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Wasserman R.L.,Medical City Childrens Hospital | Factor J.M.,Connecticut Children’s Medical Center | Baker J.W.,Emanuel Hospital | Katz Y.,Tel Aviv University | And 10 more authors.
Journal of Allergy and Clinical Immunology: In Practice | Year: 2014

Background: Peanut allergy creates the risk of life-threatening anaphylaxis that can disrupt psychosocial development and family life. The avoidance management strategy often fails to prevent anaphylaxis and may contribute to social dysfunction. Peanut oral immunotherapy may address these problems, but there are safety concerns regarding implementation in clinical practice. Objective: The purpose of this report is to communicate observations about the frequency of epinephrine-treated reactions during peanut oral immunotherapy in 5 different allergy/immunology practices. Methods: Retrospective chart review of peanut oral immunotherapy performed in 5 clinical allergy practices. Results: A total of 352 treated patients received 240,351 doses of peanut, peanut butter, or peanut flour, and experienced 95 reactions that were treated with epinephrine. Only 3 patients received 2 doses of epinephrine, and no patient required more intensive treatment. A total of 298 patients achieved the target maintenance dose for a success rate of 85%. Conclusion: Peanut oral immunotherapy carries a risk of systemic reactions. In the context of oral immunotherapy, those reactions were recognized and treated promptly. Peanut oral immunotherapy may be a suitable therapy for patients managed by qualified allergists/immunologists. © 2014 American Academy of Allergy, Asthma & Immunology.


Katz Y.,Allergy and Immunology Institute | Katz Y.,Tel Aviv University | Gutierrez-Castrellon P.,Hospital General | Gonzalez M.G.,University lle | And 4 more authors.
Clinical Reviews in Allergy and Immunology | Year: 2014

Since 1943, cases of sensitization or allergy to soy-based formulas (SBFs) have been described without any consensus on their real prevalence. We identified the adjusted prevalence of IgE-mediated soy allergies in children and performed a secondary analysis of the impact of age (less than and more than 6 months). We performed a systematic review with meta-analysis of studies published from 1909 to 2013 in PubMed, Embase, LILACS, ARTEMISA, Cochrane, Bandolier, DARE and the GRADE system for grading quality. Results are presented in tables and graphs using a forest plot. The 40 studies identified established weighted prevalence of soy allergies of 0 to 0.5 % (0.27) for the general population, 0.4 to 3.1 % (1.9) for the referred population, and 0 to 12.9 % (2.7) for allergic children. Prevalence of sensitization after the use of SBFs is 8.7 and 8.8 %, depending on the method used. The prevalence of allergies to soy and IgE sensitization to the use of SBFs is less than reported. Not enough evidence exists to show a higher risk of allergy in infants younger than 6 months. The concern about soy allergy is no reason to postpone the use of SBFs in IgE-mediated cow's milk allergy infants until the age of 6 months. © 2014 Springer Science+Business Media.


Goldberg M.,Allergy and Immunology Institute | Fremeaux-Bacchi V.,Hospital Georges Pompidou | Koch P.,Allergy and Immunology Institute | Fishelson Z.,Tel Aviv University | And 2 more authors.
Molecular Immunology | Year: 2011

Background: We identified a 4 year-old boy born to a consanguineous marriage with C3 deficiency after three episodes of invasive pneumococcal disease. The efficacy of anti-pneumococcal vaccination in C3 deficient patients is not clear. Objectives: Our objective was to identify the genetic defect resulting in his C3 deficiency and measure his ability to mount an adaptive immune response. Methods: Fibroblast cell lines were generated from the patient and parents. DNA was isolated and the C3 gene sequenced. Quantitation of C3 expression was performed by immunoprecipitation of 35S-methionine labeled protein. Isotype specific anti-pneumococcal antibodies present in the patients sera was quantitated after administration of Prevnar-7 and Pneumovax vaccines. Results: Pneumococcal types 14, 10B and 29 were identified from the blood on three separate occasions over a period of 20 months. C3 levels in the blood was <10, 71, and 66 for the patient, mother and father, respectively (90-180. mg/dl, normal). Sequencing revealed a homozygous deletion of one nucleotide located in exon 31 (delA in position 3997 of cDNA) which resulted in a transcriptional stop signal thirteen codons later. The parents were heterozygous for the mutation. No detectable C3 was noted by immunoprecipitation. The patient mounted adequate antibody responses to the protein-conjugated Prevnar and tetanus vaccines but not to the polysaccharide antigen based Pneumovax vaccine. Major immunoglobulin class levels were normal. Conclusion: C3 deficiency results in the selective impairment to mount a response against polysaccharide-based antigens. Protein-conjugated vaccines are likely to be efficacious in immunizing against encapsulated organisms in these patients. © 2011 Elsevier Ltd.


Elizur A.,Allergy and Immunology Institute | Elizur A.,Tel Aviv University | Katz Y.,Allergy and Immunology Institute | Katz Y.,Tel Aviv University
Current Opinion in Allergy and Clinical Immunology | Year: 2016

Purpose of review Until recently, nutritional guidelines did not support early introduction of allergenic foods into the diet of high-risk infants. Following recent studies, this approach is beginning to change, at least for peanuts. This review will examine the change in nutritional guidelines and the scientific data that led to these changes. Recent finding In a recent prospective controlled study, regular consumption of peanut protein in infants from 4-11 months of age with atopic dermatitis or egg allergy, was associated with lower prevalence of peanut allergy (1.9%) at 60 months of age compared with peanut avoidance (13.7%). Other studies demonstrated that earlier introduction of cow's milk protein and egg powder were also associated with decreased risk for milk and egg allergy, respectively. Summary Recent studies suggest that early rather than late introduction of allergenic foods reduces the risk of food allergy. The preferred timing of food introduction might be sooner than the current recommendation, and might apply not only to high-risk infants. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Elizur A.,Allergy and Immunology Institute | Elizur A.,Tel Aviv University | Goldberg M.R.,Allergy and Immunology Institute | Levy M.B.,Allergy and Immunology Institute | And 3 more authors.
Annals of Allergy, Asthma and Immunology | Year: 2015

Background Patients with asthma and food allergy comprise a high-risk group for life-threatening reactions at accidental exposure. Objective To examine the course and long-term outcome of patients with asthma completing milk oral immunotherapy. Methods Children at least 6 years old with (n = 101) and without (n = 93) asthma and IgE-mediated cow's milk allergy, undergoing milk oral immunotherapy from April 2010 to December 2011, were compared. Milk dose escalations were performed until patients reached full (>7.2 g of milk protein) or partial desensitization. Skin prick tests in all patients and spirometry in those with asthma were performed. Patients who completed treatment were followed for longer than 6 months. Results Before immunotherapy, patients with asthma, regardless of severity, had more anaphylactic reactions (84.2% vs 64.5%, P =.003), emergency department visits (68.3% vs 51.6%, P =.02), and hospital admissions (32.7% vs 18.3%, P =.03) compared with patients without asthma. Patients with asthma, regardless of severity, had more reactions and injectable epinephrine use during induction (P =.004) and home treatments (P =.007) of immunotherapy. Moderate to severe asthma was associated with a lower likelihood of reaching full desensitization (51.5% vs 68.8%, P =.019), but most patients with asthma (87 of 101, 86.1%), regardless of severity, reached a dose likely to protect them against accidental exposure. Most patients with asthma continued to consume milk protein freely after completion of immunotherapy. Although adverse reactions were still observed, severe reactions appeared to subside with time. Conclusion Patients with asthma are at risk for more severe reactions and are less likely to reach full desensitization during food oral immunotherapy. However, most reach limited daily consumption and most who achieve full desensitization continue to consume milk protein freely after treatment. © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.


Katz Y.,Allergy and Immunology Institute | Katz Y.,Tel Aviv University | Goldberg M.R.,Allergy and Immunology Institute | Rajuan N.,Tel Aviv University | And 2 more authors.
Journal of Allergy and Clinical Immunology | Year: 2011

Background: The prevalence and natural history for food protein-induced enterocolitis syndrome (FPIES) have not been determined. Objective: We sought to determine the prevalence, clinical manifestations, and rate of recovery for FPIES in a large-scale, population-based prospective study. Methods: In a prospective study the feeding history of 13,019 infants was obtained. Infants with probable adverse reactions to cow's milk protein (CMP) were clinically examined, skin prick tested, and challenged orally. Diagnostic criteria for CMP-induced FPIES included age less than 9 months, delayed recurrent vomiting (usually with nausea), and lethargy after exposure to CMP in the absence of other IgE-mediated symptoms, such as rash, urticaria, and respiratory symptoms. In addition, a positive challenge response to milk resulted in the above-mentioned gastrointestinal symptoms, removal of milk from the diet resulted in the resolution of those symptoms, or both. Results: Ninety-eight percent of the cohort participated in the study. The cumulative incidence for FPIES was 0.34% (44/13,019 patients). The most common symptoms were recurrent vomiting (100%), lethargy (77%) diarrhea (25%), pallor (14%), and bloody diarrhea (4.5%). All patients had FPIES within the first 6 months of life. By the age of 3 years, 90% of the patients had recovered. We did not detect any concomitant reaction to soy. Eight patients with FPIES had IgE-mediated cow's milk allergy (IgE-CMA). Conclusions: The prevalence of FPIES is significant, and its clinical presentation is distinct from that of IgE-CMA. Most patients with FPIES recover, although a proportion might convert to IgE-CMA. The likelihood for a cross-reactivity to soy in this population was less than previously estimated. © 2010 American Academy of Allergy, Asthma and Immunology.


Elizur A.,Allergy and Immunology Institute | Elizur A.,Assaf Harofeh Medical Center | Rajuan N.,Allergy and Immunology Institute | Goldberg M.R.,Allergy and Immunology Institute | And 4 more authors.
Journal of Pediatrics | Year: 2012

Objective: To describe the natural course of IgE-mediated cow's milk allergy (IgE-CMA) and to determine risk factors for its persistence in a population-based cohort. Study design: In a prospective cohort study, 54 infants with IgE-CMA were identified from a population of 13 019 children followed from birth. Diagnosis of IgE-CMA was based on history, skin prick test (SPT), and an oral food challenge (OFC) when indicated. Allergic infants were followed for 48-60 months. Families were contacted by telephone every 6 months and asked about recent exposures to milk. OFC was repeated to evaluate for recovery. Clinical characteristics, SPT, and OFC outcomes were compared between infants with persistent IgE-CMA and infants who recovered. Results: Thirty-one infants (57.4%) recovered from IgE-CMA during the study period. Most infants (70.9%) recovered within the first 2 years. Risk factors for persistence on multivariate analysis included a reaction to <10 mL of milk on OFC (or on first exposure as estimated by the guardian, if OFC was not performed) (P = .01), a larger wheal size on SPT (P = .014), and age of ≤30 days at time of first reaction (P = .05). Conclusions: Resolution occurs in most infants with IgE-CMA. Infants reacting to <10 mL of milk or in the first month of life, and those with a larger wheal size on SPT, are at increased risk for persistence. © 2012 Mosby, Inc.


Levy M.B.,Allergy and Immunology Institute | Goldberg M.R.,Allergy and Immunology Institute | Nachshon L.,Allergy and Immunology Institute | Tabachnik E.,Kaplan Medical Center | And 2 more authors.
Israel Medical Association Journal | Year: 2012

Background: Most reports in the medical literature on food allergy mortality are related to peanut and tree nut. There is limited knowledge regarding these reactions and often only a partial medical history is described. Objective: To record and characterize all known cases of mortality due to food allergy in Israel occurring during the period 2004-2011. Methods: All cases of food allergy-related mortality that were known to medical personnel or were published in the Israeli national communications media were investigated. We interviewed the parents and, when feasible, physicians who treated the final event. Results: Four cases of food-related mortality were identified: three cases were due to cow's milk and one to hazelnut. All were exposed to a hidden/non-obvious allergen. All four had a history of asthma but were not on controller medications, and none had experienced previous non-life threatening accidental reactions. Three of the four patients had not been evaluated by an allergist, nor were they prescribed injectable epinephrine. The one patient who had been prescribed injectable epinephrine did not use it during her fatal anaphylactic attack. Conclusions: Fatal reactions to cow's milk and hazelnut but not to peanut are the only reported food mortality cases in Israel. Although these patients had previous reactions following accidental exposures, none had experienced a life-threatening reaction. Patients at risk are not adequately evaluated by allergists, nor are they prescribed and instructed on the proper use of injectable epinephrine. Cow's milk should be considered a potentially fatal allergen.


Katz Y.,Allergy and Immunology Institute | Katz Y.,Tel Aviv University | Rajuan N.,Tel Aviv University | Goldberg M.R.,Allergy and Immunology Institute | And 4 more authors.
Journal of Allergy and Clinical Immunology | Year: 2010

Background: The diversity in the perceived prevalence, recovery, and risk factors for cow's milk allergy (CMA) necessitated a large-scale, population-based prospective study. Objective: We sought to determine the prevalence, cross-reactivity with soy allergy, and risk factors for the development of CMA. Methods: In a prospective study the feeding history of 13,019 infants was obtained by means of telephone interview (95.8%) or questionnaire (4.2%). Infants with probable adverse reactions to milk were examined, skin prick tested, and challenged orally. Results: Ninety-eight percent of the cohort participated in the study. The cumulative incidence for IgE-mediated CMA was 0.5% (66/13,019 patients). The mean age of cow's milk protein (CMP) introduction was significantly different (P < .001) between the healthy infants (61.6 ± 92.5 days) and those with IgE-mediated CMA (116.1 ± 64.9 days). Only 0.05% of the infants who were started on regular CMP formula within the first 14 days versus 1.75% who were started on formula between the ages of 105 and 194 days had IgE-mediated CMA (P < .001). The odds ratio was 19.3 (95% CI, 6.0-62.1) for development of IgE-mediated CMA among infants with exposure to CMP at the age of 15 days or more (P < .001). Sixty-four patients with IgE-mediated CMA tolerated soy, and none had a proved allergy to soy. Conclusions: IgE-mediated CMA is much less common than generally reported. Early exposure to CMP as a supplement to breast-feeding might promote tolerance. Finally, soy is a reasonable feeding alternative in patients with IgE-mediated CMA. © 2010 American Academy of Allergy, Asthma & Immunology.


Levy M.B.,Allergy and Immunology Institute | Elizur A.,Allergy and Immunology Institute | Elizur A.,Tel Aviv University | Goldberg M.R.,Allergy and Immunology Institute | And 3 more authors.
Annals of Allergy, Asthma and Immunology | Year: 2014

Background Avoidance strategies in patients with cow's milk allergy occasionally fail to protect these patients from inadvertent exposures, leading to life-threatening reactions. Objective To assess the safety and efficacy of milk oral immunotherapy as an alternative therapeutic strategy. Methods Patients (n = 280, >4 years old) with IgE-mediated cow's milk allergy were enrolled into a milk oral immunotherapy program at a single hospital center. High-risk patients were not excluded. The treatment protocol consisted of 3 rounds of oral induction performed every 4 weeks. On day 1, a patient's reaction threshold was determined. On days 2 and 3, a tolerated starting dose below the threshold was confirmed. Day 4 mimicked the home treatment, which continued until the next induction. Results The median initial starting dose was 52.5 mg of cow's milk protein. Excluding those whose treatment failed in the first week (n = 5) or are still undergoing treatment (n = 15), 61.5% (160 of 260 patients) achieved 7,200 mg and 85.4% of patients were consuming at least 180 mg of milk protein. Reactions at home requiring the use of injectable epinephrine occurred in 15.7% of patients (44 of 280) and in 0.075% (58 of 77,098) of doses administered. Predictors for achieving a full dose in multivariate analysis included a starting dose higher than 30 mg of milk protein (odds ratio 4.6, P <.001), not requiring epinephrine during induction (odds ratio 5.2, P <.001) or home treatment (odds ratio 2.6, P =.037), and the lack of nonanaphylactic type symptoms (odds ratio 15.6, P <.001). Conclusion Milk oral immunotherapy, carried out in a highly controlled setting, is successful in protecting the overwhelming majority of patients from accidental exposures to cow's milk protein. © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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