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Safety of a Single Day Aspirin Desensitization Protocol
S36 Abstracts
SATURDAY
137
Safety of a Single Day Aspirin Desensitization Protocol B. L. Buchmiller, D. A. Khan; University of Texas Southwestern Medical School at Dallas, Dallas, TX. RATIONALE: Aspirin desensitization followed by aspirin therapy has been shown to be an effective therapy for patients with aspirin exacerbated respiratory disease (AERD). The most widely used protocol administers aspirin at three hour intervals. We evaluated the safety of administering aspirin at one hour intervals in a subset of patients with AERD who historically reacted to aspirin within one hour. METHODS: A retrospective chart analysis of 7 patients was performed who underwent aspirin desensitization using hourly interval dose escalation. The protocol for desensitization typically started at 40 mg of aspirin (20 mg for history of severe reactions), followed by doses of 81, 120, 162, 325, and 650 mg. No routine respiratory medications were withheld. Five patients were taking montekulast, 5 were taking inhaled steroids and 4 were on inhaled steroids and long acting ß agonists. RESULTS: All seven patients had AERD with refractory nasal polyposis. Three out of seven (43%) patients were able to complete the desensitization in one day. The remaining patients completed the desensitization on the second day. One patient had a nasoocular reaction. The remaining patients had bronchospasm alone. The median dose of first reaction was 141 mg with a median time to reaction of 50 minutes. At follow up, 4 out of 7 (57%) of patients noted improvement on aspirin therapy. CONCLUSIONS: AERD patients who have a history of symptoms less than 1 hour after aspirin can safely be desensitized with a one hour protocol that can often be completed in a single day.
138
Rapid Oral Aspirin Challenge-Desensitization in Patients With Symptomatic Acute Coronary Syndrome M. Michelis, K. Bianco, T. Selvaggi, A. Oughourli; Hackensack University Medical Center, Hackensack, NJ. RATIONALE: A 1 day aspirin challenge-desensitization protocol for aspirin sensitive patients with acute coronary syndrome requiring stent(s) was undertaken to determine if patients can safely be desensitized to begin aspirin therapy immediately. METHODS: Retrospective review of 12 patients’ records who underwent a rapid aspirin challenge-desensitization procedure was performed. Each patient’s outcome to the doses given and timing between doses was determined by reactions observed during the procedure, as well as rhinometry and spirometry results. RESULTS: The challenge-desensitization of 6 males (age 42-71, mean 57.5) and 6 females (age 63-85, mean 76) were reviewed. One had Aspirin Exacerbated Respiratory Disease and there were 8 cutaneous, 1 anaphylactoid, and 2 blended reactions. All 12 patients were discharged on aspirin, 1 required a second challenge-desensitization. The starting dose ranged from 20.25-40.5 mg and the maximum dose tolerated ranged from 81-650 mg given between 90-150 minutes for 11 patients and 30 minutes for 1 patient. Seven patients had symptoms during the desensitization and 2 required treatment. Five patients had doses or dose schedules altered. Five of the 7 patients are still taking daily aspirin 3 months to 5 years following the procedure and 2 discontinued due to symptoms. CONCLUSIONS: Successful desensitization of patients with acute coronary syndrome pending coronary stents using an abridged protocol is possible. It is important to assess risks and benefits of the procedure and make adjustments based on each patient’s clinical severity.
139
Severe Drug-Induced Anaphylaxis: Survey of Case Reports by Allergy Vigilance Network J. M. C. Renaudin, G. Kanny, F. Codreanu, E. Beaudouin, D. A. Moneret-Vautrin; University Hospital, Nancy, FRANCE. RATIONALE: Case reports of severe drug-induced anaphylaxis, collected and performed by the Allergy Vigilance Network (AVN), were examined to document prevalence of causative agents, diagnostic criteria, and benefit of allergic testing. METHODS: Severe anaphylaxis cases after causality assessment were documented by the 326 allergists of AVN. Since 2003, 144 anaphylactic
J ALLERGY CLIN IMMUNOL JANUARY 2007
adverse drug reactions (ADRs) have been filed, defined as immediate, systemic, or life-threatening reactions with need for emergency care. Drug allergy during anesthesia as not included. RESULTS: These declarations include 87 females and 57 males, with mean age 41 6 18 years (4 to 78 years). The clinical features are: anaphylactic shock or severe systemic reaction (117 cases), laryngeal or facial edema (19), generalized urticaria (7), and severe acute asthma (1). Epinephrine was used 63 times (43.7%). Emergency hospitalization was required in 121 cases (84%), of wich 39 required the reanimation medical unit. The clinical history and pharmacological imputability were confirmed in 130 cases (90.3%) by skin tests (78.5%), challenge tests (7%), and biological analysis (4.8%). The principal drugs incriminated were: amoxicillin (54 cases including 1 death), cephalosporins (25), NSAIDs (11), quinolones (8), contrast media (8), pristinamycin (5) and acetaminophen (5). CONCLUSIONS: AVN represents an advancement in understanding of severe drug anaphylaxis. It provides data on the etiology of anaphylactic ADRs and may offer alert messages. Antibiotics represent 67.4% of drug allergy, especially beta-lactams (58.3%). The possibility of establishing a precise diagnosis by non-invasive tests in addition to classical imputability criteria could be fruitful and essential for proposing targeted avoidance.
140
Specific Subpopulation Involved in Allergic Delayed Responses to Amoxicillin in an in Vitro System with Autologous Dendritic Cells R. R-Pena1, S. Lopez1, C. Antunez1, P. Chaves1, C. Mayorga1, M. J. Torres2, T. D. Fernandez1, J. A. Cornejo-Garcia1, M. Blanca2; 1Research Laboratory, Fundacion IMABIS-Carlos Haya Hospital, Ma´laga, SPAIN, 2 Allergy Service, Carlos Haya Hospital, Ma´laga, SPAIN. RATIONALE: Dendritic cells (DCs) are essential for initiating immune reactions mediated by T lymphocytes. Delayed type hypersensitivity reactions (DTHR) to amoxicillin (AX) are mediated by specific lymphocytes that recognize the haptenized drug. The aim of our work was to explore the immunological response generated by DCs in presence of AX compared to other penicillins in allergic subjects to AX by analyzing the specific proliferative response in vitro. The use of CFSE allowed us to test the proliferative response of different lymphocytes subpopulations. METHODS: Patients with a DTHR to betalactam and a positive delayed intracutaneous test to AX were included. Peripheral DCs were generated from monocytes by incubating with IL4 and GM-CSF. Lymphocytes were treated with 1mM CFSE prior the culture with autologous DCs and the corresponding drug (AX or other penicillin). The specific subpopulations proliferation was analyzed by flow cytometry. RESULTS: Proliferation was only detected when AX was used in the culture. We found a high proliferation of both CD4 and CD8 memory T-lymphocytes and also, although in less extent, of B-lymphocytes (CD191) and NK (CD3-CD561). We did not observed any proliferative response of naive T-lymphocyte or CLA1 cells in our system. CONCLUSIONS: The lymphocyte proliferation induced by monocytederived DCs in patients with a DTHR to AX was strictly related to this drug. Cells implicated were mostly CD4 and CD8 memory lymphocytes, as well as B and NK cells. The use of CFSE is a useful tool for discriminating the subpopulations that proliferate in an in vitro system. Funding: Spanish Healthy Ministry FIS PIO52290 and the Junta Andalucia 199/04
SATURDAY
137
Safety of a Single Day Aspirin Desensitization Protocol B. L. Buchmiller, D. A. Khan; University of Texas Southwestern Medical School at Dallas, Dallas, TX. RATIONALE: Aspirin desensitization followed by aspirin therapy has been shown to be an effective therapy for patients with aspirin exacerbated respiratory disease (AERD). The most widely used protocol administers aspirin at three hour intervals. We evaluated the safety of administering aspirin at one hour intervals in a subset of patients with AERD who historically reacted to aspirin within one hour. METHODS: A retrospective chart analysis of 7 patients was performed who underwent aspirin desensitization using hourly interval dose escalation. The protocol for desensitization typically started at 40 mg of aspirin (20 mg for history of severe reactions), followed by doses of 81, 120, 162, 325, and 650 mg. No routine respiratory medications were withheld. Five patients were taking montekulast, 5 were taking inhaled steroids and 4 were on inhaled steroids and long acting ß agonists. RESULTS: All seven patients had AERD with refractory nasal polyposis. Three out of seven (43%) patients were able to complete the desensitization in one day. The remaining patients completed the desensitization on the second day. One patient had a nasoocular reaction. The remaining patients had bronchospasm alone. The median dose of first reaction was 141 mg with a median time to reaction of 50 minutes. At follow up, 4 out of 7 (57%) of patients noted improvement on aspirin therapy. CONCLUSIONS: AERD patients who have a history of symptoms less than 1 hour after aspirin can safely be desensitized with a one hour protocol that can often be completed in a single day.
138
Rapid Oral Aspirin Challenge-Desensitization in Patients With Symptomatic Acute Coronary Syndrome M. Michelis, K. Bianco, T. Selvaggi, A. Oughourli; Hackensack University Medical Center, Hackensack, NJ. RATIONALE: A 1 day aspirin challenge-desensitization protocol for aspirin sensitive patients with acute coronary syndrome requiring stent(s) was undertaken to determine if patients can safely be desensitized to begin aspirin therapy immediately. METHODS: Retrospective review of 12 patients’ records who underwent a rapid aspirin challenge-desensitization procedure was performed. Each patient’s outcome to the doses given and timing between doses was determined by reactions observed during the procedure, as well as rhinometry and spirometry results. RESULTS: The challenge-desensitization of 6 males (age 42-71, mean 57.5) and 6 females (age 63-85, mean 76) were reviewed. One had Aspirin Exacerbated Respiratory Disease and there were 8 cutaneous, 1 anaphylactoid, and 2 blended reactions. All 12 patients were discharged on aspirin, 1 required a second challenge-desensitization. The starting dose ranged from 20.25-40.5 mg and the maximum dose tolerated ranged from 81-650 mg given between 90-150 minutes for 11 patients and 30 minutes for 1 patient. Seven patients had symptoms during the desensitization and 2 required treatment. Five patients had doses or dose schedules altered. Five of the 7 patients are still taking daily aspirin 3 months to 5 years following the procedure and 2 discontinued due to symptoms. CONCLUSIONS: Successful desensitization of patients with acute coronary syndrome pending coronary stents using an abridged protocol is possible. It is important to assess risks and benefits of the procedure and make adjustments based on each patient’s clinical severity.
139
Severe Drug-Induced Anaphylaxis: Survey of Case Reports by Allergy Vigilance Network J. M. C. Renaudin, G. Kanny, F. Codreanu, E. Beaudouin, D. A. Moneret-Vautrin; University Hospital, Nancy, FRANCE. RATIONALE: Case reports of severe drug-induced anaphylaxis, collected and performed by the Allergy Vigilance Network (AVN), were examined to document prevalence of causative agents, diagnostic criteria, and benefit of allergic testing. METHODS: Severe anaphylaxis cases after causality assessment were documented by the 326 allergists of AVN. Since 2003, 144 anaphylactic
J ALLERGY CLIN IMMUNOL JANUARY 2007
adverse drug reactions (ADRs) have been filed, defined as immediate, systemic, or life-threatening reactions with need for emergency care. Drug allergy during anesthesia as not included. RESULTS: These declarations include 87 females and 57 males, with mean age 41 6 18 years (4 to 78 years). The clinical features are: anaphylactic shock or severe systemic reaction (117 cases), laryngeal or facial edema (19), generalized urticaria (7), and severe acute asthma (1). Epinephrine was used 63 times (43.7%). Emergency hospitalization was required in 121 cases (84%), of wich 39 required the reanimation medical unit. The clinical history and pharmacological imputability were confirmed in 130 cases (90.3%) by skin tests (78.5%), challenge tests (7%), and biological analysis (4.8%). The principal drugs incriminated were: amoxicillin (54 cases including 1 death), cephalosporins (25), NSAIDs (11), quinolones (8), contrast media (8), pristinamycin (5) and acetaminophen (5). CONCLUSIONS: AVN represents an advancement in understanding of severe drug anaphylaxis. It provides data on the etiology of anaphylactic ADRs and may offer alert messages. Antibiotics represent 67.4% of drug allergy, especially beta-lactams (58.3%). The possibility of establishing a precise diagnosis by non-invasive tests in addition to classical imputability criteria could be fruitful and essential for proposing targeted avoidance.
140
Specific Subpopulation Involved in Allergic Delayed Responses to Amoxicillin in an in Vitro System with Autologous Dendritic Cells R. R-Pena1, S. Lopez1, C. Antunez1, P. Chaves1, C. Mayorga1, M. J. Torres2, T. D. Fernandez1, J. A. Cornejo-Garcia1, M. Blanca2; 1Research Laboratory, Fundacion IMABIS-Carlos Haya Hospital, Ma´laga, SPAIN, 2 Allergy Service, Carlos Haya Hospital, Ma´laga, SPAIN. RATIONALE: Dendritic cells (DCs) are essential for initiating immune reactions mediated by T lymphocytes. Delayed type hypersensitivity reactions (DTHR) to amoxicillin (AX) are mediated by specific lymphocytes that recognize the haptenized drug. The aim of our work was to explore the immunological response generated by DCs in presence of AX compared to other penicillins in allergic subjects to AX by analyzing the specific proliferative response in vitro. The use of CFSE allowed us to test the proliferative response of different lymphocytes subpopulations. METHODS: Patients with a DTHR to betalactam and a positive delayed intracutaneous test to AX were included. Peripheral DCs were generated from monocytes by incubating with IL4 and GM-CSF. Lymphocytes were treated with 1mM CFSE prior the culture with autologous DCs and the corresponding drug (AX or other penicillin). The specific subpopulations proliferation was analyzed by flow cytometry. RESULTS: Proliferation was only detected when AX was used in the culture. We found a high proliferation of both CD4 and CD8 memory T-lymphocytes and also, although in less extent, of B-lymphocytes (CD191) and NK (CD3-CD561). We did not observed any proliferative response of naive T-lymphocyte or CLA1 cells in our system. CONCLUSIONS: The lymphocyte proliferation induced by monocytederived DCs in patients with a DTHR to AX was strictly related to this drug. Cells implicated were mostly CD4 and CD8 memory lymphocytes, as well as B and NK cells. The use of CFSE is a useful tool for discriminating the subpopulations that proliferate in an in vitro system. Funding: Spanish Healthy Ministry FIS PIO52290 and the Junta Andalucia 199/04