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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.

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 kU(A)/L) that were beginning in early life. In contrast, 94% had transient symptoms and low median IgE levels (early life: 0.63 kU(A)/L, 8y: 0.72 kU(A)/L; 16 years: 1.1 kU(A)/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.

Food allergy is a public health issue, particularly among children, and seems to be increasing worldwide. Allergic reactions to foods vary in terms of symptoms and severity. Anaphylaxis, the most severe allergic reaction, can be fatal. Food allergy has significant negative impact in the daily lives of allergic children and their families. The overall aim of this thesis was to gain knowledge about severe reactions to foods among Swedish children with regard to epidemiology, clinical perspectives (study I and II respectively), and risk management (study III). Study I (paper I and II) is an emergency department (ED) medical record study based on a retrospective chart review performed at three hospitals in Stockholm targeting children with anaphylaxis and allergic reactions to foods during 2007. Study II (paper III) is a cohort study where children identified in study I were investigated in relation to new ED visits during the follow-up period 1 January 2007 – 30 June 2010. Study III (paper IV) is a qualitative study where 10 focus group discussions were conducted with 31 parents of food-allergic children to explore strategies of risk management. The main findings in relation to the three study areas in this thesis are: Epidemiology: The incidence of anaphylaxis managed at paediatric EDs in Stockholm during 2007 was 32 per 100 000 person-years and food was involved in 92% (paper II). The incidence of subsequent ED visits for reactions to foods among children with a prior ED visit due to reactions to foods was 92 per 1000 person-years. Previously known food allergy was a risk factor for subsequent ED visits (paper III). Clinical perspectives: The current guidelines presented in the European Academy of Allergology and Clinical Immunology position paper on anaphylaxis in children were not entirely easy to apply when classifying and grading the severity of anaphylaxis in our study population. We attribute this difficulty to lack of description of some respiratory and neurol