WAC 2011 Debates 4 6 December 2011 10

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

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

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

Normal variation for s. Ig. E vs SPT Immuno. CAP s. Ig. E Total CV < 10% Skin Prick test Intra CV = 50% (within patient) Value: 0. 35 k. UA/L 0. 28 Value: 3 mm Visually observed variation 0. 42 k. UA/L Johansson SG et. al. Allergy 2005; 60: 1192 -1199

Skin test or in-vitro Test for Food Allergy? Inter-individual variation n Between performers (nurses/doctors) - how to puncture… n Between devices used n Between interpretation modes n 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 Mc. Cann et al. Ann All Asthma Immun 2002; 89: 36 Vohlonen I et al. Allergy 1989; 44: 525 -531

Inter-individual variation for SPT Test result Nurse 1 (mm) Nurse 2 (mm) Nurse 3 (mm) Nurse 4 (mm) CV (%) Negative control 0. 1 0. 4 0. 2 55. 9 Histamine 11. 7 9. 7 12. 9 14. 5 16. 6 Gras 2. 1 2. 5 4. 7 5. 2 42. 8 Mugwort 7. 7 4. 8 7. 4 9. 1 24. 7 Dog 1. 5 1. 1 3. 0 2. 5 43. 3 House dust mite 1. 7 2. 2 1. 6 2. 8 26. 5 Vohlonen I et al. Allergy 1989; 44: 525 -531

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

Variables that affect skin test results Patient’s factor Technical factor Age Testing device Location on the body Quality of the extracts Chronobiology Proximity 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

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 -27

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

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

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

Skin test or in-vitro Test for Food Allergy? Pro SPT arguments n SPT is more sensitive n SPT is visual and rapid Not valid arguments… because n Immuno. CAP measuring down to 0, 1 k. U/l gives sensitivity similar to SPT n Immuno. CAP Rapid gives visual results direct

Probability Curve 0. 8 0. 6 Probability 1 0. 8 Probability 1 0. 4 0. 2 < 1 year ³ 2 year 0 0. 3 10 Ig. E antibody concentration (k. U Egg (n=764) 30 A /L) ³ 2 year 100 0 0. 3 10 Ig. E antibody concentration (k. U 30 A 100 /L) Milk (n=861) T. Komata, L. Soderstorm, M. P. Borres, H. Tachimoto , and M. Ebisawa J Allergy Clin Immunol, 119(5); 1272 -1274

The relationship between egg white specific Ig. E and SPT(－) 3 cases (3. 4%) Egg white specific Ig. E positive (≧class 1) 87 cases SPT(+) 84 cases (96. 6%) Egg white specific Ig. E negative (＜ class 1) 89 cases SPT(+) 40 cases (44. 9%) 0% SPT(－) 49 cases (55. 1%) 50% 100% ( n=176) Ogata M, AAAAI 2009 Arerugi, 2008； 57(7)： 843852

The relationship between cow’s milk specific Ig. E and SPT Cow’s milk specific Ig. E positive (≧class 1) 44 cases SPT(+) 36 cases (81. 8%) Cow’s milk specific Ig. E negative (＜ class 1) 124 cases SPT(+) 34 cases (27. 4%) 0% SPT(－) 8 cases (18. 2%) SPT(－) 90 cases (72. 6%) 50% 100% ( n=168) n Immuno. CAP measuring down to 0, 1 k. U/l gives sensitivity similar to SPT Ogata M, AAAAI 2009 Arerugi, 2010； 59（7）： 839 -

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

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