudinal observational studies. In recent years, an increasing number of studies have used longitudinal design. This review aims to help readers understand and apply the findings from longitudinal studies. Using a cohort of children with juvenile dermatomyositis (JDM), we illustrate how to study evolution of disease activity in JDM using longitudinal methods.


Assuntos
Dermatomiosite/epidemiologia , Estudos Observacionais como Assunto/métodos , Doenças Reumáticas/epidemiologia , Análise de Variância , Bioestatística , Criança , Humanos , Estudos Longitudinais , Modelos Biológicos , Estudos Observacionais como Assunto/estatística & dados numéricos , Prognóstico
18.
Arthritis Care Res (Hoboken) ; 69(12): 1887-1894, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28182833

RESUMO

OBJECTIVE: Although juvenile-onset proliferative lupus nephritis (PLN) leads to significant morbidity and mortality, there is no clinical trials-based evidence to support the treatment effectiveness of any therapy for juvenile-onset PLN. Marginal structural models enable us to estimate treatment effectiveness using observational data while accounting for confounding by indication. METHODS: We used prospectively collected data to examine the effect of mycophenolate mofetil (MMF), compared to the use of other therapies, on the long-term outcome of a juvenile-onset PLN cohort (age at PLN onset <18 years). The major outcome variable was the estimated glomerular filtration rate (GFR) using the revised Schwartz formula. Confounding by indication was corrected for marginal structural model. RESULTS: A total of 172 subjects with juvenile-onset PLN, with a mean followup duration of approximately 4 years, were included. Overall, MMF was superior to other therapies, with a relative effect estimate for MMF of 1.06, i.e., 6% better estimated GFR on average (95% confidence interval 0.7, 11.3), corrected for potential confounding by indication. We found that beginning in year 4 there was a significant improvement in estimated GFR in the patients who were treated with MMF versus other therapies. This improvement was maintained until the end of the study. CONCLUSION: MMF was more beneficial than other therapies in improving/maintaining long-term renal function in patients with juvenile-onset PLN up to a maximum followup of 7 years. This finding is consistent with evidence from adult PLN clinical trials.


Assuntos
Taxa de Filtração Glomerular/efeitos dos fármacos , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Adolescente , Idade de Início , Criança , Pesquisa Comparativa da Efetividade , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/efeitos adversos , Rim/imunologia , Rim/fisiopatologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/imunologia , Nefrite Lúpica/fisiopatologia , Masculino , Modelos Estatísticos , Ácido Micofenólico/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
19.
Prenat Diagn ; 37(4): 375-382, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28177533

RESUMO

OBJECTIVE: Mothers carrying anti-Ro antibodies are frequently referred for weekly echocardiograms to early detect and treat antibody-mediated fetal heart disease. We tested a surveillance strategy based on anti-Ro antibody titers. METHODS: From 2009 to 2014, 232 pregnancies were referred for maternal anti-Ro antibodies. At the baseline echocardiogram, anti-Ro titers were measured by enzyme-linked immunosorbent essay and results categorized as negative (<8 U/mL; n = 43; excluded), low-moderate positive (8-49 U/mL; n = 62; group 1) or high positive (50 - >100 U/mL; n = 127; group 2). Serial echocardiograms to ≥24 weeks were only recommended for group 2 mothers. RESULTS: Group 1 patients underwent significantly less fetal echocardiograms when compared with group 2 mothers (median 2 vs. 4; p < 0.001). Isolated endocardial fibroelastosis (n = 1) and incomplete (n = 4) or complete (n = 4) heart block were diagnosed in 9 (8%) pregnancies with anti-Ro titers >100 U/mL but none with lower titers (odds ratio 17.78; p = 0.004). Incomplete block and endocardial fibroelastosis regressed with transplacental corticosteroid and immune globulin therapy. CONCLUSIONS: Limiting serial fetal echocardiograms to women with high anti-Ro antibody levels is safe and more cost effective. While numbers of echocardiograms were significantly reduced in referrals with anti-Ro titers <50 U/mL, reversible abnormalities with prenatal treatment were detected by serial echocardiography in group 2 patients. © 2017 John Wiley & Sons, Ltd.


Assuntos
Ecocardiografia , Doenças Fetais/diagnóstico , Monitorização Fetal/métodos , Cardiopatias/diagnóstico , Doenças do Sistema Imunitário/diagnóstico , Ultrassonografia Pré-Natal/métodos , Adulto , Ecocardiografia/métodos , Fibroelastose Endocárdica/diagnóstico , Fibroelastose Endocárdica/tratamento farmacológico , Feminino , Doenças Fetais/tratamento farmacológico , Bloqueio Cardíaco/congênito , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/tratamento farmacológico , Cardiopatias/congênito , Cardiopatias/tratamento farmacológico , Humanos , Doenças do Sistema Imunitário/congênito , Doenças do Sistema Imunitário/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Gravidez , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
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