David A. Cabral

Prevalent Vertebral Fractures among Children Initiating Glucocorticoid Therapy for the Treatment of Rheumatic Disorders

Vertebral fractures are an under‐recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid therapy.

EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation

Objectives To report methodology and overall clinical, laboratory and radiographic characteristics for Henoch–Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) classification criteria. Methods The preliminary Vienna 2005 consensus conference, which proposed preliminary criteria for paediatric vasculitides, was followed by a EULAR/PRINTO/PRES - supported validation project divided into three main steps. Step 1: retrospective/prospective web-data collection for HSP, c-PAN, c-WG and c-TA, with age at diagnosis ≤18 years. Step 2: blinded classification by consensus panel of a subgroup of 280 cases (128 difficult cases, 152 randomly selected) enabling expert diagnostic verification. Step 3: Ankara 2008 Consensus Conference and statistical evaluation (sensitivity, specificity, area under the curve, κ-agreement) using as ‘gold standard’ the final consensus classification or original treating physician diagnosis. Results A total of 1183/1398 (85%) samples collected were available for analysis: 827 HSP, 150 c-PAN, 60 c-WG, 87 c-TA and 59 c-other. Prevalence, signs/symptoms, laboratory, biopsy and imaging reports were consistent with the clinical picture of the four c-vasculitides. A representative subgroup of 280 patients was blinded to the treating physician diagnosis and classified by a consensus panel, with a κ-agreement of 0.96 for HSP (95% CI 0.84 to 1), 0.88 for c-WG (95% CI 0.76 to 0.99), 0.84 for c-TA (95% CI 0.73 to 0.96) and 0.73 for c-PAN (95% CI 0.62 to 0.84), with an overall κ of 0.79 (95% CI 0.73 to 0.84). Conclusion EULAR/PRINTO/PRES propose validated classification criteria for HSP, c-PAN, c-WG and c-TA, with substantial/almost perfect agreement with the final consensus classification or original treating physician diagnosis.

Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study.

To determine the frequency of incident vertebral fractures (IVF) 12 months after glucocorticoid (GC) initiation in children with rheumatic diseases and to identify children at higher risk.

Mucoid Pseudomonas aeruginosa Resists Nonopsonic Phagocytosis by Human Neutrophils and Macrophages

ABSTRACT. Mucoid Pseudomonas aeruginosa is an important respiratory pathogen in patients with cystic fibrosis, and once acquired is virtually impossible to eradicate. Although mucoid P. aeruginosa is generally believed to be resistant to phagocytosis, the mechanism is not understood fully. We studied the nonopsonic phagocytosis by human neutrophils or macrophages of eight mucoid/nonmucoid P. aeruginosa pairs (three isogenic and five “wild-type”). Mucoid strains were relatively resistant to nonopsonic phagocytosis but the nonmucoid types were phagocytosis-susceptible as assessed by visual inspection and chemiluminescence assays. The mucoid and nonmucoid variants had equal numbers of pili but different surface characteristics as determined by biphasic partitioning in polyethylene glycol and dextran. The mucoid exopolysaccharide of mucoid strains appears to alter the surface characteristics of P. aeruginosa thereby rendering them resistant to nonopsonic phagocytosis. The resistance of mucoid variants of P. aeruginosa to nonopsonic phagocytosis may provide a survival advantage to these bacteria early in the course of pulmonary infection before opsonic antibody and complement are present in respiratory secretions.

Prospective study of computed tomography in acute bacterial meningitis

We performed serial CT scans at the time of admission and discharge, and again after 6 to 18 months, in children older than 2 months of age with bacterial meningitis. During the 2-year study period, 60 patients with bacterial meningitis were admitted to British Columbias Childrens Hospital. Forty-one were included in the study, two of whom died soon after admission. The infecting organism was Haemophilus influenzae in 29, Neisseria meningitidis in six, and Streptococcus pneumoniae in six. Abnormalities on the first two CT scans included subdural effusion in eight patients, focal infarction in five, and pus in the basal cisterns in one. All patients with focal infarction or cisternal pus had hemiparesis. Marked cerebral edema was seen in the two patients who died. Transient mild dilation of the subarachnoid space was a common finding; the size of the ventricles or subarachnoid space was increased on the second scan in 29 of 36 patients, and decreased to normal on the third scan in 30 of 33 patients. Clinical management was not influenced by the CT findings, which failed to reveal any clinically significant abnormalities that were not suspected on neurologic examination.

High Incidence of Vertebral Fractures in Children With Acute Lymphoblastic Leukemia 12 Months After the Initiation of Therapy

PURPOSE Vertebral fractures due to osteoporosis are a potential complication of childhood acute lymphoblastic leukemia (ALL). To date, the incidence of vertebral fractures during ALL treatment has not been reported. PATIENT AND METHODS We prospectively evaluated 155 children with ALL during the first 12 months of leukemia therapy. Lateral thoracolumbar spine radiographs were obtained at baseline and 12 months. Vertebral bodies were assessed for incident vertebral fractures using the Genant semiquantitative method, and relevant clinical indices such as spine bone mineral density (BMD), back pain, and the presence of vertebral fractures at baseline were analyzed for association with incident vertebral fractures. RESULTS Of the 155 children, 25 (16%; 95% CI, 11% to 23%) had a total of 61 incident vertebral fractures, of which 32 (52%) were moderate or severe. Thirteen (52%) of the 25 children with incident vertebral fractures also had fractures at baseline. Vertebral fractures at baseline increased the odds of an incident fracture at 12 months by an odds ratio of 7.3 (95% CI, 2.3 to 23.1; P = .001). In addition, for every one standard deviation reduction in spine BMD Z-score at baseline, there was 1.8-fold increased odds of incident vertebral fracture at 12 months (95% CI, 1.2 to 2.7; P = .006). CONCLUSION Children with ALL have a high incidence of vertebral fractures after 12 months of chemotherapy, and the presence of vertebral fractures and reductions in spine BMD Z-scores at baseline are highly associated clinical features.

Central nervous system involvement in neonatal lupus erythematosus.

Abstract: Computerized tomography (CT) of the brain was performed in 10 of 11 consecutive infants with neonatal lupus erythematosus (NLE) (five boys and six girls). Ten of the 11 infants had brain neurosonography. Nine of 10 infants had abnormal CT scans. There was diffuse, markedly reduced attenuation of the cerebral white matter in four infants studied in the first week of life, and also in an infant 5 weeks of age. Patchy reduced subcortical white matter attenuation was observed in another 5‐week‐old infant. Basal ganglia calcifications were present in two infants at 2 months of age, one of whom also had mild ventriculomegaly. A patient with macrocephaly studied at 4 months of age had enlarged ventricles and subarachnoid spaces consistent with benign macrocephaly of infancy. Cerebral ultrasound examination was abnormal in all five infants studied in the first week of life and in one infant at 2 months of age. Findings included subependymal cysts (4), echogenic white matter (3), and echogenic lenticulostriate vessels (3). Apart from one case of macrocephaly, there was no clinical evidence of neurologic disease and the subsequent development of these infants has been normal. Subclinical central nervous system (CNS) disease in NLE is likely to be a transient phenomenon that resolves as maternal antibodies are cleared from the infants circulation. It is important to be aware of these neuroimaging abnormalities to avoid misdiagnosis of congenital viral infection in a newborn with multisystem NLE. The potential for neurologic sequelae is uncertain.

The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort

Objective To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments. Methods Children newly diagnosed with JIA at 16 Canadian paediatric rheumatology centres from 2005 to 2010 were included. Kaplan–Meier survival curves for each JIA category were used to estimate probability of ever attaining an active joint count of 0, inactive disease (no active joints, no extraarticular manifestations and a physician global assessment of disease activity <10 mm), disease remission (inactive disease >12 months after discontinuing treatment) and of receiving specific treatments. Results In a cohort of 1104 children, the probabilities of attaining an active joint count of 0 exceeded 78% within 2 years in all JIA categories. The probability of attaining inactive disease exceeded 70% within 2 years in all categories, except for RF-positive polyarthritis (48%). The probability of discontinuing treatment at least once was 67% within 5 years. The probability of attaining remission within 5 years was 46–57% across JIA categories except for polyarthritis (0% RF-positive, 14% RF-negative). Initial treatment included joint injections and non-steroidal anti-inflammatory drugs for oligoarthritis, disease-modifying antirheumatic drugs (DMARDs) for polyarthritis and systemic corticosteroids for systemic JIA. Conclusions Most children with JIA managed with contemporary treatments attain inactive disease within 2 years of diagnosis and many are able to discontinue treatment. The probability of attaining remission within 5 years of diagnosis is about 50%, except for children with polyarthritis.

Early outcomes and improvement of patients with juvenile idiopathic arthritis enrolled in a Canadian multicenter inception cohort

To determine early outcomes and early improvements in a prospective inception cohort of children with juvenile idiopathic arthritis (JIA) treated with current standard therapies.

Disease activity assessment in childhood vasculitis: development and preliminary validation of the Paediatric Vasculitis Activity Score (PVAS)

Background Rare chronic childhood vasculitides lack a reliable disease activity assessment tool. With emerging new treatment modalities such a tool has become increasingly essential for both clinical practice and therapeutic trials to reproducibly quantify change in disease state. Objective To develop and validate a paediatric vasculitis activity assessment tool based on modification of the Birmingham Vasculitis Activity Score (BVASv.3). Methods A paediatric vasculitis registry was reviewed to identify clinical features missing in the BVASv.3. A modified nominal group technique was used to develop a working version of the Paediatric Vasculitis Activity Score (PVAS). Prospective validation provided tool reliability, reproducibility and responsiveness to change. Training of assessors was done according to the BVAS principles. Results BVAS items were redefined (n=22) and eight paediatric items added in Cutaneous (n=4), Cardiovascular (n=3) and Abdominal (n=1) sections. The final PVAS has 64 active items in nine categories. The principles of new/worse and persistently active disease were retained as were the overall score and weighting of categories. The median PVAS in 63 children with systemic vasculitis was 4/63 (0–38/63). There was a high interobserver agreement for the overall as well as for subsystem scores (linear-weighted-κ ≥0.87). PVAS correlated with physicians global assessment (p<0.01); treatment decision (p=<0.01) and erythrocyte sedimentation rate (ESR) (p=0.01). In response to treatment, 15/19 patients assessed demonstrated a significant fall in PVAS (p=0.002), with good agreement among assessors for this change. Conclusions The PVAS validity in children with systemic vasculitis was demonstrated. Like the BVAS, we anticipate that the PVAS will provide a robust tool to objectively define disease activity for clinical trials and future research.