2. Food allergy in adults: what’s new on the menu? Penny Fitzharris August 2010

3. Food allergy in adults  What is it?  What foods are involved?  Who is affected?  How, when and why does it develop?  How is it diagnosed and managed?  What treatment is available?  What problems are associated?  How do we improve services?

4. Food allergy is an immune-mediated adverse reaction to food – failure of immune tolerance   In developed countries food allergy present in 6 - 8 % of children, 2 - 3 % of adults   Immune mechanisms include: - IgE mediated e.g. anaphylaxis - non IgE mediated e.g. coeliac disease - reactions involving IgE and non-IgE e.g. eosinophilic oesophagitis

5. IgE mediated mast cell mediator release

6. Symptoms of IgE-mediated Food Allergy   rapid onset (minutes, up to 2 hours)   multiple organ systems often involved   result from chemical mediators released from mast cells and basophils   manifestations include: - acute urticaria (hives), angioedema - throat tightness, stridor, chest tightness, wheezing, persistent cough, voice change, rhinitis, conjunctivitis - nausea, vomiting, abdominal pain, diarrhoea - alteration of consciousness, hypotension - anaphylaxis

7. Food allergy in adults  What is it?  What foods are involved?  Who is affected?  How, when and why does it develop?  How is it diagnosed and managed?  What treatments are available?  What problems are associated?  How do we improve services?

8. Food allergens of plant origin   Legumes - peanuts roasted > boiled or fried - soya - lentils, beans, peas, lupin   Cereal grains - wheat, barley, rye, oats, corn, rice cross reactivity between cereal and grass pollens cereal allergens in bourbon, whisky   Umbelliferae - celery, carrot, parsley, fennel, dill   Solanaceae - tomato, potato, peppers, aubergine, coffee   Tree nuts, seeds - hazel, almond, brazil, sesame   Fruits - increasingly common in Europe

9. Allergens of animal origin   cow’s milk - several allergens, heat labile and heat stable   hen’s egg - egg white > egg yolk but chicken allergy may occur with yolk allergy (egg-bird syndrome)   fish - cooking vapours may be a problem, not cross reactive with crustacea   crustacea - cross reactions within crustacea family frequent   molluscs - true allergy not frequent - snails: cross reactivity with mite   goat and sheep milk   meat e.g. pork, beef, chicken

10. What makes a protein an allergen is still not known but…   Allergens have been mapped to only 5% of structural protein families: e.g. profilins from plants tropomyosins and caseins from animals pathogenesis related proteins from both   Biochemical functions of allergens are also limited and include enzymes, binding and storage proteins,

11. Prolamin family

12. Suspected precipitant for community onset anaphylaxis (Smith & Empson) 2000/2001 (129)2005/2006 (116) Medication44 (34)27 (23) Antibiotic18 (14)9 (8) Β-lactam14 (11) 7 (6) Β-lactam14 (11) 7 (6) NSAID11 (9)11 (10) ACEI 5 (4)5 (4) Food40 (31)32 (28) Shellfish / fish21 (16)15 (13) Peanut7 (5)4 (3) Treenut2 (2)3 (3) Other food10 (8)10 (9) Hymenoptera sting10 (8)7 (6) Honey bee7/10 (5)4/7 (3) Other*2 (2)2 (2) Unknown32 (25)48 (41) *This includes multiple possible precipitants, exercise etc

13. Allergy to fish/shellfish?   May develop in adult life.   Allergy to seafood (scaly fish, crustaceans and mollusks, including bivalves, cephalopods, gastropods) is more common where fish is commonly eaten.   Individuals may react only to scaly fish or crustaceans or mollusks, but some react to more than one group. Within each group there is often cross reactive allergy.   Other causes include…

14. Histamine fish poisoning (scombroid poisoning)   Histamine fish poisoning (HFP) is a chemical intoxication which occurs after eating fish of the dark meat varieties including tuna, kahawai, mackerel, bonito, butterfly kingfish, anchovies   Histamine is commonly the result of high temperature spoilage (>21°C), and often occurs if dead fish remain in set nets during warm sea temperatures, or improper or delayed refrigeration.   Histamine is not destroyed by freezing, cooking, smoking, curing or canning.   Should be considered in a patient who regularly eats fish, without a previous reaction

15. Anisakis: a nematode which infects marine animals

16. Food allergy in adults  What is it?  What foods are involved?  Who is affected?  How, when and why does it develop?  How is it diagnosed and managed?  What treatments are available?  What problems are associated?  How do we improve services?

17. Community-onset anaphylaxis (Smith & Empson) Number of patients (%) 2000/2001 2005/2006 Female77/129 (60) 73/116 (63) Age (avg, range)40.7 (15-81) 43.8 (15-88) European81 (63) 71 (61) NZ Maori8 (6) 5 (4) Pacifika13 (10) 16 (14) Asian14 (11) 17 (15) Other13 (10) 7 (6) Atopic disease60 (47) 34 (29) Asthma44 (34) 29 (25) Hx of allergic reaction68 (53) 59 (51) Prev seen at allergy clinic8/68 (12) 15/59 (25) Precipitant known47/68 (69) 43/59 (88) Prev Anaphylaxis55 (43) 40 (34) Had adrenaline autoinjector6/55 (11) 10/40 (25)

18. Food allergy in adults  What is it?  What foods are involved?  Who is affected?  How, when and why does it develop?  How is it diagnosed and managed?  Who should diagnose and manage?  What problems are associated?  How do we improve services?

19. Why has May become allergic to peanut?   Family history? Neither parents has atopic disease   As a first child she is at higher risk of allergy “Hygiene hypothesis” – microbial exposures   Infant diet? allergens and other nutrients   Weaning advice in the last decade? What aspects of route, timing, duration and extent of exposure may be relevant?

20. June 1998 COT recommended that “pregnant women who are atopic, or for whom the father or any sibling of the unborn child has an atopic disease, may wish to avoid eating peanuts and peanut products during pregnancy and lactation”. “pregnant women who are atopic, or for whom the father or any sibling of the unborn child has an atopic disease, may wish to avoid eating peanuts and peanut products during pregnancy and lactation”. It was also recommended that these infants should avoid peanut and peanut products during weaning and until at least 3 years of age. In common with all children, exclusive breast feeding for 4-6 months was recommended

21.  1072 children born 1999 / 2000 (after COT advice)  61% of mothers recalled hearing advice, unaffected by atopic status  Many mothers (42%) reduced peanut consumption  Few (3.8%) avoided peanut entirely  Diet change more likely with first child and when child’s father was atopic Hourihane et al JACI 2007;119:1197- 202

22.  65% of the children had consumed peanut by age 4-5y  mean introduction of peanut was at 36m Isle of Wight cohort born 1989/90 - 12.6m  1.8% had peanut allergy (challenge) 2.8% were sensitised to peanut 2.8% were sensitised to peanut  children with peanut allergy had high likelihood of eczema history

23. Avon Longitudinal Study of Parents and Children (ALSPAC) Avon Longitudinal Study of Parents and Children (ALSPAC) Lack et al, NEJM 2003 348 977-85   Study children were history positive to age 38m, studied at age 4-6y   23 of 29 with positive skin test had a positive DBPCFC (50mg-8g) (No responses to placebo)   children with eczema were 4 times more likely to have peanut allergy   if oozy, crusted eczema then 25 times more likely to have peanut allergy   If had used creams containing peanut oil were 8 times more likely to have peanut allergy

24. Household consumption as a risk factor for the development of peanut allergy - Fox AT JACI 2009;123:417-23   Study examined different routes of peanut exposure in the development of allergy   Questionnaires at time of allergy clinic attendance, usually with eczema. Known peanut allergy excluded. Routine investigations in clinic.   peanut allergy cases (133) high risk controls -egg allergy (160) low risk controls (150)

25. Fox AT JACI 2009;123:417-23   Eczema present in first year in 92% PA cases, 88% egg allergy cases, 42% low-risk controls   90% breast fed (no group differences)   Median household peanut protein consumption: Household peanut protein consumption Low risk controls6.9g/week High risk controls (egg allergic) 1.9g/week Peanut allergic cases 18.6g/week

28.  Prevalence of peanut allergy: Jewish children in UK (5171)1.85% Jewish children in Israel (5615)0.17% (p<.001) Jewish children in UK (5171)1.85% Jewish children in Israel (5615)0.17% (p<.001)  Introduction of peanut by 9 months of age: 69% of Israelis v 10% of UK infants 69% of Israelis v 10% of UK infants  Median monthly consumption in first year: 7.1g in Israel, 0 in UK 7.1g in Israel, 0 in UK Du Toit G et al, JACI 2008;122:984-91

29.  Introduction of egg, soya, wheat, vegetables, fruit and tree nuts was similar in both countries  Small differences in introduction of cow’s milk/dairy, breast feeding and exclusive breast feeding  Peanut protein and major peanut allergen content similar in commonly used products

30. COT Dec 2008  “There is now limited human evidence, consistent with a larger body of animal data, suggesting that non-oral routes of exposure to peanut, such as the skin, may be relevant.”

31. COT statement Dec 2008  “The shift in the balance of evidence since 1998 is such that the Committee believes that the previous precautionary advice to avoid peanut consumption during pregnancy, breast feeding and infancy, where there is atopy or atopic disease in family members, is no longer appropriate.”  Expert opinion in Europe, US and Australasia is similar

34. May  Is it possible to predict whether her allergy will persist? whether she is at risk of a more severe reaction? can persisting allergy be treated?

35. Skin prick tests – detect sensitisation (presence of IgE) not clinical allergy Used for inhalants, foods, venoms and some drugs Detect specific IgE bound to mast cells in the skin

36. Can skin tests predict clinical response?  100% of children with wheals over a certain size reacted to food challenge (urticaria, severe eczema, asthma, rhinitis, vomiting, other g-I, anaphylaxis) Cow’s milk8mm< 2years6mm Egg7mm<2 years5mm Peanut8mm< 2 years4mm  Specificity of 100%   May’s skin test: Peanut13mm Sporik et al, Clin Exp Allergy, 1999

37. Measurement of specific IgE in the blood eg RAST HA Sampson 2004

38. Does further investigation of purified allergen component specificity help in prognosis?   Not yet- potential for the future. Peeters et al, Clin Exp Allergy 2007;37:108-115

39. “Component resolved diagnosis” allergen specific diagnosis Gradual transition towards component resolved diagnosis seems inevitable. Many purified or recombinant allergens are now available for use in the ImmunoCAP RAST method. First available allergen at Lab+ is the wheat allergen rTri a 19 (omega-5 gliadin). Sensitisation to this allergen is associated with wheat- dependent exercise induced anaphylaxis

40. Louise  4-6 episodes itching and urticaria in different circumstances since December 2007  April 2008- shopping at K-Mart after BK chicken fillet burger – collapse-adrenaline used at EM  September 2008 K-Mart, BK chicken fillet burger again and Nurofen. Collapse, Epipen used  Eats wheat, bread, chicken, many foods without problem

41. Louise (2)   Skin tests showed: weak positive (3mm) wheat, RAST to wheat 2+, 3KU/L, wide range of other foods negative, negative to chicken   Clinical Impression: probably food-dependent exercise induced anaphylaxis advised to avoid wheat before exercise and NSAIDs before exercise Subsequently:   skin tested “fresh” BK burger and fries – negative   2 further episodes anaphylaxis after eating small very amounts of wheat, followed by exercise (hospital treatment)   RAST to omega-5 gliadin peptide 4+, 13KU/L   Subsequent exercise challenge (avoiding wheat) negative

42. If allergy persists into older childhood?  Desensitisation (immunotherapy) is an effective treatment in IgE mediated allergy to insect venoms and inhalant allergens  Can it be used in IgE-mediated food allergy?

43. Successful oral tolerance induction in severe peanut allergy Clark AT et al, Allergy 2009 800mg peanut protein=2.5mls smooth peanut butter 50mg approx ¼ - 1 / 5 of a peanut 1 peanut approx 200-240mg protein

44. JACI 2009

45. Hofmann, 2009, JACISafety aspects

46. Oral IT to foods   Large resource implications for paediatric and adult allergy services!   Not just peanut but many other foods   Safety concerns remain an issue   Will effects persist if oral intake is discontinued?

47. Food allergy in adults  What is it?  What foods are involved?  Who is affected?  How and When does it develop?  How is it diagnosed and managed?  What treatments are available?  What are the effects on quality of life?  How do we improve services?

51. RB limitations due to behavioural problems BP severity/frequency of pain/limitations assoc GH perceptions of overall health

52. SF social functioning VT vitality and liveliness GH general health

53. SF social functioning RP physical problems BP pain GH general health

54. Food allergy in adults  What is it?  What foods are involved?  Who is affected?  How and When does it develop?  How is it diagnosed and managed?  What treatments are available?  What problems are associated?  How do we improve services?

56. PPV – proportion of those identified as positive by the (skin) test where this is correct Specificity – proportion of those who don’t have the condition, correctly identified as negative

67. In summary   Food allergy affects 1-2% of the population   Fish, shellfish, peanuts and nuts are the main offenders   Food allergy is responsible for about 1/3 of anaphylaxis in Auckland   Most (but not all) food allergy develops in childhood   Food allergy strongly linked with early eczema   Allergen entry through the skin may be important   There is no evidence to advise maternal avoidance

68.   There is no evidence to recommend maternal avoidance of allergens in pregnancy or breast feeding (unless allergy in mother or child)   Early introduction of foods (not before 4 months) may help induce oral tolerance   Oral desensitisation may become a useful treatment. More research needed.   Quality of life affected in food allergy   Several bodies are developing diagnosis and management guidelines which will be helpful.   Still a complex area!

70. Lack et al, NEJM 2003 348 977-85

72. Component-resolved diagnosis from latex allergy by microarray Authors: Ebo, D. G. 1 ; Hagendorens, M. M. 2 ; De Knop, K. J. 1 ; Verweij, M. M. 1 ; Bridts, C. H. 1 ; De Clerck, L. S. 1 ; Stevens, W. J. 1 Source: Clinical & Experimental Allergy, Volume 40, Number 2, February 2010, pp. 348-358(11) 1 2 1 Clinical & Experimental Allergy 1 2 1 Clinical & Experimental Allergy  26 healthy controls  22 latex allergic patients All showed specific IgE to Hev b 1, Hev b 3, Hev b 5 or Hev b 6.02  20 latex sensitised but clinically non reactive None were sensitised to above allergens. >75% sensitised to Hev b 8

73. Tropomyosin family

74. Other candidates in the diet and gene- environmental interactions?   Folic acid – potential epigenetic regulation effects e.g. methylation influences IFNγ gene promoter, affecting TH1 and Treg expression   n-3 polyunsaturated fatty acids (fish oil)   Prebiotics – oligosaccharides   Probiotics – effects appear strain specific   Vitamin D   Antioxidants   Role of breast milk TGFβ in inducing tolerance

75. Effects of oral IT with peanut   Reduced basophil activation   Initial rise then fall in specific IgE   Increase in specific IgG and IgG4   Changes in FoxP3+ T regulatory cells   Down-regulation of genes in apoptotic pathways

76. Hourihane et al JACI 2007;119:1197-202 No of children Year of birth Age (y) when studied Prevalence of sensitisation (95% CI) Prevalence of peanut allergy (95% CI) Tariq et al 1996 981 1989-90 4-5 SPT 1.1% (0.5-1.6)0.5%(0.1-0.8) Grundy et al 2002 1246 1994-1995 3-4 SPT, OFC 3.3% (2.3-4.3)1%(0.8-2.1) Hourihane et al 2007 1072 1999-2000 4-5 SPT, sIgE, DBPCFC 2.8% (1.8-3.8)1.8%(1.1-2.7) Prevalence of peanut allergy in three UK studies 1996-2006

77. Increasing prevalence of allergy Hospital admissions data from 1990/91 to 2000/01 in England. Gupta et al, BMJ 2003 Over 11 years total admissions for these disorders increased from 0.02% - 0.06%. (1960 to 6752 out of 49,300 admissions in total).