L’Allergia Alimentare
Elena Lionetti
Dipartimento di Scienze Mediche e Pediatriche
Università di Catania
L’allergia alimentare: Le linee guida
NIAID Guidelines, J Allergy Clin Immunol 2010
WAO Guidelines, Ped Allergy Immunol 2010
NICE guidelines, nice.org.uk.guidance 2011
ESPGHAN guidelines, JPGN 2012
L’allergia alimentare: definizione
‘‘Food allergy is an adverse health effect arising from a specific immune
response that occurs reproducibly on exposure to a given food”
NIAID Guidelines, J Allergy Clin Immunol 2010
WAO Guidelines, Ped Allergy Immunol 2010
NICE guidelines, nice.org.uk.guidance 2011
ESPGHAN guidelines, JPGN 2012
L’allergia alimentare: classificazione
NIAID Guidelines for the Diagnosis and Management of Food Allergy , J Allergy Clin Immunol 2010
L’allergia alimentare
1. Epidemiologia
Epidemiologia
3%
12%
Sacherer S et al, J Allergy Clin Immunol 2011
Eziopatogenesi
1. Clustering familiare
ambiente
2. Prevalenza in familiari >5 pop. generale
3. Concordanza in monozigoti del 65%
15m
24m
36m
Tot
geni
Sicherer S et al. JACI 2014
Tan T. et al. Clin Experimental Allergy 2012
Eziopatogenesi
15m
24m
36m
Food allergy
Tot
HLA class II
FOXP3
STAT6
TNF
SPINK5
IL13
CD14
IL10
Sicherer S et al. JACI 2014
Tan T. et al. Clin Experimental Allergy 2012
Eziopatogenesi
ambiente
Deficit vitamina D
Ridotto consumo di antiossidanti e omega 3
Esposizione al fumo
Aumentata igiene
Obesità
Utilizzo di anticidi
15m
24m
36m
Tot
Timing di introduzione dei cibi
geni
Sicherer S et al. JACI 2014
Tan T. et al. Clin Experimental Allergy 2012
Eziopatogenesi
Sicherer S et al. JACI 2014
Tan T. et al. Clin Experimental Allergy 2012
Gli allergeni alimentari
Uova, latte, arachidi, noci, soia,
grano, crostacei, pesce
Gli allergeni alimentari
Schoemaker AA, et al. Allergy 2015
Storia naturale dell’allergia alimentare
Schoemaker AA, et al. Allergy 2015
Storia naturale dell’allergia alimentare
Saarinen KM et al. JACI 2005
Fattori di rischio per allergia persistente
Meccanismo IgE-mediato
Elevata positività SPT (>6-8 mm)
IgE specifiche anti-epitopi lineari
Severa sintomatologia cutanea
Sintomatologia respiratoria (rinite/asma)
Co-sensibilizzazione ad altri aero-trofoallergeni
Fiocchi A. Ann Allergy Asthma Immunol 2008
Jarvinen KM et al. JACI 2002
L’allergia alimentare
2. Quadro clinico
Allergia alimentare: quadro clinico
Allergia alimentare: quadro clinico
Manifestazioni gastro-intestinali
Manifestazioni cutanee
Sindrome orale allergica
Eczema atopico
Reflusso gastro-esofageo
Orticaria-Angioedema
Esofagite eosinofila
Sindrome orale allergica
Enteropatia
Enterocolite
Manifestazioni respiratorie
Proctite/proctocolite
Rinite
Stipsi
Asma
Gastroenterite eosinofila
Coliche del lattante
Manifestazioni sistemiche
Anafilassi
Allergia alimentare: timing
Reazioni IgE mediate
vomito, dolore addominale spesso
crampiforme, nausea, diarrea.
Reazioni cellulo-mediate
Enteropatia
Enterocolite
Proctocolite
Proctite
Reazioni cellulo-mediate: Dietary protein proctocolitis
 In 50% of cases due to breast-feeding , but also to cow milk, soy, hydrolyzed
formula
 Start: 2-6 weeks
 Satisfactory growth
 No vomiting, no abdominal distention
 Rectal bleeding mild
 Rarely clinically important anemia
 Rectosigmoidoscopies and biopsies lead to diagnosis in cases which do not
respond to the removal of the protein. Affectation of the colon tends to be
patchy, with areas of edematous mucosa and possible superficial erosions or
ulcers.
 In rectal biopsies, there is infiltration by more than 20 eosinophils/HPF in the
thickness of the mucosa and lamina propria
Scand J Gastroent 2010
Reazioni IgE mediate e cellulo-mediate (miste)
Esofagite
Gastrite
Reazioni non-IgE mediate: FPIES
 Non-IgE-mediated gastrointestinal food hypersensitivity
 It manifests as profuse, repetitive vomiting, often with diarrhea, leading to
acute dehydration, hypotension and lethargy (or weight loss and failure to
thrive if chronic)
 Family history of atopy in 40-80%
 Oral food challenge, in doubtful cases
 Skin prick test negative and IgE negative
 Endoscopy:rectal alteration and bleeding
 Hystology: villous atrophy, tissue edema,
lymphocytes, eosinophils and mast cells
crypt
abscess
and
increased
 Exclusion of other causes ………
Fiocchi A et al. J Allergy Clin Immunol Pract. 2013
Reazioni non-IgE mediate: FPIES
Differential diagnosis of FPIES
Fiocchi A et al. J Allergy Clin Immunol Pract. 2013
L’allergia alimentare
3. Diagnosi
7 colonne per una diagnosi corretta
I.
Sintomatologia clinicca compatibile
II. Esclusione difetti anatomici, patologie metaboliche, infettive, etc
III. Chiara relazione temporale con assunzione di un particolare cibo
IV. Segni di atopia (DA, asma, IgE/SPT)
V.
Scarsa risposta clinica al trattamento convenzionale per reflusso, stipsi, etc..
VI. Chiara risposta clinica alla dieta di eliminazione
VII. Test di provocazione orale positivo
Sampson HA, JPGN 2000
Algoritmo diagnostico
ESPGHAN guidelines, JPGN 2012
APLV: diagnosi
If oral food challenge required for IgE mediated allergy – do only food challenge and
no other tests.
High pretest probability: No food challenge – use SPT with ≥ 3 mm cut-off to
diagnose FA.
Average pretest probability - do only food challenge and no other tests to diagnose or
rule out FA.
Low pretest probability: No food challenges – use SPT < 3 mm to rule out FA
I test allergologici: performance diagnostica
Sicherer S et al. Pediatrics 2012
Berni Canani R, et al. Allergy 2007
I test allergologici

“Screening panels of food allergens without previous consideration of the history is not
recommended, because sensitization without clinical allergy is common.

A negative SPT or serum sIgE test result does not entirely exclude a diagnosis of a food allergy.
Caution is needed when tests are negative when a specific food allergy history is convincing; a
medically supervised oral food challenge may be needed.

Cross-reactivity among homologous proteins of aeroallergens and food allergens may result in
positive tests to foods, often without clinical allergy (eg, birch pollen with hazelnut, peanut, soy;
grass pollen with wheat, peanut; dust mite with shrimp).

Strong positive test results correlate with increasing probability of clinical allergy, and particularly
high values may indicate a high degree (>95%) of likely allergy; however, there are few studies
correlating outcomes to test results, and results vary by age, disease, and other factors.

The routine use of measuring total serum IgE should not be used to make a diagnosis of FA.

APT should not be used in the routine evaluation of FA.

Component resolved diagnostic test are not currently reccomended for the routine diagnosis of FA.
NIAID Guidelines for the Diagnosis and Management of Food Allergy , J Allergy Clin Immunol 2010
Sicherer S et al. Pediatrics 2012
Durata della dieta di eliminazione diagnostica
 Lattanti con reazione clinica immediata (es. Orticaria acuta o
ostruzione bronchiale entro 2 ore): 3-5 giorni
 Lattanti
con
reazione
clinica
ritardata
(es.
Esacerbazione
dell’eczema nei giorni successivi): 1-2 settimane
 Lattanti con alcune reazioni gastrointestinali (es. Diarrea cronica,
ritardo di crescita): 2-4 settimane, talvolta più a lungo
Koletzko S. et al. J Pediatr Gastroenterol Nutr 2012
Test da non eseguire per la diagnosi
L’allergia alimentare
4. Terapia
Allergia alimentare: Terapia
Dieta di Eliminazione
Allergia alimentare: cross-reattività
Allergia alimentare: Terapia (APLV)
Idrolisati spinti delle proteine del latte vaccino
(caseina o sieroproteine)
Amminoacidi elementari
Soya
Idrolisati delle proteine di riso
Idrolisati parziali del latte vaccino
Latte di capra, pecora, asina, etc…
Allergia alimentare: Terapia (APLV)
Idrolisati spinti delle proteine del latte vaccino
(caseina o sieroproteine)
Amminoacidi elementari
NIAID Guidelines, J Allergy Clin Immunol 2010
WAO Guidelines, Ped Allergy Immunol 2010
NICE guidelines, nice.org.uk.guidance 2011
ESPGHAN guidelines, JPGN 2012
Allergia alimentare: terapia
In children with IgE-mediated cow’s milk allergy at high risk of anaphylactic reactions
(prior history of anaphylaxis and currently not using extensively hydrolysed milk
formula), we suggest amino acid formula rather than extensively hydrolysed milk.
In children with IgE-mediated cow’s milk allergy at low risk of anaphylactic reactions
(no prior history of anaphylaxis or currently on extensively hydrolysed milk formula),
we suggest extensively hydrolysed milk formula over amino acid formula.
In children with IgE-mediated cow’s milk allergy, we suggest extensively hydrolysed
milk formula rather than soy formula.
Dieta senza proteine del latte vaccino
Problematiche nutrizionali
(differente pattern amminoacidico, deficit ac. folico, zinco, calcio, ferro)
Costi elevati
Palatabilità
Scarsa compliance
Prospettive future
1. Immunoterapia
Oral immunotherapy (OIT)
Sublingual immunotherapy (SLIT)
Epicutaneneus immunotherapy (EIT)
2. Immunonutrizione
Trattamento termico
Probiotici
Prospettive future
Obiettivi
1. Ridurre il rischio di reazioni gravi
2. Migliorare la qualità della vita
Forme miste: Allergic esofagitis/gastritis eosinophilic
•
Caratterizzato da infiltrazione eosinofila mucosa (esofago, stomaco); eosinofilia in
circa il 50 % dei pazienti
•
Forma più comune: RGE (esofagite eosinofila)
•
Disfagia, pirosi, epigastralgia, dolori addominali, scarsa crescita
•
8 settimane per risoluzione dei sintomi e 12 settimane per la normalizzazione
istologica.
Sicherer S. Pediatrics 2007
Algoritmo diagnostico
NIAID Guidelines for the Diagnosis and Management of Food Allergy , J Allergy Clin Immunol 2010