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GIRISH VITALPUR, MD, FAAP, FAAAAI ASSISTANT PROFESSOR OF CLINICAL PEDIATRICS, RILEY CHILDREN’S HOSPITAL, INDIANA UNIVERSITY SCHOOL OF MEDICINE, INDIANAPOLIS,

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Presentation on theme: "GIRISH VITALPUR, MD, FAAP, FAAAAI ASSISTANT PROFESSOR OF CLINICAL PEDIATRICS, RILEY CHILDREN’S HOSPITAL, INDIANA UNIVERSITY SCHOOL OF MEDICINE, INDIANAPOLIS,"— Presentation transcript:

1 GIRISH VITALPUR, MD, FAAP, FAAAAI ASSISTANT PROFESSOR OF CLINICAL PEDIATRICS, RILEY CHILDREN’S HOSPITAL, INDIANA UNIVERSITY SCHOOL OF MEDICINE, INDIANAPOLIS, IN USA FOOD ALLERGIES: CLINICAL CASES AND FUTURE TRENDS. 2013

2 COMMERCIAL DISCLOSURES NONE.

3 OBJECTIVES Review 3 cases that convey different presentations of food allergies Discuss diagnosis of IgE-mediated food allergies Review the role of food allergies in atopic dermatitis Discuss management options for each case

4 CASE 1 Alex is 2, and has had mild eczema since infancy. Hives and wheezing associated with peanut butter two months ago. No other immediate food reactions. Food allergy profile test done: – Milk IgE-2.01ku/ l; – Egg IgE—0.85ku/l; – Peanut IgE—1.50ku/l – All other foods are negative.

5 CASE 1 Egg and milk now removed from Alex’s diet. – No known reactions to egg or milk ever. – Stressful for the entire family Family questions why peanut IgE is lower than milk IgE Family questions need for Epipen Jr.

6 DEFINITIONS Food allergy=“An immunologically mediated hypersensitivity reaction to any food, including IgE-mediated and/ or non-IgE-mediated reactions.” (Greer, 2008) Food allergy: An adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food. – Requires sensitization to a food AND development of specific signs and symptoms. (Boyce 2010)

7 Definitions Food intolerance: Non-immunologically mediated adverse reactions Sensitization: Allergen-specific IgE is present to an allergen, but no clinical symptoms occur on exposure to that food. Allergy: Allergen-specific IgE is present to an allergen, and clinical symptoms DO occur on exposure to that food Boyce, 2010

8 SPECTRUM OF FOOD ALLERGY IgE-mediated disorders (Nearly always occur within two hours) – Anaphylaxis – Acute urticaria and angioedema – Oral allergy syndrome/ Pollen-food allergy syndrome – Immediate-type gastrointestinal hypersensitivity – Acute bronchospasm Non IgE-mediated disorders – Dietary protein-induced enterocolitis – Celiac disease – Dermatitis herpetiformis Mixed IgE-mediated and non-IgE-mediated disorders – Eosinophilic esophagitis and gastroenteritis – Atopic dermatitis (AD) ---Food proteins may also produce delayed, non-IgE-mediated responses, in the skin and the gut. Sellge,2008.

9 IGE-MEDIATED REACTIONS Mild to moderate reactions Hives/ itching Swelling of the lips, eyes, or face Vomiting Severe reactions Shortness of breath/ wheezing Combination of vomiting, coughing, and angioedema Low blood pressure Any report of anaphylaxis Reported of children with food allergy Gupta, 2011

10 FOOD ALLERGY: EPIDEMIOLOGY & IMPACT 1 out of every 25 children in the US have a food allergy— in 13 children in the US affected by IgE-mediated food allergy—2011. million children) Overall prevalence of food allergy in the US: 2.5% Negative impact on health-related quality of life, compared with other allergic conditions Hospitalizations due to food allergies: – : year. – Most common among adolescents with asthma. – Most associated with peanut, tree nut or shellfish Branum & Lukacs, 2008; Gupta, 2011; Liu, 2010; Ostblom 2008; Branum & Lukacs, 2008; Munoz-Furlong & Weiss, 2009

11 STUDIES IN FOOD ALLERGY: METHODOLOGY ISSUES Gold standard for diagnosis of food allergy= double-blind, placebo-controlled oral food challenge (DBPCFC). Studies limited by: – Self-report data Only 40% of pts’ histories of food-induced allergic reactions can be verified through DBPCFC. – Variations in definition of food allergy – Population variations --Sicherer & Leung, 2008; Kim JS, 2008.

12 PREVALENCE OF COMMON FOOD ALLERGIES FOODCHILDRENADULTOVERALL POPULATION MILK1.8% a 0.4% a EGG1.8% a 0.2% a PEANUT % b,d % a,d TREE NUT1.1% d 0.5-1% b,c,d SOY0.4% f <1% e WHEAT0.4% f <1% e FISH0.2% b ; 0.5% f 0.5% b SHELLFISH0.5% b ; 1.4% f 2.5% b SESAME0.1% d a=Liu, 2010; b=Boyce, 2010; c=Sicherer, 2011; d=Sicherer, 2010 e=Zuidmeer, 2008 f=Gupta, 2011

13 FOOD ALLERGEN TRAITS Major food allergens ◦ Water soluble glycoproteins ◦ Fairly stable to heat, acid and proteases (Sampson, 1999) Peanut—allergens identified thus far (Ara h 1-14) ◦ Seed storage proteins, profilins (Burks, 2008) ◦ ARA H 2—Fairly specific for anaphylaxis (Klemans, 2013) Soy—protease and amylase inhibitors (Gly m 1-6) as of 2009 (Holzhauser, 2009) Wheat—protease and amylase inhibitors, peroxidase, seed storage proteins [ex-omega-5 gliadin (Tri a 19)] (Ahlstedt, 2008) Milk—beta lactoglobulin (Bos d 5), alpha lactalbumin (Bos d 4), casein (Bos d 8), whey (Wal, 2002) Egg white—lysozyme, ovalbumin, ovomucoid, ovotransferrin (Gal d 1-4); egg yolk—alpha-livitin (Poulsen 2001) Fish: parvalbumin (Gad c 1)—found in white muscle (Pascual, 2008) Shellfish: tropomyosin

14 FOOD ALLERGY: DIAGNOSIS HISTORY, HISTORY, HISTORY SKIN PRICK TESTING SPECIFIC IGE STUDIES COMPONENT DIAGNOSTICS

15 ALLERGY SKIN PRICK TESTING

16 SKIN PRICK TESTING

17 ALLERGY SKIN PRICK TESTING

18 DIAGNOSIS OF FOOD ALLERGY Skin Prick Testing Negative predictive value > 90% Positive predictive value < 50% Low specificity – Ex: False + skin tests to wheat can occur in those with grass pollen allergy Large wheals and flares may have more predictive value. Ex: 8.6% of the US pop shows +peanut Spt, which may affect 0.4% of the overall population. (Arbes, 2005) Standardized extracts not available for all allergens Can be done on infants

19 DIAGNOSIS OF FOOD ALLERGY Specific IgE studies Negative predictive value>90% – As sensitive as, or less sensitive than, skin prick tests, depending on the food. Positive predictive value<50%  Higher specific IgE levels may suggest more likelihood of a reaction, but not the severity of that reaction.  Specific IgE values may also vary by age, in terms of relevance  Circulating IgE may not quantitatively correlate well with the specific IgE bound at the target tissue. Random food allergy panels not recommended “Class” not as helpful as actual specific IgE value. Can be done on infants

20 DIAGNOSIS OF FOOD ALLERGY A POSITIVE SKIN OR IMMUNOCAP TEST IS ASSOCIATED WITH CLINICAL REACTIONS ONLY 50% OF THE TIME. Tests may also stay + for some time AFTER clinical reactivity has resolved. Trial elimination diets may be needed to determine relevance. Oral food challenges in the office may be needed to determine reactivity or resolution.

21 COMPONENT DIAGNOSTICS/ MOLECULAR ARRAYS ISAC test, from Phadia. Quantifies IgE to a single allergen protein, ex: Ara h 2 Assesses for antibodies towards – Allergens – Cross-reactive proteins, eg, Profilins Storage proteins Non-specific lipid transfer proteins PR-10 protein, homologue to a birch antigen, etc. Vieira, 2011

22 CASE 1 Skin prick tests were + to peanut (and tree nuts). Recommend: – Avoidance of peanut (and tree nuts) – Referral to the Food Allergy and Anaphylaxis Network (www.foodallergy.org)www.foodallergy.org – Have Epipen Jr available at all times – MedicAlert tag Resumed milk and egg without complications

23 ORAL IMMUNOTHERAPY (OIT)— PEANUT & OTHER FOODS NOT READY FOR CLINICAL USE Significant risks of reactions during escalation phases 18% of patients drop out of peanut trials b/c of side effects. Milk OIT appears to have HIGHER risks of reactions than peanut. Wide variation in dosing protocols Postdesensitization strategies—unclear. Goals vary—cure? Raise threshold for reactions? Adverse effects? Thyagarajan 2010

24 REFERENCES Greer FR, Sicherer SH, Burks AW et al. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics 2008;121: Johannsson SG, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Deborg S, Haahtela T, et al. A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy 2001; 56: Sellge G, Bischoff SC. The immunological basis of IgE-mediated reactions. In Food Allergy: Adverse reactions to foods and food additives, 4 th ed. (DD Metcalfe, HA Sampson, RA Simon, editors). Malden, MA: Blackwell Publishing, 2008, p.15. Sicherer SH & Leung DYM. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in J Allergy Clin Immunol 2008; 121: Branum AM & Lukacs SL. Food allergy among US children: trends in prevalence and hospitalizations. CDC NCHS Data Brief; Kim, JS. Pediatric atopic dermatitis: the importance of food allergens. Semin Cutan Med Surg. 2008; 27: Sicherer SH, Sampson HA. 9.Food allergy. J Allergy Clin Immunol 2006; 117: S Hourihane JO et al. The impact of government advice to pregnant mothers regarding peanut avoidance on the prevalence of peanut allergy in United Kingdom children at school entry. J Allergy Clin Immunol 2007; 119: Sicherer SH, Munoz-Furlong A, Sampson HA. Prevalence of peanut and tree nut allergy in the United States determined by a random digit dial telephone survey: a 5-year follow-up study. J Allergy Clin Immunol 2003; 112:

25 REFERENCES Ostblom E, Egmar AC, Gardulf A et al. The impact of food hypersensitivity reported in 9-year-old-children on health-related quality of life. Allergy. 2008; 63(2): Munoz-Furlong A & Weiss CC. Characteristics of food-allergic patients placing them at risk for a fatal anaphylactic episode. Curr Allergy Asthma Rep. 2009; 9(1): Sampson HA. Update on food allergy. J Allergy Clin Immunol. 2004; 113: Zuidmeer L, Goldhahn K, Rona RJ et al. The prevalence of plant food allergies: a systematic review. J Allergy Clin Immunol. 2008; 121(5): e4. Sampson HA. Food allergy. Part 1: immunopathogenesis and clinical disorders. J Allergy Clin Immunol 1999; 103: Burks AW. Peanut allergy Lancet 2008; 371: Ahlstedt S, Soderstrom L, Kober A. In Vitro Diagnostic Methods in the Evaluation of Food Hypersensitivity. In Food Allergy: Adverse reactions to foods and food additives, 4 th ed. (DD Metcalfe, HA Sampson, RA Simon, editors). Malden, MA: Blackwell Publishing, 2008, p.257. Cartwright RC & Dolen WK. Consultation with the specialist: who needs allergy testing and how to get it done. Pediatr Rev. 2006; 27(4): Arbes SJ, Gergen PJ, Elliott L et al. Prevalences of positive skin test responses to 10 common allergens in the US population: Results from the third National Health and Nutrition Examination survey. J Allergy Clin Immunol. 116; , Wal J-M. Cow’s milk proteins/ allergens. Ann Allergy Asthma Immunol 2002;89 (Suppl):3-10. Poulsen LK, Hansen TK, Norgaard A et al. Allergens from fish and egg. Allergy 2001; 56 Suppl 67: Garcia-Careaga M & Kerner JA. Gastrointestinal manifestations of food allergies in pediatric patients. Nutr Clin Pract 2005; 20:

26 REFERENCES Lack G. Epidemiologic risks for food allergy. J Allergy Clin Immunol 2008; 121: Chapman JA, Bernstein L, Lee RE et al. Food allergy: a practice parameter. Annals of Allergy,Asthma and Immunology. March 2006; Supplement: S Sicherer SH. Food allergens: overview of clinical features and cross-reactivity. October 7, 2008.www.uptodate.com Skripak J et al. J Allergy Clin Immunol. 2007; 120: Savage J, Matsui EC, Skripak JM, Wood RA. The natural history of egg allergy. J Allergy Clin Immunol. 2007; 120: Ando H, Moverare R, Kondo Y et al. Utility of ovomucoid-specific IgE concentrations in predicting symptomatic egg allergy. J Allergy Clin Immunol. 2008; 122: 583. Gangur V, Kelly C, Navuluri L. Sesame allergy: a growing food allergy of global proportions. Ann Allergy Asthma Immunol. 2005; 95:4-11. Cohen A, Goldberg M, Levy B et al. Sesame food allergy and sensitization in children: the natural history and long-term follow-up. Pediatr Allergy Immunol. 2007; 18: Green TD, Labelle VS, Steele PH et al. Clinical characteristics of peanut-allergic children: recent changes. Pediatrics 2007; 120:

27 REFERENCES Simonte SJ, Ma S, Mofidi S, Sicherer SH. Relevance of casual contact with peanut butter in children with peanut allergy. J Allergy Clin Immunol. 2003; 112 (1): Beyer K, Morrow E, Li XM, et al. Effects of cooking methods on peanut allergenicity. J Allergy Clin Immunol. 2001; 107(6): Thyagarajan A, Varshney P, Jones SM et al. Peanut oral immunotherapy is not ready for clinical use. J Allergy Clin Immunol 2010; 126: Immune Tolerance Network. About the LEAP Study. Available at: study_about.html. Accessed September 5, E Untersmayr & E Jensen-Jarolim. The role of protein digestibility and antacids on food allergy outcomes. J Allergy Clin Immunol. 2008; 121: Bock SA, Munoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol 107: 191-3, Toit GD. Food-dependent exercise-induced anaphylaxis in childhood. Pediatr Allergy Immunol 2007; 18: Woo MY, Scinn AA, Dickinson G, & Yang WH. Food-dependent exercise-induced anaphylaxis. CJEM 2001; 3(4):

28 REFERENCES Kelso JM. Pollen-food allergy syndrome. Clin Exp Allergy. 2000; 30: Spergel JM, Andrews T, Brown-Whitehorn T et al. Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests. Ann Allergy Asthma Immunol. 2005; 95: Rance F. Food allergy in children suffering from atopic eczema. Pediatr allergy immunol. 2008; 19: Leung D & Bieber T. Atopic dermatitis. Lancet 2003; 361: Krakowski AC, Eichenfiel LF, Dohil MA. Management of atopic dermatitis in the pediatric population. Pediatrics 2008; 122: Gupta RS, Springston EE, Warrier MR et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics, 2011; 128 (1): e9-e17. Vieira T, Lopes C, Pereira AM et al. Microarray based IgE detection in poly-sensitized allergic patients with suspected food allergy—an approach in four clinical cases. Allergol Immunopathol (Madr), 2011: 1-9.

29 REFERENCES Sicherer SH, Munoz-Furlong A, Godbold JH, Sampson HA. US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up. J Allergy Clin Immunol.2010; 125(6): Boyce JA, Assa’ad A, Burks AW et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel report. J Allergy Clin Immunol. 2010; 126 (6): supplement. Sicherer SH & Leung DYM. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect stings in J Allergy Clin Immunol. 2011; 127: Liu AH, Jaramillo R, Sicherer SH et al. National prevalence and risk factors for food allergy and relationship to asthma: results from the National Health and Nutrition Examination Survey J Allergy Clin Immunol 2010; 126 (4): Von Mutius E. 99 th Dahlem conference on infection, inflammation and chronic inflammatory disorders: farm lifestyles and the hygiene hypothesis. Clin Exp Immunol 2010; 160(1): Visness CM, London SJ, London JL. Association of obesity with IgE levels and allergy symptoms in children and adolescents: results from the National Health and Nutrition Examination Survey J Allergy Clin Immunol May;123(5): Association of obesity with IgE levels and allergy symptoms in children and adolescents: results from the National Health and Nutrition Examination Survey

30 CASE 2 Alison is an 8mo old child who presents for assessment of food allergies. Hives and wheezing, or hives alone, since beginning solid foods recently Severe eczema, with rashes and itching, since early infancy. Uncertain what, if any, foods worsen the eczema since the skin always has a rash.

31 Case 2 Has had blood tests that showed specific IgE against many foods (milk, egg, peanut, soy) Family has tried eliminating various foods for days at a time without improvement in the daily skin itching and rashes

32 Case 2 Hives and wheezing after accidental peanut butter consumption Hives and coughing when father was eating peanuts next to her Hives with some egg preparations but not others

33 Case 2 Review of systems: Notable for frequent runny nose, itchy skin and two bouts of wheezing assoc with URIs. Birth History —full term, uncomplicated Feeding history —breast fed, then used multiple formulas. Partial improvement of skin with extensively hydrolyzed formula. Immunizations up to date

34 Case 2 Past Medical History —no surgeries or hospitalizations. Family history —Father: AR, asthma; mother— AR; brother—mild eczema Social history –lives with both parents, older brother, dog, cat. No smokers. Meds –cetirizine prn, topical steroids prn.

35 CASE 2--ISSUES Anaphylaxis to foods (egg and peanut) Severe atopic dermatitis (AD) Family concerns regarding adequate nutrition Family fears regarding anaphylaxis

36 Case 2 Exam –notable for multiple excoriations, dry skin, dry red patches on wrists, arms, legs.

37 Case 2

38

39 ATOPIC DERMATITIS (AD) & FOOD ALLERGY IgE-mediated food allergy affects 33-66% of children with AD. ◦ Far more pronounced under age 2y. ◦ Increases with severity of of AD pts will have specific IgE + to foods and inhalants. ◦ 46% of infants with eczema have detectable specific IgE to milk, egg, or peanut. Rance, 2008; Kim, 2008.

40 EVALUATING FOOD ALLERGY IN ATOPIC DERMATITIS 1. Improve & optimize skin care – Itch control – Aggressive skin hydration and moisturization – Treat skin infections 2. Assess for IgE towards milk, egg, peanut, soy, wheat, and fish (cod) 3. Diagnostic elimination diet for 4 weeks 4. If no improvement, re-introduce foods into diet, and reassess skin issues. Bergmann et al. J Allergy Clin Immunol: In Practice. 2013; 1(1): 22-8.

41 Case 2—Management Avoid all egg and peanut items. (anaphylactic reactions) Avoid all tree nuts as well IMPROVE SKIN CARE—ITCH CONTROL, MOISTURIZATION, TREAT INFECTIONS Detailed dietary history week trials of food exclusion of foods with + specific IgE – Trial of amino acid formula, in this case

42 Case 2--Management Nutrition counseling Anaphylaxis – Injectable epinephrine – Food Allergy and Anaphylaxis Network (www.foodallergy.org)www.foodallergy.org – Medical identification Atopic dermatitis (www.nationaleczema.org)www.nationaleczema.org

43 Case 2--Management No significant improvement with soy and milk avoidance Baked egg items vs. other egg preparations – Egg allergy resolves by age 16y in 68%. tolerate baked egg white, but it cannot be predicted based on SPT/ Immunocap. – May improve likelihood of resolution of egg allergy Peanut allergy

44 Case 2—Management: Atopic March the natural history of atopic manifestations, characterized by a typical sequence of progression of clinical signs of atopic disease, with some signs (allergic rhinitis, asthma) becoming more prominent while others (AD) subside.

45 Case 2--Course Age 2y—Alison had a peanut candy: Developed hives and wheezing No epinephrine gadget located. Called 911 and gave antihistamines Required IV fluids, epinephrine, and albuterol. Reinforced need to have injectable epinephrine available at all times.

46 Case 2—Summary: AD and food allergies Early onset eczema: Freq. assoc with food allergy IgE often detected to multiple foods, but significance requires careful history and guidance Address nutritional needs Prepare for anaphylaxis Monitor for other atopic conditions

47 Case 2--References Rance F. Food allergy in children suffering from atopic eczema. Pediatr allergy immunol. 2008; 19: Noimark L, Cox HE. Nutritional problems related to food allergy in childhood. Pediatr allergy immunol. 2008; 19: Krakowski AC, Eichenfiel LF, Dohil MA. Management of atopic dermatitis in the pediatric population. Pediatrics 2008; 122: Savage JH, Matsui EC, Skripak JM, Wood RA. The natural history of egg allergy. J Allergy Clin Immunol. 2007; 120(6): Ando H, Moverare R, Kondo Y et al. Utility of ovomucoid-specific IgE concentrations in predicting symptomatic egg allergy. J Allergy Clin Immunol. 2008; 122(3): Konstantinou GN, Giavi S, Kalobatsou A et al. J Allergy Clin Immunol. 2008; 122(2): Bergmann et al. J Allergy Clin Immunol: In Practice. 2013; 1(1): 22-8.

48 CASE 3 Kevin is a 15yo male who presents with severe sneezing, runny nose, nasal congestion and eye itching x ten years. Sx perennial, but worse in spring and fall. No help with any OTC meds, or multiple prescription antihistamines and nasal steroids.

49 CASE 3 ROS: Negative for asthma, hives, eczema and other issues. Denies food allergies, but: – Mouth itching and tongue swelling with cucumber and raw carrots – Lip swelling with apples – Chest tightness, stomach cramps, and throat itching with cantaloupe and watermelon. Family hx—Father with AR, similar sx with celery. Sister with asthma.

50 CASE 3 PMH, Social hx unremarkable. Exam: Allergic nasal crease, congested boggy mucosa with scant discharge. Eyes— cobblestone conjunctiva. Skin tests to inhalants--+dust mites, multiple pollens (ragweed, mugwort, birch, oak, maple, and others) Dx—Allergic rhinitis, allergic conjunctivitis.

51 CASE 3—WHAT ABOUT THE FRUITS AND VEGETABLES? Pollen-food allergy syndrome=oral allergy syndrome Definition: An IgE-mediated allergy caused by homologous proteins and cross-reacting antigenic determinants in pollen and various fruits, vegetables, and nuts. Cross-reacting proteins—heat labile. Degrade while cooking  cooked versions of the fruits/ vegetables often well-tolerated Prevalence in AR: 5%-50%.

52 POLLEN-FOOD ALLERGY SYNDROME Common cross-reactivities: – Birch with fresh apple, hazelnuts, cherry, celery and carrot – Ragweed with banana, kiwi and gourd family (melons, zucchini, & cucumber) – Mugwort with celery – Grass and tree pollens with apple, tree nuts, peaches, oranges, pears, cherries, fennel, tomatoes, and carrots – Different species of apples can have different degrees of allergenicity Symptoms: Usually localized to the can progress to have systemic reactions

53 POLLEN-FOOD ALLERGY SYNDROME Management—no consensus – Self-injectable epinephrine, if history of systemic reaction – Avoidance of all forms of the food if history of anaphylaxis – Avoidance of raw forms of the food if oral reaction only. Those who react to fruits and DO NOT have AR may be at higher risk of systemic reactions.

54 Case 3--REFERENCES Ma S, Sicherer SH, & Nowak-Wegrzyn A. A survey on the management of pollen-food allergy syndrome in allergy practices. J Allergy Clin Immunol 2003; 112: Carnes J, Ferrer A, 7 Fernandez-Caldas E. Allergenicity of 10 different apple varieties. Ann Allergy Asthma Immunol. 2006; 96(4): Kelso JM. Pollen-food allergy syndrome. Clin Exp Allergy. 2000; 30:

55 THANK YOU FOR YOUR ATTENDANCE AND PARTICIPATION.


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