Individually dosed omalizumab facilitates peanut oral immunotherapy in peanut allergic adolescents.

BACKGROUND: Peanut oral immunotherapy (pOIT) has showed good short-term outcomes, but allergic reactions may prevent effective up-dosing and is a major cause of stopping OIT. In placebo-controlled trials, omalizumab has been shown to facilitate allergen immunotherapy and increase tolerance to peanut. OBJECTIVE: We hypothesized that by combining omalizumab with pOIT, and monitor treatment effects with basophil allergen threshold sensitivity tests (CD-sens), peanut allergic patients could safely initiate pOIT and thereafter slowly withdraw omalizumab. METHODS: This is the 2nd part of a one-armed open phase-2 study where peanut allergic adolescents (n = 23) started pOIT after an individualized omalizumab treatment. The pOIT dose was increased from 280 to 2800 mg peanut protein in 8 weeks followed by an individualized step-wise withdrawal of omalizumab, based on clinical symptoms and CD-sens levels. pOIT continued for 12 weeks followed by an open peanut challenge. Peanut CD-sens and allergen-binding activity (ABA) and IgE-ab, IgG-ab and IgG4-ab to peanut and its components were measured during the study. RESULTS: All 23 patients successfully reached the 2800 mg maintenance dose. Moderate/systemic allergic reactions were rare while receiving full-dose omalizumab. Eleven of 23 (48%) successfully continued with pOIT after omalizumab was stopped. Compared to treatment failures, median baseline IgE-ab to peanut components Ara h 1-3 and CD-sens to peanut were significantly lower among successfully treated patients and IgG4-ab to peanut, Ara h 2 and 6 increased significantly more during treatment. CONCLUSIONS AND CLINICAL RELEVANCE: This study indicates that omalizumab is an effective adjunctive therapy for initiation and rapid up-dosing of pOIT; however, adverse events from pOIT become more frequent as omalizumab doses are decreased. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov; NCT02402231. EudraCT; 2012-005625-78.

Classification of anaphylaxis and utility of the EAACI Taskforce position paper on anaphylaxis in children.

Correct management and classification of anaphylaxis is mandatory. Records of emergency department (ED) visits to any of the three pediatric hospitals in Stockholm, because of reactions to foods during 2007, were identified. A retrospective analysis of clinical ED records of 371 children with 381 unique occasions of reactions to foods was performed. Symptoms/signs of reactions to foods recorded for classification of anaphylaxis were related to those presented in the EAACI Taskforce position paper on Anaphylaxis in Children (Allergy 2007; 62: 857). Forty-six different symptoms/signs of reactions to foods were retrieved. Several severe signs or symptoms from the respiratory tract and signs indicating reduced brain perfusion were not described in detail in the EAACI paper, hampering correct classification of anaphylaxis including grading of severity in our material. After modification of the EAACI classification including such signs and symptoms, we were able to classify 128 (35%) children with anaphylaxis. Seventy children (19%) did not fulfill our modified EAACI's criteria for anaphylaxis. They had been given adrenaline before or at arrival to hospital, possibly preventing anaphylaxis. Another 173 (47%) children/adolescents had neither been given adrenalin, nor fulfilled the criteria for anaphylaxis. Classification of food-induced anaphylaxis and severity grading should be built on signs and symptoms to facilitate diagnosis. The existing EAACI tool is helpful, but for Swedish children it is not quite applicable, in particular because of the lack of description of some respiratory, neurological or possible cardiovascular signs and symptoms.

Milk-Related Symptoms and Immunoglobulin E Reactivity in Swedish Children from Early Life to Adolescence.

Cow’s milk often causes symptoms in infants. Whereas, some continue to experience symptoms through childhood, others become tolerant. Yet, the ages at which persistence and tolerance occur are less clear. Thus, we examined the age of onset and persistence of milk-related symptoms from early life to adolescence, and Immunoglobulin E (IgE) milk reactivity, focusing on gender differences in a large, population-based birth cohort. Overall, 20.0% (537/2985) of children, with a comparable gender distribution, had early life milk-related symptoms. At 16y, approximately 2% (62/2985) children had persistent symptoms and high milk IgE levels (e.g., median at 4 years: 1.5 kUA/L) that were beginning in early life. In contrast, 94% had transient symptoms and low median IgE levels (early life: 0.63 kUA/L, 8y: 0.72 kUA/L; 16 years: 1.1 kUA/L). Also, at 16 years, approximately 6% of females and 3% of males without any previously reported symptoms reported adolescent-onset of symptoms (p < 0.001). Such symptoms were almost exclusively gastrointestinal symptoms and were not associated with detectable IgE. In conclusion, early life milk-related symptoms are common, although most cases are transient by 16 years. Twice as many females vs. males report adolescent-onset symptoms, and particularly gastrointestinal symptoms. Children with persistent symptoms have both a higher prevalence and higher milk IgE levels, as compared to other phenotypes.

Anaphylactic Reactions to Novel Foods: Case Report of a Child With Severe Crocodile Meat Allergy.

Availability of "exotic" foods is steadily increasing. In this report, we describe the first case of anaphylaxis to crocodile meat. The patient was a 13-year-old boy with severe immunoglobulin E-mediated allergy to chicken meat. When tasting crocodile meat for the first time, he developed an anaphylactic reaction. Cross-reactivity between chicken and crocodile meat was suspected to have triggered this reaction. Basophil activation and immunoglobulin E testing confirmed the boy's allergic reaction to crocodile meat proteins. Molecular analysis identified a crocodile α-parvalbumin, with extensive sequence homology to chicken α-parvalbumin, as the main cross-reactive allergen. We conclude that crocodile meat can be a potent food allergen and patients with allergy to chicken meat should be advised to avoid intake of meat from crocodile species. Both foods and people travel around the world and accessibility to exotic foods is steadily growing. As a result, novel allergic cross-reactivities are likely to become a challenge in the management of food allergy and, as our report illustrates, cross-reactivity has to be considered even between foods that might not intuitively be perceived as related.

[New perspectives on the diagnosis and treatment of food allergies in children]. / Nya perspektiv på diagnos och behandling av matallergier hos barn.

Acute allergic reactions to food are often IgE mediated. Symptoms vary in severity; from mild oral itching to anaphylactic reactions. Where birch pollen allergy is endemic, mild allergic reactions from e.g. fresh fruits and nuts are most likely caused by cross reactivity between pollen and plants (cross reactions). These mild symptoms, if caused by cross reactivity, do not progress to more severe symptoms, in contrast to ¼true« food allergy. However, making this distinction is a delicate task, since more severe reactions also often start with mild oral symptoms. Also conventional allergy tests, such as skin-prick test and blood test to detect IgE-antibodies (IgE-ab) to foods, discriminate poorly between cross reactions and true allergy. Component resolved diagnostics, i.e. analysis of IgE-ab to specific proteins in an allergen and CD-sens (Basophil allergen threshold sensitivity), can differentiate pollen-related cross reactions from true allergic reactions that may cause anaphylaxis. There is no widely accepted or evidence based treatment for food allergy, but reports from several studies have been published and many are in progress, where oral immunotherapy probably is the most promising form of treatment.

Food-Related Symptoms and Food Allergy in Swedish Children from Early Life to Adolescence.

BACKGROUND: Risk factors for persistence of food-related symptoms (FRS) and food allergy (FA) from early life to adolescence are incompletely understood. The aim of this study was to identify risk factors for FRS and FA in adolescence amongst children with FRS or FA in the first four years of life (early life). METHODS: In children enrolled in a Swedish birth cohort and followed to 16 years (n = 2572), we defined children with early life FRS in the absence of FA, and FA. Corresponding phenotypes were defined at 16 years. Associations between potential risk factors at 4 years and FRS and FA at 16 years were investigated using logistic regression. RESULTS: Early life FRS and FA prevalences were 12.2% and 6.8%, respectively. Amongst children with early life FRS, 35.7% had FRS or FA at 16 years, whereas 74.3% of the children with early life FA had FA at 16 years. For each of the early life phenotypes, parental allergy, early life allergic multimorbidity, early life reactions to peanuts/tree nuts and IgE reactivity at 4 years were statistically significantly associated with FRS or FA at 16 years. In contrast, male sex was associated with an increased risk of FA at 16 years among children with early life FA only. CONCLUSIONS: In early life, food-related symptoms are twice as common as food allergy. Unlike food allergy, food-related symptoms often remit by adolescence. Yet, these phenotypes have many common risk factors for persistence to adolescence.

The management of situated risk: a parental perspective on child food allergy.

Food allergy is an illness that requires constant risk management in everyday life. To date, there is no cure or preventive treatment, and the only way to manage the condition is therefore careful avoidance of the offending foodstuff and treatment of reactions when they occur. This article draws on a socio-cultural approach to explore parents' understandings and management of child food allergy in the context of everyday life, as 'situated' risk. A focus group study was carried out with 31 parents of children diagnosed with food allergy at two children's hospitals. The analysis of the focus group material reveals how the management of allergy risk seems to permeate most aspects of everyday life as well as how the parents draw on a dominant norm of risk avoidance as well as a counter-discourse of calculated risk taking. The patterns of risk management found in this study are discussed in terms of how risk avoidance and risk taking are intertwined and balanced in the context of moral parenthood.