1. Colloquium SCINSCAN PAAMOST dr. N.W. de Jong Erasmus MC Rotterdam

2. Topics  Factors influencing skin test  Literature  Erasmus MC  Demonstration  Cut-off value  Distribution

3. Factors influencing skin prick test result Allergen: quantity potency quality Design of lancet: Needle hight needle thickness Shape of shoulder Drawing of the wheal: Performance Pen thickness Ink diffusion in skin and adhesive tape Performance: Pressure Angle Time Histological features: Density of mast cells IgE on mast cells Thickness of skin Density of receptors Area determination: Plus signs (1+ - 5+) Mean diameter L + W /2 Area calculation: π x (D mean/2) 2 L.K. Poulsen, C. Bindslev- Jensen, H.J. Malling Clun. Exp. Allergy 1993,23;61-8

4. Scanning skin test results  Advantages  Reproducibility ?  Accuracy ?  Efficiency?  Digital ?  Cut-off values?  Statistical analysis? Elips Polygonal  Wohrl S, Vigl K, Binder M, Stingl G, Prinz M. Exp Dermatol. 2006 Feb;15(2):119-24

5. 1.Poulsen LK, Lijsberg C, Binslev-Jensen C, Mailing HJ. Precise area determination of skin prick tests: validation of a scanning device and software for a personal computer. Clin Exp Allergy 1993;23:61-8. 2.Poulsen LK, Binslev- Jensen C, Rihoux JP. Quantitative determination of skin reactivity by two semiautomatic devices for skin prick test area measurements. Agents Actions. 1994 Jun;41 Spec No:C134-5. 3.Pijnenborg H, Nilsson L, Dreborg S. Estimation of skin prick tests reactions with a scanning program. Allergy 1996:51:782-8. 4.Eigenmann PA, Sampson HA. Interpreting skin prick tests in the evaluation of food allergy in children. Pediatr Allergy Immunol. 1998 Nov;9(4):186-91. 5.Wohrl S, Vigl K, Binder M, Stingl G, Prinz M. Automated measurement of skin prick tests: an advance towards exact calculation of wheal size. Exp Dermatol. 2006 Feb;15(2):119-24 Literature scanning method

6. 1.Poulsen LK, Lijsberg C, Binslev-Jensen C, Mailing HJ. Precise area determination of skin prick tests: validation of a scanning device and software for a personal computer. Clin Exp Allergy 1993;23:61-8. -Cutting and weighting paper -Area by diameters -Hand held scanner Conclusion: hand held scanner highly precise, easy to use, time consuming (5 min/ skin test) Literature

7. 2.Poulsen LK, Binslev- Jensen C, Rihoux JP. Quantitative determination of skin reactivity by two semiautomatic devices for skin prick test area measurements. Agents Actions. 1994 Jun;41 Spec No:C134-5. comparing 2080 spt’s -digitizer pen -hand held scanner Conclusion: digitizer gives larger areas than the scanner, scanner more precise Literature

8. 3.Pijnenborg H, Nilsson L, Dreborg S. Estimation of skin prick tests reactions with a scanning program. Allergy1996:51:782-8. Comparing 160 SPT’s: -Area = π x (D mean/2) 2 -Scanning method: encircled, transferred to a record sheet by means of translucent tape Conclusion: Area scanner significant more precise, better CV Literature

9. 4. Eigenmann PA, Sampson HA. Interpreting skin prick tests in the evaluation of food allergy in children. Pediatr Allergy Immunol. 1998 Nov;9(4):186-91. Comparing two SPT’s recording methods with oral food challenge (n=160) -mean wheal diameter -hand held scanner sensitivity/ specificity Conclusion: no significant differences in predictive values between methods Literature

10. 5.Wohrl S, Vigl K, Binder M, Stingl G, Prinz M. Automated measurement of skin prick tests: an advance towards exact calculation of wheal size. Exp Dermatol. 2006 Feb;15(2):119-24 Software automatically analysis scanned images and calculates the size of wheals inner border. Pilot study: Comparing 110 SPT’s Histamine. CV area versus Diameter CV horizontal diameter: 37.9% CV maximal/ minimal diameter: 25.9% CV scanning method: 11.9% Literature

11. Scanning method Wohrl S, Vigl K, Binder M, Stingl G, Prinz M. Exp Dermatol. 2006 Feb;15(2):119-24 a.Original image b.Blue color to grey c.Increase contrast d.Wheal’s contour middle e.Close gaps f- isuperimposition of reconstruction

12. NW de Jong*, E Hoorn**, PGH Mulder***,H de Groot*, R Gerth van Wijk* * Department of Allergology, **Department of Information and Technology, ***Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, the Netherlands SKINSCAN development 1998- … -Poster 2002: Determination of ICT and SPT reactions with a scanning program -Analyse 2005: Calculating Heic and Hep index with a scanning program. -Thesis N.W. de Jong 2004: Reproducibility and stability of "in house manufactured" extracts used in the diagnosis of IgE mediated allergy.

13. NW de Jong*, E Hoorn**, PGH Mulder***,H de Groot*, R Gerth van Wijk* * Department of Allergology, **Department of Information and Technology, ***Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, the Netherlands Results: Reproducibility SPT; histamine response 8 replicate observations per subject. Intraoperator c.v 0.82%, Interoperator c.v.: 0.95%, day-to-day c.v. : 1.53% Comparing with Pijnenborg et al.: Intraoperator c.v.: 1.4%, Interoperator: 2.3%, day -to- day c.v.: 1.9%

14. Skinscan  Demonstration

15. Suppression of histamine and grass pollen induced early and late phase skin reaction by levocetirizine (LCTZ). (In press) Dr. N.W de Jong*, E. Hoorn**, Dr. PGH Mulder ***, Prof. Dr. R. Gerth van Wijk*  N = 240  Histamine  CV SPT 19% (Niemeyer 27.2%)  (Lower SPT areas may lead to big measurement errors when calculated by hand.)  CV ICT 15% (Niemeyer 15.9 %)  Grass pollen  CV SPT 20%  CV ICT 13%  CV late phase skin 26%. (N = 120) The use of the skinscan program to calculate skin test areas in scientific research. Coefficient of variation

16. Chapter 7: Optimization of Skin testing, evaluation of cut-off values Optimally cut-off value using mean wheal diameter: ICT 0.7, SPT 0.4 Predictive value: ICT: RAST 83%; Anamnesis 77% SPT: RAST 77%; Anamnesis 86% Examples: ICT Histamine 8 mm; grass pollen 5 mm: 5/8 = 0.62 (negative) or 6/8 = 0.75 (positive) SPT Histamine 7 mm; peanut 3 mm: 3/7 = 0.42 (positive) Skin test reagent in the diagnosis of atopic disease N.R. Niemeyer; thesis 1996

17. n = 1500 6 different inhalation allergens: D. pteronyssius Birch Grass Mugwort Kat Dog Determination of cut-off values using skin test area HEIC index: Histamine Equivalent Intracutanous index Area versus diameter  HEIC Cut off value X (diameter) = 0.7; Y (AREA) = 0.55

18. HEP Cut off value X (diameter) = 0.4; Y = (AREA) = 0.21 Determination of cut-off values using skin test area HEP index: Histamine Equivalent Prick index Area versus diameter  n = 1200 10 different Food allergens: Scrimp Curry Egg- white Cows milk Peanut Soy Peach Wheat Celery Tomato

19. Skinscan  Advantages  Reproducibility:low CV intra, inter & day to day  Accuracy:low CV SPT & ICT  Efficiency:fast, easy, cheap  Digital:step forward to electronic dossier  Cut-off valuesmore research on predictive values  Statistical analysisvia access, statistics are easily done  Future:Dutch data bank skin test results

20. St. Elisabeth ziekenhuis, Tilburg Leids Universitair Medisch, Centrum Universitair Centrum, Maastricht Universitair Medisch Centrum, Groningen Maasstad, Rotterdam Diakonessenhuis, Utrecht Diakonessenhuis, Voorburg Scinscan distribution

21. Colloquium SkinScan PAAMOST Dept. of Information and Technology: Ed Hoorn Nico Drost Dept of Epidemiology & Biostatistics: Paul Mulder Dept. of Allergology: Nicolette de Jong Ilse Groenendijk Hans de Groot Roy Gerth van Wijk