- Email: [email protected]
Threshold dose for egg allergy during egg desensitization procedure
S168 Abstracts
Threshold Dose for Egg Allergy During Egg Desensitization Procedure L. Christie1, K. A. Althage1, A. W. Burks2, A. M. Scurlock1, T. T. Perry1, A. D. Buchanan2, R. M. Helm3, L. A. Pons2, S. Andrzejewski2, P. Steele2, S. M. Jones1; 1Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital Research Institute, Little Rock, AR, 2Pediatrics, Duke University Medical Center, Durham, NC, 3Microbiology/Immunology, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital Research Institute, Little Rock, AR. RATIONALE: Very little data is available to determine the threshold dose for egg allergic individuals. Threshold information could be used by the regulatory agencies and food industry to develop guidelines for cross contact testing. METHODS: Children, ages 1-13 yrs, diagnosed with egg allergy by either a serum CAP-FEIA to egg protein >2 kU/L or positive egg challenge within 6 months have undergone an oral desensitization procedure to determine if oral desensitization is a treatment option. The desensitization procedure begins with 0.1 mg of egg protein, increasing the dose until 50 mg of egg protein is tolerated. The cumulative dose associated with the first objective symptoms of an allergic reaction is reported. RESULTS: Thirteen subjects have been enrolled to date. One child reacted after a cumulative dose of 3 mg; another reacted after ingesting 6 mg. Two children reacted after ingesting 12 mg; 3 children reacted after 24 mg. One child reacted after ingesting 87 mg, 4 children reacted after 99 mg, and 1child reacted after 137 mg. The allergic symptoms involved the skin, respiratory and gastrointestinal systems. The CAP-FEIA values ranged from 0.67 to 71.2 kU/L. The children with the highest CAP-FEIA did not coincide with the children who reacted at the lowest dose of egg protein. CONCLUSION: These results have important implications in the establishment of threshold levels for egg protein cross contact. This data demonstrates that the specific serum IgE levels cannot predict clinical reactivity associated with threshold dosing.
669
Skin Localisation of Cow’s Milk Proteins Delivered by a New Ready-to-Use APT D. SOURY1, G. PONCHEL1, H. CHACUN1, P. LEGRAND1, C. DUPONT2, G. BARRATT1; 1UMR CNRS 8612, Chatenay-malabry, FRANCE, 2Cochin-Saint Vincent de Paul Hospital, Paris, FRANCE. RATIONALE: Atopy patch tests (APTs) allow the detection of delayed allergic reactions. An experimental model was designed to investigate the transdermal passage of -lactoglobulin delivered into the skin by an innovative ready-to-use APT (E-patch®) and to assess the efficacy and safety of this device. METHODS: The E-patch® containing 200 g of milk proteins (20 g of -lactoglobulin) and 1 Ci of -lactoglobulin A-[methyl-14C] (34.5 g) was placed for 24 hours in contact with hairless rat skin mounted in a Franz diffusion cell, used to evaluate the passage of molecules through the skin. Transdermal passage was monitored by measurement of radioactivity in the receiver compartment of the cell before and after precipitation of proteins. A technique of iterative skin stripping allowed measurement of the radioactivity penetrating the first skin layers. RESULTS: After 24 hours, most of radioactivity remained on the skin (92%). The analysis of the solution in the receiver compartment did not show the presence of radioactive -lactoglobulin, indicating that intact protein did not cross the skin. Residual radioactivity measured in iterative skin strips showed a high concentration of -lactoglobulin in the stratum corneum. This concentration was 135 higher than that in the epidermis-dermis. CONCLUSIONS: The E-patch® system allows milk allergens to concentrate in the stratum corneum, in the vicinity of Langerhans cells, but does not lead to systemic delivery of -lactoglobulin. Therefore, it creates ideal conditions for promoting a topical response for a positive test without any risk of anaphylactic reaction. Funding: Paris-Sud University
670
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
Diagnostic Accuracy of Skin Prick Testing in Relation to Challenge Outcome in Children With Wheat Allergy R. G. Heine, V. Pootong, D. Bannister, D. J. Hill; Department of Allergy, Royal Children’s Hospital, Melbourne, AUSTRALIA. RATIONALE: Wheat is increasingly recognized as a major food allergen. Data on the diagnostic accuracy of skin prick testing (SPT) in children with wheat allergy are limited. METHODS: A retrospective review was performed of children with suspected wheat allergy who had undergone at least one wheat challenge. SPT weal diameters (obtained within 6 months of the challenge) were correlated with challenge outcome, and positive predictive values (PPV) for each SPT weal diameter were calculated. RESULTS: Of 186 open wheat challenges performed at the RCH between 1988-2003, 47 (25%) were positive, 113 (61%) negative, and 26 (14%) inconclusive. Forty-two children (median age at first challenge: 1.6 years; range 0.6 to 7.8; 29 male, 13 female) with challengeproven wheat allergy were identified. Of these, 32 (76%) developed immediate-onset reactions (including one patient with anaphylaxis), and 10 (24%) had late-onset reactions. All patients had evidence of IgE sensitization (≥3 mm) to at least one other food allergen (cow milk 74%, egg 79%, peanut 28%, other 36%). The mean SPT diameter in children with immediate-onset reactions was significantly greater than in those with late-onset reactions (4.7±3.38 vs 1.4±1.58 mm, p<0.001). SPT weal diameters in children with late-onset reactions were <4 mm. The PPV of a weal diameter to wheat ≥3 mm was 41%, and 71% for a SPT ≥6 mm. A SPT ≥8 mm was 100% predictive and specific, but lacked sensitivity (19%). CONCLUSION: A SPT weal diameter ≥8 mm was diagnostic of IgEmediated wheat allergy. The sensitivity of SPT was low, particularly in children with late-onset reactions.
671
MONDAY
Standardizing the Interpretation of Atopy Patch Testing to Food in Children R. G. Heine1, A. Verstege2, A. Mehl2, U. Staden2, C. Rolinck-Werninghaus2, B. Niggemann2; 1Department of Allergy, Royal Children’s Hospital, University of Melbourne, Melbourne, AUSTRALIA, 2Department of Pediatric Pneumology and Immunology, Children’s Hospital Charité, Humboldt University, Berlin, GERMANY. RATIONALE: The interpretation of the atopy patch test (APT) to foods is subjective and not standardised. This study aimed to validate the diagnostic accuracy of individual APT skin signs. METHODS: 87 children (mean age 2.4±2.53 years, range 0.5 to 13.5; 57 male) with suspected food allergies underwent APT to cow milk, egg, soy and wheat flour. Skin changes were graded at 48 and 72 hours for erythema, induration, papule formation, vesiculation and ‘crescendo’ (increase of lesions from 48 to 72 hours). Food allergy was assessed by doubleblind placebo-controlled challenges (DBPCFC). Sensitivity, specificity and positive predictive value (PPV) were calculated for each individual skin sign, in relation to DBPCFC outcome. RESULTS: Of 165 DBPCFC, 70 (38%) were positive. At 72 hours, presence of any erythema (sensitivity 77%) or any papules (sensitivity 59%) were the most sensitive parameters. Moderate erythema, skin induration or presence of ≥7 papules at 72 hours had a specificity of ≥95%. Induration with blurred margins and vesicular lesions were the most specific changes (specificity ≥99%), but lacked sensitivity (4-10%). Although a ‘crescendo’ was highly specific (91%), its PPV was only 44%. The highest PPV’s at 72 hours were found for ≥7 papules (76%), induration with blurred margins (88%) and vesicular lesions (100%). The combination of moderate erythema and presence of ≥7 papules at 72 hours provided the best PPV (76%) and specificity (95%). CONCLUSION: Presence of moderate erythema and ≥7 papules at 72 hours was the skin sign combination with the highest PPV and specificity in the diagnosis of food allergy.
672
Threshold Dose for Egg Allergy During Egg Desensitization Procedure L. Christie1, K. A. Althage1, A. W. Burks2, A. M. Scurlock1, T. T. Perry1, A. D. Buchanan2, R. M. Helm3, L. A. Pons2, S. Andrzejewski2, P. Steele2, S. M. Jones1; 1Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital Research Institute, Little Rock, AR, 2Pediatrics, Duke University Medical Center, Durham, NC, 3Microbiology/Immunology, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital Research Institute, Little Rock, AR. RATIONALE: Very little data is available to determine the threshold dose for egg allergic individuals. Threshold information could be used by the regulatory agencies and food industry to develop guidelines for cross contact testing. METHODS: Children, ages 1-13 yrs, diagnosed with egg allergy by either a serum CAP-FEIA to egg protein >2 kU/L or positive egg challenge within 6 months have undergone an oral desensitization procedure to determine if oral desensitization is a treatment option. The desensitization procedure begins with 0.1 mg of egg protein, increasing the dose until 50 mg of egg protein is tolerated. The cumulative dose associated with the first objective symptoms of an allergic reaction is reported. RESULTS: Thirteen subjects have been enrolled to date. One child reacted after a cumulative dose of 3 mg; another reacted after ingesting 6 mg. Two children reacted after ingesting 12 mg; 3 children reacted after 24 mg. One child reacted after ingesting 87 mg, 4 children reacted after 99 mg, and 1child reacted after 137 mg. The allergic symptoms involved the skin, respiratory and gastrointestinal systems. The CAP-FEIA values ranged from 0.67 to 71.2 kU/L. The children with the highest CAP-FEIA did not coincide with the children who reacted at the lowest dose of egg protein. CONCLUSION: These results have important implications in the establishment of threshold levels for egg protein cross contact. This data demonstrates that the specific serum IgE levels cannot predict clinical reactivity associated with threshold dosing.
669
Skin Localisation of Cow’s Milk Proteins Delivered by a New Ready-to-Use APT D. SOURY1, G. PONCHEL1, H. CHACUN1, P. LEGRAND1, C. DUPONT2, G. BARRATT1; 1UMR CNRS 8612, Chatenay-malabry, FRANCE, 2Cochin-Saint Vincent de Paul Hospital, Paris, FRANCE. RATIONALE: Atopy patch tests (APTs) allow the detection of delayed allergic reactions. An experimental model was designed to investigate the transdermal passage of -lactoglobulin delivered into the skin by an innovative ready-to-use APT (E-patch®) and to assess the efficacy and safety of this device. METHODS: The E-patch® containing 200 g of milk proteins (20 g of -lactoglobulin) and 1 Ci of -lactoglobulin A-[methyl-14C] (34.5 g) was placed for 24 hours in contact with hairless rat skin mounted in a Franz diffusion cell, used to evaluate the passage of molecules through the skin. Transdermal passage was monitored by measurement of radioactivity in the receiver compartment of the cell before and after precipitation of proteins. A technique of iterative skin stripping allowed measurement of the radioactivity penetrating the first skin layers. RESULTS: After 24 hours, most of radioactivity remained on the skin (92%). The analysis of the solution in the receiver compartment did not show the presence of radioactive -lactoglobulin, indicating that intact protein did not cross the skin. Residual radioactivity measured in iterative skin strips showed a high concentration of -lactoglobulin in the stratum corneum. This concentration was 135 higher than that in the epidermis-dermis. CONCLUSIONS: The E-patch® system allows milk allergens to concentrate in the stratum corneum, in the vicinity of Langerhans cells, but does not lead to systemic delivery of -lactoglobulin. Therefore, it creates ideal conditions for promoting a topical response for a positive test without any risk of anaphylactic reaction. Funding: Paris-Sud University
670
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
Diagnostic Accuracy of Skin Prick Testing in Relation to Challenge Outcome in Children With Wheat Allergy R. G. Heine, V. Pootong, D. Bannister, D. J. Hill; Department of Allergy, Royal Children’s Hospital, Melbourne, AUSTRALIA. RATIONALE: Wheat is increasingly recognized as a major food allergen. Data on the diagnostic accuracy of skin prick testing (SPT) in children with wheat allergy are limited. METHODS: A retrospective review was performed of children with suspected wheat allergy who had undergone at least one wheat challenge. SPT weal diameters (obtained within 6 months of the challenge) were correlated with challenge outcome, and positive predictive values (PPV) for each SPT weal diameter were calculated. RESULTS: Of 186 open wheat challenges performed at the RCH between 1988-2003, 47 (25%) were positive, 113 (61%) negative, and 26 (14%) inconclusive. Forty-two children (median age at first challenge: 1.6 years; range 0.6 to 7.8; 29 male, 13 female) with challengeproven wheat allergy were identified. Of these, 32 (76%) developed immediate-onset reactions (including one patient with anaphylaxis), and 10 (24%) had late-onset reactions. All patients had evidence of IgE sensitization (≥3 mm) to at least one other food allergen (cow milk 74%, egg 79%, peanut 28%, other 36%). The mean SPT diameter in children with immediate-onset reactions was significantly greater than in those with late-onset reactions (4.7±3.38 vs 1.4±1.58 mm, p<0.001). SPT weal diameters in children with late-onset reactions were <4 mm. The PPV of a weal diameter to wheat ≥3 mm was 41%, and 71% for a SPT ≥6 mm. A SPT ≥8 mm was 100% predictive and specific, but lacked sensitivity (19%). CONCLUSION: A SPT weal diameter ≥8 mm was diagnostic of IgEmediated wheat allergy. The sensitivity of SPT was low, particularly in children with late-onset reactions.
671
MONDAY
Standardizing the Interpretation of Atopy Patch Testing to Food in Children R. G. Heine1, A. Verstege2, A. Mehl2, U. Staden2, C. Rolinck-Werninghaus2, B. Niggemann2; 1Department of Allergy, Royal Children’s Hospital, University of Melbourne, Melbourne, AUSTRALIA, 2Department of Pediatric Pneumology and Immunology, Children’s Hospital Charité, Humboldt University, Berlin, GERMANY. RATIONALE: The interpretation of the atopy patch test (APT) to foods is subjective and not standardised. This study aimed to validate the diagnostic accuracy of individual APT skin signs. METHODS: 87 children (mean age 2.4±2.53 years, range 0.5 to 13.5; 57 male) with suspected food allergies underwent APT to cow milk, egg, soy and wheat flour. Skin changes were graded at 48 and 72 hours for erythema, induration, papule formation, vesiculation and ‘crescendo’ (increase of lesions from 48 to 72 hours). Food allergy was assessed by doubleblind placebo-controlled challenges (DBPCFC). Sensitivity, specificity and positive predictive value (PPV) were calculated for each individual skin sign, in relation to DBPCFC outcome. RESULTS: Of 165 DBPCFC, 70 (38%) were positive. At 72 hours, presence of any erythema (sensitivity 77%) or any papules (sensitivity 59%) were the most sensitive parameters. Moderate erythema, skin induration or presence of ≥7 papules at 72 hours had a specificity of ≥95%. Induration with blurred margins and vesicular lesions were the most specific changes (specificity ≥99%), but lacked sensitivity (4-10%). Although a ‘crescendo’ was highly specific (91%), its PPV was only 44%. The highest PPV’s at 72 hours were found for ≥7 papules (76%), induration with blurred margins (88%) and vesicular lesions (100%). The combination of moderate erythema and presence of ≥7 papules at 72 hours provided the best PPV (76%) and specificity (95%). CONCLUSION: Presence of moderate erythema and ≥7 papules at 72 hours was the skin sign combination with the highest PPV and specificity in the diagnosis of food allergy.
672