Muferet Erguven

Two Randomized Trials of Canakinumab in Systemic Juvenile Idiopathic Arthritis

BACKGROUND Interleukin-1 is pivotal in the pathogenesis of systemic juvenile idiopathic arthritis (JIA). We assessed the efficacy and safety of canakinumab, a selective, fully human, anti-interleukin-1β monoclonal antibody, in two trials. METHODS In trial 1, we randomly assigned patients, 2 to 19 years of age, with systemic JIA and active systemic features (fever; ≥2 active joints; C-reactive protein, >30 mg per liter; and glucocorticoid dose, ≤1.0 mg per kilogram of body weight per day), in a double-blind fashion, to a single subcutaneous dose of canakinumab (4 mg per kilogram) or placebo. The primary outcome, termed adapted JIA ACR 30 response, was defined as improvement of 30% or more in at least three of the six core criteria for JIA, worsening of more than 30% in no more than one of the criteria, and resolution of fever. In trial 2, after 32 weeks of open-label treatment with canakinumab, patients who had a response and underwent glucocorticoid tapering were randomly assigned to continued treatment with canakinumab or to placebo. The primary outcome was time to flare of systemic JIA. RESULTS At day 15 in trial 1, more patients in the canakinumab group had an adapted JIA ACR 30 response (36 of 43 [84%], vs. 4 of 41 [10%] in the placebo group; P<0.001). In trial 2, among the 100 patients (of 177 in the open-label phase) who underwent randomization in the withdrawal phase, the risk of flare was lower among patients who continued to receive canakinumab than among those who were switched to placebo (74% of patients in the canakinumab group had no flare, vs. 25% in the placebo group, according to Kaplan-Meier estimates; hazard ratio, 0.36; P=0.003). The average glucocorticoid dose was reduced from 0.34 to 0.05 mg per kilogram per day, and glucocorticoids were discontinued in 42 of 128 patients (33%). The macrophage activation syndrome occurred in 7 patients; infections were more frequent with canakinumab than with placebo. CONCLUSIONS These two phase 3 studies show the efficacy of canakinumab in systemic JIA with active systemic features. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT00889863 and NCT00886769.).

Evaluation of immune response to hepatitis A vaccination and vaccine safety in juvenile idiopathic arthritis.

Background: Autoimmune mechanisms and drugs used in treatment increase the risk of liver disease in patients with juvenile idiopathic arthritis (JIA) and hepatitis A virus (HAV) vaccination is important, especially in intermediate‐endemicity areas like Turkey. In our study, we aimed to evaluate the immune response to hepatitis A vaccine and vaccine safety in children with JIA. Methods: This study was carried out in our hospital’s Pediatric Rheumatology outpatient clinic and Healthy Child clinic between the years 2003 and 2008. The study group consisted of 47 children with JIA (23 male and 24 female) diagnosed according to International League of Associations for Rheumatology diagnostic criteria. The control group consisted of 67 healthy children (31 female, 36 male) who did not have a history of hepatitis A infection or vaccination. Both groups were vaccinated with two doses of hepatitis A vaccine at 6‐month intervals. Anti‐HAV IgG >80 MIU was accepted as positive response. Results: There was no significant difference between the groups in terms of age and sex. None of the patients with JIA had fever, clinical worsening, or disease activation after vaccination. Anti‐HAV IgG positivity rate was significantly higher in the control group (p < 0.05). Anti‐HAV IgG was negative in only four cases, and they were all male patients with systemic JIA who had active disease under anti‐tumor necrosis factor treatment. Conclusion: Hepatitis A vaccine was safe in patients with JIA, and response to vaccine did not differ between healthy children and patients with JIA except for children with active systemic JIA receiving anti‐tumor necrosis factor alpha drugs.

A Case of Early Diagnosed Carnitine Deficiency Presenting with Respiratory Symptoms

Introduction: Carnitine deficiency is an autosomal recessively inherited disease characterized by a low carnitine concentration in plasma and tissues. Primary carnitine deficiency (PCD) is caused by a deficiency in the plasma membrane carnitine transporter, with urinary carnitine wasting causing systemic carnitine depletion. The most common presentation of PCD is hypoketotic hypoglycemic encephalopathy. Cardiomyopathy can also be seen. Case Report: A 9-month-old girl was admitted to our clinic with wheezing, respiratory distress and nighttime cough. She was pale, expirium was prolonged, breath sounds were coarse bilaterally and were increased in the right hemithorax. Results: She had hypochromic microcytic anemia and the serum CPK level was elevated. Cardiothoracic index was increased (0.62). In the chest X-ray there was hyperaeration especially in the upper regions of the left lung, and paracardiac infiltration in the right lung. The echocardiogram showed dilated cardiomyopathy. In pulmonary perfusion scintigraphy, perfusion of the right lung was 26% and of the left lung 74%. Cardiomegaly and dilatation in main the pulmonary artery was detected in the MR angiogram. Plasma carnitine and acylcarnitine levels were found to be significantly low. Fat accumulation in myocytes and rare atrophic fibers were detected in a muscle biopsy. Oral carnitine supplementation was started at a dose of 100 mg/kg. All the symptoms and findings regressed within a short period of time. Discussion: This case was presented to emphasize that carnitine deficiency can present with respiratory tract symptoms like wheezing and recurrent respiratory tract infections. Although PCD usually presents with hypoketotic hypoglycemia in infants, it also has to be suspected in the etiology of dilated cardiomyopathy. Treatment is very easy and lifesaving once the correct diagnosis is made, and the prognosis is excellent with lifelong carnitine supplementation.

Complementary and Alternative Medicine in Children with Type 1 Diabetes Mellitus

Objective: Complementary and alternative medicine (CAM) is increasingly utilized in adults and children for treatment of various conditions. Studies on CAM in diabetes have mainly focused on the adult population and its application in children has not been well established. The aim of this study was to examine the prevalence and characteristics of CAM use in Turkish children with type 1 diabetes mellitus (T1DM). Methods: The information was acquired by a questionnaire completed by a face-to-face interview with the parents of children with T1DM. Results: A total of 195 subjects (mean age: 14.02±4.7 years; F/M: 103/92) were included in this survey. Use of CAM was reported in 85 subjects (43.6%). Herbal medicines were used in 64 subjects (75.3%). Sixty-nine subjects (81.2%) did not inform the diabetes specialist about CAM use. Thirty-eight subjects (44.7%) evaluated CAM as efficacious. Only 3 subjects (3.5%) interrupted the insulin injections to use CAM. No relationships were found between CAM use and parental education or insulin dose. There were significant correlations between CAM use and higher family income (p=0.027), urban residence (p=0.05), presence of complications (p=0.03), dissatisfaction with medical therapy (p=0.034) and prior CAM use among parents (p=0.001). Conclusion: CAM use is a frequent practice among diabetic children, which is usually not shared with their physicians and sometimes leads to cessation of medical treatment. Conflict of interest:None declared.

Efficacy and safety of canakinumab, a long acting fully human anti-Interleukin-1β antibody, in systemic juvenile idiopathic arthritis with active systemic features: results from a phase III study

Efficacy and safety of canakinumab, a long acting fully human anti-Interleukin-1b antibody, in systemic juvenile idiopathic arthritis with active systemic features: results from a phase III study N Ruperto, H Brunner, G Horneff, P Quartier, T Constantin, Y Berkun, M Erguven, T Kallinich, R Brik, NM Wulffraat, MA Ferrandiz, L Rutkowska-Sak, H Ozdogan, L McCann, K Lheritier, R Preiss, L Tseng, A Martini, DJ Lovell, For the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG)

Does Hypereosinophilic Syndrome Precede Common B Acute Lymphoblastic Leukaemia in Childhood? A Case Report

Hypereosinophilic syndrome (HES) and the association of hypereosinophilia with acute lymphoblastic leukaemia (ALL) are both rare in children. Some acute myelogenous leukaemias can present with eosinophilia, but the relationship between HES and ALL is not well known and is rarer than the relationship between HES and acute myelogenous leukaemia. Patients are diagnosed with HES when no cause is found to explain the eosinophilia leading to end organ damage. For this reason, it is recommended that patients presenting with hypereosinophilia be carefully assessed to exclude any malignant clonal proliferation. HES may present with severe clinical manifestations such as high leucocyte count, anaemia, thrombocytopaenia, hepatosplenomegaly or cardiac and neurological involvement, all of which are primarily features of myeloproliferative disorders. Some patients with HES can develop chronic eosinophilic leukaemia. Successful treatment of HES with agents used in chronic myeloid leukaemia supports the idea that HES can be a chronic myeloid disorder. There are few cases reporting an association between ALL and hypereosinophilia that precedes or is concomitant with ALL. Here we report the case of a 14-year-old girl who developed common B ALL 7 months after diagnosis and treatment of HES. Interestingly, eosinophilia was not concomitant with the diagnosis of ALL.

Vaginal Dialysate Leakage in a Child on Peritoneal Dialysis

1. Henderson S, Brown E, Levy J. Safety and efficacy of percutaneous insertion of peritoneal dialysis catheters under sedation and local anaesthetic. Nephrol Dial Transplant 2009; 24:3499–504. 2. Tzamaloukas AH, Gibel LJ, Eisenberg B, Goldman RS, Kanig SP, Zager PG, et al. Early and late peritoneal dialysate leaks in patients on CAPD. Adv Perit Dial 1990; 6:64–70. 3. Campos RP, Chula DC, Riella MC, Ronco C, Crepaldi C, Cruz DN, et al. Complications of the peritoneal access and their management: peritoneal dialysis—from basic concepts to clinical excellence. Contrib Nephrol 2009; 163:183–97. 4. Leblanc M, Ouimet D, Pichette V. Dialysate leaks in peritoneal dialysis. Semin Dial 2001; 14:50–4. doi:10.3747/pdi.2010.00016

Urinary tract infections in children with myelodysplasia in whom clean intermittent catheterization was administered

AIM In this study, it was aimed to evaluate the frequency of significant bacteriuria and antibiotic resistance characteristics in children with myelodysplasia in whom clean intermittent catheterization was administered. MATERIAL AND METHODS The study group was composed of 71 patients with myelodysplasia who were found to have significant bacteriuria (age: 8.20±4.57 years; 39 girls) and the control groups was composed of 49 children who were diagnosed with community-acquired urinary tract infection (age: 7.94±4.17 years; 29 girls). The patient and control groups were evaluated in terms of the microorganisms grown in urinary cultures and antibiotic resistance characteristics. The study approved by the ethics committe (14/02/2012-19/E). RESULTS Growth of Escherichia coli (E. coli) was found with the highest rate in myelodysplasic patients. However, when compared with the control group in terms of microorganism types, an increase in the growth rates of the microorganisms excluding E. coli was observed in the patients with myelodysplasia which was close to the significance limit (p=0.055). When antibiotic resistance properties were examined, a significantly increased resistance against cotrimaxazole was found in the patient group compared to the control group (p=0.001). 84.5% of the patients were using prophylactic antibiotic including mainly co-trimoxazole. A significantly increased co-trimoxazole resistance was also found in the patients who were using prophylactic antibiotic compared to the patients who were not using prophylactic antibiotic (p=0.025). The rate of symptomatic UTI was found to be 21% in the patients with myelodysplasia and a significant increase was found in the complaints of abdominal/side pain and nausea/vomiting as well as fever in these patients compared to the patients with asymptomatic bacteriuria (p=0.029 and p=0.032, respectively). CONCLUSION Our results show that UTI is still a significant problem in patients with myelodysplasia. In addition, they show that use of prophylactic antibiotic may increase the frequency of development of resistance and co-trimoxazole used for this objective is not a good option..

ACUTE PERITONEAL DIALYSIS IN NEONATES WITH ACUTE KIDNEY INJURY AND HYPERNATREMIC DEHYDRATION

♦ Objective: We aimed to evaluate the efficacy of acute peritoneal dialysis (PD) and clinical outcomes in neonates with acute kidney injury (AKI) and hypernatremic dehydration. ♦ Methods: The medical records of 15 neonates with AKI and hypernatremic dehydration who were treated with acute PD were reviewed. The diagnoses were AKI with hypernatremic dehydration with or without sepsis in 13 patients and AKI with hypernatremia and congenital nephropathy in 2 patients. The main indications for PD were AKI with some combination of oligoanuria, azotemia, hyperuricemia, and metabolic acidosis unresponsive to initial intensive medical treatment. ♦ Results: The mean age of the patients at dialysis initiation was 11.9 ± 9 days, and the mean duration of PD was 6.36 ± 4.8 days. In 7 patients (46.7%), hypotension required the use of vasopressors, and in 6 patients (40%), mechanical ventilation was required. Peritoneal dialysis-related complications occurred in 7 patients (46.7%), the most common being catheter malfunction (n = 6). Four episodes of peritonitis occurred in the 15 patients (26.7%), 2 episodes in patients with congenital renal disease and 2 episodes in patients with sepsis and multiorgan failure, who did not survive. Congenital renal disease, septicemia, and the need for mechanical ventilation were important factors influencing patient survival. All patients with no pre-existing renal disease or sepsis recovered their renal function and survived. ♦ Conclusions: In neonates with AKI and hypernatremic dehydration, PD is safe and successful, and in patients without congenital renal disease or sepsis, the prognosis is good. Peritoneal dialysis should be the treatment of choice in neonates with AKI and hypernatremic dehydration who do not respond to appropriate med ical treatment.

Frequency of Pericardial Effusion in Childhood Acute Lymphoblastic Leukemia and Clinical Features of These Patients

In this study, we aimed to determine the frequency of pericardial effusion (PE) in children diagnosed with acute lymphoblastic leukemia (ALL). Clinical features of patients with effusion were evaluated. For this purpose, we reviewed the medical records of ALL patients who had pretherapy echocardiograms. A total of 90 patients aged between 1.8 and 16.3 years were analyzed retrospectively. In 23 of 90 (25.6%) patients, PE was detected at initial diagnosis. The age of patients with PE ranged between 1.8 and 14.8 years (mean 5.05 ± 3.77 years). The female/male ratio was 9/14. Six (26.1%) patients were T-lineage and 17 (73.9%) were B-lineage ALL. Nine (39%) patients were in standard risk group, 13 (57%) were in median risk group, 1 (4%) patient was in high-risk group. Mean initial white blood cell count was 40.756 ± 38.653/mm3 (range 23.000–130.000/mm3). Mean initial hemoglobin count was 7.3 ± 1.39 gr/dL (range 5.5–10.1 gr/dL), mean initial platelet count was 35.200 ± 26.300/mm3 (range 4.000–118.000 mm3). Size of effusions was between 2 and 6 mm (mean size 3.3 ± 1.8 mm). All patients had normal left ventricular systolic function. In 87% of patients, effusions disappeared in the first 7 days and, in 13%, disappeared between 8th and 15th days of chemotherapy. None of the patients required pericardiocentesis. Cardiac dysfunction did not occur among any of these patients during chemotherapy. In conclusion, PE is not frequent in childhood ALL. It usually does not cause cardiac impairment. It responds to treatment of leukemia.