Milchunverträglichkeiten welche Milchalternativen für wen? Prof. Dr. Rudolf Valenta 1

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1 Milchunverträglichkeiten welche Milchalternativen für wen? 1

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3 Classification of food intolerance 3

4 Non-immune mediated adverse reactions to milk are much more frequent than milk allergy: Lactose intolerance

5 Lactase Genetics 5

6 Prevalence of lactose maladsorption or lactase nonpersistence in different populations Bayless M. et al; Curr Gastroenterol Rep,

7 Diagnosis of lactose intolerance Lactose tolerance test: Reduced increase of blood glucose following lactose-containing ingested sample Hydrogen breath test: Increased hydrogen in exhaled air after intake of lactose-containing substances Stool acidity test: Measurement of lactic acid in stool samples after ingestion of lactosecontaining substances Genetic testing 7

8 Time course, pathogenesis and manifestations of food allergy 8

9 Time course, pathogenesis and manifestations of food allergy 9

10 Clinical manifestations of food allergy 1. Skin reactions Contact urticaria Urticaria/ angioedema Flush, pruritus Oral allergy syndrome(local itching and tingling and/or edema of lips, tongue, palate and pharynx) Protein contact dermatitis Atopic eczema 2. Reactions of respiratory system Rhinoconjunctivitis Asthma bronchiale Laryngeal and/or pharyngeal edema Hoarseness 3. Reactions of the gastrointestinal tract Abdominal pain Abdominal distension Nausea, vomiting Gastritis Gastroenteritis with diarrhea Anorexia Flatulence Colitis 4. Reactions of the cardiovasular system Cardiac dysarhythmia Hypotension Vascular collaps Anaphylactic shock 10

11 IgE-associated milk allergy starts early in life but is not highly prevalent 11

12 IgE-associated milk allergy starts early in life but is not highly prevalent Östblom E. et al, Clin& ExpAllergy,

13 Milk allergic patients can experience lifethreatening anaphylactic reactions but they are rare 13

14 Milk allergic patients can experience life-threatening anaphylactic reactions but they are rare Vetander M., et al, Clin& ExpAllergy,

15 Milk can causes anaphylactic reactions mainly in children but this is rare 15

16 Milk can causes anaphylactic reactions mainly in children but this is rare Grabenheinrich L et al, J Allergy Clin Immunol,

17 Cow s milk allergy is rare 17

18 Cow s milk allergy is rare SchoenmakerA. et al, Allergy,

19 Aspects of allergy diagnosis 19

20 Allergy diagnosis will fundamentally change From established procedures: Medical history skin and provocation testing blood testing partial result - Medical history skin and provocation testing blood testing partial result - Medical history skin and provocation testing blood testing partial result - Medical history skin and provocation testing blood testing partial result - Medical history skin and provocation testing blood testing partial result - etc. etc. etc. etc. etc for often several years (requiring multiple visits, including failed treatment attempts, requiring high health care costs, generating frustrated patients looking for alternative treatment) until correct diagnosis is achieved and best possible treatment is performed. 20

21 From allergen sources to allergen extracts and allergen molecules

22 Marker allergens Speciesspecific marker allergens Prediction of symptoms Cross-reactive marker allergens Genuine sensitization against a certain allergen source Crosssensitization 22

23 Component-resolved diagnosis of food allergy 23

24 2002: The birth of multiallergen tests 24

25 2016: Allergy diagnosis will fundamentally change To a rational approach based on: Establishment of complete molecular allergy diagnosis by chip testing medical history eventually confirmatory provocation testing correct diagnosis and initiation of appropriate treatment 25

26 2018: Allergy diagnosis will continue to change fundamentally The allergy march in childhood: sensitization disease severe disease Food allergies Genetic, environmenta l, host factors Atopic dermatitis Bronchial asthma Statement: We will start to diagnose and treat allergic sensitization before symptoms and severe disease occurs 26

27 European-wide assessment of the molecular evolution of allergic sensitization in birth cohorts: MeDALL

28 Cow s milk contains several molecules with different allergenic activity Hochwallner H., et al, Methods,

29 Information gained by molecular testing Hochwallner H., et al, Methods,

30 Allergen molecules in cow s milk show different allergenic activity 30

31 Allergen molecules in cow s milk show different allergenic activity Hochwallner H. et al, Clin. & Exp. Allergy,

32 IgE testing with micro-arrayed milk allergens identifies children who outgrow allergy Hochwallner H. et al, Clin& ExpAllergy,

33 Cow milk allergy cannot be diagnosed by IgG antibody testing!!!!! 33

34 International allergy societies warn about inappropriate measurement of food-specific IgG

35 International allergy societies warn about inappropriate measurement of food-specific IgG 35

36 Prevention and therapy of food allergy Prevention Avoiding sensitization Tolerance induction Prophylactic vaccination Passive immunization Therapy Avoidance, diet Symptomatic medication Anti-IgE treatment Allergen-specific immunotherapy (SIT) 36

37 From avoiding sensitization to tolerance induction: Hypoallergenic milk formulas for the prevention of milk allergy 37

38 Allergy 2016; DOI: /all

39 Identification of milk formulas without proinflammatory properties Milk samples Product Manufacturer Source Condition Protein content Endotoxin content (casein or whey) (g/ 100g) (EU in 100 µg protein) M1 Enfamil premium MJN C+W non-hydrolyzed (NH) M2 Enfamil HA-Gentlease MJN C+W partially (PH) M3 Nutramigen MJN C extensively (EH) M4 Nutramigen AA MJN AA amino acids (AA) M5 Nan HA Nestle W partially (PH) M6 Friso Allergycare R.Friesland F. C extensively (EH) M7 Alimentum Advance Ross C extensively (EH) M8 Alfare Nestle W extensively (EH) M9 MJN whole milk protein control M10 MJN whey protein concentrate 35% HA, hypoallergenic; MJN, Mead Johnson Nutrition; C, casein; W, whey; AA, amino acids 1,3-22: CM allergic patients 23,24: subjects with problems after milk consumption but without without CM-specific IgE 25: non-allergic control 2, 26-28: patients with CM-specific IgE, but without symptoms 1, 3-22: CM allergic patients 23,24: subjects with problems after milk consumption but without without CMspecific IgE 25: non-allergic control 2, 26-28: patients with CMspecific IgE, but without symptoms 39

40 Identification of milk formulas without proinflammatory properties 40

41 Modern forms of allergen-specific immunotherapy and allergen-specific prophylaxis under development Hochwallner H., et al, Methods,

42 Mothers can transfer protective antibodies to children via breast milk Mother to child transition and early development of allergen-specific IgG in infancy analyzed by allergen-microarray: Protective effect of maternal IgG? Heidrun Hochwallner 1, PhD; Christian Lupinek 1, MD; Catharina Johansson 2, PhD; Axel Mie 3, PhD; Eva Wollmann 1, MD, PhD; Helena Marell Hesla 3, MD, PhD; Sara Fagerstedt 2, PhD; Georg Heinze 4, PhD; Annika Scheynius 2, MD, PhD; Johan Alm 3, MD, PhD; Rudolf Valenta 1, MD*.

43 Towards prevention of allergy by vaccination and tolerance induction 43

44 Towards prevention of allergy by vaccination and tolerance induction 44

45 Early feeding with non-allergenic T cell epitopecontaining allergen peptides prevents allergic sensitization 45

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