Elizabeth Harvey

Severe Ulcerative Colitis After Rituximab Therapy

B-cell–depletion therapy with rituximab is efficacious against steroid-dependent nephrotic syndrome (NS) in children and adults. Safety data are limited. Results of small studies have suggested that rituximab is usually well tolerated but that adverse events (such as severe mucocutaneous reactions, fatal infusion reactions, progressive multifocal leukoencephalopathy, and bowel perforation) can occur. We report here the first case (to our knowledge) of a pediatric patient with refractory minimal-change NS who developed severe immune-mediated ulcerative gastrointestinal disease 42 days after rituximab therapy. The disease was characterized by deep ulcers throughout the intestines and predominantly affected the colon. The child presented with severe abdominal pain, bloody diarrhea, weight loss, and fever. Her inflammatory markers were significantly elevated. Extensive evaluation revealed no evidence of infections and no characteristics of defined inflammatory bowel disease or Behçet disease. Colonoscopy revealed severe intestinal inflammation with deep ulcers. Histology of the colonic biopsy specimens revealed extensive infiltrates predominantly composed of CD8+ T lymphocytes and evidence of high forkhead box P3 (FOXP3) expression. During this significant gastrointestinal disease, the NS remained quiescent. Corticosteroid therapy successfully controlled the severe immune-mediated intestinal inflammation after rituximab therapy. NS relapsed subsequently when CD19+ and CD20+ B-cell populations recovered.

Ethnic Differences in Pediatric Systemic Lupus Erythematosus

Objective. Prevalence and severity of systemic lupus erythematosus (SLE) in adults is suggested to be distinctly different between ethnic groups. The impact of ethnicity is not as well delineated in pediatric SLE (pSLE). We compared prevalence and extent of major organ involvement, disease activity, and damage in pSLE between different ethnic groups. Methods. Ethnic demographic profiles of an inception cohort of 265 patients with pSLE followed at Sick Kids Hospital in Toronto were determined and compared to the Metropolitan Toronto at-risk population. Patients were categorized into ethnic subsets based on self-designated ethnic origins. Disease characteristics including major organ involvement, disease activity, and damage measures were longitudinally determined and compared among ethnic groups. Results. Ethnicity data were available on 259/265 pSLE patients (99.6%); the majority were non-Caucasian (60%) compared to the Metropolitan Toronto at-risk population (40%) (p < 0.0001). Non-Caucasian patients were younger at diagnosis than Caucasian patients, Black patients being the youngest at diagnosis (12.6 vs 14.6 yrs; p = 0.007). Renal disease was significantly more common in non-Caucasian than in Caucasian pSLE patients (62% vs 45%; p = 0.01). There was a trend toward increased prevalence of central nervous system disease in Black patients compared to Asian patients (p = 0.108). There was no difference in gender ratio, SLE Disease Activity Index, or damage scores between ethnic groups. Conclusion. Non-Caucasian ethnicity is associated with increased pSLE disease prevalence. Non-Caucasian pSLE patients were significantly younger and more likely to have nephritis. However, disease activity and damage were strongly associated with major organ disease independent of the patient’s ethnicity.

Prostatic Abscess Due to Burkholderia pseudomallei: 81 Cases From a 19-Year Prospective Melioidosis Study

PURPOSE We review the epidemiology, clinical presentation, management and outcome of prostatic abscess secondary to Burkholderia pseudomallei infection in the Northern Territory, Australia. We highlight the frequency of prostatic abscess occurrence in melioidosis, and formulate recommendations for its detection and management. MATERIALS AND METHODS We reviewed a prospective database of all culture confirmed melioidosis cases in the Northern Territory between October 1989 and July 2008. This review was supplemented with data obtained from a review of case notes and postmortem records during the same period. RESULTS There were 514 patients with 561 episodes of melioidosis, and of these patients 394 (70%) were male. A prostatic abscess was identified, usually by computerized tomography, in 81 (21%) of these episodes, in 77 patients. In 75 (93%) of the 81 episodes there was clinical evidence of prostatic infection or positive urine culture for B. pseudomallei. Kava use and hazardous alcohol use were independent predictors of prostatic abscesses compared to male patients without prostatic abscesses. All were treated with antibiotics and in 57 of the 81 episodes the abscesses were drained. Ultrasound guided needle drainage was used in 51 instances and open drainage in 28 (transurethral 13, transrectal 11, transperineal 4). There were 20 patients who underwent multiple procedures while 24 underwent no procedures. CONCLUSIONS Prostatic abscess is common in melioidosis. Clinical signs are usually present but may be subtle. Detection is enhanced by routine computerized tomographic screening of the abdomen and pelvis for occult visceral abscesses in all cases of melioidosis. Ultrasound guided needle drainage is adequate initial therapy in conjunction with appropriate antibiotics.

End-tidal CO2-arterial CO2 differences: a useful intraoperative mortality marker in trauma surgery.

OBJECTIVE The gradient of end-tidal CO2 to arterial CO2 (Pa-ET)CO2 has been identified as a predictor of mortality in patients undergoing emergency trauma surgery. In an effort to further elucidate this phenomena, we accumulated additional data on trauma patients undergoing emergency surgery. METHODS Five-hundred and one patients undergoing emergent trauma surgery at an Urban Level I Trauma Center were used as a database. Data were obtained both prospectively and retrospectively. End-tidal and CO2 measurements were serially obtained during surgery. Data were arbitrarily placed in three categories: initial OR, post-resuscitation, and final OR. (Post-resuscitation was identified after bleeding controlled and vital signs normalizing). Correlation of the end-tidal CO2 with the PACO2 difference were correlated with various factors including survival. RESULTS Overall mortality was 29%. Mean ISS was 22 +/- 9.8. Mean emergency department systolic blood pressure was 81 mm Hg. Sixty-three people died in the operating room, 54 died within 24 hours post-op, and 30 patients died greater than 24 hours post-op. The average (Pa-ET)CO2 difference was <10 mm Hg in all survivors at all measurement times. The average (Pa-ET)CO2 was >10 mm Hg in non-survivors in patients that died at all time intervals. CONCLUSION (Pa-ET)CO2 can be used as a predictor of mortality and may be useful as an intraoperative tool for assessing the physiologic conditions of the patient. This predictor of mortality was valid even in patients that died greater than 24 hours after surgery. This information is almost always already available and may be used to further guide the decisions regarding patient care, particularly in decisions regarding damage control surgery.

Predicting longitudinal trajectory of bone mineral density in paediatric systemic lupus erythematosus patients

Objectives (1) To identify the average lumbar spine (LS) bone mineral density (BMD) trajectory in paediatric systemic lupus erythematosus (pSLE) patients, and (2) to identify predictors of BMD trajectory. Methods 68 consecutive newly diagnosed pSLE patients prospectively followed in our lupus cohort with three annual dual energy x-ray absorptiometry (DEXA) examinations were studied. Low LS BMD was defined as z-score ≤−2.0. Baseline and longitudinal clinical features including disease activity, treatment and bone physiology markers were collected. Hierarchical linear modelling was used to model trajectory of LS BMD and identify predictors. Results Women constituted 84% of the cohort and median age at diagnosis was 13.1 years. The mean LS BMD z-scores decreased over time (−0.42 at first, −1.02 at second and −1.11 at third DEXA). Initially 9% of patients had a low BMD, which increased to 19% by 3 years after diagnosis. 35% of patients deteriorated in BMD category from the first to third DEXA. LS BMD (adjusted by height-for-age z-score) followed a general deteriorating trajectory of −0.06 z-score/year from diagnosis. Increased rate of deterioration of BMD trajectory was predicted by pubertal status at diagnosis, increased interval cumulative steroid exposure and decreased weight z-scores. Conclusions The LS BMD of pSLE patients followed a general deteriorating trend over time and could be predicted by a combination of pubertal status at diagnosis, interval cumulative doses of steroids and weight z-scores. Interval cumulative steroid dose represents an important target that clinicians may modify to ameliorate deteriorating BMD trajectory over time.

Low bone mineral density is present in newly diagnosed paediatric systemic lupus erythematosus patients

Objectives The objectives of this study were to (1) determine the prevalence of low bone mineral density (BMD) in a large prospective cohort of newly diagnosed patients with paediatric systemic lupus erythematosus (pSLE) and (2) identify risk factors associated with low BMD. Methods Single-centre cohort study of 80 children and adolescents who underwent a dual-energy x-ray absorptiometry within 3 months of diagnosis. Low lumbar spine (LS) BMD was defined as z score ≤−2.0. BMD was correlated with baseline demographic, clinical and laboratory markers of disease activity and biochemical markers of bone health. Risk factors of BMD were evaluated with univariable and multivariable linear and logistic regression analyses. Results Low BMD at any site was found in 15% of newly diagnosed pSLE patients. LS BMD was associated with body mass index (BMI) z score and corrected calcium (r2=0.31, p<0.0001). Hip BMD was associated with BMI z score and intact parathyroid hormone (iPTH) (r2=0.26, p=0.002). Higher BMI z score was protective against low BMD at any site (OR 0.35). Conclusions One in six newly diagnosed pSLE patients had low BMD (at any site). Low BMI z score, low calcium and high iPTH identified children at risk for low BMD at diagnosis of pSLE.

Rapid development of an immunoblastic lymphoma and death in children following cadaveric renal transplantation

We report on three children who underwent cadaveric renal transplantation and subsequently developed an immunoblastic lymphoma, leading to death in two patients. The development of the lymphoma occurred following a multi-drug immunosuppression regimen ending with monoclonal antilymphocyte (OKT3) treatment for biopsy-proven cellular and vascular acute rejection. These patients represent three of 11 children who received OKT3 treatment for rejection in the last 18 months at this institution. Following the diagnosis of lymphoma, all three patients were treated by transplant nephrectomy, cessation of immunosuppression, and administration of intravenous acyclovir. The first two patients died at 4 days and 4 weeks, respectively, after the definitive diagnosis was made with widespread metastatic disease. The remaining child is a short-term survivor (13 months), free of demonstrable malignancy. Multidrug regimens for immunosuppression have a profound effects on T cell function. These effects, when combined with a primary infection by the Epstein-Barr virus, are implicated in the rapid development of the lymphomas and are responsible for the death of these two children.

Idiopathic Urinary Bladder Perforation in Early Childhood

INTRODUCTION U rinary ascites is a rare condition characterized by abdominal distention and renal impairment on biochemical investigation. Most often it occurs secondary to trauma, abdominal surgery, or after chemotherapy. In the neonate, it can occur either spontaneously or secondary to a urogenital malformation or umbilical catheterization. We describe a unique case of spontaneous urinary bladder perforation presenting with urinary ascites and an acute kidney injury picture in early childhood without underlying urogenital anomaly or trauma.

Management of Severe Hyponatremia With a Custom Continuous Renal Replacement Therapy in an Infant With Newly Diagnosed Chronic Kidney Disease

Marie-Michèle Gaudreault-Tremblay, MD, Hassan Faqeehi, MD, Valérie Langlois, MD, Diane Hébert, MD, Dimitri A. Parra, MD, Gail Annich, MD, Elizabeth Harvey, MD and Mathieu Lemaire, MDCM, PhD Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada; Division of Interventional Radiology, The Hospital for Sick Children, Toronto, Ontario, Canada; Division of Critical Care Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada; and Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada

Does routine ultrasound change management in the follow-up of patients with vesicoureteral reflux?

INTRODUCTION Children with vesicoureteral reflux (VUR) usually need a renal ultrasound (RUS). There is little data on the role of follow-up RUS in VUR. We evaluated the impact of follow-up RUS on the change in clinical management in patients with VUR. METHODS We prospectively analyzed children with a previous diagnosis of VUR seen in the outpatient clinic with a routine follow-up RUS within 4 months. Variables collected included: demographic data, VUR history, dysfunctional voiding symptoms and concurrent ultrasound findings. Change in management was defined as addition of new medication, nurse counselling, surgery or further investigations. RESULTS The study included 114 consecutive patients. The mean patient age was 4.5 years old, mean age of VUR diagnosis was 1.7 years, with average follow-up of 2.8 years. A change in management with stable RUS occurred in 14 patients, in which the change included ordering a DMSA in 9, nurse counselling for dysfunctional voiding in 3, and booking surgery in 2 patients. Change on RUS was seen in 4 patients. Multivariable analysis showed that history of urinary tract infection (UTI) since the last follow-up visit was more significant than RUS findings. CONCLUSIONS The RUS findings in most patients followed for VUR remain stable or with minimal changes. The variable showing a significant effect on change in management in our study was history of UTI since the last follow-up visit rather than RUS findings. The value of follow-up RUS for children with VUR may need to be revisited.