mutations cause skeletal dysplasia, immune deficiency, and developmental delay.

We studied three patients with severe skeletal dysplasia, T cell immunodeficiency, and developmental delay. Whole-exome sequencing revealed homozygous missense mutations affecting exostosin-like 3 (EXTL3), a glycosyltransferase involved in heparan sulfate (HS) biosynthesis. Patient-derived fibroblasts showed abnormal HS composition and altered fibroblast growth factor 2 signaling, which was rescued by overexpression of wild-type cDNA.

Disease activity accounts for long-term efficacy of IL-1 blockers in pyogenic sterile arthritis pyoderma gangrenosum and severe acne syndrome.

Objective: To provide a rationale for anti-IL-1 treatment in pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) by defining whether IL-1β secretion is enhanced; requires NLRP3; and correlates with proline-serine-threonine phosphatase-interacting protein 1 mutations, disease activity and/or the clinical picture in PAPA.

Methods: Monocytes were isolated from 13 patients and 35 healthy donors and studied at baseline and following activation. Secretion pattern of IL-1β, IL-1α, IL-1Ra, IL-6, IL-18 and TNF-α was assessed in supernatants by ELISA.

Dissecting the heterogeneity of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.

Objective: To seek insights into the heterogeneity of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA) through the analysis of a large patient sample collected in a multinational survey.

Methods: International pediatric rheumatologists and hemato-oncologists entered their patient data, collected retrospectively, in a Web-based database. The demographic, clinical, laboratory, histopathologic, therapeutic, and outcome data were analyzed in relation to (1) geographic location of caring hospital, (2) subspecialty of attending physician, (3) demonstration of hemophagocytosis, and (4) severity of clinical course.

Whole-body MRI as an unconventional diagnostic tool in a pediatric patient with systemic infection.

Anaplasma phagocytophilum, an obligate intracellular bacterium, is the causative agent of human granulocytic anaplasmosis (HGA), a tickborne infection usually manifesting as fever, malaise, cytopenia, spleen enlargement, and hepatitis. Herein, we report a case of a 14-year-old girl with HGA whose whole-body magnetic resonance imaging (MRI) disclosed an unusual picture characterized by small, widespread punctuate millimetric nodules, hypointense on T1-weighted and hyperintense on STIR sequences. This firstly reported finding may represent an alternative tool for identifying atypical infectious diseases.

Cytomegalovirus-related necrotising vasculitis mimicking Henoch-Schönlein syndrome.

Viral vasculitides have been previously reported in the literature, the role of infections in their pathogenesis ranging from direct cause to trigger event. Here we report the case of a 3-year-old immunocompetent girl who developed a systemic vasculitis leading to ileal perforation, mimicking a full blown picture of Henoch-Schönlein purpura. High dosage steroid treatment was started, with good response.

Clinical overview and outcome in a cohort of children with polyarteritis nodosa.

Objectives: Polyarteritis nodosa (PAN) is a rare vasculitis in childhood and poor information is known about its long-term outcome. Our aim was to describe the clinical features, at onset and during the disease course, of childhood-onset PAN and identify a potential correlation with persistent organ damage and worse outcome in a cohort of paediatric patients with a confirmed diagnosis of PAN.

Methods: A retrospective collection of demographic and clinical data of 52 Caucasian children diagnosed with PAN, fulfilling the EULAR/PRES diagnostic criteria, recruited from eight paediatric rheumatologic centres and one transition unit, was performed.

Whole-body MRI in the assessment of disease activity in juvenile dermatomyositis.

Objective: To compare whole-body MRI (WB-MRI) with clinical examination in the assessment of disease activity in juvenile dermatomyositis (JDM).

Methods: WB-MR images were obtained from 41 JDM patients and 41 controls using a 1.5 T MRI scanner and short τ inversion recovery sequences.

Recurrent pericarditis in Myhre syndrome.

Myhre syndrome is a rare disorder characterized by pre- and postnatal short stature, brachydactyly, facial dysmorphism (short palpebral fissures, maxillary hypoplasia, prognathism and short philtrum), thick skin, muscular-appearing body build, decreased joint mobility, mixed hearing loss, and cleft lip and palate. Other clinical features include skeletal dysplasia, developmental delay with intellectual disability and/or behavioral disturbance, cardiac defects, cryptorchidism, and bone anomalies. The disease is caused by recently identified SMAD4 mutations.

Factors associated with achievement of inactive disease in children with juvenile idiopathic arthritis treated with etanercept.

Objective: To evaluate the rate of inactive disease in children with juvenile idiopathic arthritis (JIA) treated with etanercept, and to identify clinical characteristics associated with attainment of inactive disease.

Methods: Clinical charts of patients who were given etanercept between January 2002 and January 2011 were evaluated retrospectively. For each patient, all visits from initiation of etanercept to the last followup evaluation in which the patient was still receiving etanercept were examined to establish whether the patient had reached the state of inactive disease and to identify the first visit in which inactive disease was documented.

MRI versus conventional measures of disease activity and structural damage in evaluating treatment efficacy in juvenile idiopathic arthritis.

Objective: To compare the American College of Rheumatology paediatric (ACRp) response criteria and conventional radiography with MRI findings in a cohort of patients with juvenile idiopathic arthritis.

Methods: Forty consecutive patients (30 girls, 10 boys; median age 10.8 years) with arthritis of the wrist starting treatment with disease-modifying antirheumatic drugs or biological agents were recruited.

Novel automated system for magnetic resonance imaging quantification of the inflamed synovial membrane volume in patients with juvenile idiopathic arthritis.

Objective: To introduce a novel automated method for the quantification of the inflamed synovial membrane volume (SV) using magnetic resonance imaging (MRI), and to investigate its feasibility and validity in patients with juvenile idiopathic arthritis (JIA).

Methods: The tool was tested on 58 patients with JIA and wrist involvement. Thirty-six patients had a 1-year MRI followup.

Role of IL-1 beta in the development of human T(H)17 cells: lesson from NLPR3 mutated patients.

Background: T helper 17 cells (T(H)-17) represent a lineage of effector T cells critical in host defence and autoimmunity. In both mouse and human IL-1β has been indicated as a key cytokine for the commitment to T(H)-17 cells. Cryopyrin-associated periodic syndromes (CAPS) are a group of inflammatory diseases associated with mutations of the NLRP3 gene encoding the inflammasome component cryopyrin.

Comparison of clinical features and drug therapies among European and Latin American patients with juvenile dermatomyositis.

Objectives: To compare the demographic features, presenting manifestations, diagnostic investigations, disease course, and drug therapies of children with juvenile dermatomyositis (JDM) followed in Europe and Latin America.

Methods: Patients were inception cohorts seen between 1980 and 2004 in 27 paediatric rheumatology centres. The following information was collected through the review of patient charts: sex; age at disease onset; date of disease onset and diagnosis; onset type; presenting clinical features; diagnostic investigations; course type; and medications received during disease course.

Development and preliminary validation of a paediatric-targeted MRI scoring system for the assessment of disease activity and damage in juvenile idiopathic arthritis.

Objectives: To develop and validate a paediatric-targeted MRI scoring system for the assessment of disease activity and damage in juvenile idiopathic arthritis (JIA). To compare the paediatric MRI score with the adult-designed. Outcome Measures in Rheumatology Clinical Trials-Rheumatoid Arthritis MRI Score (RAMRIS), whose suitability for assessing growing joints was tested.

Predictors of poor response to methotrexate in polyarticular-course juvenile idiopathic arthritis: analysis of the PRINTO methotrexate trial.

Objectives: To determine whether baseline demographic, clinical, articular and laboratory variables predict methotrexate (MTX) poor response in polyarticular-course juvenile idiopathic arthritis.

Methods: Patients newly treated for 6 months with MTX enrolled in the Paediatric Rheumatology International Trials Organization (PRINTO) MTX trial. Bivariate and logistic regression analyses were used to identify baseline predictors of poor response according to the American College of Rheumatology pediatric (ACR-ped) 30 and 70 criteria.

EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria.

Objectives: To validate the previously proposed classification criteria for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA).

Methods: Step 1: retrospective/prospective web-data collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis View Article and Find Full Text PDF

Development and testing of reduced joint counts in juvenile idiopathic arthritis.

Objective: To develop and test reduced joint counts in children with juvenile idiopathic arthritis (JIA).

Methods: Four reduced joint counts including 45, 35, 27, and 10 joints were devised by a panel of experienced pediatric rheumatologists, who selected the joints to be included based on the ease of technical assessment, functional relevance, and frequency of involvement. Three large samples of patients with JIA (total n=4353) who had a detailed joint assessment available were used to develop and test reduced joint counts.

Magnetic resonance imaging, ultrasonography, and conventional radiography in the assessment of bone erosions in juvenile idiopathic arthritis.

Objective: To compare magnetic resonance imaging (MRI), conventional radiography, and ultrasonography in identifying bone erosions in patients with juvenile idiopathic arthritis (JIA), and to determine the validity and reliability of an MRI scale in detecting and grading joint damage.

Methods: In 26 JIA patients, the clinically more affected wrist was studied with MRI, radiography, and ultrasonography, coupled with standard clinical assessment and biochemical analysis. MR images were assessed independently by 2 readers according to an apposite devised scoring system.

Treatment of Takayasu's arteritis with tumor necrosis factor antagonists.

Four children with Takayasu's arteritis were treated with tumor necrosis factor antagonists because of disease relapse during conventional therapy or as a first-line agent. Two patients went into remission; in the other 2, the response was partial. Anti-tumor necrosis factor agents can have a role in the treatment of Takayasu's arteritis; further controlled studies are required.

The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis.

Objective: To assess the clinical response to interleukin-1 (IL-1) blockade and in vitro IL-1beta and IL-18 secretion in patients with systemic-onset juvenile idiopathic arthritis (JIA).

Methods: Twenty-two patients with systemic-onset JIA were treated with the IL-1 receptor antagonist (IL-1Ra) anakinra. Monocytes from 18 patients and 20 healthy donors were activated by different Toll-like receptor ligands.

Persistent efficacy of anakinra in patients with tumor necrosis factor receptor-associated periodic syndrome.

Objective: To evaluate the efficacy and safety of treatment with the interleukin-1 receptor antagonist anakinra in patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS) requiring high cumulative doses of steroids.

Methods: Four children (mean age 9.1 years [range 4-13 years]) and 1 adult (age 33 years) with TRAPS were enrolled in the study.

Childhood thalidomide neuropathy: a clinical and neurophysiologic study.

Thalidomide was recently reintroduced to treat several immune-mediated pathologies. Peripheral neuropathy is a significant side effect limiting its clinical use. Our aims include: (1) describing and identifying the incidence of clinical or electrophysiologic peripheral neuropathy in children, (2) determining whether peripheral neuropathy correlates with cumulative dose of thalidomide and with age, and (3) defining its reversibility rate.

Agreement between physicians and parents in rating functional ability of children with juvenile idiopathic arthritis.

Objective: To investigate concordance between physicians and parents in rating the degree of functional ability of children with juvenile idiopathic arthritis (JIA).

Methods: The attending physician and a parent were asked to rate independently the level of physical functioning of 155 patients with disease duration >/= 5 years on a 6-point scale ranging from 1 = no disability (i.e.