Urinary MCP-1/creatinine in Henoch-Schönlein purpura and its relationship with nephritis.

BACKGROUND: Monocyte chemotactic protein-1 (MCP-1) plays a direct role in the infiltration of macrophages and monocytes during the early stages of Henoch-Schönlein purpura (HSP) nephritis. The aim of this study was to compare the urinary MCP-1/creatinine levels in children with and without HSP nephritis and determine if they are associated with the severity of renal lesions. METHODS: We included 77 patients with HSP and 25 healthy control children. Levels of serum creatinine, urinalysis, and 12-h proteinuria assessments were performed. Urinary MCP-1 levels were determined by ELISA. RESULTS: Fifty-seven patients had nephritis (74 %). Urinary MCP-1/creatinine levels were significantly higher in patients with HSP nephritis (median, 653 pg/mg) compared to those with HSP without nephritis (median, 269 pg/mg) or healthy children (191 pg/mg). In addition, higher MCP-1/creatinine levels were observed in HSP patients who had renal biopsy (median, 1,412 pg/mg) in comparison to HSP patients without renal biopsy (median, 302 pg/mg). The urinary MCP-1 cut-off value of 530 pg/mg could be used to distinguish patients who undergo renal biopsy with a sensitivity of 81 % and specificity of 77 %. CONCLUSIONS: Urinary MCP-1/creatinine levels are elevated in the early stages of severe HSP nephritis and can be used as a biomarker for HSP nephritis.

Development and External Validation of a Model Predicting New-Onset Chronic Uveitis at Different Disease Durations in Juvenile Idiopathic Arthritis.

OBJECTIVE: To develop and externally validate a prediction model for new-onset chronic uveitis in children with juvenile idiopathic arthritis (JIA) for clinical application. METHODS: Data from the international Pharmachild registry were used to develop a multivariable Cox proportional hazards model. Predictors were selected by backward selection, and missing values were handled by multiple imputation. The model was subsequently validated and recalibrated in 2 inception cohorts: the UK Childhood Arthritis Prospective Study (CAPS) study and the German Inception Cohort of Newly diagnosed patients with juvenile idiopathic arthritis (ICON) study. Model performance was evaluated by calibration plots and C statistics for the 2-, 4-, and 7-year risk of uveitis. A diagram and digital risk calculator were created for use in clinical practice. RESULTS: A total of 5,393 patients were included for model development, and predictor variables were age at JIA onset (hazard ratio [HR] 0.83 [95% confidence interval (95% CI) 0.77-0.89]), ANA positivity (HR 1.59 [95% CI 1.06-2.38]), and International League of Associations for Rheumatology category of JIA (HR for oligoarthritis, psoriatic arthritis, and undifferentiated arthritis versus rheumatoid factor-negative polyarthritis 1.40 [95% CI 0.91-2.16]). Performance of the recalibrated prediction model in the validation cohorts was acceptable; calibration plots indicated good calibration and C statistics for the 7-year risk of uveitis (0.75 [95% CI 0.72-0.79] for the ICON cohort and 0.70 [95% CI 0.64-0.76] for the CAPS cohort). CONCLUSION: We present for the first time a validated prognostic tool for easily predicting chronic uveitis risk for individual JIA patients using common clinical parameters. This model could be used by clinicians to inform patients/parents and provide guidance in choice of uveitis screening frequency and arthritis drug therapy.

Antiphospholipid syndrome in Mexican children.

BACKGROUND: Data on pediatric antiphospholipid syndrome (APS) are very sparse. OBJECTIVES: To describe the main clinical characteristics, laboratory data and complications of pediatric APS patients, and to analyze the differences between primary APS and APS associated with systemic lupus erythematosus (SLE). METHODS: We retrospectively reviewed clinical and laboratory data of 32 children at the Federico Gomez children's hospital in Mexico. Nineteen patients had SLE, 12 (37.5%) had primary APS and 1 (3%) had immune thrombocytopenic purpura. We collected information on sociodemographic variables, vaccinations, age at onset, and family history of rheumatic disease, hematological disorders, skin disorders and non-thrombotic neurological disorders. Immunological features included immunoglobulin (Ig) G and IgM anticardiolipin antibodies, IgG and IgM anti-beta2 glycoprotein I antibodies, lupus anticoagulant, and anti-dsDNA and antinuclear antibodies. RESULTS: The patients included 24 females and 8 males. The most common thrombotic events were small vessel thrombosis (44%), venous thrombosis (28%) mainly deep venous thrombosis (DVT) in lower extremities, and arterial thrombosis (25%). The most common clinical non-thrombotic manifestations were hematological (53%) and neurological disorders (22%). There were no significant differences between groups with regard to the site of thrombosis, nonthrombotic clinical manifestations or laboratory features. CONCLUSIONS: There were some important differences between the clinical manifestations of APS in children compared with adults, but we found no significant differences between patients with primary and APS associated with SLE. Larger studies in Latin American APS children are necessary to determine whether there are differences between ethnic groups.

Absence of Association Between Abatacept Exposure and Initial Infection in Patients With Juvenile Idiopathic Arthritis.

OBJECTIVE: To assess the relationship between infection risk and abatacept (ABA) exposure levels in patients with polyarticular-course juvenile idiopathic arthritis (pJIA) following treatment with subcutaneous (SC) and intravenous (IV) ABA. METHODS: Data from 2 published studies (ClinicalTrials.gov: NCT01844518, NCT00095173) of ABA treatment in pediatric patients were analyzed. One study treated patients aged 2-17 years with SC ABA and the other treated patients aged 6-17 years with IV ABA. Association between serum ABA exposure measures and infection was evaluated using Kaplan-Meier plots of probability of first infection vs time on treatment by ABA exposure quartiles and log-rank tests. Number of infections by ABA exposure quartiles was investigated. RESULTS: Overall, 343 patients were included in this analysis: 219 patients received SC ABA and 124 patients received IV ABA. Overall, 237/343 (69.1%) patients had ≥ 1 infection over 24 months. No significant difference in time to first infection across 4 quartiles of ABA exposure levels was observed in the pooled (P = 0.45), SC (2-5 yrs: P = 0.93; 6-17 yrs: P = 0.48), or IV (P = 0.50) analyses. Concomitant use of methotrexate and glucocorticoids (at baseline and throughout) with ABA did not increase infection risk across the ABA exposure quartiles. There was no evidence of association between number of infections and ABA exposure quartiles. No opportunistic infections related to ABA were reported. CONCLUSION: In patients aged 2-17 years with pJIA, no evidence of association between higher levels of exposure to IV ABA or SC ABA and incidence of infection was observed.

Reliability of ultrasonography to detect inflammatory lesions and structural damage in juvenile idiopathic arthritis.

BACKGROUND: Musculoskeletal Ultrasonography (MSUS) is an important tool for the clinical assessment in Juvenile Idiopathic Arthritis (JIA). The objective of this study was to evaluate the reliability of MSUS to detect elementary lesions: synovitis, tenosynovitis, cartilage damage and bone erosions in the wrist and metacarpal (MCP) joints of patients with JIA. METHODS: Thirty children in various subgroups of JIA according to ILAR criteria, were included in this cross-sectional study. Clinical data including painful, swollen and limited joints were recorded. Five rheumatologist ultrasonographers, blinded to the clinical evaluation, evaluated the presence of elementary lesions in the wrist and MCP 2 and 3 joints bilaterally. The synovitis was graded in B-Mode and Power Doppler (PD). In addition to descriptive statistics intra- and inter-observer reliability was calculated using Cohen's kappa according to Landis and Koch. RESULTS: US detected more synovitis than the clinical examination (62% vs 28%, 30% vs 23% and 22% vs 17% in the wrist, second and third MCP joints respectively). The intra-observer concordance for synovitis in all joints was excellent in B-Mode (k 0.84 .63-1.0 p = 0.001), except for MCP 2, where it was good (0.61, IC 95% .34-89, p = 0.001). For both modalities (PD, B-Mode) tenosynovitis, cartilage damage and bone erosions it was also excellent. Regarding synovitis grading the concordance was excellent for all grades (0.83-1.0, IC 95% 0.51.1.0, p = 0.001), except for grade 1 where it was good (0.61, IC 95% 0.43-.83, p = 0.001). Reliability inter-observer for grayscale synovitis (0.67-0.95, IC 95% 0.67-1.0, p = 0.001), tenosynovitis grayscale (0.89, IC 95% 0.78-0.99, p.001), damage cartilage (0.89, IC 95% 0.78-0.99, p = 0.001), PD (0.66, IC 95% 0.39-1.0, p = 0.001). The concordance for grading synovitis was excellent, but for grayscale grade 1 and 2 (.66, IC 95% .53-.74, p = 0.007) and PD grade 1 and 2 (0.63, IC 95% .58-.91, p = 004) was good. CONCLUSIONS: The intra- and inter-observer reliability of MSUS for inflammatory and structural lesions is good to excellent for the wrist and MCP in patients with JIA.

[Clinical characteristics of children with scleroderma in a referral hospital]. / Características clínicas de niños con esclerodermia en un hospital de referencia.

INTRODUCTION: Scleroderma is an autoimmune disease that involves the connective tissue characterized by skin fibrosis, classified as localized and systemic (participation of one or more internal organs). The primary objective of this study is to describe and analyze the clinical and laboratory findings in a group of children diagnosed with scleroderma at a referral hospital. MATERIAL AND METHODS: Extraction of data from clinical charts of children with scleroderma in the rheumatology department at the Hospital Infantil de México Federico Gómez, between January 2000 and December 2007. RESULTS: Sixty two patients were included in the group. All of them completed the classification criteria for juvenile sclerodema, both systemic and localized. The mean age at diagnosis was 7.8 (1-14) years. The mean time from disease onset to diagnosis, based on clinical manifestations, was 23 months. The lesions found were: linear scleroderma (42%), mixed morphea (22%), circumscribed morphea (19%), generalized morphea (13%) and panclerotic morphea (4%). Involvement associated with Systemic Scleroderma was gastrointestinal 100% (18 patients), pulmonary 100% (18/18), Raynaud's phenomenon 89% (16/18), proximal sclerosis 89% (16/18), sclerodactilia 67% (12/18), joint pain 28% (5/18), calcinosis 56% (10/18). Positive antinuclear antibodies (ANA) were present in 14/62 (23%) patients (10 with systemic range and 4 localized), antiSCL 70 in 2/62 (4%) cases. The most common drug used was methotrexate. CONCLUSION: The most common skin lesions found were linear morphea, followed by the mixed and circumscribed types. In systemic scleroderma the most involved systems are the gastrointestinal, respiratory and vascular (associated with Raynaud's phenomenon). There is a special need for knowledge of this disease in first contact physicians for a faster and better diagnosis and treatment, in order to avoid complications. It is also necessary to improve resources in developing countries for complimentary studies, classification, treatment and follow-up.