Safety of Epicutaneous Immunotherapy in Peanut-Allergic Children: REALISE Randomized Clinical Trial Results.

BACKGROUND: Treatment options for peanut allergy are limited. In previous clinical trials, epicutaneous immunotherapy with a patch containing 250-µg peanut protein (Viaskin Peanut 250 µg [VP250]) was well tolerated and statistically superior to placebo in desensitizing peanut-allergic children. OBJECTIVE: To examine the safety of VP250 in children, using a study design approximating potential real-world use. METHODS: REAL LIfe Use and Safety of EPIT (REALISE) is a phase 3 multicenter study consisting of a 6-month, randomized, double-blind, placebo-controlled period followed by open-label active treatment. Children aged 4 to 11 years with physician diagnosis of peanut allergy received daily treatment with placebo (6 months) or VP250 (up to 36 months). Data from the 6-month, randomized, controlled phase of REALISE are reported. RESULTS: Three hundred ninety-three children were randomized 3:1 to receive VP250 (n = 294) or placebo (n = 99) for 6 months; 284 (72.3%) children had a history of peanut anaphylaxis. According to parent diary, all participants receiving VP250 and 83.8% receiving placebo reported at least 1 episode of local skin reaction, with frequency decreasing over time. Only 4 participants (1.4%) receiving VP250 discontinued because of adverse events (AEs). Epinephrine was administered for allergic reactions attributed to VP250 in 7 children (2.4%), of whom 5 remained in the study; none involved severe anaphylaxis. Overall, AE rates were similar among participants with and without a history of peanut anaphylaxis. CONCLUSIONS: In a study designed to mirror real-world use, VP250 was observed to be well tolerated in peanut-allergic children, consistent with previous phase 2b and 3 studies.

COLA (Conferences On-Line Allergy) at 10 Years - Evolution of an Online Fellowship Curriculum.

Online learning has been present since the early days of the Internet. As with any new technology, users look to make their life easier and to save time. Experts in medical education are no different than other users. They want to adapt new technologies to their fullest. Medical educators have been challenged with keeping education interesting and up to date, while maximizing their resources. The challenges with any online educational program include being able to reach large numbers of learners, having content that is relevant and timely, and having it available thorough many different formats to suit the user. There are many examples of online learning programs in all fields of medicine and many specific to Allergy/Immunology. In this review, we describe a form of real-time videoconferencing referred to as Conferences On-Line Allergy (COLA), which was developed at Children's Mercy Hospital and Clinics. This program, which started as a once a month webinar, has transformed into a well-known curriculum used by many Allergy/Immunology training programs across the United States. It provides not only live interactive conferences but also a library of recorded lectures and workshops that can be used at the learner's convenience. Taking advantage of the generosity of many volunteer presenters, it allows sharing of resources and provides benefits to the Allergy/Immunology community.

The Role of the Environment in Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disease with incompletely understood pathogenesis. Though disease manifestations were initially ascribed to a delayed reaction to food allergens, emerging evidence suggests that modifiable host factors and environmental allergen exposure may also play critical roles in the pathogenesis and ongoing manifestations of EoE. As with other atopic diseases, lack of early-life exposure to microbial pathogens leads to an immune tolerance defect and reprograms the commensal gut microflora toward a type 2 T helper (Th2) phenotype; the esophageal microbiota, a rich environment consisting of diverse bacterial species, is greatly altered by inflammation. Although multiple early life microbiome-altering factors are associated with EoE development, no causative, direct relationships have been identified. Interestingly, large, cross-sectional analyses of several populations identify an inverse relationship between Helicobacter pylori presence and EoE, likely via virulence factors that downregulate Th2 inflammation, though causality has not been proven. In regard to environmental allergens, some studies support seasonal variation in EoE diagnosis and flares, and EoE can be generated after a large, identifiable aeroallergen exposure. Examples include mouse models of intranasal Aspergillus dosing and following initiation of oral immunotherapy to foods or environmental allergens. Conversely, treatment of allergic rhinoconjunctivitis may improve EoE symptoms, though data is limited to case reports and small series. Unfortunately, biologic therapies for atopic conditions have failed to improve EoE symptoms despite improvement in esophageal eosinophil count, though dupilumab shows promise in ongoing studies. Overall, this chapter shows that EoE pathogenesis is likely multifactorial, and the environment is a key component in our understanding of EoE.

Food allergy: practical considerations for primary care.

Food allergy is increasing in frequency and so is the misunderstanding of what constitutes a true food allergy. This article will review basic concepts of classic IgE reactions to food as well as discuss some that occur through other mechanisms. The importance of a detailed history is emphasized. Information is provided on optimal evaluation, interpretation of results and treatment of these potentially life-threatening reactions. Finally the role an allergist can play in co-management is discussed.

Useful biomarkers in pediatric eosinophilic duodenitis and their existence: a case-control, single-blind, observational pilot study.

OBJECTIVES: The aim of this study was to determine whether screening for food hypersensitivity could be a clinically useful biomarker for eosinophilic duodenitis in the pediatric population. PATIENTS AND METHODS: Twenty-two patients with functional dyspepsia and 19 controls with no significant history of gastrointestinal or allergic disorders were enrolled. Participants underwent skin prick, atopy patch, and serum-specific (S)-IgE, -IgG, and -IgG4 testing to corn, wheat, soy, peanut, milk, and egg. Participants in the patient group also underwent endoscopy with biopsies as part of standard care. RESULTS: Three participants in the patient group did not exhibit duodenal eosinophilia on biopsy and were excluded from data analyses. The patient group consisted of 13 females and 6 males, 8 to 17 years of age. The control group consisted of 10 females and 9 males, 8 to 17 years of age. Seven patients had at least 1 positive reaction to food by skin prick, atopy patch, or SIgE testing compared with 7 controls; odds ratio 1; 95% confidence interval 0.3 to 3.7. Receiver operating characteristics curves showed SIgG and SIgG4 performed poorly or no better than chance for predicting group assignment. CONCLUSIONS: Allergy screening for the foods tested was not useful as a biomarker for eosinophilic duodenitis in this small study. A higher rate of positive reactions to patch testing was observed in the control group than previous studies have reported. The incidence of a positive food patch test in nonselected subjects needs further investigation. Method standardization and establishment of reference intervals are needed for atopy patch tests, SIgG, and SIgG4 to better evaluate the clinical value of these measures.

Changes in exhaled nitric oxide levels with immunotherapy.

The mechanisms by which immunotherapy (IT) modulates allergic airway response are not entirely clear. Exhaled nitric oxide (eNO) is a sensitive marker of airway inflammation in allergic respiratory disorders. We hypothesize that eNO may serve as a barometer of the immunomodulatory changes occurring during IT. We aimed to characterize the pattern of eNO levels in children undergoing traditional IT (TradIT) and rush IT (RushIT). Off-line measurements of eNO were obtained in children electing to undergo RushIT or TradIT at a University-based Allergy/Asthma Clinic. The eNO was measured before IT (pre-IT, week 0) was initiated, and at 2, 4, 6, 8, and 12 weeks after starting IT. Nine children received TradIT and 10 children received RushIT. Pre-IT eNO in the RushIT group averaged 12.6 parts per billion (ppb). This was followed by a rise to 17.7 ppb at week 2. The elevated eNO levels persisted till week 8, and then dramatically dropped below the pre-IT values to 8.9 ppb at week 12 (p = 0.038). Similar changes in eNO were not seen in the TradIT group. The difference in eNO levels between the two groups was most marked at 4 weeks (p = 0.014). Initiation of IT produces significant immunomodulatory changes such as a rise in eNO levels. Temporally, the changes appear to be accelerated in the RushIT group compared with the TradIT group, with return to baseline as maintenance IT levels are achieved.