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עמוד בית
Sat, 20.04.24

January 2012


Original Articles
Ronit Lubetzky, MD, Galit Zaidenberg-Israeli, MD, Francis B. Mimouni, MD, Shaul Dollberg, MD, Eyal Shimoni, PhD, Yael Ungar, PhD and Dror Mandel, MD

Background: Human milk produced during prolonged lactation (> 1 year) is extraordinarily rich in fat and has a higher energy content than human milk produced during short lactation.

Objectives: To estimate the fatty acid (FA) profile of human milk and to test the hypothesis that the proportion of C12 and C14 (two dietary saturated FA known to most promote hypercholesterolemia) in human milk during prolonged lactation is similar to that in short lactation.

Methods: We conducted a cross-sectional study of 30 mothers of term infants lactating for more than 1 year as compared with 25 mothers of full-term infants who lactated for 2–6 months. Milk was collected by manual expression in mid-breastfeeding.

Results: The two groups did not differ in maternal height, weight, body mass index, diet, infant birth weight and gestational age, but mothers in the prolonged lactation group were significantly older. There was a significant correlation between lactation duration and C12 or C14. The percentage of all FA combined (except for C12 and C14) decreased significantly over time. In contrast, C12:0 and C14:0 combined increased significantly during lactation (R2 = 10.0%, P < 0.03).

Conclusions: Women who lactated for more than 1 year had higher C12 and C14 FA percentages in their milk than women who lactated for 2–6 months.

Nirit Segal, MD, Ben-Zion Garty, MD, Vered Hoffer, MD and Yael Levy, MD.

Background: Patients with allergy as well as their parents frequently fail to use the self-administered epinephrine injection (EpiPen®) properly in cases of allergic emergencies.

Objectives: To determine the benefit of an instruction session with follow-up instruction.

Methods: We evaluated 141 patients aged 1.9–23.4 years (median 5.8 years, 83% with food allergy) or their parents (for those aged < 12 years) who were trained in the use of the EpiPen during the first diagnostic visit to the allergy clinic during 2006–2009. At the next follow-up visit, the patients or their parents were asked to list the indications for epinephrine administration and to demonstrate the five steps involved in using the EpiPen. Each step was scored on a scale of 0–2.

Results: Fourteen participants (9.9%) had used self-injectable epinephrine in the past. Only 65 (46%) brought the device with them to the follow-up visit. The mean total score for the whole sample was 4.03 ± 3. Fifty-three participants (38%) failed to remove the cap before trying to apply the device. Only 8 (5.6%) had a maximum score. The patients and their parents were reinstructed in the use of the device: 41 participants were reexamined at a subsequent follow-up visit after 1.02 ± 0.56 years their mean score improved from 4.71 ± 3.04 to 6.73 ± 3.18 (P < 0.001).

Conclusions: Patients with severe allergic reactions, as well as their parents, are not sufficiently skilled in the use of the EpiPen after only one instruction session with a specialist. Repeated instruction may improve the results and we therefore recommend that the instructions be repeated at every follow-up visit.

Roberta Onesimo, MD, Valentina Giorgio, MD, Stefania Pili, MD, Serena Monaco, MD and Stefano Miceli Sopo, MD

Fish is a common cause of food allergy. The reactions usually occur after its ingestion. In most immunoglobulin E-mediated reactions, the allergens are gastroresistant and heat-stable proteins of low molecular weight (parvalbumin). On the other hand, isolated contact urticaria following the handling of raw fish but without symptoms after its ingestion was found among cooks and professional fish handlers. In these cases, the fish allergens are gastrosensitive and thermolabile, as demonstrated by the decrease in the diameter of the wheal in the skin-prick test using cooked fish. To the best of our knowledge isolated fish contact urticaria in children has not been previously reported. We analyze the features of three pediatric cases of contact urticaria from cod (one of them was sensitized to parvalbumin), with tolerance after ingestion of this fish on oral food challenge.

 

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.


Antonella Cianferoni, MD, PhD, Jackie P. Garrett, MD, David R. Naimi, MD, Karishma Khullar, BS and Jonathan M. Spergel, MD, PhD.

Background: Skin-prick tests (SPT), food-specific immunoglobulin E level (sIgE) and clinical history have limited value individually in predicting the severity of outcome of the oral food challenge (OFC). 

Objectives: To develop a score that accounts for SPT, sIgE and clinical history to predict the risk of severe reaction to the OFC. 

Methods: A 5 year retrospective chart review was performed on 983 children who underwent OFC to egg, milk and peanut. 

Results: Using multilogistic regression, four major indicators were found to be independently associated with failed OFC: sIgE (odds ratio = 1.04, P < 0.0001) , wheal size of the SPT (OR = 1.23, P < 0.0001), a history of any prior reaction to the food (OR = 1.13, P < 0.01), and a history of a prior non-cutaneous reaction (OR = 1.99, P < 0.01)  and three were independently associated with anaphylaxis: wheal size (OR = 1.16, P < 0.001), a history of a prior non-cutaneous reaction (OR = 4.24, P < 0.01), and age (OR = 1.07, P < 0.03). A Food Challenge Score (0–4) was developed which accounted for SPT wheal, sIgE, a history of a prior non-cutaneous reaction, and age. A score of 0–1 had a negative predictive value for multisystem reaction to the OFC: 95% for milk, 91% for egg and 93% for peanut. A score of 3–4 had a positive predictive value for anaphylaxis:  62% for milk, 92% for egg and 86% for peanut.

Conclusions: Severe reaction to milk, egg and peanut OFC can be predicted using a simple score that takes into account clinical data that are commonly available prior to the challenges.

Michael B. Levy, MD, Michael R. Goldberg, MD, PhD, Liat Nachshon, MD, Elvan Tabachnik, MD and Yitzhak Katz, MD

Background: Most reports in the medical literature on food allergy mortality are related to peanuts and tree nuts. 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 all 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.




 



 
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.

Michael D. Keller, MD, Michele Shuker, RD, Jennifer Heimall, MD and Antonella Cianferoni, MD, PhD.

Background: Alternatives to cow’s milk and soy milk are often necessary for children with food allergies. Although hydrolyzed and elemental formulas are appropriate replacements, other milk products such as rice and almond milk are insufficient protein sources for children under 2 years of age. A chart review on three patients treated for protein malnutrition in association with multiple diagnosed food allergies that resulted in refractory eczema revealed adverse outcomes that resulted from elimination diets. The use of rice milk resulted in hypoalbuminemia and poor weight gain in all cases, and multiple secondary infections in one patient. These cases illustrate the need for careful nutritional guidance in the management of food allergy, as well as the importance of cautious use and interpretation of testing for food allergies in the absence of a clear clinical history of reaction.

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.

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[1] IgE = immunoglobulin E

Reviews
Giuseppe Crisafulli, PhD, Lucia Caminiti, MD and Giovanni B. Pajno, MD
Intan H. Ismail, MD, MMed and Mimi L.K. Tang, MB, BS, PhD

Food allergies have increased significantly over recent decades, and are the most common cause of admissions for anaphylaxis in childhood, particularly in children under 5 years of age. Current management of food allergy is limited to strict food allergen avoidance together with education on the recognition and emergency management of allergic reactions, and in some cases provision of self-injectable adrenalin. Although this supportive management approach is generally effective, it is burdensome for patients and families, and in turn leads to reduced quality of life. Patients with food allergy would benefit greatly from a definitive treatment that could achieve long-term tolerance. Recent studies demonstrate that oral immunotherapy (OIT) can induce desensitization and modulate allergen-specific immune responses. However, it remains uncertain whether long-term tolerance can be achieved with current OIT regimens. Increased allergen dose, duration of OIT and/or inclusion of an immune modifying adjuvant may enhance the tolerogenic potential of OIT. Allergic reactions during OIT are common, although severe reactions are infrequent. Oral immunotherapy holds promise as a novel approach to the definitive treatment of food allergy.

Shmuel Kivity, MD

The prevalence of food allergy is increasing in both the pediatric and adult populations. While symptom onset is mostly during childhood, there are a considerable number of patients whose symptoms first begin to appear after the age of 18 years. The majority of patients with adult‑onset food allergy have the pollen-plant allergy syndromes. Many of them manifest their allergy after exercise and consuming food to which they are allergic. Eosinophilic esophagitis, an eosinophilic inflammation of the esophagus affecting individuals of all ages, recently emerged as another allergic manifestation, with both immediate and late response to the ingested food. This review provides a condensed update of the current data in the literature on adult-onset allergy.

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