L’allergia alimentare: novità in tema di trattamento

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1 L’allergia alimentare: novità in tema di trattamento
Mauro Calvani Azienda Ospedaliera S. Camillo-Forlanini UOC di Pediatria Ambulatorio Pediatrico Allergologico Roma

2 EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy
Muraro A et al, Allergy 2014; 69:

3 EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy
The clinical management of food allergy includes short-term interventions to manage acute reactions and long-term strategies to minimize the risk of further reactions. The latter aim is primarily achieved through dietary modification, education and behavioral approaches to avoid allergens and pharmacological and nonpharmacological management strategies for further reactions. There is growing interest in the effectiveness of potential immunomodulatory treatment approaches, including sublingual and oral immunotherapy to induce tolerance. Muraro A et al, Allergy 2014; 69:

4 EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy
In our systematic review, we found weak evidence to support the benefits of H1 antihistamines for children and adults with acute non-life-threatening symptoms from food allergy in three randomized trials and two nonrandomized comparisons. Importantly, there is no evidence for efficacy of antihistamines in the treatment of more severe symptoms. Muraro A et al, Allergy 2014; 69:

5 2015 update of the evidence base: World
Allergy Organization anaphylaxis guidelines International guidelines concur that epinephrine (adrenaline) is the medication of first choice in anaphylaxis because it is the only medication that reduces hospitalization and death Simons FE et al, WAO Journal DOI /s

6 Trattamento della fase acuta
Adrenalina la dose è 0.01 ml/kg di una soluzione acquosa di adrenalina 1:1000 (dose max 0.5 mg) per via intramuscolare profonda, preferibilmente nel muscolo vasto laterale della coscia.

7 La adrenalina contrasta tutti i meccanismi
patogenetici della Anafilassi Simons FER, JACI 2004

8 Campbell RL et al, JACI In Practice 2015; 3: 76-80
Epinephrine in Anaphylaxis: Higher Risk of Cardiovascular Complications and Overdose After Administration of Intravenous Bolus Epinephrine Compared with Intramuscular Epinephrine 19/08/2019 Objective: To compare rates of CV adverse events and epinephrine overdoses associated with anaphylaxis management between various routes of epinephrine administration among patients with anaphylaxis in the emergency department. Methods: This was an observational cohort study from April 2008 to July Patients in the emergency department who met diagnostic criteria for anaphylaxis were included. Results: The study cohort included 573 patients, of whom, 301 (57.6%) received at least 1 dose of epinephrine. A total of 362 doses of epinephrine were administered to 301 patients: 67.7% intramuscular (IM) autoinjector, 19.6% IM injection, 8.3% subcutaneous injection, 3.3% intravenous (IV) bolus, and 1.1% IV continuous infusion. The outcomes of interest were epinephrine overdose and adverse CV events associated with epinephrine, including arrhythmia, cardiac ischemia, stroke, angina, or hypertension (HTN). Epinephrine overdose was defined as a dose that exceeded the recommended dose in published anaphylaxis guidelines (0.01 mg/kg, with a maximum dose of 0.5 mg for intramuscular (IM) epinephrine and 100 mg given as an IV bolus).1, Campbell RL et al, JACI In Practice 2015; 3: 76-80

9 Campbell RL et al, JACI In Practice 2015; 3: 76-80
Epinephrine in Anaphylaxis: Higher Risk of Cardiovascular Complications and Overdose After Administration of Intravenous Bolus Epinephrine Compared with Intramuscular Epinephrine 19/08/2019 Su 362 somministrazioni di adrenalina sono state rilevate 4 overdose e 8 effetti avversi di tipo cardiovascolare La 4 overdose, tutte legate a somministrazione di adrenalina in bolo, sono state associate in 3 casi a ischemia cardiaca e in un caso a aritmia Campbell RL et al, JACI In Practice 2015; 3: 76-80

10 Campbell RL et al, JACI In Practice 2015; 3: 76-80
Epinephrine in Anaphylaxis: Higher Risk of Cardiovascular Complications and Overdose After Administration of Intravenous Bolus Epinephrine Compared with Intramuscular Epinephrine Le somministrazioni IM con autoiniettore sono state associate in 1 solo caso a angina (dolore o oppressione senza elevazione della troponina) e in 2 casi a ipertensione. In 1 caso di somministrazione IM ischemia (dolore con elevazione della troponina) La somministrazione di adrenalina EV in bolo è gravata da più frequenti complicanze cardiovascolari (10% vs 1.3%) e overdose (13.3% vs 0%) rispetto alla via IM Campbell RL et al, JACI In Practice 2015; 3: 76-80

11 Terapia di secondo livello
Antistaminici (os o IM o EV) (se orticaria angioedema) ad es cetirizina (os) 2,5 mg (< 2 anni), 5 mg (2-5 anni), 10 mg (> 5 anni) ad es difenidramina (IM-EV) 1 mg/kg/dose Steroidi (os o Im o EV) ad es Prednisone o Metilprednisolone 1 mg/kg Anti H2 (se orticaria angioedema) ad es Ranitidina (os/EV) 1 mg/kg/dose Glucagone (se in terapia con -bloccanti e ipotensione persistente) da 20 a 30 mcg/kg/EV in 5 minuti seguito da 5-15 mcg/kg/min in pompa Blu di metilene? (0.5 mg/kg o 100 mg)

12 Simons FER, J Allergy Clin Immunol 2006; 117: 367-77
ANTISTAMINICI ANTI H1 19/08/2019 “Although H1-antihistamines relieve itch and hives, in usual doses they do not relieve airway obstruction, gastrointestinal symptoms, or shock, or prevent mediator release from mast cells and basophils. After administration by mouth, H1-antihistamine absorption and onset of action are slow, taking at least 1 to 2 hours. In many anaphylaxis episodes, the rapid improvement attributed to an orally administered H1-antihistamine is likely due to spontaneous improvement” E anche per gli antistaminici occore qulche oora prima che se ne possa apprezzare l’effetto Simons FER, J Allergy Clin Immunol 2006; 117:

13 Systemic corticosteroids have no role
CORTICOSTEROIDI 19/08/2019 Joint Task Force on Practice Parameters for Allergy & Immunology Systemic corticosteroids have no role in the acute management of anaphylaxis because they might have no effect for 4 to 6 hours, even when administered intravenously. E questo nemmeno se il cortisone viene somministrato per via endovenosa Lieberman P et al, JACI 2005; 115: s

14 Biphasic Anaphylactic Reactions in Pediatrics
19/08/2019 Analisi retrospettiva su 106 bambini ricoverati per anafilassi in un Ospedale Pediatrico nel periodo La somministrazione di adrenalina invece sembrerebbe in grado di ridurre la anafilassi bifasica La precoce somministrazione di adrenalina e non quella di steroidi sembra preventire la anafilassi bifasica Lee JM et al, Pediatrics 2000; 106: 762-6

15 Michelson KA et al, J Pediatr 2015; 167: 719-24
Glucocorticoids and Hospital Length of Stay for Children with Anaphylaxis: A Retrospective Study Objective To evaluate whether glucocorticoid administration is associated with improved outcomes in children with anaphylaxis. Study design We included children from the Pediatric Health Information System database who were diagnosed with anaphylaxis at 35 US children’s hospitals between 2009 and Patients were stratified by disposition from the emergency department (ED), either hospitalized or discharged. We evaluated the association between glucocorticoid administration and prolonged length of stay (LOS), defined as hospital stay  2 days, and subsequent epinephrine administration among hospitalized children. Among discharged children, we assessed the association between glucocorticoid administration and ED revisits within 3 days. Michelson KA et al, J Pediatr 2015; 167:

16 Michelson KA et al, J Pediatr 2015; 167: 719-24
Glucocorticoids and Hospital Length of Stay for Children with Anaphylaxis: A Retrospective Study La somministrazione di cortisone si associa inversamente al rischio di ricovero oltre 2 giorni nella analisi corretta e alla somministrazione di adrenalina nelle 24 ore successive (anafilassi protratta o bifasica). Michelson KA et al, J Pediatr 2015; 167:

17 QUADRO CLINICO MONOFASICO BIFASICO PROTRATTO 19/08/2019
Una presentazione clinica particolare della anafilassi è la forma bifasica. Essa si manifesta in percentuali molto variabili nelle varie casistiche, dall’1% al 20%, [i]. In sostanza consiste in una ripresa della sintomatologia anafilattica, dopo almeno un’ora dalla sua iniziale apparente risoluzione, senza essere stato di nuovo esposto all’allergene. Nella gran parte dei casi la ripresa della sintomatologia si ha entro 4-6 ore ma sono descritti casi in cui la anafilassi è nuovamente insorta dopo oltre 24 ore. La gravità del successivo quadro clinico è molto variabile, da forme di gravità lieve moderata a casi gravi e talora mortali. La gran parte delle informazioni sulla anafilassi bifasica derivano da casistiche che hanno arruolato per la gran parte, se non del tutto, popolazione adulta. Solo 2 studi hanno indagato la anafilassi bifasica in età pediatrica. Nello studio di Lee e Greenes[ii], una reazione bifasica si verificava in 6/108 (5.5%) episodi. Lo studio evidenziava come il ritardo nella somministrazione di adrenalina costituisce un possibile fattore di rischio per il verificarsi di una reazione bifasica. Il secondo studio è quello di Mehr [iii], il quale ha descritto 109 episodi di anafilassi, verificatisi in 104 bambini, di cui 12 (11%) di tipo bifasico. Fattori di rischio per la anafilassi bifasica erano l’aver somministrato un maggior numero di dosi adrenalina e di boli di liquidi per la iniziale manifestazione. 9 di questi 12 episodi erano causati da alimenti e uno di questi era dovuto al latte vaccino. La mediana di tempo trascorso tra la prima reazione e la seconda era di 8.8 ore. Il secondo episodio fu meno grave del precedente in 7 casi (58%) simile in 4 casi (33.3%) (tra cui quello dovuto al latte vaccino) e più grave in 1 (8.3%) caso. [i] Lieberman P: Biphasic anaphylactic reactions. Ann Allergy Asthma Immunol 2005; 95: [ii] Lee JM, Greenes DS. Biphasic anaphylactic reactions in pediatrics. Pediatrics. 2000;106:762–766. [iii] Mehr S, Liew WK, Tey D and Tang MLK: Clinical predictors for biphasic reactions in children presenting with anaphylaxis. Clin Exp Allergy 2009; 1-7

18 TRATTENERE IN OSSERVAZIONE IN RELAZIONE AL QUADRO CLINICO
19/08/2019 In tutti i casi TRATTENERE IN OSSERVAZIONE PER 6-8 ORE O PIU’, IN RELAZIONE AL QUADRO CLINICO In tutti i casi comunque è suggerita una osservazione per almeno 6-8 ore, per scongiurare la insorgenza della anafilassi bifasica

19 Time of Onset and Predictors of Biphasic Anaphylactic
Reactions: A Systematic Review and Meta-analysis We conducted a systematic review and meta-analysis to synthesize the existing literature on biphasic reactions and address the following objectives: to describe the time frame in which biphasic reactions occur; to investigate potential risk factors for biphasic reactions in patients with anaphylaxis; and to determine whether use of steroids or epinephrine for the treatment of the initial anaphylactic episode is associated with the risk of developing a biphasic reaction Lee S et al J Allergy Clin Immunol in Practice 2015; 3:

20 Time of Onset and Predictors of Biphasic Anaphylactic
Reactions: A Systematic Review and Meta-analysis Tra i fattori ricercati sono risultati positivamente correlati la ipotensione come sintomo iniziale e la eziologia sconosciuta, mentre la anafilassi da alimenti risulta negativamente associata Lee S et al J Allergy Clin Immunol in Practice 2015; 3:

21 SUGGERIMENTI SU COME EVITARE L’ALLERGENE E SULLA DIETA
VALUTAZIONE DEL RISCHIO DI RECIDIVA DEI POSSIBILI COFATTORI E PRESCRIZIONE ADRENALINA AUTOINIETTABILE IMMUNOTERAPIA SPECIFICA

22 ICON: Food allergy TREATMENT OPTIONS AND PREVENTION
The primary therapy for food allergy is strict avoidance of the causal food or foods. This is true for IgE-mediated, non–IgE mediated, and mixed IgE- and non–IgE-mediated food allergy syndromes. Although allergen avoidance is unproved in randomized controlled trials, it is the safest strategy for managing food allergy. Burks AW et al, J Allergy Clin Immunol 2012; 129;

23 A practice parameter update—2014
Food allergy: A practice parameter update—2014 Summary Statement 36: The primary therapy for food allergy is strict avoidance of the causal food or foods. This is true for all types of food allergy, including IgE-mediated and non–IgE-mediated food allergy. Sampson HA et al, J Allergy Clin Immunol 2014, 134:

24 A practice parameter update—2014
Food allergy: A practice parameter update—2014 …. The appropriate elimination diet must be tailored to each patient. The clinician should recognize that a proper diet can vary from regular exposure to some modified proteins (eg, a baked egg– or baked milk–tolerant patient) to strict avoidance of allergen. Although a strict avoidance diet of all allergic foods is typically recommended, recent studies indicate that regular exposure of heat-modified egg and milk protein in allergic patients is not only well tolerated in up to 70% of allergic patients but might be clinically beneficial… Sampson HA et al, J Allergy Clin Immunol 2014, 134:

25 Lemon Mulè H et al, JACI 2008; 122: 977-83
Immunologic changes in children with egg allergy ingesting extensively heated egg Inizialmente arruolati 127 bambini (età media 6.9 anni). Dopo il TPO 27 erano allergici all’uovo cotto, 64 tolleravano l’uovo cotto in matrice di grano e 23 non allergici all’uovo. Quindi 70% (64/91) dei bambini con allergia all’uovo tolleravano l’uovo cotto (Muffin) During each oral food challenge, a muffin and a waffle that each contained one third of an egg (approximately 2.2 g of egg protein) were ingested. The muffin was baked at 350F for 30 minutes in an oven, and the waffle (<0.625 inches thick to ensure thorough heating) was cooked in a waffle maker at approximately 500F for 3 minutes. Lemon Mulè H et al, JACI 2008; 122:

26 Tolerance to extensively heated milk in children with cow’s milk allergy
19/08/2019 100 bambini di 6 mesi-21 anni (media 7.5 anni) con SPT o IgE specifiche per latte e storia di reazione entro 6 mesi o valori superiori ai cut-off consigliati 68/100 bambini tolleravano il latte cotto in matrice di grano Ciascun muffin e waffle contenevano 1.3 gr di proteine del latte. Il TPO consisteva nella somministrazione di 1 muffin e 1 waffle (2.6 gr) Ciascun muffin e waffle contenevano 1.3 gr di proteine del latte. Il TPO consisteva nella somministrazione di 1 muffin e 1 waffle (2.6 gr) Ai tolleranti veniva somministrato 240 ml di latte (o 8-10 gr di proteine) Ai tolleranti veniva somministrato 240 ml di latte (o 8-10 gr di proteine) Muffin cotto a 350°F (176° celtius) per 30 minuti Waffle cotto a 500° F (260° celtius) per 3 minuti Nowak Wegrzyn A et al, J Allergy Clin Immunol 2008

27 Alimenti contenenti UOVO
Allergia Ben Cotto (Baked egg) ( ° x > 30 min) Torte Biscotti Pasta all’uovo Barrette al cioccolato Hamburger Cottura intermedia (Regular egg) (~ 100° x 3-5 min) Frittata Homelette Creme caramel Creme Brullee Meringhe Crudo Maionese Sorbetto Mousse con uovo Gelati con uovo Salsa tartara Fesa di tacchino IgE per l’uovo Tolleranza

28 Basophil reactivity, wheal size, and immunoglobulin levels
distinguish degrees of cow’s milk tolerance Obiettivo: identificare dei biomarker in grado di diagnosticare i diversi gradi di tolleranza nei confronti del latte “cotto in matrice” Metodi: 132 bambini (di 4-10 anni) con storia di allergia al latte e IgE specifiche > 35 Ku/l (esclusi quelli con anafilassi recente) sono stati sottoposti a TPO con alimenti contenenti latte sempre meno “cotto” e come tale Muffin (1,5 gr di proteine del latte/Muffin cotto a 350 F per 30’) Pizza (4 gr di proteine del latte cotta a 425 F per 13’) Budino di riso (7,7 gr di proteine del latte cotto a 325 F per 90’) Latte (10 gr di proteine, non cotto, solo pastorizzato) Ford L et al, J Allergy Clin Immunol 2013; 131: 80-6

29 Basophil reactivity, wheal size, and immunoglobulin levels
distinguish degrees of cow’s milk tolerance In questa popolazione risultavano 37/132 (28%) allergici al latte (cotto e crudo) 31/132 (23.4%) allergici al latte, tollerano il muffin, no pizza budino 12/132 (9%) allergici al latte, tollerano muffin e pizza no budino 44/132 (33%) allergici al latte ma tolleranti muffin pizza e budino 8/132 (6%) non allergici al latte Ford L et al, J Allergy Clin Immunol 2013; 131: 80-6

30 Thermal and Nonthermal Methods for Food Allergen Control
19/08/2019 Shriver SK et al Food Eng. Rev. 2011; 3 :26–43 30 30

31 Baked Milk- and Egg-Containing Diet in the Management of Milk and Egg Allergy
Leonard SA et al, J Allergy Clin Immunol in Practice 2015; 3: 13-23

32 SUGGERIMENTI SU COME EVITARE L’ALLERGENE E SULLA DIETA
VALUTAZIONE DEL RISCHIO DI RECIDIVA DEI POSSIBILI COFATTORI E PRESCRIZIONE ADRENALINA AUTOINIETTABILE IMMUNOTERAPIA SPECIFICA

33 BSACI guideline: prescribing an adrenaline auto-injector
Valutazione del rischio di una recidiva di anafilassi e della utilità della prescrizione di adrenalina autoiniettabile Ewan P et al,Cl Exp Allergy 2016; 46:

34 About the role and underlying mechanisms of cofactors in anaphylaxis
I più frequenti cofattori in grado di aumentare la gravità delle reazioni allergiche sono l’esercizio, l’alcool, le infezioni, gli antiinfiammatori non steroidei Wolbing F et al, Allergy 2013; 68:

35 About the role and underlying mechanisms of cofactors in anaphylaxis
I cofattori probabilmente facilitano l’assorbimento dell’antigene e in questo modo riducono la dose soglia in grado di determinare una reazione Wolbing F et al, Allergy 2013; 68:

36 EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy
Prescrizione della Adrenalina autoiniettabile Absolute indications with adrenaline autoinjector include previous anaphylaxis to any food, food allergy associated with persistent or severe asthma, exercise-induced food-dependent anaphylaxis Relative indications for adrenaline autoinjector with food allergy food allergies that are likely to be persistent; mild-to-moderate allergic reaction to peanut and/or tree nut; (iii) mild-to-moderate reaction to very small amounts of food; (iv) specific high-risk groups, e.g., adolescents, young adult males, poor access to medical care IV D Expert opinion, IV–V* C–D* Expert opinion, Muraro A et al, Allergy 2014; 69:

37 BSACI guideline: prescribing an adrenaline auto-injector
Valutazione del rischio di una recidiva di anafilassi e della utilità della prescrizione di adrenalina autoiniettabile Ewan P et al, Cl Exp Allergy 2016; 46:

38 FASTJECT JEXT Adrenalina Adrenalina tartrato dose 165 – 330 mcg 150 – 300 mcg eccipienti Sodio metabisolfito Sodio cloruro Acido cloridrico Sodio metabisolfito Sodio cloruro Acido cloridrico validità 18 mesi 18 mesi precauzioni Conservare a T non > 25° c Non congelare lunghezza ago 12-15 mm 12-15 mm costo 77,90 eu (classe H) 74,10 (classe H)

39 BSACI guideline: prescribing an adrenaline auto-injector
Esiste in commercio in Inghilterra un autoiniettore con ago più lungo e dose di 0.5 mg Ewan P et al,Cl Exp Allergy 2016; 46:

40 Guerlain S et al, Ann Allerg Asthma Immunol 2010; 105: 480-4
Intelliject’s novel epinephrine autoinjector: sharps injury prevention validation and comparable analysis with EpiPen and Twinject Objectives: To validate the sharps injury prevention features of the NEA and to obtain feedback on, and preference for, features of the NEA compared with Twinject and EpiPen Methods: Twenty-eight health care professionals experienced with using the EpiPen or Twinject each injected 18 NEAs into an orange and provided confirmation of needle injection and retraction. Half of the injections were conducted using wet hands to replicate diaphoretic hands or wet environmental conditions. Guerlain S et al, Ann Allerg Asthma Immunol 2010; 105: 480-4

41 ACTION PLAN Come somministrare Adrenalina
19/08/2019 ACTION PLAN Come somministrare Adrenalina 1) Prendere la Adrenalina auto-iniettabile e togliere il tappo 2) Puntare contro il muscolo anterolaterale della coscia 3) Premere con forza fino a che non si sente un click e mantenerlo premuto per almeno 10 secondi In tutti i bambini che abbiano manifestato una anafilassi è consigliabile la prescrizione della adrenalina autoiniettable. Alla prescrizione deve essere associata una chiara spiegazione di come e quando somministrare il farmaco. Meglio se la spiegazione è scritta, come ad esempio nell’Action Plan pubblicato alcunii anni fa sulla RIAP dalla Commissione Allergie Alimentari Anafilassi e Dermatite Atopica 4) Estrarre la siringa e massaggiare la sede della iniezione per almeno 10 secondi. Mantenere sdraiato il bambino. Chiamare il 118 o portarlo ad un Pronto Soccorso

42 Design and validation of pictograms in a pediatric
anaphylaxis action plan Disegno: Studio prospettico volto a validare i pittogrammi inclusi in un action plan per anafilassi. Ricercati Trasparenza: capacità di indovinare il significato senza conoscerlo Traslucenza: forza del rapporto tra l’immagine e il suo significato Richiamo: capacità di ricordarne il significato Mok G et al, Pediatr Allergy Immunol 2015; 26:

43 Efficacy of a management plan based on severity assessment in longitudinal and case-controlled studies of 747 children with nut allergy: proposal for good practice Studio prospettico su 747 bambini con allergia alle arachidi e/o ai semi. L’impiego di un piano di trattamento scritto con informazioni su come evitare gli allergeni e come trattare l’anafilassi è efficace nel ridurre la gravità e la frequenza degli episodi successivi Ewan PW et al, Cl Exp Allergy 2005

44 What are the ‘ideal’ features of an adrenaline (epinephrine)
auto-injector in the treatment of anaphylaxis? Problems with the use of adrenaline auto-injectors Needle phobia Incorrect self administration technique Incorrect route of administration – suboptimal injection site Needle stick injury Poor absorption and adrenaline resistance Outdate auto-injectors Large size of devices Lack of standardized assessment criteria Frew AJ et al, Allergy 2011; 68: 15-24

45 Srisawat C1, et al, Asian Pac J Allergy Immunol 2016; 34: 38-43
A preliminary study of intranasal epinephrine administration as a potential route for anaphylaxis treatment. The intranasal (IN) administration of epinephrine could be an alternative route for anaphylaxis treatment. Although IN epinephrine absorption has been demonstrated in animals, such data in humans are still lacking. OBJECTIVE: To study the pharmacokinetics of IN epinephrine absorption in humans. METHODS: Each healthy adult (n=5) was administered IN saline, IN epinephrine at various doses, and intramuscular (IM) epinephrine at 0.3 mg… RESULTS: Significant systemic absorption of epinephrine via IN route was observed only at the dose of 5 mg, and the absorption thereof was comparable to that of IM epinephrine; CONCLUSION: This preliminary study showed that epinephrine can be significantly absorbed via the IN route in humans. However, it requires a higher IN dose (5 mg) than the usual IM dose (0.3 mg) to achieve comparable systemic epinephrine absorption. Srisawat C1, et al, Asian Pac J Allergy Immunol 2016; 34: 38-43

46 SUGGERIMENTI SU COME EVITARE L’ALLERGENE E SULLA DIETA
VALUTAZIONE DEL RISCHIO DI RECIDIVA DEI POSSIBILI COFATTORI E PRESCRIZIONE ADRENALINA AUTOINIETTABILE IMMUNOTERAPIA SPECIFICA

47 Edwards HE Can Med Assoc J 1940; 234-6
ORAL DESENSITIZATION IN FOOD ALLERGY It is my purpose in this paper to discuss only one phase of allergy, namely, oral desensitization. ……The first reference to oral desensitization as a method of treatment that I have found is that of Finkelstein, in 1905, who suggested treating milk idiosyncrasy in nurslings by the administration of two to three drops of milk daily with subsequent increase. In 1908 Schofield reported the treatment of an extreme case of egg-poisoning in a boy aged thirteen years. He gave pills containing 1/10,000th part of a raw egg and two grains of calcium lactate daily, which dose was gradually increased. His course of treatment took eight months but was completely successful. He stated that he had been able to find no previous record of the successful treatment of food poisoning. Edwards HE Can Med Assoc J 1940; 234-6

48 Nelson: studio su IT SC per arachidi
Longo: RCT per latte in bambini anafilattici Burks: primo RCT-DB per uovo Begin: primo studio x allergeni multipli Schofield: case report di DOPA per uovo Enrique: primo RCT SLIT (con nocciola) Varshney: primo RCT-DB per arachidi Vichery: lunga tolleranza per arachidi 1908 1997 2005 2008 2011 2012 2014 2014 1905 1984 2003 2004 2007 2008 2009 2012 2014 2015 Finkelstein : case report DOPA per latte Mempel: case report SLIT kiwi Goldberg: Baked immunotherapy Skripak: primo RCT-DB con latte Keet: RCT Orale vs SLIT x latte Hofmann: primo studio DOPA su arachidi Narisety primo RCT SLIT vs OIT Meglio: report di casi Staden: primo RCT orale con latte e uovo Patriarca : report di casi di DOPA x alimenti

49 EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy
The two systematic reviews found mixed evidence and suggested that oral immunotherapy should not currently be recommended as routine treatment (81, 82). In light of its potential benefit, it should be performed only in highly specialized centers, with expert staff and adequate equipment, and in accordance with clinical protocols approved by local ethics committees. Muraro A et al, Allergy 2014; 69:

50 Efficacy of baked milk oral immunotherapy in baked milk–reactive allergic patients
Fifteen patients (>4 years) who previously failed to complete our milk OIT program were enrolled into the BM OIT protocol. A dose of BM (180°C for 30 minutes) which was less than the eliciting dose was increased 50% monthly while under medical supervision until the primary outcome dose of 1.3 g/d BM protein was achieved Goldberg MR et al, J Allergy Clin Immunol 2015: 136;

51 Efficacy of baked milk oral immunotherapy in baked milk–reactive allergic patients
Solo 3/15 (29%) hanno raggiunto la possibilità di ingerire 1.3 gr di proteine del latte cotte estensivamente. Non infrequentemente soggetti che avevano tollerato una dose > 1 mese hanno in seguito avuto reazioni alla stessa dose e 1 pur avendo raggiunto a dose finale in seguito ha dovuto ridurla molto a causa di continue reazioni Goldberg MR et al, J Allergy Clin Immunol 2015: 136;

52 Safety and feasibility of oral immunotherapy to
multiple allergens for food allergy Background: Thirty percent of children with food allergy are allergic to more than one food.. .This study aimed at evaluating the safety of a modified OIT protocol using multiple foods at one time. Methods: Participants underwent double-blind placebo-controlled food challenges up to a cumulative dose of 182 mg of food protein to peanut followed by other nuts, sesame, dairy or egg. Those meeting inclusion criteria for peanut only were started on single-allergen OIT while those with additional allergies had up to 5 foods included in their OIT mix. . Begin P et al, Allergy Asthma Clin Immunol 2014; 10: 1

53 Safety and feasibility of oral immunotherapy to
multiple allergens for food allergy La incidenza di effetti collaterali è stata simile nei due gruppi, utilizzando un protocollo che prevedeva la somministrazione di una simile quantità di allergene Conclusions: Preliminary data show oral immunotherapy using multiple food allergens simultaneously to be feasible and relatively safe when performed in a hospital setting with trained personnel. Additional, larger, randomized studies are required to continue to test safety and efficacy of multi-OIT Begin P et al, Allergy Asthma Clin Immunol 2014; 10: 1

54 Grazie per l’attenzione!