1. WAC 2011 Debates 4, 6 December 2011: 10:45 - 11:45 Skin test or in-vitro Test for Food Allergy? IgE “In vitro” Rebuttal Motohiro Ebisawa, MD, PhD

2. Skin test or in-vitro Test for Food Allergy? Why use SPT, a test which is labor intensive is potentially dangerous has many contraindications in patients who do not want it ?

3. Skin test or in-vitro Test for Food Allergy? Patients preference Taking blood may induce a short little pain, but skin prick testing is itching and painful! If you ask the patients what they prefer, you will know …

4. ImmunoCAP sIgE Total CV < 10% Value: 0.35kU A /L 0.280.42 kUA/L Normal variation for sIgE vs SPT Skin Prick test Intra CV = 50% (within patient) Value: 3 mm Johansson SG et.al. Allergy 2005; 60: 1192-1199 Visually observed variation

5. Inter-individual variation Between performers (nurses/doctors) - how to puncture… Between devices used Between interpretation modes May lead to false negative and false positive results - with the consequence of unnecessary diets or harm to the patients Portnoy J Curr All Asthma Reports 2006:6:455-461 McCann et al. Ann All Asthma Immun 2002; 89: 368-371 Vohlonen I et al. Allergy 1989; 44: 525-531 Skin test or in-vitro Test for Food Allergy?

6. Inter-individual variation for SPT Test resultNurse 1 (mm) Nurse 2 (mm) Nurse 3 (mm) Nurse 4 (mm) CV (%) Negative control 0.10.40.2 55.9 Histamine11.79.712.914.5 16.6 Gras2.12.54.75.2 42.8 Mugwort7.74.87.49.1 24.7 Dog1.51.13.02.5 43.3 House dust mite 1.72.21.62.8 26.5 Vohlonen I et al. Allergy 1989; 44: 525-531

7. SPT Intra-individual variation Between different parts of the body – left /right arm, back… Between days Cox L et al. Ann Allergy Asthma Immunol. 2008; 101: 580-592 McCann et al. Ann All Asthma Immun 2002; 89: 368-371 Vohlonen I et al. Allergy 1989; 44: 525-531 Johansson SGO et.al. Allergy 2005; 60: 1192-1199 Skin test or in-vitro Test for Food Allergy?

8. Variables that affect skin test results Patient’s factorTechnical factor AgeTesting device Location on the bodyQuality of the extracts ChronobiologyProximity to the positive control or other allergens Severe eczema Sun damage of skin Other diseases Medication β-blockers,antihistamines and tricyclic antidepressants Adverse Reactions to Allergy Skin Tests Six fatalities have been reported previously by the American Academy of Allergy, Asthma and Immunology Linda Cox, Ann Allergy Asthma Immunol. 2008;101:580–592

9. SPT extracts poorly standardized Bet v 1 content of extracts from 6 producers (A-F) Der p 1 and Der p 2 content of extracts from 7 producers (A-G) Van Ree R. JACI 2007; 119: 270-277

10. 10 Skin conditions & color In most eczema, performance of an SPT is not possible In urticaria, false positive SPT are likely Staphyloccocal infection is a contraindication for performing SPT Pigmented skin is difficult to ”read” Pregnancy It is recommended NOT to test pregnant women Bacharier LB et al. Allergy 2008; 63: 5-34 (PRACTALL) Skin test or in-vitro Test for Food Allergy?

11. Drug interaction Most antihistamines suppress skin tests for 3-7 days Withdrawal of antihistamines is not always possible (e.g. in chronic urticaria) False negative tests are likely Several other drugs interfere  long term steroids  beta-blockers ……. Bacharier LB et al. Allergy 2008; 63: 5-34 (PRACTALL) Cox L et al. Ann Allergy Asthma Immunol. 2008; 101: 580-592 Skin test or in-vitro Test for Food Allergy?

12. SPT issues Safety - reactions occur! No standardization of procedure and reagents Poor reproducibility Labor intensive Drug interactions Dependant on skin condition No quantitative results - Decision points not possible Patient’s discomfort IgE Skin test or in-vitro Test for Food Allergy?

13. Pro SPT arguments SPT is more sensitive SPT is visual and rapid ImmunoCAP measuring down to 0,1 kU/l  gives sensitivity similar to SPT ImmunoCAP Rapid gives visual results direct Not valid arguments… because

14. Egg (n=764)Milk (n=861) T. Komata, L. Soderstorm, M.P. Borres, H. Tachimoto,and M.Ebisawa J Allergy Clin Immunol, 119(5); 1272-1274 Probability Curve

15. Egg white specific IgE negative ( ＜ class 1) 89cases Egg white specific IgE positive ( ≧ class 1) 87cases SPT(+) 40cases (44.9%) SPT(+) 84cases (96.6%) SPT( － ) 49 cases (55.1%) SPT( － ) 3 cases (3.4%) 0%50%100% ( n=176) The relationship between egg white specific IgE and SPT Ogata M, AAAAI 2009 Arerugi, 2008 ； 57(7) ： 843- 852

16. Cow’s milk specific IgE negative ( ＜ class 1) 124cases Cow’s milk specific IgE positive ( ≧ class 1) 44cases 0%50%100% ( n=168) The relationship between cow’s milk specific IgE and SPT Cow’s milk specific IgE （ mean±SD) SPT(+) 34cases (27.4%) SPT(+) 36cases (81.8%) SPT( － ) 90 cases (72.6%) SPT( － ) 8 cases (18.2%) Ogata M, AAAAI 2009 Arerugi, 2010 ； 59 （ 7 ）： 839- 846 ImmunoCAP measuring down to 0,1 kU/l  gives sensitivity similar to SPT

17. Advancements in serum IgE testing Linda Cox,Curr Allergy Asthma Rep. 2011 Dec;11(6):447-53. - specific IgE assays utilize allergen extract reagents. Development of molecular diagnostic tests Development of molecular diagnostic tests (= component-resolved diagnostics) Skin testing and measurement of serum-specific IgE have similar diagnostic value in terms of sensitivity and specificity - purified native or recombinant allergens to detect IgE sensitivity to individual allergen molecules

18. Do you know who wins? “Shifted to Immuno CAP from SPT, more and more” by Dr. Hugh Sampson Thank you for your attention!