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עמוד בית
Thu, 26.12.24

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April 2012
A. Achiron, B.-Z. Garty, S. Menascu, D. Magalashvili, M. Dolev, B. Ben-Zeev and O. Pinhas-Hamiel
Background: Multiple sclerosis (MS) occurs in young adults and infrequently appears in childhood.

Objectives: To determine the incidence of MS and describe the clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) findings at onset MS in children in Israel.

Methods: Incidence and case-specific data were obtained through the MS Center Database and Israeli Health Statistics Census Data over 15 years, from 1995 to 2009, and compared between patients with childhood (< 12 years), juvenile (> 12 years, < 18 years) and adult (> 18 years) onset MS.

Results: Of 1129 eligible MS patients, we identified 10 (0.89%) with childhood-onset MS, 74 (6.55%) with juvenile-onset MS, and 1045 (92.56%) with adult-onset MS. There were 0 to 3 incident childhood cases/year, leading to an annual incidence of 0.1/100,000 among Israeli children the incidence of juvenile and adult MS was 2.6 and 5.4/100,000, respectively. Neurological presentation among children with MS was optic neuritis, motor weakness or brainstem involvement. CSF oligoclonal immunoglobulin (IgG) were positive in 62.5%. The most frequent MRI finding was the occurrence of ¡Ý 3 periventricular white matter lesions followed by corpus callosum lesions, with 71% co-occurrence. Cervical and thoracic lesions occurred in 33% and 43%, respectively. Time to second neurological event ranged from 0.3 to 4.2 years and none of the patients with childhood MS reached EDSS=6.0 within a mean follow-up period of 8.4 years.

Conclusions: Childhood-onset MS is rare, with an incidence of 0.1/100,000 Israeli children. Childhood MS does not differ significantly from juvenile and adult-onset MS in terms of clinical, laboratory and imaging findings.
January 2012
Mauro Calvani, MD, Iride Dello Iacono, MD, Valentina Giorgio, MD, Stefano Miceli Sopo, Valentina Panetta, MD and Salvatore Tripodi, MD.

Background: The diagnostic gold standard for food allergy is an oral food challenge (OFC) with the suspected food. Usually, an OFC is stopped at the onset of mild objective symptoms for fear of severe reactions. However, there is no consensus on this issue.

Objective: To investigate the effectiveness and side effects of a new model of oral milk challenge in order to increase the diagnostic accuracy of cow¡¯s milk protein allergy and reduce the number of many useless elimination diets. This model is characterized by a conservative diagnostic protocol and ¡°step-up cow’s milk administered dosing.¡± The secondary aim was to investigate possible factors influencing severe reactions.   

Methods: Sixty-six children (median age 1 year, range 1¨C18) with suspected immunoglobulin E (IgE)-mediated cow’s milk allergy performed a conservative oral food challenge (OFC), i.e., the OFC was continued even in the presence of subjective, even repeated, or mild local or multiple organ objective symptoms. If the first objective reaction occurred when the quantity of milk was > 10 ml, the investigator would decide whether to continue the OFC or prescribe a gradual increase in milk feeding at home.

Results: Symptoms developed during the OFC in 42.4% of the children. Local, generalized and severe generalized reactions developed in 11 (16.7%), 11 (16.7%) and 6 (9.1%) children, respectively. Only 14/28 (50%) who developed objective symptoms during the OFC were considered to be affected by cow’s milk allergy. In the remaining 14 both subjective and objective symptoms developed and the OFC was continued without the emergence of additional symptoms. Epinephrine was administered to 6 of the 28 children (21.4%) who developed objective symptoms. All but one had subjective symptoms following the early doses of milk, whereas all children who later tolerated milk had their first subjective or mild symptoms following doses ¡Ý 10 ml.

Conclusions: This new model of oral milk challenge criteria led to frequent severe allergic reactions hence its use in daily practice seems inadvisable. However, our study provides evidence that a severe allergic reaction does not invariably occur if the offending food continues to be administered after the onset of symptoms. If mild symptoms appear at doses higher than 10 ml, continued milk administration, on the same day or in subsequent days, seems to facilitate the development of tolerance and may reduce the number of useless elimination diets.


Pedro Ojeda, MD, MPH, Isabel Ojeda, MD, Gema Rubio, MD and Fernando Pineda, PhD.

Background: In the last decade the use of different types of oral immunotherapy for food-allergic patients has increased with generally satisfactory outcomes. Cow’s milk and hen’s egg, a common element in the daily diet, have received the main interest. Most of these immunotherapy regimens are performed in the hospital, causing inconvenience for both children and their parents.

Objectives: To assess the efficacy and safety of a home-based oral immunotherapy regimen with raw pasteurized egg.

Methods: The study group comprised children aged 6 years and older with allergy to hen’s egg proteins, proven by positive skin prick-tests (SPT) and/or specific immunoglobulin E (sIgE) and positive open oral food challenge (OOFC) with boiled or raw egg. Patients who met the inclusion criteria and signed the informed consent form underwent egg immunotherapy according to an established schedule.

Results: The treatment was given to 31 of the 36 recruited patients: 80.6% of the intention to treat population achieved complete tolerance to the maximum dose equivalent to one raw hen’s egg, 3.2% achieved incomplete tolerance, and 16.2% did not achieve an acceptable tolerance dose. Most of the latter patients had a positive baseline OOFC with low doses of boiled egg. The average number of reactions per treated patient was 5.8, most of them grades 1 and 2 there were no grade 4 reactions.

Conclusions: This home-based oral immunotherapy protocol proved to effectively induce tolerance to hen’s egg in most of the egg-allergic children and its safety profile was acceptable.

Silvia Sanchez-Garcia, MD, Pablo Rodriguez del Rio, MD, Carmelo Escudero, MD, Cristina Garcia-Fernandez, MD, Antonio Ramirez, MD and M.D. Ibanez, MD, PhD

Background: In the last two decades milk oral immunotherapy has gained interest as an effective treatment option for milk-allergic patients.

Objectives: To report on the efficacy of a milk oral immunotherapy.

Methods: Children with immunoglobulin E-mediated cow’s milk allergy were included in the protocol. The treatment consisted of an induction phase in which milk doses were increased weekly in the hospital, while the tolerated dose was continued daily at home. The goal was to achieve a minimum milk intake of 200 ml a day. During the maintenance phase, patients ingested at least 200 ml of milk in a single dose every day.

Results: The protocol was applied to 105 milk-allergic children diagnosed by specific IgE to milk and controlled oral food challenge. The mean duration of the induction phase was 19 weeks. Of the 105 subjects, 86 (81.9%) successfully complied with the protocol and 19 (19.1%) failed. Causes of failure were moderate/severe reactions in 12 patients (12.44%) and personal reasons in 7 (6.66%). A total of 182 adverse reactions occurred during the induction phase, most of them mild. Baseline specific IgE to milk and casein were significantly lower (P < 0.05) in the successfully treated group compared to the group in which the treatment failed.

Conclusions: Milk oral immunotherapy is a safe and effective treatment for milk-allergic children, although adverse reactions may occur. Baseline milk and casein-specific IgE may be useful to predict a good response to milk oral immunotherapy.

______

[1] IgE = immunoglobulin E

September 2011
E. Lahat, E. Heyman, A. Livne, M. Goldman, M. Berkovitch and D. Zachor

Background: Several studies have suggested that iron deficiency may be related to the pathophysiology of attention deficit hyperactivity disorder (ADHD) due to the role of iron in the production of dopamine and noradrenaline.

Objectives: To evaluate the status of iron deficiency in ADHD children, using ferritin levels, a reliable measure of iron storage in body tissue, as an iron status marker, and to investigate a possible correlation between ferritin levels and the diagnosis of ADHD.

Methods: The study group included 113 newly referred ADHD children aged 5–15 years (mean age 8.8 ± 2.7).

Results: Ferritin levels were below 20 ng/ml in 67 children (59%) and above 20 ng/ml in 45 (41%). There was a very low inverse statistical correlation between scores on Conners’ Rating Scale and ferritin levels, probably without clinical significance. 

Conclusions: Our findings suggest that low iron stores may be related to ADHD pathophysiology; therefore, ferritin should be included in the overall evaluation of children with ADHD.

 
 

I.N. Kochin, T.A Miloh, R. Arnon, K.R. Iyer, F.J Suchy and N. Kerkar

Background: Primary liver masses in children may require intervention because of symptoms or concern about malignant transformation.

Objectives: To review the management and outcomes of benign liver masses in children. Methods: We conducted a retrospective chart review of children with liver masses referred to our institution during the period 19972009.

Results: Benign liver masses were identified in 53 children. Sixteen of these children (30%) had hemangioma/infantile hepatic hemangioendothelioma (IHH) and 15 (28%) had focal nodular hyperplasia. The remainder had 6 cysts, 4 hamartomas, 3 nodular regenerative hyperplasia, 2 adenomas, 2 vascular malformations, and one each of polyarteritis nodosa, granuloma, hepatic hematoma, lymphangioma, and infarction. Median age at presentation was 6 years, and 30 (57%) were female. Masses were initially noticed on imaging studies performed for unrelated symptoms in 33 children (62%), laboratory abnormalities consistent with liver disease in 11 (21%), and palpable abdominal masses in 9 (17%). Diagnosis was made based on characteristic radiographic findings in 31 (58%), but histopathological examination was required for the remaining 22 (42%). Of the 53 children, 27 (51%) were under observation while 17 (32%) had masses resected. Medications targeting masses were used in 9 (17%) and liver transplantation was performed in 4 (8%). The only death (2%) occurred in a child with multifocal IHH unresponsive to medical management and prior to liver transplant availability.

Conclusions: IHH and focal nodular hyperplasia were the most common lesions. The majority of benign lesions were found incidentally and diagnosed radiologically. Expectant management was sufficient in most children after diagnosis, although surgical intervention including liver transplant was occasionally necessary.
 

August 2011
A. Fattal-Valevski, H. Bassan, J. Bernheim, B. Redianu, Y. Leitner and S. Harel

Background: Epidemiological studies have found that intrauterine growth retardation (IUGR) is closely related to hypertension and is associated with a reduced number of nephrons that may be a predisposing factor for the development of hypertension.

Objectives: To determine whether blood pressure levels of children with a history of IUGR are higher than those of children without IUGR.

Methods: Diastolic, systolic and mean arterial blood pressure levels were measured in 64 children aged 8–12 years old with a history of IUGR (mean birth weight 1780
± 422 g) and compared with 64 age and gender-matched controls who had a normal birth weight (mean 3134 ±  594 g).

Results: Contrary to previous reports, systolic blood pressure values were significantly lower in the IUGR group compared to the controls (91.6
±11.3 vs. 96.6 ±13.9, P = 0.027). There was no difference in diastolic blood pressure values. In the IUGR group, systolic blood pressure correlated significantly with current weight (P < 0.01) and body mass index (P < 0.05), and diastolic blood pressure with weight gain between age 2 and 4 years (P < 0.05). None of the blood pressure values correlated with birth weight.

Conclusions: Children born with IUGR have lower systolic blood pressure levels than matched controls at age 8–12 years. These data indicate that postnatal weight gain in this group has a greater impact on systolic blood pressure than birth weight.
 

July 2011
I. Nevo, M. Erlichman, N. Algur and A. Nir

Background: Cardiac patients express elevated levels of B-type natriuretic peptide and the amino terminal segment of its prohormone (NT-proBNP). However, there are non-cardiac causes of NT-proBNP level elevation.

Objectives: To determine the upper limit of NT-proBNP for pediatric patients with acute non-cardiac disease.

Methods: We compared NT-proBNP concentrations in healthy children and children with acute non-cardiac, mostly febrile, and acute cardiac disease. We used the Student t-test and Mann-Whitney test for group comparisons, and Pearson's and Spearman's correlation coefficients to test relationships between variables. 

Results: In 138 patients with acute non-cardiac diseases (mean age 3.7 years, 53% male), median NT-proBNP concentration was 162 pg/ml, upper limit (95% percentile) 1049 pg/ml. The level did not vary significantly by disease category; was negatively correlated with weight, weight percentile, age and hemoglobin level; and positively correlated with creatinine level. Multivariant analysis showed weight to be the only factor influencing NT-proBNP level. Levels were higher in children with acute non-cardiac diseases versus healthy children (median 88 pg/ml, P < 0.001, n= 59), and lower than levels in patients with acute cardiac disease (median 29,986 pg/ml, P < 0.001, n=29). Receiver operating characteristic analysis showed good NT-proBNP performance for differentiation between children with acute cardiac versus non-cardiac disease (area under the curve 0.958), at a cutoff of 415 pg/ml.

Conclusions: NT-proBNP levels are higher in children with acute non-cardiac diseases than in healthy children, but lower than in children with acute cardiac disease. NT-proBNP negatively correlated with weight and weight percentile.
 

May 2011
S. Perl, M. Goldman, M. Berkovitch and E. Kozer

Background: Diarrhea is a leading cause of child mortality worldwide. Rotavirus is one of the most common causes of severe diarrhea and dehydration in children.

Objectives: To compare the demographic, clinical and laboratory characteristics of patients with rotavirus gastroenteritis to those with other causes of gastroenteritis.

Methods: The medical records of children aged 0–18 years hospitalized with acute gastroenteritis in our facility between 1 January 2004 and 31 March 2006 were retrieved. Patients with rotavirus gastroenteritis were compared with patients who were rotavirus negative.

Results: The study group comprised 533 patients; 202 tested positive for rotavirus and 331 tested negative. Compared to patients with rotavirus-negative gastroenteritis, patients with rotavirus-positive gastroenteritis had a higher incidence of vomiting (185/202 vs. 212/331, 92% vs.  64%, P < 0.001), lethargy (67 vs. 51, 33% vs. 15%, P < 0.001), and dehydration (81 vs. 78 vs. 40% vs. 24%, P < 0.001). The need for intravenous rehydration therapy and the duration of hospitalization were higher in patients with rotavirus gastroenteritis.

Conclusions: Vomiting and dehydration are more common in hospitalized children with rotavirus gastroenteritis than in children with gastroenteritis due to other causes.
 

March 2011
I. Krause, N. Herman, R. Cleper, A. Fraser and M. Davidovits

Background: Acute renal failure (ARF) is a common complication in critically ill children. It is known as an important predictor of morbidity and mortality in this population. Data on the factors affecting the choice of renal replacement therapy (RRT) modality and its impact on mortality of children with ARF[1] are limited.

Objectives: We retrospectively studied 115 children with ARF necessitating RRT[2] during the period 1995–2005 to evaluate the effect of several prognostic factors as well as RRT type on their immediate outcome.

Methods: The data collected from charts included demographics, primary disease, accompanying medical conditions, use of vasopressor support, indications for dialysis, RRT modality, and complications of dialysis. Categorical variables were analyzed using chi-square or Fisher’s exact tests. Variables associated with mortality (P < 0.1) at the univariable level were studied by a multivariable logistic regression model.

Results: The most common cause of ARF was congenital heart disease (n=75). RRT modalities included peritoneal dialysis (PD) (n=81), hemodialfiltration (HDF) (n=31) and intermittent hemodialysis (IHD) (n=18). Median RRT duration was 4 days (range 1–63 days). Overall mortality was 52.2%. IHD[3] was associated with the best survival rate (P < 0.01 vs. PD[4] and HDF[5]), while children treated with HDF had the worse outcome. Hemodynamic instability and systemic infections were associated with greater mortality, but the rate of these complications did not differ between the study groups.

Conclusions: Our results suggest that IHD[6] when applied to the right patient in an appropriate setting may be a safe and efficient RRT modality in children with ARF. Randomized prospective trials are needed to further evaluate the impact of different RRT modalities on outcome in children with ARF.






[1]               ARF = acute renal failure



[2]               RRT = renal replacement therapy



[3]               IHD = intermittent hemodialysis



[4]               PD = peritoneal dialysis



[5]               HDF = hemodialfiltration



[6]               IHD = renal replacement therapy



 
O. Beyar Katz, A. Ben Barak, G. Abrahami, N. Arad, Y. Burstein, R. Dvir, S. Fischer, J. Kapelushnik, H. Kaplinsky, A. Toren, S. Vilk-Revel, M. Weintraub, I. Yaniv, S. Linn, B. Futerman and M. Weyl Ben-Arush

Background: Survival in T cell lymphoblastic lymphoma has improved over the past 30 years, largely due to treatment protocols derived from regimens designed for children with acute lymphoblastic leukemia.

Objectives: To assess the outcome of the NHL-BFM-95 protocol in children and adolescents hospitalized during the period 1999–2006.

Methods: We conducted a retrospective multi-institutional, non-randomized study of children and adolescents up to age 21 with T cell lymphoma admitted to pediatric departments in six hospitals in Israel, with regard to prevalence, clinical characteristics, pathological characteristics, prognostic factors, overall survival (OS) and event-free survival (EFS). All patients had a minimal follow-up of one year after diagnosis. The study was based on the NHL[1]-BFM[2]-95 protocol.

Results: At a median follow-up of 4 years (range 1–9 years), OS and EFS for all patients was 86.5% and 83.8%, respectively. OS was 86.7% and 83.3% for patients with stage III and stage IV, respectively, and EFS was 83.3% and 83.3%, respectively. EFS was 62.5% for Arab patients and 89.7% for Jewish patients (P = 0.014). Patients who did not express CD45 antigen showed superior survival (P = 0.028). Five (13.5%) patients relapsed, four of whom died of their disease. Death as a consequence of therapy toxicity was documented in one patient while on the re-induction protocol (protocol IIA).

Conclusions: Our study shows that OS and EFS for all patients was 86.5% and 83.8%, respectively.






[1] NHL = non-Hodgkin lymphoma



[2] BFM = Berlin-Frankfurt-Munster


February 2011
Y. Mozer-Glassberg, I. Hojsak, N. Zevit, R. Shapiro and R. Shamir
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