Efficacy of Oral Tolerance Induction to raw apple using an Ultra-Rush protocol in 28 patients allergic to rosaceae fruits: RAAP StudyTo the Editor,The diagnosis of pollen-food allergy syndrome (PFAS) or oral allergy syndrome (OAS) relies on clinical history together with demonstration of allergen-specific IgE. PFAS is mainly observed in central and northern Europe. These symptoms follow the consumption of raw fruits1 and last 30 minutes, then stop ; but they tend to worsen over time, leading patients to avoid eating raw rosaceae fruit and many other raw fruits. This clinical presentation evolves concurrently with birch pollen allergy2. Over 70% of patients with birch allergy suffer from PFAS to rosaceae, particularly to raw apple3 . Therapeutic management is limited 4 , based on avoidance of trigger foods5.The results of betulaceae pollen immunotherapy remain limited6 . Raw Golden apple (RGA) desensitization has already been described by NUCERA et al. in 20107 in 2 patients. Likewise, RGA tolerance induction was described in 2012 by KOPAC et al8 and in 2014 by BOUVIER et al9 according to slow protocols where the maintenance dose was reached over several months.We realized a retrospective observational impact study to present an accelerated protocol or ultra-rush (UR) for resumption of RGA intake performed in two private hospitals of the Lyon region (France), the Charcot clinic and the Beaujolais clinic, on 28 patients hospitalized between June 2016 until October 2017. The study was appropriately registered (ClinicalTrials.gov Identifier: NCT04116580).Eligible patients were 10 years of age and older with allergic rhinitis related to PFAS for raw rosacea with avoidance of this family of fruits for at least 6 months. Subjects were excluded from the study in case of severe allergic reaction to rosacea or uncontrolled asthma with FEV1 < 70%. The medical procedure consisted of 4 phases. During the first consultation, each patient’s medical history was collected. Prick tests with airborne allergen and raw golden apple (RGA) were performed according to the prick-prick technic 10; specific IgE for apple, rBet v 1, rBet v 2\sout, rPru p 3 were prescribed. In total the inclusion of patients was based on their clinical history.For the UR, patients were not on antihistamines. At time 0 (T0), prick test were performed with RGA9. At T0 +20 minutes, patients took 1 g of unpeeled RGA , then by doubling regularly the doses from 2g to 128g, to reach a 255 g cumulative dose within in 3 hours.Then, half of an unpeeled RGA was consumed daily at home for one month, and one whole RGA daily the following month. For the patients who underwent the UR procedure between mid-April and mid-July, intake of other raw rosaceae was permitted at the end of week 5 post UR. A two-month evaluation consultation was conducted. Afterwards, patients had to maintain their tolerance by consuming half a raw apple of any type three times a week. A telephone interview was performed at 1 year of the UR to evidence tolerance and compliance.FIGURE 1 Shematic overview of the Ultra-Rush protocolTABLE 1 Population profile - Allergologic and Biological results

Background: Allergy is witnessing major advances, in particular with the advent of biological therapies for treating allergic diseases. Given the novelty of these therapeutics, we aimed to explore by a worldwide survey, the prescription and the management of hypersensitivity reactions (HR) of biological agents (BA) in Allergy. Method: We built up an anonymous online questionnaire, sent out by mail and social media and circulated for 40 days. Results: 348 responses were from 59 countries, with a majority from Europe (62.6%). 97% of responders practiced allergy and 48.5%, exclusively so. Allergy was mentioned as a full specialty in 69.5 % of cases. 71% of responders confirmed the right of prescription of BA for allergists in their country and 78.4 % prescribed BA in their clinical practice. Europe included almost all the allergists who did not have the right of prescribing BA (95.5%), specifically France (91%). The most prescribed BA were Anti IgE (78.1%) and anti IL5 (43.9%). The most declared HR to BA were local reactions (74.1%) followed by anaphylaxis like symptoms (6.8%) and delayed exanthemas (5.1%). Desensitization was considered in 18.9% of cases. These HR were reported in 48.8% of cases. Conclusion: Although BA are now a pillar in the treatment of allergic diseases and allergists are familiar with management of HR associated with BA, their prescription is not authorized for allergists in all countries. BA showed to be generally safe but HR, which may be severe, could occur with a lack of consensus on the management.