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Experience With Carboplatin Desensitization: A Case Series
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PGD2, LTD4 and LTE4 were increased at 60 minutes in respiratory subjects vs. cutaneous and controls. CONCLUSIONS: Subjects with hypersensitivity to NSAIDs manifested by respiratory involvement showed higher levels of mediators release in nasal lavage compared to those with cutaneous involvement.
Experience With Carboplatin Desensitization: A Case Series A. Updegraff1, D. Bestul2, D. Doshi3; 1William Beaumont Beaumont Hospital, Department of Internal Medicine and Pediatrics, Royal Oak, MI, 2William Beaumont Beaumont Hospital, Department of Pharmacology, Royal Oak, MI, 3William Beaumont Beaumont Hospital, Department of Internal Medicine and Pediatrics, Division of Allergy and Immunology, Oakland University William Beaumont School of Medicine, Royal Oak, MI. RATIONALE: Carboplatin is a platinum base chemotherapy agent utilized in multiple malignancies. Many patients have experienced either true hypersensitivity reactions or severe adverse reactions to carboplatin. Given the necessity to receive therapy, desensitization is clearly indicated in this group of patients. METHODS: This is a retrospective analysis of patients who underwent desensitization to carboplatin for clinical evidence of hypersensitivity or severe adverse reactions (non-IgE) to carboplatin from August 2005January 2011 in our institution. A multidisciplinary team developed an institutional desensitization protocol utilizing appropriate pre-medications and an accelerating, graded increase in drug concentration. All patients were admitted to the ICU for desensitization with continuous monitoring, with a board certified allergist available. RESULTS: Twenty patients with a previously identified reaction to carboplatin underwent 38 separate desensitization procedures. Of these, 35/38 (92%) procedures were completed successfully. There were no reported symptoms in 28/38 (74%) procedures. Minor symptoms were reported in 7/38 (18%) procedures which were relieved with a single dose of diphenhydramine allowing successful completion of therapy. Only 3/38 (8%) procedures were discontinued due to adverse reactions including hypertension, generalized pruritus with shortness of breath, and a reaction to another medication prior to initiating carboplatin desensitization. There were no major events of anaphylaxis or severe reactions necessitating epinephrine use or resuscitation. CONCLUSIONS: Careful and selected desensitization in appropriate patients using a rigid protocol provides a safe opportunity for patients with documented hypersensitivity and/or severe adverse reactions to receive carboplatin. This allows completion of necessary chemotherapy at required doses without compromising cancer treatment.
Anaphylaxis as a Potential Cause of Death in Heroin Users X. Zhou1, M. White1, L. Lau1, S. Williams1, A. C. Bateman2, E. Abu2, A. F. Walls1; 1University of Southampton, Southampton, UNITED KINGDOM, 2Southampton University Hospitals NHS Trust, Southampton, UNITED KINGDOM. RATIONALE: Fatalities associated with heroin abuse are common, but the processes that lead to death are frequently unclear. Reports of high levels of tryptase in the blood have raised the possibility of an anaphylactic reaction having occurred. There is a need to investigate other markers of mast cell activation and to examine the potential for allergic sensitivity. METHODS: Blood samples were collected post mortem from 20 cases of heroin-associated death (aged 27-65; median 36; 20M/0F) and 20 of nondrug-related death (aged 18-86; median 45; 13M/7F). Concentrations of mast cell carboxypeptidase, chymase and tryptase were measured by specific ELISA. The presence of heroin-specific IgE levels was determined by indirect ELISA and by measurement of b-hexosaminidase release following addition of heroin to cells of the LAD-2 mast cell line which had been passively sensitized with the serum samples. RESULTS: Concentrations of mast cell carboxypeptidase were greater in blood from heroin-associated cases than in the non-drug related deaths (p50.01). Levels of chymase were also greater (p50.03), though the difference in tryptase levels did not reach significance. Addition of heroin to LAD-2 cells provoked non-cytotoxic b-hexosaminidase release (up to 20% net) at a concentration of 10 and 100 mM, but this did not appear to be mediated through IgE. However, by ELISA, heroin-specific IgE levels were greater in the blood of heroin-associated than non-drug related deaths (p50.03). CONCLUSIONS: The evidence for extensive mast cell activation and the presence of heroin-specific IgE in the circulation calls attention to the potential for anaphylactic mechanisms underlying sudden death in heroin users.
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Nasal Inflammatory Mediators In Non-steroidal Antiinflammatory Drugs (nsaids) Cross-intolerant Subjects After Lysine Nasal Challenge I. Dona1, P. Campo1, M. Sanak2, J. Cornejo3, A. Correa1, N. Blanca-Lopez4, M. Salas1, M. Sanchez1, G. Canto4, M. Blanca1; 1Allergy Department, Hospital Carlos Haya, Malaga, SPAIN, 2Molecular Biology, Dept. of Medicine, UJ CM, Krakow, POLAND, 3Allergy Laboratory, F. IMABIS, Malaga, SPAIN, 4Allergy Department, Hospital Infanta Leonor, Madrid, SPAIN. RATIONALE: Cross-intolerant reactions to NSAIDs show differences in clinical and tissue response (respiratory/cutaneous), although it is believed that share a common mechanism by inbition of COX-1 enzyme. The aim of the study was evaluating possible differences in mediators release in subjects with hypersensitivity reactions to NSAIDs with respiratory vs. cutaneous involvement. METHODS: Subjects with confirmed history of hypersensitivity to _2 episodes with at least 2 different NSAIDs or positive drug NSAIDs (> provocation) and tolerant controls were recruited. Nasal lavage at times 0, 15, 60 and 120 minutes after lysine-aspirin challenge was analyzed for ECP, tryptase, PGE2, PGD2, LTD4 and LTE4 release. RESULTS: Twenty cutaneous, 20 respiratory subjects and 10 controls were recruited. Subjects with respiratory involvement had higher levels of ECP at baseline (51.09 mg/ml), and higher increase at 15, 60 and 120 minutes after l challenge (73.72, 88.16 and 23.8 mg/ml) compared to cutaneous involvement (2.59, 3.48, 2.9 and 2.76 mg/ml) and controls. Similar results were obtained for tryptase levels (respiratory: 2.08, 1.15, 10.56 and 1.19 mg/ml) when compared to cutaneous (1, 1, 1 and 1 mg/ml) and controls. Respiratory subjects showed higher baseline PGE2 levels (74.5 pg/ml) that decreased at 15 (55.72 pg/ml) and 30 minutes (23.18 pg/ ml) after challenge as compared to cutaneous (25.7, 18.6 and 9.8 pg/ml).
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Beta Blocker Pretreatment before Coronary CT Angiography does not Increase the Rate of Contrast Reactions C. B. Lauter, G. L. Raff, K. M. Chinnaiyan, A. Abidov; William Beaumont Hospital, Royal Oak, MI. RATIONALE: Coronary computed tomography angiography (CCTA) is an accurate noninvasive test for coronary artery disease. Beta blocker premedication is required in most patients. Previous studies suggest atopic patients are at higher risk for contrast allergy after beta blocker administration. METHODS: This retrospective study reviewed 9083 CCTA patient records between April, 2009 and July, 2010 from the Advanced Cardiovascular Imaging Consortium (ACIC), a Blue Cross Blue Shield of Michigan registry. Data was examined for prior history of contrast allergy, premedication with antihistamine and/or steroids, beta blocker administration, and allergic complications post-procedure, including anaphylaxis, respiratory distress or rash/hives. RESULTS: A total of 378 patients had history of contrast allergy: 268 patients by their history and additional 110 patients pre-medicated for presumed allergy; whereas 8705 had no evidence of prior contrast reaction. Overall, 318/378 (84%) received allergy prophylaxis. Among allergic patients, 327/378 (87%) received beta blockers; their overall rate of allergic complications was 3/327 (0.9%); whereas, 51 received no beta blockers and their rate of allergic reactions was 1/51 (2.0%) (P 50.44). Among patients without presumed contrast allergy, 6780/8705 (78%) received beta blockers, and their incidence of allergic reactions was 15/ 6780 (0.2%); whereas 1925 did not receive beta blockers and their incidence of allergic reactions was 4/1925 (0.2%) (P 51.00). CONCLUSIONS: Among patients with or without history of contrast allergy, there was no difference in the rate of allergic complications if beta blockers were administered prior to coronary CT angiography.
SATURDAY
Abstracts AB71
J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 2
PGD2, LTD4 and LTE4 were increased at 60 minutes in respiratory subjects vs. cutaneous and controls. CONCLUSIONS: Subjects with hypersensitivity to NSAIDs manifested by respiratory involvement showed higher levels of mediators release in nasal lavage compared to those with cutaneous involvement.
Experience With Carboplatin Desensitization: A Case Series A. Updegraff1, D. Bestul2, D. Doshi3; 1William Beaumont Beaumont Hospital, Department of Internal Medicine and Pediatrics, Royal Oak, MI, 2William Beaumont Beaumont Hospital, Department of Pharmacology, Royal Oak, MI, 3William Beaumont Beaumont Hospital, Department of Internal Medicine and Pediatrics, Division of Allergy and Immunology, Oakland University William Beaumont School of Medicine, Royal Oak, MI. RATIONALE: Carboplatin is a platinum base chemotherapy agent utilized in multiple malignancies. Many patients have experienced either true hypersensitivity reactions or severe adverse reactions to carboplatin. Given the necessity to receive therapy, desensitization is clearly indicated in this group of patients. METHODS: This is a retrospective analysis of patients who underwent desensitization to carboplatin for clinical evidence of hypersensitivity or severe adverse reactions (non-IgE) to carboplatin from August 2005January 2011 in our institution. A multidisciplinary team developed an institutional desensitization protocol utilizing appropriate pre-medications and an accelerating, graded increase in drug concentration. All patients were admitted to the ICU for desensitization with continuous monitoring, with a board certified allergist available. RESULTS: Twenty patients with a previously identified reaction to carboplatin underwent 38 separate desensitization procedures. Of these, 35/38 (92%) procedures were completed successfully. There were no reported symptoms in 28/38 (74%) procedures. Minor symptoms were reported in 7/38 (18%) procedures which were relieved with a single dose of diphenhydramine allowing successful completion of therapy. Only 3/38 (8%) procedures were discontinued due to adverse reactions including hypertension, generalized pruritus with shortness of breath, and a reaction to another medication prior to initiating carboplatin desensitization. There were no major events of anaphylaxis or severe reactions necessitating epinephrine use or resuscitation. CONCLUSIONS: Careful and selected desensitization in appropriate patients using a rigid protocol provides a safe opportunity for patients with documented hypersensitivity and/or severe adverse reactions to receive carboplatin. This allows completion of necessary chemotherapy at required doses without compromising cancer treatment.
Anaphylaxis as a Potential Cause of Death in Heroin Users X. Zhou1, M. White1, L. Lau1, S. Williams1, A. C. Bateman2, E. Abu2, A. F. Walls1; 1University of Southampton, Southampton, UNITED KINGDOM, 2Southampton University Hospitals NHS Trust, Southampton, UNITED KINGDOM. RATIONALE: Fatalities associated with heroin abuse are common, but the processes that lead to death are frequently unclear. Reports of high levels of tryptase in the blood have raised the possibility of an anaphylactic reaction having occurred. There is a need to investigate other markers of mast cell activation and to examine the potential for allergic sensitivity. METHODS: Blood samples were collected post mortem from 20 cases of heroin-associated death (aged 27-65; median 36; 20M/0F) and 20 of nondrug-related death (aged 18-86; median 45; 13M/7F). Concentrations of mast cell carboxypeptidase, chymase and tryptase were measured by specific ELISA. The presence of heroin-specific IgE levels was determined by indirect ELISA and by measurement of b-hexosaminidase release following addition of heroin to cells of the LAD-2 mast cell line which had been passively sensitized with the serum samples. RESULTS: Concentrations of mast cell carboxypeptidase were greater in blood from heroin-associated cases than in the non-drug related deaths (p50.01). Levels of chymase were also greater (p50.03), though the difference in tryptase levels did not reach significance. Addition of heroin to LAD-2 cells provoked non-cytotoxic b-hexosaminidase release (up to 20% net) at a concentration of 10 and 100 mM, but this did not appear to be mediated through IgE. However, by ELISA, heroin-specific IgE levels were greater in the blood of heroin-associated than non-drug related deaths (p50.03). CONCLUSIONS: The evidence for extensive mast cell activation and the presence of heroin-specific IgE in the circulation calls attention to the potential for anaphylactic mechanisms underlying sudden death in heroin users.
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Nasal Inflammatory Mediators In Non-steroidal Antiinflammatory Drugs (nsaids) Cross-intolerant Subjects After Lysine Nasal Challenge I. Dona1, P. Campo1, M. Sanak2, J. Cornejo3, A. Correa1, N. Blanca-Lopez4, M. Salas1, M. Sanchez1, G. Canto4, M. Blanca1; 1Allergy Department, Hospital Carlos Haya, Malaga, SPAIN, 2Molecular Biology, Dept. of Medicine, UJ CM, Krakow, POLAND, 3Allergy Laboratory, F. IMABIS, Malaga, SPAIN, 4Allergy Department, Hospital Infanta Leonor, Madrid, SPAIN. RATIONALE: Cross-intolerant reactions to NSAIDs show differences in clinical and tissue response (respiratory/cutaneous), although it is believed that share a common mechanism by inbition of COX-1 enzyme. The aim of the study was evaluating possible differences in mediators release in subjects with hypersensitivity reactions to NSAIDs with respiratory vs. cutaneous involvement. METHODS: Subjects with confirmed history of hypersensitivity to _2 episodes with at least 2 different NSAIDs or positive drug NSAIDs (> provocation) and tolerant controls were recruited. Nasal lavage at times 0, 15, 60 and 120 minutes after lysine-aspirin challenge was analyzed for ECP, tryptase, PGE2, PGD2, LTD4 and LTE4 release. RESULTS: Twenty cutaneous, 20 respiratory subjects and 10 controls were recruited. Subjects with respiratory involvement had higher levels of ECP at baseline (51.09 mg/ml), and higher increase at 15, 60 and 120 minutes after l challenge (73.72, 88.16 and 23.8 mg/ml) compared to cutaneous involvement (2.59, 3.48, 2.9 and 2.76 mg/ml) and controls. Similar results were obtained for tryptase levels (respiratory: 2.08, 1.15, 10.56 and 1.19 mg/ml) when compared to cutaneous (1, 1, 1 and 1 mg/ml) and controls. Respiratory subjects showed higher baseline PGE2 levels (74.5 pg/ml) that decreased at 15 (55.72 pg/ml) and 30 minutes (23.18 pg/ ml) after challenge as compared to cutaneous (25.7, 18.6 and 9.8 pg/ml).
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Beta Blocker Pretreatment before Coronary CT Angiography does not Increase the Rate of Contrast Reactions C. B. Lauter, G. L. Raff, K. M. Chinnaiyan, A. Abidov; William Beaumont Hospital, Royal Oak, MI. RATIONALE: Coronary computed tomography angiography (CCTA) is an accurate noninvasive test for coronary artery disease. Beta blocker premedication is required in most patients. Previous studies suggest atopic patients are at higher risk for contrast allergy after beta blocker administration. METHODS: This retrospective study reviewed 9083 CCTA patient records between April, 2009 and July, 2010 from the Advanced Cardiovascular Imaging Consortium (ACIC), a Blue Cross Blue Shield of Michigan registry. Data was examined for prior history of contrast allergy, premedication with antihistamine and/or steroids, beta blocker administration, and allergic complications post-procedure, including anaphylaxis, respiratory distress or rash/hives. RESULTS: A total of 378 patients had history of contrast allergy: 268 patients by their history and additional 110 patients pre-medicated for presumed allergy; whereas 8705 had no evidence of prior contrast reaction. Overall, 318/378 (84%) received allergy prophylaxis. Among allergic patients, 327/378 (87%) received beta blockers; their overall rate of allergic complications was 3/327 (0.9%); whereas, 51 received no beta blockers and their rate of allergic reactions was 1/51 (2.0%) (P 50.44). Among patients without presumed contrast allergy, 6780/8705 (78%) received beta blockers, and their incidence of allergic reactions was 15/ 6780 (0.2%); whereas 1925 did not receive beta blockers and their incidence of allergic reactions was 4/1925 (0.2%) (P 51.00). CONCLUSIONS: Among patients with or without history of contrast allergy, there was no difference in the rate of allergic complications if beta blockers were administered prior to coronary CT angiography.
SATURDAY
Abstracts AB71
J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 2