WHEAT ALLERGY A rising problem in the Asia- Pacific
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1 WHEAT ALLERGY A rising problem in the Asia- Pacific Punchama Pacharn, MD Pakit Vichyanond, MD Department of Pediatrics, Siriraj Hospital, Mahidol University December Outline Wheat as a common food allergen Epidemiology of wheat allergy Age Varying manifestations Diagnosis of wheat hypersensitivities Difficulty in management Tolerance to wheat Food allergy Food allergies affect 6% of young children Eight major causative foods: eggs, milk, soy, peanuts, seafood and wheat 1
2 Causative food of immediate type food allergy US. 1) Milk 2) Egg 3) Peanut Liu et al. J Allergy Clin Immunol 2010;126: Japan 1) Egg 2) Diary product 3) Wheat Urisu et al. Allergology Iternational 2011;60: Immediate-type food allergy in Japan Urisu et al. Allergology Iternational 2011;60: Immediate-type food allergy in Japan Urisu et al. Allergology Iternational 2011;60:
3 Wheat Allergy - epidemiology In 2 studies from UK and 1 from Germany positive wheat challenges were seen in 0.5% of children (Zuidmeer JACI et al 2008) In Finland wheat allergy was physiciandiagnosed in 0.9% of children aged 1-4 yrs (Pyrhonen et al PAI 2009) In Japan estimated prevalence of wheat allergy to school children = % (Imai 05 and Urisu 11) Manifestations IgE-mediated immediate symptoms (minutes to 2 hrs after ingestion Skin: urticaria, angioedema Resp: wheezing GI: vomiting, abdominal pain systemic anaphylaxis Atopic dermatitis Delayed reactions: include gastrointestinal symptoms and worsening of atopic dermatitis Palosuo K. Update on wheat hypersensitivity. Curr Opin Allergy Clin Immunol 2003: 3: Symptoms of wheat allergy among 103 patients at Johns Hopkins Keet et al. RA. Ann Allergy Asthma Immunol.2009;102(5):
4 Anaphylaxis Palosuo JACI 2001;108:734 Results of Food challenge in AD patients at Johns Hopkins Eigenmann et al Pediatrics 1998;101:1 Food Anaphylaxis Australia, US, UK : Peanut, Tree nuts, Seafood Bock SA, et al. J Allergy Clin Immunol 2001;107: , Pumphrey, et al. J Allergy Clin Immunol2007;119: Liew WK, et al. J Allergy Clin Immunol 2009;123: Japan (2008): 319 patients Milk 69.3%, Egg 45.1%, wheat 28.8% Imamura, et al. Pediatr Allergy Immunol2008; Korea (2008): 29 patients Wheat 20.7%, Buckwheat 13.8%, Seafood 13.8% Yang et al. Ann Allergy Asthma Immunol2008;100:31-36 Thai (2007): 24 patients Seafood 45.8%, Wheat 8.3% Jirapongsananuruk et al. Ann Allergy Asthma Immunol 2007;98:
5 Self-reported anaphylaxis in Japan Imamura, et al. Pediatr Allergy Immunol 2008;18:270 Wheat anaphylaxis in Thailand Daengsuwan T, et al. Allergy 2005:60; Classification of gluten related disorder Gluten related disorders Pathogenesis Autoimmune Allergic Not autoimmune, not allergic Celiac disease Gluten ataxia Dermatitis Herpetiformis Wheat allergy Respiratory allergy Food allergy Gluten sensitivity Wheat-dependent, exercise-induced anaphylaxis Contact urticaria Sapone et al. BMC Medicine2012;10:13 5
6 A Thai boy, 9-year-old CC: rash and drowsiness after exercise 5 days PTA PI: 3 years PTA- rash and dyspnea after exercise 1year PTA- rash and fainting after exercise admitted ICU 5days PTA- rash, dyspnea, drowsiness admitted ICU PH: No history of atopic diseases, no history of food allergy Physical examination V/S- stable Other systems- Within normal limits Provisional diagnosis Exercise induced anaphylaxis Challenge protocol Day Type of challenge Result 1 Exercise Negative 2 Wheat Negative 3 Pizza then exercise Anaphylaxis Skin prick test: Histamine: 8X6 mm Wheat: 10X6 mm Pizza: 5X5 mm 6
7 Wheat-dependent, exercise induced anaphylaxis! Food-dependent, exercise-induced anaphylaxis 167 Japanese FDEIA cases Peak: 2 nd and 4 th decade Men>women Triggering factors Food Exercise General condition (fatigue, common cold, stress, menstruation Drugs (aspirin and NSAIDs) Alcohol Morita et al. Journal of Dermatological Science (2007) 47, Food-dependent, exercise-induced anaphylaxis 7
8 Wheat-dependent, Exerciseinduced Anaphylaxis in Thai Children Pacharn P, et al. APJAI (2009) 27: Wheat allergen and pathogenesis Wheat protein Albumins: water-soluble Globulins: salt-soluble Gliadins: ethanol-soluble Gluten Glutenins: alkali/acid-soluble -5 gliadin (Tri a 19): major allergen in Wheat-dependent, exercise-induced anaphylaxis 8
9 Pathogenesis Wheat-dependent, exercise-induced anaphylaxis IgE-mediated hypersensitivity Most of patients: positive result for skin prick test and RAST test for wheat. Exercise enhance absorption of allergen? Whole peptic digest of -5 gliadin Before After Tissue transglutaminase (ttg) Enzyme in gut epithelium Released and activated after stess-liked codition Forming complex with digested gliadin Palosuo, et al. J Allergy Clin Immunol2003;111: SPT to peptic fraction B of -5 gliadin Mean wheal area (mm3) Digested gliadin forms peptide Cross-linked to ttg HMW complex Strong binding serum IgE Ab Palosuo, et al. J Allergy Clin Immunol2003;111:
10 IgE antibody level to -5 gliadin Immediate Delayed Negative Controls Palosuo, et al. J Allergy Clin Immunol 2001;108: 634 Diagnosis History Wheat is hidden in various kinds of food. Food labeling is neglected by sellers and customers Sometimes need more than one factor to trigger symptoms 10
11 Diagnosis: RAST Wheat CAP RAST (>26 KU/L)) Wheat CAP RAST (>100KU/L) Sensitivity Specificity PPV (%) NPV (%) 61% 92% 74% 87% 13% 100% 100% 76% Sampson HA. J Allergy Clin Immunol 2001;107: Predictive capacity -5 gliadin ELISA (>0.04 AU) Wheat CAP RAST (>0.35 KU/L) Wheat SPT wheal Diameter (3mm) Sensitivity Specificity PPV (%) NPV (%) 84% 100% 100% 88% 95% 67% 72% 93% 89% 71% 74% 88% Palosuo, et al. J Allergy Clin Immunol 2001;108: gliadin level and wheat allergy < 1 year: risk 5.4 fold > 1 year : risk 2.5 fold Ebisawa, et al. Int Arch Allergy Immunol2012;158:
12 Management Wheat avoidance!!! Management Management Wheat-dependent, exercise-induced anaphylaxis Avoidance of exercise 4Hrs after wheat ingestion. Avoidance of wheat after intake of aspirin and COX-1 inhibitors Education, e.g.,epinephrine injection, reading food labels 12
13 Natural history Retrospective review of 103 children with IgE-mediated wheat allergy Age at initial visit months Male 66% Associated atopic hx Eczema 87%, Asthma 67%, Allergic rhinitis 60% Family history of atopy 75% 63% underwent food challenge Keet et al. Ann Allergy Asthma Immunol2009;102: Peak wheat IgE level VS persistence of wheat allergy Keet et al. Ann Allergy Asthma Immunol2009;102: Relationship between peak wheat IgE and tolerance Keet et al. Ann Allergy Asthma Immunol2009;102:
14 Natural history 28 children in Finland Age <1 to 8 months 75% had IgE-mediated wheat allergy by SPT to wheat and gliadin 25% had nonige-mediated wheat allergy Milk allergy 60% Anaphylaxis to milk (2) egg (2) Kotaniemi-Syrjanen, et al. Pediatr Allergy Immunol 2010;21:e421-e428 Natural history Age (years) Tolerance 4 years 59% 6 years 69% 10 years 84% 16 years 96% Gliadin SPT >5mm: median age of tolerance =4.61 years Gliadin SPT <5mm: median age of tolerance = 3.65 years * Gliadin SPT >5mm associated with slow recovery (p=0.019) Kotaniemi-Syrjanen, et al. Pediatr Allergy Immunol 2010;21:e421-e428 Specific oral tolerance induction (SOTI) Indication: 1. Severe reactions to food proven by challenge 2. History of accidental exposures recently 3. Unable to avoid food on daily life 4. Age limit beyond natural acquisition of tolerance to particular food 14
15 Specific Oral Tolerance Induction (SOTI) Thai boy 4 year-old Repeated episodes of anaphylaxis from wheat since 9 months of age SPT for wheat wheal = 6X5 mm sige for wheat >100kUA/L Never ate any thing out of the homecooked food 3 episodes of wheeze, turning dusky, hypotension in the last year Wheat anaphylaxis in a Thai boy Parents requested something to be done other than avoidance Specific tolerance induction carried out Provocative dose = 300 mg Start SOTI from 150mg 1 st admission dose 500mg 2 nd admission dose 10 gm Specific Oral Tolerance Induction (SOTI) sige for wheat (kau/l) Before SOTI month after SOTI -5 gliadin (kau/l) 15 gm/piece 40 gms/pack 15
16 Cross-reactivity among cereals?? Wheat Rye Barley Oat Cereals Coix cooked Ovaltine Barley Corn flakes Honey Wheat Coix raw Milo Corn flakes original 16
17 WDEIA -70 and -35 secalins in rye -3 hordein in barley Cross-react -5 gliadin in wheat RYE BARLEY Palosuo et al. Clin Exp Allergy 2001;31: Conclusion IgE mediated allergy from wheat is becoming an alarming problem around the world Varieties of presentation with wheat allergy Lack of diagnostic parameter Avoidance can be very tough Development of tolerance may be the solution Thank you 17
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