Le allergie alimentari.

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1 Miti e realtà: Le allergie alimentari. Alessandro Fiocchi UOC Allergologia OPBG Roma, 28 ottobre 2014

2 Miti e realtà: Le allergie alimentari. Alessandro Fiocchi UOC Allergologia OPBG Roma, 28 ottobre 2014

3 Miti & realtà in allergologia pediatrica 1. L intolleranza alimentare 2. Il prick al bambino piccolo non si può fare 3. Le diete inutili e quelle pericolose 4. La OIT modifica la storia naturale dell'aa? 5. Conclusioni

4 The second wave Respiratory allergy in westernized countries plateaued at the beginning of this century Warner JO. Anaphylaxis: the latest allergy epidemic. Pediatr Allergy Immunol 2007;18: nd wave emerged in the last years Particularly in preschool children. Prescott SL. Food Allergy: riding the second wave of the allergy epidemic. PediatrAllergy Immunol 2011;22: Sicherer SH. Epidemiology of food allergy. J Allergy Clin Immunol 2011;127: and in countries where respiratory allergy had increased, e.g. UK, Australia and U.S. [

5 Food hypersensitivity Food allergy Nonallergic food hypersensitivity IgE-mediated food allergy Non-IgE-mediated food allergy Johansson SGO. Revised nomenclature for allergy for global use: Report of the Nomenclature of WAO J Allergy Clin Immunol 2004; 113; 832-6

6 Symptom-based Clinical Score (Cow's Milk Protein Intolerance Score) Vandenplas Y. Treatment of Cow's Milk Protein Allergy. Pediatr Gastroenterol Hepatol Nutr. 2014;17:1-5

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8 Symptoms Linked to food Allergies Psoriasis Haemorroids SKIN: Acne, dermatitis, eczema, itching, psoriasis. HEADACHES: various kinds including migraine. Refractive EYE CONDITIONS: conjunctivitis, eye pain, periods of blurred vision, sensitivity changes to light, tearing, temporary refractive changes. EAR CONDITIONS: hearing loss, infections, inflammations, Meniere s syndrome, tinnitus, repeated ear trouble. CARDIOVASCULAR: Bedwetting angina, high blood pressure, irregular heartbeat, low blood pressure, rapid pulse. GASTROINTESTINAL: constipation, diarrhoea, gall bladder pains, wind, gastric ulcer, gastro-intestinal bleeding, heartburn, haemorrhoids, indigestion, mucous colitis, nausea, pains or cramps, spastic colon, vomiting. RESPIRATORY: asthma, chronic rhinitis, coughing, frequent "colds", hay fever, mouth breathing, nosebleeds, postnasal discharge, sinusitis, stuffy nose, wheezing. UROLOGICAL: bedwetting, frequent Body odour night urination, frequent urination, painful or difficult urination. MUSCULO-SKELETAL: arthritis, joint pains, muscle cramps, muscle aches and pains, muscle spasms, muscle weakness. MENTAL-BEHAVIOURAL: anxiety, delusions, depression (including psychotic), Overweight dizzy spells, drowsiness, epilepsy, floating sensations, general fatigue, hallucinations, hyperactivity, insomnia, irritability, learning disorders, minimal brain dysfunction, nervousness, periods of confusion, phobias, poor concentration, poor memory, poor muscle coordination, restlessness, schizophrenia, sleeps at inappropriate times, sleeps too little, sleeps too much, tension-fatigue syndrome, unsteadiness. OTHER: Abnormal body odour, excessive sweating, general weakness, hypoglycaemia, nightsweating, overweight, underweight, virus infections

9 Unnecessary milk elimination diets in children with uncorrected diagnosis of CMA. 7% van den Hoogen S.: Suspected cow s milk allergy in everyday general practice: a retrospective cohort study on health care burden and guideline adherence. BMC Research Notes :507.

10 Unnecessary milk elimination diets in children with atopic dermatitis. 0.8% A positive CMA diagnosis was rarely established after adequate implementation and reporting of diagnostics, yet long term dietary measures were prescribed in >7% of patients. van den Hoogen S Suspected cow s milk allergy in everyday general practice: a retrospective cohort study APLVon health care burden and guideline adherence. BMC Research Notes 2014

11 Miti & realtà in allergologia pediatrica 1. L intolleranza alimentare 2. Il prick al bambino piccolo non si può fare 3. Le diete inutili e quelle pericolose 4. La OIT modifica la storia naturale dell'aa? 5. Conclusioni

12 Allen KJ. Food allergy in childhood. Med J Aust. 2006; 185:

13 Can PST be performed in infancy? Ø SPT with histamine phosphate in 50% glycosaline (10 mg/dl) Ø 297 histamine pricks in 210 patients Whole caseload 0-3 months 3-6 months 6-9 months 9-12 months >12 months n. Patients Age (months) Age SD (months) histamine wheal Ø mean (mm) Histamine wheal SD Histamine wheal Ø range (mm) Fiocchi A. Histamine reactivity dispels doubts about skin prick tests in infants. Ann Allergy Asthma Immunol 2006; 97:46

14 Miti & realtà in allergologia pediatrica 1. L intolleranza alimentare 2. Il prick al bambino piccolo non si può fare 3. Le diete inutili e quelle pericolose 4. La OIT modifica la storia naturale dell'aa? 5. Conclusioni

15 Nickel allergy. a diet regimen for diagnosis Chocolate Potatoes Salmon Nuts and Legumes (beans, lentils) Any canned food or canned fruit Hot water from the tap Anything acidic (like tomatoes) cooked in a stainless steel pan Leafy green vegetables Braga M. Systemic nickel allergy syndrome: nosologic framework and usefulness of diet regimen for diagnosis. Int J Immunopathol Pharmacol. 2013; 26:707-16

16 Nickel allergy. Myth or reality? a narrative overview Nickel is the leading cause of ACD (Allergic Contact Dermatitis). Systemic nickel allergy syndrome (SNAS) is very controversial. No challenge studies Nickel-related gastrointestinal symptoms Nickel-related chronic fatigue syndrome Nickel-related fibromyalgia Nickel-related headache Nickel-related recurring cold Nickel-related recurrent infections Nickel-related eczema In the absence of genuine certainty, we can only conclude that further and broader studies, more rigorously conducted, are needed. Pizzutelli S. Systemic nickel hypersensitivity and diet: myth or reality? Eur Ann Allergy Clin Immunol. 2011;43:5-18

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18 Avoiding milk, dairy products, and egg

19 Alessandri C. Tolerability of a fully maturated cheese in cow's milk allergic children: biochemical, immunochemical, and clinical aspects. PLoS One. 2012;7(7):e40945 CMA in toddlers

20 Jirillo F, Magrone T. Anti-inflammatory and anti-allergic properties of donkey's and goat's milk. Endocr Metab Immune Disord Drug Targets Mar;14(1):27-37 CMA in infants

21 Donkey s milk 46 children with CMA Median age: 24 mo. (mean: 36 mo.); range: mo. SPT with cow s milk: positive 29/46 Soy allergy: 35/46 Challenge with cow s milk : positive 41/46 (pear juice) - anaphylaxis: 5 - within 1 h 16/41 - between 1 and 6 h 15/41 - after 6 h 18/41 Donkey s milk tolerated in 82.6% of children Reactions in immediate CMA: 7/33 (21.2%) Monti G. Efficacy of donkey s milk in treating highly problematic cow s milk allergic children: An in vivo and in vitro study. Pediatr Allergy Immunol 2007; 18:258-64

22 Extensively Hydrolysed Rice formulae Risolac Blemil Riso

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24 Generalized edema more evident (A) in the face and (B) in the legs (fovea sign) opbg.net Novembre E. Severe hypoproteinemia in infant with AD. Allergy. 2003;58:88-9

25

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27 CMA in children with beef allergy, BA in children with CMA Beef/milk Milk/beef DBPCFC 100% 12 20% Werfel SJ. Clinical reactivity to beef in children allergic to cow s milk. J Allergy Clin Immunol 1997;99: Martelli A. Allergy to cow s milk in beef-allergic children. Ann Allergy Asthma Immunol. 2002; 89S, 25-33

28 SDS-PAGE of commercially available lactose and cow s milk proteins L Lppt BSA -La -Lg -cas -cas k-cas CM Fiocchi A. Clinical tolerance to lactose in children with cow's milk allergy. Pediatrics. 2003; 112:359-6

29 CMA in newborns

30 Miti & realtà in allergologia pediatrica 1. L intolleranza alimentare 2. Il prick al bambino piccolo non si può fare 3. Le diete inutili e quelle pericolose 4. La OIT modifica la storia naturale dell'aa? 5. Conclusioni

31 Food allergy immunotherapy goals Goals of treatment are two-fold: 1. Clinical desensitization - tolerate more food on treatment than before starting 2. Eventual clinical tolerance - off treatment can tolerate food how long off treatment? no good definition of tolerance issue in all of allergic diseases sustained unresponsiveness Burks AW, CoFAR. Oral immunotherapy for treatment of egg allergy in children. N Engl J Med Jul 19;367:233-43

32 Effector Cells SPT mean wheal size decrease by 6 mo Further decrease to 24 mo Specific-IgG4 increase by 2-3 mo Continue to increase to 24 mo, then Basophil activation decreased by 4 mo Further Specific-IgE begin decreased increase to decline to 24 mo by 2-3 mo. Decrease by 24 mo Specific-IgE Specific-IgG Time on OIT (months) Courtesy of Wesley Burks

33 Probability of persistent peanut allergy Peanut Allergy Natural history Kaplan-Meier analysis N= Age in years Courtesy of David Hill Ho M,Wong W, Allen K JACI 2014

34 Persistent CMA% Fiocchi A. Factors associated with cow's milk allergy outcomes in infant referrals: the Milan Cow's Milk Allergy Cohort study. Ann Allergy Asthma Immunol 2008;101: MiCMAC cohort: survival curve Months from diagnostic DBPCFC

35 Tolerance vs. desensitization Large number of studies evaluated the ability for OIT to induce desensitization Few OIT studies have assessed for tolerance as a study outcome: - 3 uncontrolled open studies - three RCTs

36 Tolerance vs. desensitization Open study 23 children with peanut allergy For 22 to 26 months Tolerance 4/23 (17%) Blumchen K, Ulbricht H, Staden U. Oral peanut immunotherapy in children with peanut anaphylaxis. J Allergy Clin Immunol 2011: 126:

37 Probability of persistent peanut allergy Peanut allergy natural history Kaplan-Meier analysis N= Blumchen K, Ulbricht H, Staden U. Oral peanut immunotherapy in children with peanut anaphylaxis. J Allergy Clin Immunol 2011: 126:

38 Tolerance vs. desensitization Open study 25 children with milk or egg allergy For 11 to 59 months Tolerance 9/25 (36%) Control group tolerated 35% Staden U. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy. 2007;62:1261-9

39 Tolerance vs. desensitization SOTI-group (n=25) Pattern N (%) I Responder 9 (36) II Responder (with regular daily intake) 3 (12) III Partial responder 4 (16) IV Non responder 9 (36) Staden U. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy. 2007;62:1261-9

40 Tolerance vs. desensitization SOTI-group (n=25) Control-group (n=20) Pattern N (%) Result N (%) I II Responder (natural corse or SOTI?) Responder (with regular daily intake) 9 (36) Tolerant 7 (35) 3 (12) III Partial responder 4 (16) IV Non responder 9 (36) Allergic 13 (65) Staden U. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy. 2007;62:1261-9

41 Miti & realtà in allergologia pediatrica 1. L intolleranza alimentare 2. Il prick al bambino piccolo non si può fare 3. Le diete inutili e quelle pericolose 4. La OIT modifica la storia naturale dell'aa? 5. Conclusioni

42 Food allergens accused Years ago, they were found guilty. Convicted largely circumstantial evidence, and sent into exile. They were exiled from the diets of small children all around the world. Prescott S, Fiocchi A. Avoidance or exposure to foods in prevention and treatment of food allergy? Curr Opin Allergy Clin Immunol 2010,10:258 66

43 Allergia alla fragola Act II, Scene IV The London Tower Gloucester: My Lord of Ely, when I was last in Holborn I saw good strawberries in your garden there. I do beseech you send for more of them. Ely: Where is my Lord, the Duke of Gloucester? I have sent for these strawberries.. Gloucester: thou conspired my death with devilish plots! Then be your eyes the witness of their evil Look how I am bewitch d; behold, mine arm Is llike a blasted sapling wither d up William Shakespeare, King Richard the Third, 1592

44 Allergie frequenti? lavori 2008 lavori Cortesia di Alberto Martelli

45 Allergie rare?...

46 Allergie impossibili?... Fiocchi A. Litchi chinensis allergy in a boy. Annals Allergy Asthma Immunol 2004; 92: 51-2 Astier C. First case report of anaphylaxis to quinoa, a novel food in France. Allergy 2009;64:819-20

47 Allergie impossibili?... - A twelve-year boy - allergic rhinitis to grass pollen, cat, house-dust mite - OAS for apple, watermelon - sneezing after smelling and eating a small amount of risotto - SPT with rice negative - saffron powder SPT positive Total IgE 2,872; ImmunoCAP 10.1 ku/l to saffron and 2 ku/l to rice. Fiocchi A. Spice allergies can happen also in children. Annals Allergy Asthma Immunol 2014; 112: 43-4

48 DBPCFEC DBPCFC with PLC in resting conditions and the food-exercise test after the meal negative DBPCFEC was after the meal containing 1 ml of mould solution positive Fiocchi A. Exercise-induced anaphylaxis following food-contaminant ingestion at Double-Blinded, Placebo-Controlled, Food Exercise Challenge. J Allergy Clin Immunol 1997; 100:424-25

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