Quando la diagnostica allergologica ed immunologica può evitare il test di scatenamento nelle allergie alimentari IgE e non-IgE mediate 20/09/2018 Mauro Calvani Azienda Ospedaliera S. Camillo-Forlanini U.O.C. di Pediatria Ambulatorio di allergologia pediatrica Roma - un mito: uomo che guarda il cielo - una realtà: uomo chino su piramide - un dubbio non risolto: uomo che sorregge il cielo - una riflessione su un aspetto da approfondire: uomo con piramidi

2009 2009 2012 2012 Japanese Guideline for Food Allergy 2014 2014 2014 2017 2014

The development of a standardised diet history tool to support the diagnosis of food allergy Guidelines provide expert evidence-based support for the diagnosis of FA, which includes Taking an allergy focussed history, performing appropriate tests and - food reintroduction or controlled food challenge. Skypala IJ et al, Clin Trasl Allergy 2015; DOI 10.1186/s13601-015

Prevalence of common food allergies in Europe: A systematic review and meta-analysis Prevalenza riferita e dopo TPO Latte 6 0,6 Uovo 2,5 0,1 Grano 3.6 0,3 Soia 0,4 0,2 Nwaru BI et l, Allergy 2014; 69: 992-1007

EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy Muraro A et al, Allergy 2014; 69: 1008-25

Il dosaggio delle IgG specifiche I test intradermici I Patch test Il Test di attivazione dei basofili Gli SPT e la ricerca delle IgE specifiche

Food allergy: A practice parameter update—2014 Summary Statement 38: Measurement of food-specific IgG and IgG4 antibodies in serum are not recommended for the diagnosis of non–IgE-mediated food-related allergic disorders. [Strength of recommendation: Strong; B Evidence] Sampson HA et al, J Allergy Clin Immunol 2014; 134: 1016.25

Food allergy: A practice parameter update—2014 Both serum and secretory specific IgA to dietary proteins can be produced in healthy subjects and allergic patients, and this does not predict allergy status. In some instances the levels of the local secretory IgA2 subclass might be increased in the absence of measurable levels of serum IgA (primarily IgA1). Oral ingestion of microparticles that contain dietary proteins leads to enhanced synthesis of IgA2 secretory antibodies compared with soluble proteins alone. Sampson HA et al, J Allergy Clin Immunol 2014; 134: 1016.25

Il dosaggio delle IgG specifiche I test intradermici I Patch test Il Test di attivazione dei basofili Gli SPT e la ricerca delle IgE specifiche

Food allergy: A practice parameter update—2014 Summary Statement 33: Do not perform intracutaneous testing for the diagnosis of food allergy (see discussion). [Strength of recommendation: Strong; B Evidence] Sampson HA et al, J Allergy Clin Immunol 2014; 134: 1016.25

Food allergy: A practice parameter update—2014 Intradermal skin testing for food allergy is not recommended…. Intradermal skin testing with food extracts has also been shown to have significantly higher false-positive rates compared with SPTs. Therefore if relied on, intradermal testing would not only increase systemic reaction risks but also increase risks associated with inappropriate diagnosis and unnecessary dietary elimination of foods. One possible exception to the use of intradermal testing in IgE-mediated food allergy includes the use of intradermal testing in delayed anaphylaxis associated with hypersensitivity to the carbohydrate moiety alpha-gal found in mammalian red meats. Sampson HA et al, J Allergy Clin Immunol 2014; 134: 1016.25

Il dosaggio delle IgG specifiche I test intradermici I Patch test Il Test di attivazione dei basofili Gli SPT e la ricerca delle IgE specifiche

Atopy patch tests, together with determination of specific IgE levels, reduce the need for oral food challenges in children with atopic dermatitis 20/09/2018 Score di valutazione ± Debole eritema + Eritema e lieve infiltrazione ++ Eritema, infiltrazione e papule +++ Eritema, infiltrazione, papule e vescicole Grado + Grado ++ Grado + + + Roher et al. J Allergy Clin Immunol 2001; 107: 548-53 14

EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy Atopy patch test: Due to the lack of standardized test substances and the lack of studies showing advantages of atopy patch test (APT) over SPT or sIgE, APTs are not recommended for routine diagnosis of food allergy. Muraro A et al, Allergy 2014; 69: 1008-1025

Food allergy: A practice parameter update—2014 Summary Statement 35: Although routine use of atopy patch tests for diagnosis of food allergy is not recommended, the use of food atopy patch tests in patients with pediatric eosinophilic esophagitis (EoE) have been demonstrated to be valuable in assessing potential food triggers. [Strength of recommendation: Moderate; C Evidence] Sampson HA et al, J Allergy Clin Immunol 2014; 134: 1016.25

Food allergy: A practice parameter update—2014 There is insufficient evidence to support the routine use of APTs in the diagnosis of food allergy. APTs for food allergy lack standardization, and results of previous studies show wide variability in the sensitivity and specificity of results. There is no consensus among experts regarding the appropriate reagents, methodology, or interpretation of results of APTs in the diagnosis of IgE-mediated food allergy. Food patch testing can be valuable in assessing food triggers in patients with pediatric EoE. Sampson HA et al, J Allergy Clin Immunol 2014; 134: 1016.25

Altri motivi per i differenti risultati il tipo di allergia (diverso quadro clinico) l’età della popolazione le dimensioni delle finn chiamber (12 mm è meglio di 6 mm) il tipo di allergene (liofilizzato > alimento fresco > estratto commerciale) diverso score di valutazione degli APT diverso test usato per la diagnosi di APLV etc

(Food Hypersensitivity and Patch test Ricerca sistematica (Food Hypersensitivity and Patch test (Novembre 2016) Linee Guida EAACI e Sampson, medline per articoli successivi, bibliografie degli articoli trovati 52 articoli 29 articoli

Qualunque quadro clinico Autore Casi (n) Età Sintomi OFC APT Latte PPV Uovo Majamaa 1999 143 < 2 anni Tutti 37 DBPCFC 95 aperto 20 mg di soluzione con 300 mg di latte in polvere + 0,2 ml di fisiologica 63 Osterballe 2004 22 3 anni Latte fresco Uovo fresco 57 Kalach 2005 49 5-78 mesi (media 34) Tutti (Da nel 10%, GI nel 40 e tuti nel 50) aperto 1 goccia di latte in polvere (2/3 adattato e 1/3 idrolizzato) su finn chamber vs diallertest scanpore (800 mcg di CMP) 91 vs 95 - Keskin 2005 37 1,5 – 84 mesi DBPCFC 20 mg di latte in polvere 89 Pustisek 2010 151 1-24 mesi (media 13,5 mesi) Tutti (sopattutto DA in 50, GI in 67 e 34 in tutti) NO challenge. Solo storia clinica Crema di latte in polvere + petrolato su camere di 12 mm curatest Non cercato Costa 2011 192 1-5 anni Tutti (GI 80%, cutanei 58%, respiratori 68%) 46 Levy 2012 72 1-12 anni Da solo, rinite e asma solo, sani Non eseguito Estratti al 10% in finn chamber di 8 mm in duplicato Correlano apt con SPT o rast senza fare tpo Caglayan 2015 243 media 51 mesi Tutti (GI 10%) Aperto Liofilizzato 33 0,17 PPV > 70%

Dermatite atopica PPV > 70% Autore Casi (n) Età Sintomi OFC APT Latte PPV Uovo Isolauri 1996 183 2-36 mesi (mediana 14) DA DBPCFC 20 mg di latte in polvere UTILE (SPEC 81%) Niggeman 2000 75 4 mesi-12,5 anni (mediana 2,1 anni) DA in 69/75 1 gtt di latte fresco o uovo su finn chamber 12 mm 81% per reazioni sia immediate che tardive Nello studio non differenziano tra latte e uovo Roehr 2001 98 2 mesi .11 anni (mediana 13 mesi) Latte fresco Uovo fresco 95 94 Perackis 2003 205 3-148 mesi (mediana 12 mesi) 88 85 Breuer 2004 41 Mediana 2 anni Uovo liofil 32 30 Giusti 2005 6 mesi-14 anni (media 6,3 anni) Aperto Uovo fresco + petrolato (2:1) circa 20 mg su finn chamber - 64,5 Mehl 2006 437 3 mesi-14 aa DA 90% DBPCFC nel 77% 86 Devillers 2009 135 0-3 aa aperto Latte fresco e uovo bollito NON UTILE Chung 2010 101 < 6 anni Uovo bollito 50 57 Yang 2014 150 < 2 anni Latte polvere 77 89 PPV > 70%

Solo sintomi gastrointestinali 20/09/2018 Autore Casi (n) Età Sintomi OFC APT Latte PPV Uovo De Boissieu 2003 35 Sensibilità 79% e specificità 91% Fogg 2006 19 5-30 mesi (media 15,6) PFIES Aperto Finn chamber 12mm alimento? APT + in 27/32 dei TPO positivi per alimenti vari Canani 2007 60 3-48 mesi GI aperto Latte e uovo fresco/estratto 95/66 100/100 Dupont 2010 14 1-2 mesi NON ESEGUITO DIALLERTEST PATCH POSITIVO IN 7/10 DI QUELLI CHE HANNO RISPOSTO ALLA DIETA Cudowska 2010 28 6-144 mesi Aperto < 1 anno e cieco > 1 anno 93 (tutte) 71 (reazioni tardive) Ekaterini 2011 54 6 mesi-14 anni (media 42 mesi) (stipsi cronica) Alimento fresco su finn chamber 12 mm 28/32 di quelli con APT + sono allwrgici a grano o uovo o latte Canani 2011 119 DBPCFC Latte fresco 78 Jarvinen 2012 25 1,5-16,8 anni (media 3) Pasta di latte o altro in finn chamber 40 Nocerino 2013 172 2-12 mesi 82 Mowszet et 2014 61 3-6 mesi 80 Boonwivat 2015 39 media 2,4 aa Liofili vs fresco vs estratto 85.7 PPV > 70%

Il dosaggio delle IgG specifiche I test intradermici I Patch test Il Test di attivazione dei basofili Gli SPT e la ricerca delle IgE specifiche

Basophil activation test: food challenge in a test tube or specialist research tool? The BAT is a flow cytometry-based assay where the expression of activation markers is measured on the surface of basophils following stimulation with allergen. In simple terms, the BAT can be seen as an OFC in a test tube, where instead of giving the food to a child by mouth, basophils involved in acute allergic reactions are exposed to a food extract in a test tube Santos AF et al, Clin Trasl Allergy 2016; 6: 10

Basophil activation tests (BATs) have been applied in the EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy Basophil activation tests (BATs) have been applied in the diagnosis of cow’s milk, egg, and peanut allergy, as well as in the diagnosis of pollen food syndromes in small clinical studies. Basophil activation test has shown higher specificity and negative predictive value than SPT and sIgE, without losing sensitivity or positive predictive value. However, BAT requires a specialized laboratory setting and large clinical studies on its diagnostic performance are lacking. Thus, the use of this promising test is still limited to research purposes on food allergy. Muraro A, et al, Allergy 2014; 69: 1008-25

Food allergy: A practice parameter update—2014 The role of cellular in vitro correlates as diagnostic or prognostic indicators of food allergy is currently under investigation. Basophil and eosinophilic reactivity tests have been shown to be associated with food-induced allergic responses and have been shown in current research to be modified over time during immunotherapy. Indexes of cell-mediated immunity, such as lymphocyte proliferation, have been implicated as possible correlates of food hypersensitivity, with relatively greater proliferation seen in patients with food allergy, but these assays are not specific. Sampson HA et al, J Allergy Clin Immunol 2014; 134: 1016.25

The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease Food allergy The performance of BAT in the diagnosis of different food allergies including pollen-food syndromes has been assessed in various studies. The reported sensitivity of BAT in diagnosis of food allergy ranges from 77% to 98%, and the specificity 75–100%. Basophil activation test in these studies was more accurate than sSPT and sIgE. Hoffman HJ et al Allergy 2015; 70: 1393-415

The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease Hoffman HJ et al Allergy 2015; 70: 1393-415

Basophil activation test: food challenge in a test tube or specialist research tool? Santos AF et al, Clin Trasl Allergy 2016; 6: 10

Basophil activation test: food challenge in a test tube or specialist research tool? Santos AF et al, Clin Trasl Allergy 2016; 6: 10

Basophil activation test: food challenge in a test tube or specialist research tool? Conclusions BAT is a valuable research tool and has shown promise as a clinically useful test. Recent studies have shown that BAT diagnoses food allergy with high accuracy and can be particularly useful in cases with unclear clinical history or equivocal results of other diagnostic tests, before deciding on whether oral food challenges are required. Santos AF et al, Clin Trasl Allergy 2016; 6: 10

Il dosaggio delle IgG specifiche I test intradermici I Patch test Il Test di attivazione dei basofili Gli SPT e la ricerca delle IgE specifiche

Food allergy: immune mechanisms, diagnosis and immunotherapy Yu W, et al, Nat Rev Immunol 2016; 16: 751-65

Quando si può evitare un TPO? PRO Certezza della diagnosi CONTRO Complessità del TPO Pericolosità del TPO

Food allergy: When and how to perform oral food challenges When it is decided that an oral food challenge is needed, the first step is to discuss, in detail, the procedure and its risks and benefits with the family/patient. Sicherer SH, Pediatr Allergy Immunol 1999; 10: 226-34

Food allergy: A practice parameter update—2014 Summary Statement 26: If clinical history is not consistent with anaphylaxis, perform a graded OFC to rule out food allergy. Open food challenge is both cost- and time-efficient. [Strength of recommendation: Moderate; C Evidence] Sampson HA et al, J Allergy Clin Immunol 2014, 134: 1016-25

Food allergy: A practice parameter update—2014 In many cases OFC is not prudent or necessary to make the diagnosis of IgE- mediated food allergy if the patient has an unequivocal and convincing history of clinical reactivity to a known food allergen and positive sIgE test results (SPTor sIgE measurement) Sampson HA et al, J Allergy Clin Immunol 2014, 134: 1016-25

Oral food challenge in children: an expert review Position paper of the Section of Pediatrics of the French Society of Allergology and Clinical Immunology (SFIAIC) and of the Pediatric Society of Pulmunology and Allergology (SP2A) OFC is not indicated in children with a clinical history suggestive of allergy and positive results in skin tests or specific IgE (5) (grade 1A). The clinical history is considered suggestive of allergy if associated with an IgE-dependent mechanism - if cutaneous signs (eczema, rash, urticaria, angioedema), gastrointestinal signs (nausea, vomiting, diarrhoea, abdominal pain), respiratory signs (rhinoconjunctivitis, cough, respiratory distress, bronchospasm) and/or arterial hypotension occur shortly after ingesting the food. Rancè F et al, Eur Ann Allergy Clin Immunol 2009; 41: 35-49

TABLE I-B: Key observations EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy TABLE I-B: Key observations IgE-mediated allergic reactions usually occur within 20 minutes of the ingestion and mostly within 2 hours. Non-IgE mediated immune reactions are typically more delayed in onset. Non-immune mediated reactions can be of both immediate and delayed onset. Symptoms indicate possible underlying immunological mechanisms, namely IgE or non-IgE-mediated. If the symptoms are not typical of an immune-mediated reaction then a differential diagnosis must be considered. Confusing diagnostic scenarios in immediate-type reactions include: perioral erythema and irritation provoked by contact with skin irritants (e.g. raw tomato, citrus and berries), scromboid fish reactions, chronic urticaria (for which food allergy is a rare cause).

EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy TABLE I-A: Questions Description of food-induced allergic symptoms Che sintomi ha presentato e in che tempi? Come sono stati trattati i sintomi? In quanto tempo sono regrediti? Eliciting food allergen Quale alimento avrebbe causato la reazione? E’ un allergene tipico per l’età e per le nostre abitudini alimentari? Timing of the reaction post exposure Quanto tempo dopo averlo ingerito si è verificata la reazione? Reproducibility La reazione si è ripetuta altre volte? Food Processing La reazione si è verificata con alimenti crudi o cotti e come cotti? Route of allergen exposure Attraverso quale via è stato esposto all’allergene alimentare? (ingestione? Inalazione? Contatto?) Amount of allergen Che quantità ne ha assunto prima di avere la reazione?

EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy TABLE I-A: Questions Concomitant diseases Di quali altri problemi soffre o soffriva il bambino? (Inclusi quelli allergici) Co-factors Aveva assunto alcool o fatto esercizio prima di aver assunto l’alimento sospetto? Co and Cross reactivity Assume altri alimenti simili all’alimnto sospetto e sono tollerati? C’è cross reattività tra l’alimento sospettato e eventuali inalanti? E’ allergico al Latex? Other foods E’ in grado di mangiare (altri alimenti)? Dietary intake La allergia alimentare compromette la sua dieta? History of previous elimination diets Ha mai tolto l’alimento dalla dieta e se si con quale risultato?

Di allergia IgE mediata Storia Convincente Di allergia IgE mediata Quadro clinico compatibile (orticaria angioedema, etc) Tempo: entro 2 ore Alimento probabile allergene: latte, uovo, grano, etc Ingestione dell’alimento isolato Età: compatibile con l’allergia alimentare sospetta Episodi analoghi in precedenza Resto della dieta congrua con il sospetto diagnostico

POSITION PAPER EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy Diagnostic tests for food allergy In vivo SPT and sIgE for food allergens are the first-line tests to assess IgE sensitization. However, like the patient history, these tests cannot always accurately diagnose food allergy. Muraro A et al, Allergy 2014; 69: 1008-25

Quadro clinico sospetta allergia IgE mediata Reazione immediata importante (orticaria, vomito, etc) Storia clinica Convincente IgE specifiche Positive Negative SPT Parere dei genitori/bambino? TPO Dieta

Quadro clinico sospetta PFIES 1 criterio maggiore e 3 criteri minori e episodi ripetuti Storia clinica Convincente Nowak Wegrzyn A, et al J Allergy Clin Immunol 2017, in press

A practice parameter update—2014 Food allergy: A practice parameter update—2014 Summary Statement 36: The physician should use the patient’s medical history, response to a trial of elimination of the suspected food, and OFC to establish a diagnosis of FPIES. However, when the history indicates that infants or children have experienced hypotensive episodes or multiple reactions to the same food, a diagnosis can be based on a convincing history and absence of symptoms when the causative food is eliminated from the diet. [Strength of recommendation: Strong; B Evidence] Sampson HA et al, J Allergy Clin Immunol 2014, 134: 1016-25

Reazione immediata (orticaria, vomito, etc) Reintroduzione a domicilio Quadro clinico Reazione immediata (orticaria, vomito, etc) Storia clinica Suggestiva IgE specifiche Positive Negative SPT Cut-off? Reintroduzione a domicilio Tipo di alimento? Parere dei genitori/bambino? TPO Dieta

I cut-off

Work Group report: Oral food challenge testing These guidelines for deciding when to perform an OFC on the basis of the results of serum food-specific IgE and SPT are constantly evolving and need to be frequently updated according to new evidence Nowak-Wegrzyn A et al, J Allergy Clin Immunol 2009; 124: s 365-83

The predictive value of skin prick testing for challenge-proven food allergy: A systematic review Although data for these studies are almost always gathered from highrisk populations, the 95% positive predictive values (PPVs) vary substantially between studies. SPT thresholds with a high probability of food allergy generated from these studies may not be generalizable to other populations, because of highly selective samples and variability in participant’s age, test allergens, and food challenge protocol. Peters RL et al, Pediatr Allergy Immunol 2011;

The predictive value of skin prick testing for challenge-proven food allergy: A systematic review < 2 anni > 2 anni PbP Peters RL et al, Pediatr Allergy Immunol 2011;

Alimenti contenenti UOVO Allergia Ben Cotto (Baked egg) Torte Biscotti Pasta all’uovo Barrette al cioccolato Hamburger Cottura intermedia (Regular egg) 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

Diagnostic oral food challenges: Procedures and biomarkers Jarvinen Km et al, J Immunol Methods 2012; 383: 30-38

Is it possible to make a diagnosis of raw, heated and baked egg allergy in children using cut-offs? A systematic review Calvani M et al, Pediatr Allergy Immunol 2015; 26: 509-21

Is it possible to make a diagnosis of raw, heated and baked egg allergy in children using cut-offs? A systematic review Calvani M et al, Pediatr Allergy Immunol 2015; 26: 509-21

Is it possible to make a diagnosis of raw, heated and baked egg allergy in children using cut-offs? A systematic review On the contrary, a cut-off value for sIgE for heated egg allergy seems hard to suggest. In fact, the only two prospective studies for heated egg allergy in children older than 2 years suggested very different cut-offs. Finally, no cut-off seems advisable for SPT and for sIgEs for baked egg allergy. In fact, the included studies proposed rather different cut-offs. However, it seems likely that children with baked egg allergy have higher SPT wheal sizes and sIgEs than children suffering from raw or heated egg allergy. Calvani M et al, Pediatr Allergy Immunol 2015; 26: 509-21

Diagnosi di allergia alle proteine del latte vaccino: le IgE specifiche e i cut-off diagnostici Indicazioni cliniche pratiche Nei bambini di eta inferiore a 2 anni e per quanto riguarda le sIgE per il latte, 2 studi entrambi prospettici, con un discreto risultato alla valutazione QUADAS 2 e con discreta numerosita, hanno indicato un cut-off, con il 95% di VPP, abbastanza simile (Garcia-Ara 2001 = ≥ 5 KUA/L e Saarinen 2001 = ≥ 3,5 KUA/L .. Un altro studio, e cioe quello di Keskin del 2005 14 .. ha ottenuto un cut-off vicino ai 2 precedenti, con specificita e VPP pari al 100% (4,18 KUA/L). Indirli GC et al, RIAP 2016; 4: 15-23

Revisione sistematica sul valore predittivo degli SPT nella diagnosi di allergia alle proteine del latte vaccino Bianchi A. et al, RIAP 2016; 2: 27-41

Making the Most of In Vitro Tests to Diagnose Food Allergy Interpretation of allergy test results The ultimate goal of the allergy test result is to determine the probability of clinical allergy; this is then used to decide whether an OFC is warranted… …The clinical history provides information that enable the clinician to establish a pretest probability of FA that will be taken into account to determine the probability of clinical allergy for a given allergy test result, that is, the post-test probability. Santos A et al, JACI in practice 2017; 5: 237-48

Miceli Sopo S, et al, Pediatr Allergy Immunol 2007; 18: 575-82 The predictive value of specific IgE levels for the first diagnosis of cow’s milk allergy. A critical analysis of pediatric literature Il VPP del 100% riscontrato da Sampson nella sua popolazione, dove la prevalenza di AA è del 60% diventerebbe di poco più del 50% in una popolazione meno selezionata, dove la prevalenza di AA fosse di circa il 10% Miceli Sopo S, et al, Pediatr Allergy Immunol 2007; 18: 575-82

EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy The pre-test probability is determined through combining the likely risk determined through clinical history, data on the local prevalence of the disease, personal clinical experience and published reports. The use of the LR places an emphasis on obtaining a robust clinical history as well as an understanding of the disease in a local setting. Muraro A et al, Allergy 2014; 69: 1008-25

la storia clinica + i cut-off

Likelihood of clinical allergy from history EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy Figure I-C 2. An approach to diagnosing food allergy Likelihood of clinical allergy from specific IgE (kU/L) or SPT (mm) results Low (<0.35 or <3) Intermediate (0.35 to <15 or 3 to < 8) High (</= 15 or > /= 8) Likelihood of clinical allergy from history eg. Urticaria and wheeze on 2 exposures Possible allergy Probable allergy Allergy eg. Urticaria on a single exposure eg. Non-IgE mediated symptoms No allergy Children and adolescents in the possible allergy box require an OFC for a definitive diagnosis. Specific IgE and SPT values are specific for peanuts. Muraro A et al, Allergy 2014; 69: 1008-25

PROBABILITA’ DI ALLERGIA Valori di SPT o IgE specifiche (diagnosi iniziale) Valori di SPT o IgE specifiche BASSI MEDI ALTI ALTA Ad es. storia suggestiva e ripetuta PROBABILE MOLTO PROBABILE POSSIBILE Storia clinica MEDIA POSSIBILE POSSIBILE PROBABILE Ad es. Orticaria in una sola occasione BASSA MOLTO IMPROBABILE POSSIBILE POSSIBILE Ad es. Non sintomi immediati

PROBABILITA’ DI ALLERGIA UOVO (frittata) (< 2 anni) Uovo estratto > 5 mm Uovo CAP > 1.7 KU/l BASSI MEDI ALTI ALTA Ad es. storia suggestiva e ripetuta ABBASTANZA PROBABILE MOLTO PROBABILE PROBABILE Storia clinica MEDIA POSSIBILE POSSIBILE PROBABILE Ad es. Orticaria in una sola occasione BASSA MOLTO IMPROBABILE POSSIBILE POSSIBILE Ad es. Non sintomi immediati

PROBABILITA’ DI ALLERGIA al LATTE < 2 anni Latte (estratto) > 6 mm Latte PbP > 8 mm Latte CAP > 5 KU/l BASSI MEDI ALTI ALTA Ad es. storia suggestiva e ripetuta ABBASTANZA PROBABILE MOLTO PROBABILE PROBABILE Storia clinica MEDIA POSSIBILE POSSIBILE PROBABILE Ad es. Orticaria in una sola occasione BASSA MOLTO IMPROBABILE POSSIBILE POSSIBILE Ad es. Non sintomi immediati

DunnGalvin A et al, JACI 2011; 127: 633-39 Highly accurate prediction of food challenge outcome using routinely available clinical data Studio effettuato in 3 fasi: Sviluppo di un modello diagnostico Valutazione retrospettiva del modello Valutazione prospettica del modello Le variabili di rischio per reazione al TPO sono SPT oltre i decision point (8 mm per arachidi e latte e 7 mm per uovo) IgE specifiche (15 Ku/l per latte e arachidi e 7 Ku/l per uovo) Età (più è grande peggio è) Sesso (Maschi>Femmine) Sintomi precedenti (multiorgano) DunnGalvin A et al, JACI 2011; 127: 633-39

Highly accurate prediction of food challenge outcome using routinely available clinical data 20/09/2018 Il modello, che prende in considerazione non solo il valore degli SPT e delle IgE specifiche ma anche e soprattutto la storia clinica ottiene un ottimo valore predittivo, individuando 37/38 TPO positivi e 30/32 dei negativi DunnGalvin A et al, JACI 2011; 127: 633-39

The Likelihood of Remission of Food Allergy in Children: When Is the Optimal Time for Challenge? Given these key considerations, I believe that my key role as the food allergy specialist is to provide my best estimate for the chance of a successful challenge and the potential for risk and then let the family decide whether a challenge to that particular food makes sense to them. We rarely pressure a child or family to do a challenge unless we believe that the child’s quality of life or nutritional status is being adversely affected by unnecessary food avoidance. Wood RA, Curr Allergy Asthma rep 2011; DOI 10.1007/s11882-011-0237-0

Grazie per l’attenzione!