Israel Medical Association Journal

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.

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.

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[1] IgE = immunoglobulin E

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.

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 1997–2009.

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.
 

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.
 

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.
 

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.
 

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.

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.

Background: Data regarding the validity of self-reported weight and height in adolescents are conflicting.

Objectives: To evaluate the validity of self-reported weight and height among 13–14 year old schoolchildren. 

Methods: We conducted a cross-sectional study of 517 schoolchildren aged 13–14 years and compared self-reported and measured weight and height by gender, population group, parental education and crowdedness.

Results: Females under-reported their weight on average by 0.79 ± 5.46 kg (P = 0.03), resulting in underestimation of the body mass index with borderline significance (mean difference 0.28 ± 2.26 kg/m², P = 0.06). Males over-reported their height on average by 0.75 ± 5.81 cm (P = 0.03). Children from less crowded homes (≤ 1 person per room) overestimated their height more than children from more crowded homes, resulting in a significant underestimation of BMI[1] (mean difference between reported BMI and measured values was 0.30 ± 2.36 kg/m², P = 0.04). Measured BMI was a significant predictor of the difference between self-reported and measured BMI, adjusted for gender, population group, parents' education, and crowdedness (β = -0.3, P < 0.0001). As a result of this reporting bias, only 54.9% of children with overweight and obesity (BMI ≥ 85th percentile) were classified correctly, while 6.3% of children were wrongly classified as overweight and obese. The largest difference in BMI was observed in obese females (4.40 ± 4.34) followed by overweight females (2.18 ± 1.95) and underweight females (-1.38 ± 1.75). Similar findings were observed for males, where the largest difference was found among obese males (2.83 ± 3.44).

Conclusions: Studies based on self-reported weight and height in adolescents may be biased. Attempts should be made to correct this bias, based on the available data for each population.

Background: Poisonings are a significant cause of pediatric morbidity and mortality. The Israel Poison Information Center provides clinical consultations on poisonings and drug information 24 hours a day.

Objective: To evaluate epidemiologic characteristics of pediatric poison exposures in Israel.

Methods: We reviewed computerized queries and performed a descriptive analysis of the Poison Center database pertaining to patients less than 18 years old during 2007.

Results: A total of 15,005 pediatric poison exposures were recorded, 80.3% of them occurring in children under 6 years old. Of the calls to the Poison Center, 78.6% were made by the public, 20.7% by physicians, and in 74.4% the call was within 2 hours of exposure. Most exposures occurred at home (89.3%) and were unintentional (89.5%). Among adolescents, most exposures were intentional (49.3%, 38.2% suicides), the time lapse until consultation was longer (37% > 2 hours), and more physicians (54.8%) consulted the Poison Center. Most cases were asymptomatic or mildly affected (92.3%), 54.4% in adolescents. The commonest substances involved in single poison exposure were detergents, antimicrobials, topical preparations, acetaminophen and scale removers; in adolescents the most common substances were acetaminophen, methylphenidate, non-steroidal anti-inflammatory drugs, atropine and ethanol. Moderate to severe toxicity was commonly associated with organophosphates, alkali, ethanol, Vipera palaestinae and neuroleptics. Most patients could be observed at home (66.6%), while more adolescents were referred to emergency departments (42.2% vs. 9.9%) or hospitalized (14.5% vs. 1.9%).

Conclusions: Pediatric poisonings are a significant health problem. The magnitude of the problem is greater in the young age group but more severe in adolescence, probably due to deliberate self-poisoning. Greater national efforts should be directed towards improved poison prevention, rational management of pediatric poisoning, and creating a national poisoning registry.