Nufar Marcus

Anaphylaxis in Israel: Experience with 92 hospitalized children

To cite this article: Hoffer V, Scheuerman O, Marcus N, Levy Y, Segal N, Lagovsky I, Monselise Y, Garty BZ. Anaphylaxis in Israel: Experience with 92 hospitalized children. Pediatr Allergy Immunol 2011; 22:172–177.

Streptococcus acidominimus infection in a child causing Gradenigo syndrome

UNLABELLED Gradenigo syndrome is a rare presentation of acute petrositis. The clinical triad of Gradenigo syndrome consists of acute suppurative otitis media, severe unilateral headache and abducens nerve palsy. We report the first case of Gradenigo syndrome caused by Streptococcus acidominimus, a Gram-positive coccus of the Streptococcus viridans group, which rarely causes deep-seated infection in humans. CONCLUSION Gradenigo syndrome may complicate acute otitis media and should be suspected in case of unilateral headache and abducens nerve palsy. Conservative medical treatment without surgery may be considered in some patients.

Chronic Granulomatous Disease: Clinical, Functional, Molecular and Genetic Studies. The Israeli Experience with 84 patients

Chronic granulomatous disease (CGD) is an innate immunodeficiency with a genetic defect of the nicotinamide adenosine dinucleotide phosphate, reduced, oxidase components. This leads to decreased reactive oxygen species (ROS) production, which renders patients susceptible to life‐threatening infections. Over the course of 30 years, we diagnosed CGD in 84 patients from 61 families using functional, molecular, and genetic studies. The incidence of CGD in Israel is 1.05 per 100,000 live‐births in the Jewish population and 1.49 in the Israeli Arab population. We diagnosed 52 patients (62%) with autosomal recessive inheritance (AR‐CGD) and 32 (38%) with X‐linked recessive inheritance (XLR‐CGD). Consanguinity was detected in 64% of AR‐CGD families (14% in Jews and 50% in Israeli Arabs). We found 36 different mutations (23 in XLR‐CGD and 13 in AR‐CGD patients), 15 of which were new. The clinical spectrum of CGD varied from mild to severe disease in both XLR and AR forms, although the AR subtype is generally milder. Further, residual ROS production correlated with milder clinical expression, better prognosis and improved overall survival. Patients with recurrent pyogenic infections developed fibrosis and hyperinflammatory states with granuloma formation. The management of CGD has progressed substantially in recent years, evolving from a fatal disease of early childhood to one of long‐term survival. Our present cohort displays an encouraging 81% overall long term survival. Early hematopoietic stem cell transplantation is advisable before tissue damage is irreversible. Successful transplantation was performed in 18/21 patients. Therapeutic gene modification could become an alternative cure for CGD. Am. J. Hematol. 92:28–36, 2017.

The September epidemic of asthma in Israel.

Background. The seasonality of asthma morbidity is well recognized. A peak in asthma exacerbations in September has been noted for years at our center. Objective. To examine the hypothesis that the increment in asthma exacerbations in September is influenced by the beginning of the kindergarten and school year. Methods. The monthly admission rate for asthma in patients of different ages was retrospectively evaluated in seven hospitals from various areas in Israel from January 2003 to December 2005. Results. Of the 408,242 hospital admissions during the study period, 8,011 were for asthma exacerbations: 4,091 in adults (1.3% of adult admissions) and 3,920 in children (3.8% of pediatric admissions). The asthma admission rates varied considerably throughout the year, with a peak of 4% of total admissions in the winter months and a nadir of 2% in the summer months. September was unique for its particularly high rate of admissions for asthma attacks in children (6% of total admissions), especially toddlers and the school-age group. In adults there was a progressive increase in asthma admissions from September through December without a unique peak in September. Conclusions. There is a characteristic increase in asthma exacerbations and admissions in September in the pediatric age group. This phenomenon might be explained by the increased exposure to respiratory viruses, to new allergen exposure in school or kindergarten, increased emotional stress due to start of the new school year, or poor compliance and withdrawal of treatment during the summer. Clinicians should consider administering prophylactic treatment for asthma in children before onset of the school year.

Endocarditis After Closure of Ventricular Septal Defect by Transcatheter Device

Advances in interventional cardiology have enabled the treatment of severe congenital heart defects without the need for surgery. The percutaneous closure of atrial septal defects and, more recently, ventricular septal defects is considered a safe procedure with fewer complications and less morbidity compared with surgery. We report on a 2-year-old child who developed endocarditis after ventricular septal defect closure with an Amplatzer device. The patient recovered after intravenous antibiotics and anticoagulation. To the best of our knowledge, this is the first report of endocarditis associated with ventricular septal defect closure device insertion.

Acute Hemorrhagic Edema of Infancy Associated with Herpes Simplex Type 1 Stomatitis

Abstract:  Acute hemorrhagic edema of infancy is a benign leukocytoclastic vasculitis occurring in children younger than 2 years. The etiology is unknown. Viral or bacterial infections, immunizations, and the use of several medications, mainly antibiotics, may be involved in the pathogenesis. We report the first instance of this disease associated with herpesvirus type 1 stomatitis.

Pneumocystis jirovecii pneumonia in a baby with hyper-IgE syndrome

A 4-month-old baby with a family history of hyper-IgE syndrome acquired Pneumocystis jirovecii pneumonia. The patient’s hyper-IgE syndrome score was low, but a genetic study yielded a STAT3 mutation. P. jirovecii pneumonia can be added to the infections associated with hyper-IgE syndrome. In some cases, it may be the presenting manifestation of this immunodeficiency.

Transient Hypoparathyroidism Due to Amphotericin B—Induced Hypomagnesemia in a Patient with β–Thalassemia

OBJECTIVE: To report a case of transient hypoparathyroidism that developed in a β-thalassemic patient due to amphotericin B—induced hypomagnesemia. CASE SUMMARY: A 21-year-old man with β-thalassemia was treated with amphotericin B for Candida albicans intravenous line sepsis. After five days of treatment (cumulative dose 160 mg), he developed hypomagnesemia, which caused hypoparathyroidism and hypocalcemia; all three abnormalities resolved after the drug was withdrawn. DISCUSSION: Patients with β-thalassemia may develop endocrinologic abnormalities due to excessive iron deposition. Some may have subclinical hypoparathyroidism that clinically emerges after even a mild homeostasis disturbance. Amphotericin B is associated with variable adverse effects including renal tubular insult, which may induce hypomagnesemia following relatively short treatment. The resolution of hypomagnesemia, hypocalcemia, and hypoparathyroidism in our patient after discontinuation of amphotericin B treatment suggests that the endocrine dysfunction was due to a drug-related adverse effect and not to parathyroid dysfunction caused by iron deposition. CONCLUSIONS: This case demonstrates a known but rarely reported adverse effect of amphotericin B, namely hypomagnesemia, that may occur even at a low cumulative dose. It also emphasizes that patients with an underlying disease, such as thalassemia, may be more susceptible to hypoparathyroidism and hypocalcemia during treatment with amphotericin B.

Hypersensitivity to methylprednisolone sodium succinate in children with milk allergy.

Rare but potentially fatal hypersensitivity reactions to intravenous corticosteroids have been described in the literature in recent years. Most reactions involve succinylated corticosteroids. The pathogenesis is considered to be immune-IgE mediated, in which the corticosteroid molecule serves as a hapten. The succinate esters seem to have a sensitizing potential. Adverse drug reactions may be caused by the active molecule itself or excipients (including food ingredients) added to the drug during preparation. In a 2009 report from Schneider Children’s Medical Center of Israel, we described an anaphylactic reaction (urticaria and wheezing) in 3 children with asthma, 2 of whom also had IgE-mediated cow milk allergy, after treatment with intravenous methylprednisolone sodium succinate. After this experience, we designed a study to prospectively identify additional children in 2008 to 2011. Inclusion criteria were children up to age 18 years old who exhibited signs and symptoms of systemic allergic reaction (urticaria or rash and at least 1 additional organ system involvement) immediately after intravenously or intramuscularly injected corticosteroid preparation. Afterward, the patients were referred from the emergency department and wards to our allergy clinic. Their clinical and laboratory data were retrieved from the computerized records of Schneider Children’s Medical Center of Israel, and an allergy evaluation was performed within 1 to 5 months of the

Disruption of thrombocyte and T lymphocyte development by a mutation in ARPC1B

Regulation of the actin cytoskeleton is crucial for normal development and function of the immune system, as evidenced by the severe immune abnormalities exhibited by patients bearing inactivating mutations in the Wiskott–Aldrich syndrome protein (WASP), a key regulator of actin dynamics. WASP exerts its effects on actin dynamics through a multisubunit complex termed Arp2/3. Despite the critical role played by Arp2/3 as an effector of WASP-mediated control over actin polymerization, mutations in protein components of the Arp2/3 complex had not previously been identified as a cause of immunodeficiency. Here, we describe two brothers with hematopoietic and immunologic symptoms reminiscent of Wiskott–Aldrich syndrome (WAS). However, these patients lacked mutations in any of the genes previously associated with WAS. Whole-exome sequencing revealed a homozygous 2 bp deletion, n.c.G623DEL-TC (p.V208VfsX20), in Arp2/3 complex component ARPC1B that causes a frame shift resulting in premature termination. Modeling of the disease in zebrafish revealed that ARPC1B plays a critical role in supporting T cell and thrombocyte development. Moreover, the defects in development caused by ARPC1B loss could be rescued by the intact human ARPC1B ortholog, but not by the p.V208VfsX20 variant identified in the patients. Moreover, we found that the expression of ARPC1B is restricted to hematopoietic cells, potentially explaining why a mutation in ARPC1B has now been observed as a cause of WAS, whereas mutations in other, more widely expressed, components of the Arp2/3 complex have not been observed.