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Comparing conventional and acetoneprecipitated dog allergen extract skin testing
744 Letters to the Editor
J ALLERGY CLIN IMMUNOL APRIL 2001
3. Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 1979;76:4350-4. 4. Kolberg J, Sletten K. Purification and properties of a mitogenic lectin from Lathyrus sativus seeds. Biochim Biophys Acta 1982;704:26-30. 5. Srivenugopal KS, Adiga PR. Enzymic conversion of agmatine to putrescine in Lathyrus sativus seedlings. Purification and properties of a multifunctional enzyme (putrescine synthase). J Biol Chem 1981;256:9532-41. 6. Ramakrishna S, Adiga PR. Arginine decarboxylase from Lathyrus sativus seedlings. Purification and properties. Eur J Biochem 1975;59:377-86. 7. Valdivieso R, Quirce S, Sainz T. Bronchial asthma caused by LSF. Allergy 1988;43:536-9.
1/8/113567 doi:10.1067/mai.2001.113567
Double-blind, placebo-controlled corn challenge resulting in anaphylaxis To the Editor: There are few reports of documented corn allergy, particularly corn-induced anaphylaxis. The first report of anaphylaxis to corn in 19841 described a corn-induced reaction in a child on reintroduction of sweet corn after an elimination diet to treat eczema. There are 3 reports of anaphylaxis attributed to cornstarch in surgical glove powder.2-4 Most recently, Pauls and Cross5 reported food-dependent exercise-induced anaphylaxis to corn in an adult. Although these studies suggest corn-induced anaphylaxis exists, only the last was observed in a controlled setting. This study reports the first patient with classic anaphylaxis to corn observed in a double-blind, placebo-controlled food challenge. A 44-year-old woman was referred for evaluation of corn allergy. Her first reaction to corn (1982) consisted of an oral tingling sensation after licking corn meal from her fingers. The symptoms resolved without medical intervention. However, since 1994, with limited exposure she has had 4 reactions to corn requiring emergency department visits for pruritis, urticaria, vomiting, and diarrhea. The most recent reaction, 6 months previously, also involved difficulty breathing; subsequently, she avoids corn and corn products. The patient experienced urticaria, vomiting, and diarrhea in response to pecans and peanuts and therefore carries injectable epinephrine. She received immunotherapy years ago for allergic rhinitis (now treated with nasal budesonide and fexofenadine). She had never had asthma, eczema, or adverse reactions to medications, latex, or insect stings. Her environmental history is unremarkable. She has smoked a half pack of cigarettes per day for 30 years and currently takes bupropion hydrochloride. Her siblings have allergic rhinitis. Her other medical problems include gastroesophageal reflux disease and hypercholesterolemia, treated with omeprazole and simvastatin, respectively. Antihistamines were discontinued 1 week before her evaluation. Except for enlarged, pale nasal turbinates, her physical examination findings were normal. Baseline peak flow measurements averaged 460 (L/min). She came to the General Clinical Research Center for evaluation. The Tulane Committee on Use of Human Subjects approved the protocol, and informed consent was obtained from the patient. Skin prick testing revealed positive results for histamine (10 mm), cooked corn (10 mm), uncooked corn (35 mm), corn pollen (39 mm), peanut (28 mm), rice (20 mm), grass mix (20 mm), and dust mites (25 mm). Negative test responses occurred for PBS, lentil, challenge vehicle, wheat, milk, soy, shrimp, egg, oat, rye, ragweed, oak, cat, dog, and molds. We prepared the corn, placebo, and challenge vehicle extracts; the rest were from Greer. The challenge consisted of 2 phases: corn flour (baked ground corn kernels) or placebo (baked ground lentils), where incremental amounts were given at 30-minute intervals. The 2 phases were separated by 2 hours. Neither the patient nor the physician knew the
challenge sequence. The corn flour or placebo was mixed with applesauce, apple juice, peach puree, and sugar to mask the taste. During the first phase the patient did not have subjective or objective reactions. After a 2-hour break, she performed the second phase of the challenge (corn flour), and a reaction occurred. After receiving the first dose of corn (2 g), she described feeling “fullness,” but her vital signs and peak flow remained baseline. After the second dose of corn (8 g), she reported mild throat pruritis that resolved, but no objective changes were observed. Thirty minutes after the third corn dose (16 g), erythematous sclera, nasal congestion, and generalized urticaria developed. She was given diphenhydramine and observed. Fifteen minutes later, classic signs of anaphylaxis developed, including hypotension (systolic 99 mm Hg/diastolic 53 mm Hg), tachycardia (126 bpm), vomiting, and wheezing. Unfortunately, a tryptase level could not be documented. Treatment with epinephrine, oxygen, albuterol, methylprednisolone, and intravenous fluids commenced immediately. She was admitted to the General Clinical Research Center overnight for continued observation. By morning her symptoms had resolved, and her vital signs had returned to baseline for several hours. The subject was discharged in good condition and reported no ill effects thereafter. Telephone follow-up revealed that she remained well and had had no further problems. This is the first case of anaphylaxis to corn documented with a double-blind, placebo-controlled food challenge. Neither the physician performing the challenge nor the test subject knew in which phase the patient received corn until the challenge was terminated. This patient experienced anaphylaxis after a total of 26 g of corn flour (approximately equivalent to 6 corn chips). This study indicates that although corn allergy may be a rare event, when it occurs it can produce a severe reaction. Further studies are in progress to evaluate corn allergy. Linda G. Tanaka, MD Jane M. El-Dahr, MD Samuel B. Lehrer, PhD Tulane University School of Medicine New Orleans, La REFERENCES 1. David TJ. Anaphylactic shock during elimination diets for severe atopic eczema. Arch Dis Child 1984;59:983-6. 2. Seggev JS, Mawhinney TP, Yunginger JW, Braun SR. Anaphylaxis due to cornstarch surgical glove powder. Ann Allergy 1990;65:152-5. 3. Assalve D, Cicioni C, Perno P, Lisi P. Contact urticaria and anaphylactoid reaction from cornstarch surgical glove powder. Contact Dermatitis 1988;19:61. 4. Fisher AA. Contact urticaria and anaphylactoid reaction due to cornstarch surgical glove powder. Contact Dermatitis 1987;16:224-5. 5. Pauls JD, Cross D. Food-dependent exercise-induced anaphylaxis to corn. J Allergy Clin Immunol 1998;101:853-4.
We would like to thank Annie Stell, RN, and Marjorie McCants, BS, for their invaluable assistance and the General Clinical Research Center for use of their facility. Funding for this study was provided by Agreevo, Aventis, Dupont, and Pioneer Hi-Bred. 1/8/113765 doi:10.1067/mai.2001.113765
Comparing conventional and acetoneprecipitated dog allergen extract skin testing To the Editor: The major allergen of dog, Can F-1, has been isolated, purified, and expressed.1 Therefore it is now possible to analyze allergen extracts for potency expressed as content of major allergen. Reports from ALK-Abello Inc indicated that unstandardized dog extracts
Letters to the Editor 745
J ALLERGY CLIN IMMUNOL VOLUME 107, NUMBER 4
TABLE I. Mean diameter titrated skin prick tests Conventional 1:10 dilution AP dilution
None 1:10 1:100 1:1000
Conventional full strength
Mean difference (mm)
Paired t test
Mean difference (mm)
Paired t test
–9.2 –6.5 –3.6 –0.7
0.02 0.01 0.01 0.55
–6.3 –3.5 –0.8 2.3
0.04 0.03 0.39 0.09
contain about 5 µg of Can F-1 per milliliter.2 Acetone-precipitated (AP) dog extract (Hollister-Stier) has been reported to contain approximately 180 µg of Can F-1 per milliliter (in-house analysis by Hollister-Stier, personal communication from Terrance Kordash, MD). Recently our institution began using 2 different Can F-1 preparations for dog dander sensitization testing. This study looks at the data compiled over a period of time and then compares 2 dog dander extracts by titrated skin prick tests. Data were compiled from 123 sequential skin test subjects, all of whom had skin testing with conventional Can F-1 dog extract (Greer) and AP dog extract (Hollister-Stier). The results were compared, and means were calculated. From the cohort of 123 subjects, 59 (48% of all subjects) had mean wheals of 3 mm or more to at least 1 extract. Of those with positive results, 59 (100%) tested positive to AP (mean wheal 6.9 mm), and 35 (59%) tested positive to regular dog (mean wheal 3.4 mm). Of the 35 with positive results to both extracts, 31 (89%) had a mean wheal size after exposure to AP dog that was greater than that after exposure to regular dog. No person was found to test AP negative but conventional positive. After institutional review board approval, volunteers (aged 18 to 70 years and without severe chronic illness) were recruited who had a history of skin prick test positivity to dog. Subjects were brought to the skin-testing laboratory and gave informed consent to the procedure. To qualify, they were required to have a mean histamine wheal of 3 mm or more and mean conventional and AP dog wheals of 5 mm or more. Six subjects had titrated skin tests performed on their backs.3 A standard small pox needle (Hollister-Stier) was used for all skin testing.4 The conventional dog extract was Hollister-Stier Dog HairDander, 1:10 wt/vol, and the AP dog extract was Hollister-Stier Acetone Precipitated Dog Hair-Dander, 1:50 wt/vol. Four rows of testing were used: row 1 (top to bottom), full-strength conventional dog extract followed by serial (log) 3-fold dilutions down to 1:1000 dilution; row 2, 1:1000 dilution followed by serial (log) 3-fold increase to full strength; and rows 3 and 4, same pattern but with the AP preparation. The titrated skin tests were then compared and put into tabu-
lar form (Table I). During this study there were no adverse events, and skin testing with both forms of dog extract was tolerated well. Mean wheal sizes to full-strength conventional and AP dog extract were 7.2 and 13.4 mm, respectively. Paired t tests were used to assess the significance of difference between the 2 skin test extracts. Relative potency of the 2 extracts was determined by the concentrations producing a 5-mm mean wheal (approximately 1:10 dilution for standard and 1:1000 dilution for AP). AP diluted 1:100 is roughly equivalent to full-strength conventional, and AP diluted 1:1000 is roughly equivalent to conventional diluted 1:10 strength. These results show that previous dog skin testing methods may have been inadequate in revealing many patients allergic to dog. AP dog extract may be used in the future to identify more patients allergic to dog and may also be better for use in allergen immunotherapy. Because this is a more potent extract, care should be taken when it is used for potential immunotherapy. John B. Meiser, MD* Harold S. Nelson, MD National Jewish Medical and Research Center 1400 Jackson St, K735 Denver, CO 80206 *Michael and Eleanore Stobin Pediatric Fellow REFERENCES 1. Baldwin L, Plunkett G, Eddy J, Dailey F, Naugler D. Analysis of dog hair and epithelial extracts by immunoblotting (IB) and IgE ELISA [abstract 117]. J Allergy Clin Immunol 1999;103:S30. 2. Nelson H. The use of standardized extracts in allergen immunotherapy. J Allergy Clin Immunol 2000;106:41-5. 3. Dreborg S. The skin prick test: methodological studies and clinical applications [dissertation]. Linkoping, Sweden: Linkoping University Medical; 1987. No. 239. 4. Nelson H, Lahr J, Buchmeier A, McCormick D. Evaluation of devices for skin prick testing. J Allergy Clin Immunol 1998;101:153-6.
1/8/114340 doi:10.1067/mai.2001.114340
J ALLERGY CLIN IMMUNOL APRIL 2001
3. Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 1979;76:4350-4. 4. Kolberg J, Sletten K. Purification and properties of a mitogenic lectin from Lathyrus sativus seeds. Biochim Biophys Acta 1982;704:26-30. 5. Srivenugopal KS, Adiga PR. Enzymic conversion of agmatine to putrescine in Lathyrus sativus seedlings. Purification and properties of a multifunctional enzyme (putrescine synthase). J Biol Chem 1981;256:9532-41. 6. Ramakrishna S, Adiga PR. Arginine decarboxylase from Lathyrus sativus seedlings. Purification and properties. Eur J Biochem 1975;59:377-86. 7. Valdivieso R, Quirce S, Sainz T. Bronchial asthma caused by LSF. Allergy 1988;43:536-9.
1/8/113567 doi:10.1067/mai.2001.113567
Double-blind, placebo-controlled corn challenge resulting in anaphylaxis To the Editor: There are few reports of documented corn allergy, particularly corn-induced anaphylaxis. The first report of anaphylaxis to corn in 19841 described a corn-induced reaction in a child on reintroduction of sweet corn after an elimination diet to treat eczema. There are 3 reports of anaphylaxis attributed to cornstarch in surgical glove powder.2-4 Most recently, Pauls and Cross5 reported food-dependent exercise-induced anaphylaxis to corn in an adult. Although these studies suggest corn-induced anaphylaxis exists, only the last was observed in a controlled setting. This study reports the first patient with classic anaphylaxis to corn observed in a double-blind, placebo-controlled food challenge. A 44-year-old woman was referred for evaluation of corn allergy. Her first reaction to corn (1982) consisted of an oral tingling sensation after licking corn meal from her fingers. The symptoms resolved without medical intervention. However, since 1994, with limited exposure she has had 4 reactions to corn requiring emergency department visits for pruritis, urticaria, vomiting, and diarrhea. The most recent reaction, 6 months previously, also involved difficulty breathing; subsequently, she avoids corn and corn products. The patient experienced urticaria, vomiting, and diarrhea in response to pecans and peanuts and therefore carries injectable epinephrine. She received immunotherapy years ago for allergic rhinitis (now treated with nasal budesonide and fexofenadine). She had never had asthma, eczema, or adverse reactions to medications, latex, or insect stings. Her environmental history is unremarkable. She has smoked a half pack of cigarettes per day for 30 years and currently takes bupropion hydrochloride. Her siblings have allergic rhinitis. Her other medical problems include gastroesophageal reflux disease and hypercholesterolemia, treated with omeprazole and simvastatin, respectively. Antihistamines were discontinued 1 week before her evaluation. Except for enlarged, pale nasal turbinates, her physical examination findings were normal. Baseline peak flow measurements averaged 460 (L/min). She came to the General Clinical Research Center for evaluation. The Tulane Committee on Use of Human Subjects approved the protocol, and informed consent was obtained from the patient. Skin prick testing revealed positive results for histamine (10 mm), cooked corn (10 mm), uncooked corn (35 mm), corn pollen (39 mm), peanut (28 mm), rice (20 mm), grass mix (20 mm), and dust mites (25 mm). Negative test responses occurred for PBS, lentil, challenge vehicle, wheat, milk, soy, shrimp, egg, oat, rye, ragweed, oak, cat, dog, and molds. We prepared the corn, placebo, and challenge vehicle extracts; the rest were from Greer. The challenge consisted of 2 phases: corn flour (baked ground corn kernels) or placebo (baked ground lentils), where incremental amounts were given at 30-minute intervals. The 2 phases were separated by 2 hours. Neither the patient nor the physician knew the
challenge sequence. The corn flour or placebo was mixed with applesauce, apple juice, peach puree, and sugar to mask the taste. During the first phase the patient did not have subjective or objective reactions. After a 2-hour break, she performed the second phase of the challenge (corn flour), and a reaction occurred. After receiving the first dose of corn (2 g), she described feeling “fullness,” but her vital signs and peak flow remained baseline. After the second dose of corn (8 g), she reported mild throat pruritis that resolved, but no objective changes were observed. Thirty minutes after the third corn dose (16 g), erythematous sclera, nasal congestion, and generalized urticaria developed. She was given diphenhydramine and observed. Fifteen minutes later, classic signs of anaphylaxis developed, including hypotension (systolic 99 mm Hg/diastolic 53 mm Hg), tachycardia (126 bpm), vomiting, and wheezing. Unfortunately, a tryptase level could not be documented. Treatment with epinephrine, oxygen, albuterol, methylprednisolone, and intravenous fluids commenced immediately. She was admitted to the General Clinical Research Center overnight for continued observation. By morning her symptoms had resolved, and her vital signs had returned to baseline for several hours. The subject was discharged in good condition and reported no ill effects thereafter. Telephone follow-up revealed that she remained well and had had no further problems. This is the first case of anaphylaxis to corn documented with a double-blind, placebo-controlled food challenge. Neither the physician performing the challenge nor the test subject knew in which phase the patient received corn until the challenge was terminated. This patient experienced anaphylaxis after a total of 26 g of corn flour (approximately equivalent to 6 corn chips). This study indicates that although corn allergy may be a rare event, when it occurs it can produce a severe reaction. Further studies are in progress to evaluate corn allergy. Linda G. Tanaka, MD Jane M. El-Dahr, MD Samuel B. Lehrer, PhD Tulane University School of Medicine New Orleans, La REFERENCES 1. David TJ. Anaphylactic shock during elimination diets for severe atopic eczema. Arch Dis Child 1984;59:983-6. 2. Seggev JS, Mawhinney TP, Yunginger JW, Braun SR. Anaphylaxis due to cornstarch surgical glove powder. Ann Allergy 1990;65:152-5. 3. Assalve D, Cicioni C, Perno P, Lisi P. Contact urticaria and anaphylactoid reaction from cornstarch surgical glove powder. Contact Dermatitis 1988;19:61. 4. Fisher AA. Contact urticaria and anaphylactoid reaction due to cornstarch surgical glove powder. Contact Dermatitis 1987;16:224-5. 5. Pauls JD, Cross D. Food-dependent exercise-induced anaphylaxis to corn. J Allergy Clin Immunol 1998;101:853-4.
We would like to thank Annie Stell, RN, and Marjorie McCants, BS, for their invaluable assistance and the General Clinical Research Center for use of their facility. Funding for this study was provided by Agreevo, Aventis, Dupont, and Pioneer Hi-Bred. 1/8/113765 doi:10.1067/mai.2001.113765
Comparing conventional and acetoneprecipitated dog allergen extract skin testing To the Editor: The major allergen of dog, Can F-1, has been isolated, purified, and expressed.1 Therefore it is now possible to analyze allergen extracts for potency expressed as content of major allergen. Reports from ALK-Abello Inc indicated that unstandardized dog extracts
Letters to the Editor 745
J ALLERGY CLIN IMMUNOL VOLUME 107, NUMBER 4
TABLE I. Mean diameter titrated skin prick tests Conventional 1:10 dilution AP dilution
None 1:10 1:100 1:1000
Conventional full strength
Mean difference (mm)
Paired t test
Mean difference (mm)
Paired t test
–9.2 –6.5 –3.6 –0.7
0.02 0.01 0.01 0.55
–6.3 –3.5 –0.8 2.3
0.04 0.03 0.39 0.09
contain about 5 µg of Can F-1 per milliliter.2 Acetone-precipitated (AP) dog extract (Hollister-Stier) has been reported to contain approximately 180 µg of Can F-1 per milliliter (in-house analysis by Hollister-Stier, personal communication from Terrance Kordash, MD). Recently our institution began using 2 different Can F-1 preparations for dog dander sensitization testing. This study looks at the data compiled over a period of time and then compares 2 dog dander extracts by titrated skin prick tests. Data were compiled from 123 sequential skin test subjects, all of whom had skin testing with conventional Can F-1 dog extract (Greer) and AP dog extract (Hollister-Stier). The results were compared, and means were calculated. From the cohort of 123 subjects, 59 (48% of all subjects) had mean wheals of 3 mm or more to at least 1 extract. Of those with positive results, 59 (100%) tested positive to AP (mean wheal 6.9 mm), and 35 (59%) tested positive to regular dog (mean wheal 3.4 mm). Of the 35 with positive results to both extracts, 31 (89%) had a mean wheal size after exposure to AP dog that was greater than that after exposure to regular dog. No person was found to test AP negative but conventional positive. After institutional review board approval, volunteers (aged 18 to 70 years and without severe chronic illness) were recruited who had a history of skin prick test positivity to dog. Subjects were brought to the skin-testing laboratory and gave informed consent to the procedure. To qualify, they were required to have a mean histamine wheal of 3 mm or more and mean conventional and AP dog wheals of 5 mm or more. Six subjects had titrated skin tests performed on their backs.3 A standard small pox needle (Hollister-Stier) was used for all skin testing.4 The conventional dog extract was Hollister-Stier Dog HairDander, 1:10 wt/vol, and the AP dog extract was Hollister-Stier Acetone Precipitated Dog Hair-Dander, 1:50 wt/vol. Four rows of testing were used: row 1 (top to bottom), full-strength conventional dog extract followed by serial (log) 3-fold dilutions down to 1:1000 dilution; row 2, 1:1000 dilution followed by serial (log) 3-fold increase to full strength; and rows 3 and 4, same pattern but with the AP preparation. The titrated skin tests were then compared and put into tabu-
lar form (Table I). During this study there were no adverse events, and skin testing with both forms of dog extract was tolerated well. Mean wheal sizes to full-strength conventional and AP dog extract were 7.2 and 13.4 mm, respectively. Paired t tests were used to assess the significance of difference between the 2 skin test extracts. Relative potency of the 2 extracts was determined by the concentrations producing a 5-mm mean wheal (approximately 1:10 dilution for standard and 1:1000 dilution for AP). AP diluted 1:100 is roughly equivalent to full-strength conventional, and AP diluted 1:1000 is roughly equivalent to conventional diluted 1:10 strength. These results show that previous dog skin testing methods may have been inadequate in revealing many patients allergic to dog. AP dog extract may be used in the future to identify more patients allergic to dog and may also be better for use in allergen immunotherapy. Because this is a more potent extract, care should be taken when it is used for potential immunotherapy. John B. Meiser, MD* Harold S. Nelson, MD National Jewish Medical and Research Center 1400 Jackson St, K735 Denver, CO 80206 *Michael and Eleanore Stobin Pediatric Fellow REFERENCES 1. Baldwin L, Plunkett G, Eddy J, Dailey F, Naugler D. Analysis of dog hair and epithelial extracts by immunoblotting (IB) and IgE ELISA [abstract 117]. J Allergy Clin Immunol 1999;103:S30. 2. Nelson H. The use of standardized extracts in allergen immunotherapy. J Allergy Clin Immunol 2000;106:41-5. 3. Dreborg S. The skin prick test: methodological studies and clinical applications [dissertation]. Linkoping, Sweden: Linkoping University Medical; 1987. No. 239. 4. Nelson H, Lahr J, Buchmeier A, McCormick D. Evaluation of devices for skin prick testing. J Allergy Clin Immunol 1998;101:153-6.
1/8/114340 doi:10.1067/mai.2001.114340