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Tolerability Of Aztreonam In Patients With IgE-mediated Allergy To Betalactams
S68 Abstracts
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Role of Effector Cells In Drug-induced Maculopapular Exanthema T. D. Ferna´ndez1, M. J. Torres2, C. Antunez1, J. A. Cornejo-Garcı´a1, M. F. del Prado3, G. Requena2, M. Blanca2, C. Mayorga1; 1Research Laboratory, Carlos Haya Hospital-Fundacion IMABIS, Ma´laga, SPAIN, 2 Allergy Service, Carlos Haya Hospital, Ma´laga, SPAIN, 3Emergency Unit, Carlos Haya Hospital, Ma´laga, SPAIN. RATIONALE: Drug-induced maculopapular exanthema is a cutaneous delayed allergic reaction where Th1 lymphocytes are involved as effector cells. One type of effector cells, CCR7-CD27-, are characterised by a high capacity for responding to specific antigens. Among this CCR7-CD27-, those with CCR10 expression are recruited to skin. We analyzed the presence of effector cells and their influence in drug-induced maculopapular exanthema. METHODS: Peripheral blood mononuclear cells (PBMCs) extracted from 12 patients during the acute phase and the resolution period and from 8 healthy controls were analyzed. Different T-cells subsets (CD4, CD8), effector phenotype (CCR7, CD27) and skin homing receptor CCR10 were analyzed by flow cytometry at baseline and after culturing with and without the culprit drug. RESULTS: At baseline, we found a significant increase of CCR7-CD27cells in both acute and resolution phase compared with controls (p 5 0,003 and p 5 0,032 respectively). The percentage of CCR7-CD27- in CD41 and CCR101 subpopulations was significantly increased at the acute phase compared with the resolution period (p 5 0,001 and p 5 0,045 respectively). After the culture with the culprit drug, we found a significant increase of CCR7-CD27- cells (p 5 0,003) and in CCR101CCR7-CD27- cells (p 5 0,006) at the resolution period compared to controls. No differences in cultured PBMCs were found between acute phase compared to controls. CONCLUSIONS: Cutaneous effector cells are present in patients with drug-induced maculopapular exanthema, especially in CD41 subpopulation. These effector cells increase after culturing with the drug involved in the non-immediate reaction.
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Tolerability Of Aztreonam In Patients With IgE-mediated Allergy To Betalactams D. Schiavino, A. Buonomo, C. Lombardo, G. Altomonte, E. Nucera, G. Patriarca; Allergy Unit, Catholic University of the Sacred Heart, Rome, ITALY. RATIONALE: Cross-reactivity between aztreonam and penicillins is poor, but clinical tolerance of aztreonam has been assessed, by means of tolerance challenge tests, just in few groups of penicillin-allergic patients. The aim of this study is to evaluate tolerability of aztreonam in a large group of betalactam-allergic patients. METHODS: Forty-two patients (>14 years of age), with a clinical history of immediate reactions to any betalactam and with positive immediate-type skin tests and/or positive specific IgE to any of the studied betalactam underwent an intramuscular challenge with aztreonam; they were studied by means of: skin prick and intradermal tests with penicilloyl polylysine, minor determinant mixture, semisynthetic penicillins, cephalosporins, aztreonam and imipenem; detection of specific IgE to penicillin G, penicillin V, ampicillin, amoxicillin, cefaclor and ceftriaxone. RESULTS: Forty-two patients (mean age 47.26 6 14.82 years), 26 females and 16 males, had positive skin tests and/or specific IgE to at least one of the studied betalactams. The most involved drugs were amoxicillin (21 cases), ampicillin (9 cases), penicillin G (8 cases) and other betalactams in the remaining cases. The most frequent reactions were anaphylaxis (25 cases) and urticaria (14 cases). All patients had negative intradermal tests with aztreonam and all patients tolerated the intramuscular graded challenge. Intradermal tests with aztreonam showed to have a negative predictive value of 100% in betalactam-allergic patients. CONCLUSIONS: Our data confirm the lack of cross-reactivity between betalactams and aztreonam. Immediate-type skin tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in betalactam-allergic patients who urgently need this drug.
J ALLERGY CLIN IMMUNOL FEBRUARY 2008
262
Successful Implementation of a Standardized Rapid Drug Desensitization Protocol for Chemotherapy and Rituximab in 413 Cases H. Legere, N. M. Tennant, D. E. Sloane, N. Barrett, D. Hong, F. I. Hsu, T. M. Laidlaw, S. Nallamshetty, R. I. Palis, J. Rao, M. C. Castells; Brigham and Women’s Hospital, Boston, MA. RATIONALE: Temporary tolerance to chemotherapeutic drugs, including monoclonal antibodies, has been acheived at our institution with a standardized rapid desensitization protocol. We evaluated the safety and efficacy of this protocol. METHODS: 98 patients (97 with solid tumors, 1 with polymyositis) with hypersensitivity reactions (HSRs) to chemotherapeutic agents received rapid desensitization to carboplatin, cisplatin, oxaliplatin, paclitaxel, pegylated doxorubicin, adriamycin, or rituximab according to a standardized 12-step protocol, via either the intravenous or intraperitoneal route. The inclusion criteria were: 1) age 18 years; 2) ability to provide informed consent; and 3) HSR to a chemotherapeutic drug or monoclonal antibody occurring during the infusion or shortly after (within 48 hours). Patients with delayed reactions, serum sickness, Stevens-Johnson syndrome, or toxic epidermal necrolysis were excluded. Initial desensitizations occurred in the Medical Intensive Care Unit and most subsequent infusions in the outpatient setting. Data on the safety and efficacy of the protocol were obtained by review of treatment records. RESULTS: 413 desensitizations were performed, 94% of which induced limited or no side effects. During desensitizations, no life-threatening HSRs or deaths occurred, and all patients received their full target dose. For patients who were desensitized multiple times, most reactions occurred during the first desensitization. During any given desensitization, most reactions occurred at the last step of the protocol. The protocol was equally effective intravenously and intraperitoneally. CONCLUSIONS: Rapid drug desensitization using our standardized 12step protocol is safe and effective. This approach should be the standard of care in treating patients with HSRs to chemotherapeutic drugs, including monoclonal antibodies. Funding: Ovations For The Cure
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Differences in the Clinical Presentation of Anaphylaxis in Patients with Indolent Systemic Mastocytosis (ISM) versus Idiopathic Anaphylaxis (IA) A. P. Koterba1, C. Akin2; 1University of Michigan, Department of Medicine, Ann Arbor, MI, 2University of Michigan, Department of Medicine, Division of Allergy & Immunology, Ann Arbor, MI. RATIONALE: Recurrent anaphylaxis is a common clinical feature of ISM and IA. We sought to investigate the clinical presentation of anaphylaxis in patients with ISM compared to IA. METHODS: Thirty consecutive patients referred for evaluation of mastocytosis underwent bone marrow biopsy. Symptoms/signs of anaphylaxis were tabulated and tryptase, IgE levels, and hematologic parameters were compared. RESULTS: Fifteen patients (8 female/7 male, ages 25-58) had confirmed ISM according to WHO criteria. Fifteen patients (12 female/3 male, ages 17-54) who did not fit criteria were designated with IA. Tryptase levels were significantly elevated with ISM compared to IA (71.5 vs 7.6 ng/ml, p < 0.001). Conversely, those with IA had significantly higher IgE levels (109.6 vs 43.3 IU/ml, p < 0.05). Hematologic parameters did not significantly differ between groups. Notably, no patients with ISM endorsed urticaria during anaphylactic episodes. Urticaria was reported more frequently with IA versus ISM (33% vs 0%, p < 0.005). GI symptoms (60% ISM, 73% IA), flushing (80% ISM, 67% IA), hypotension (40% ISM, 47% IA), and syncope (67% ISM, 67% IA) were commonly reported amongst both groups, however no significant intergroup difference was observed. Angioedema was noted in 2/15 with ISM and 4/15 with IA. 4/15 with ISM and 3/15 with IA reported bronchospasm. CONCLUSIONS: Urticaria is a negative clinical indicator for the presence of mast cell disease in patients with anaphylaxis. Other clinical features of anaphylaxis in patients with mast cell disease were similar to
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260
Role of Effector Cells In Drug-induced Maculopapular Exanthema T. D. Ferna´ndez1, M. J. Torres2, C. Antunez1, J. A. Cornejo-Garcı´a1, M. F. del Prado3, G. Requena2, M. Blanca2, C. Mayorga1; 1Research Laboratory, Carlos Haya Hospital-Fundacion IMABIS, Ma´laga, SPAIN, 2 Allergy Service, Carlos Haya Hospital, Ma´laga, SPAIN, 3Emergency Unit, Carlos Haya Hospital, Ma´laga, SPAIN. RATIONALE: Drug-induced maculopapular exanthema is a cutaneous delayed allergic reaction where Th1 lymphocytes are involved as effector cells. One type of effector cells, CCR7-CD27-, are characterised by a high capacity for responding to specific antigens. Among this CCR7-CD27-, those with CCR10 expression are recruited to skin. We analyzed the presence of effector cells and their influence in drug-induced maculopapular exanthema. METHODS: Peripheral blood mononuclear cells (PBMCs) extracted from 12 patients during the acute phase and the resolution period and from 8 healthy controls were analyzed. Different T-cells subsets (CD4, CD8), effector phenotype (CCR7, CD27) and skin homing receptor CCR10 were analyzed by flow cytometry at baseline and after culturing with and without the culprit drug. RESULTS: At baseline, we found a significant increase of CCR7-CD27cells in both acute and resolution phase compared with controls (p 5 0,003 and p 5 0,032 respectively). The percentage of CCR7-CD27- in CD41 and CCR101 subpopulations was significantly increased at the acute phase compared with the resolution period (p 5 0,001 and p 5 0,045 respectively). After the culture with the culprit drug, we found a significant increase of CCR7-CD27- cells (p 5 0,003) and in CCR101CCR7-CD27- cells (p 5 0,006) at the resolution period compared to controls. No differences in cultured PBMCs were found between acute phase compared to controls. CONCLUSIONS: Cutaneous effector cells are present in patients with drug-induced maculopapular exanthema, especially in CD41 subpopulation. These effector cells increase after culturing with the drug involved in the non-immediate reaction.
261
Tolerability Of Aztreonam In Patients With IgE-mediated Allergy To Betalactams D. Schiavino, A. Buonomo, C. Lombardo, G. Altomonte, E. Nucera, G. Patriarca; Allergy Unit, Catholic University of the Sacred Heart, Rome, ITALY. RATIONALE: Cross-reactivity between aztreonam and penicillins is poor, but clinical tolerance of aztreonam has been assessed, by means of tolerance challenge tests, just in few groups of penicillin-allergic patients. The aim of this study is to evaluate tolerability of aztreonam in a large group of betalactam-allergic patients. METHODS: Forty-two patients (>14 years of age), with a clinical history of immediate reactions to any betalactam and with positive immediate-type skin tests and/or positive specific IgE to any of the studied betalactam underwent an intramuscular challenge with aztreonam; they were studied by means of: skin prick and intradermal tests with penicilloyl polylysine, minor determinant mixture, semisynthetic penicillins, cephalosporins, aztreonam and imipenem; detection of specific IgE to penicillin G, penicillin V, ampicillin, amoxicillin, cefaclor and ceftriaxone. RESULTS: Forty-two patients (mean age 47.26 6 14.82 years), 26 females and 16 males, had positive skin tests and/or specific IgE to at least one of the studied betalactams. The most involved drugs were amoxicillin (21 cases), ampicillin (9 cases), penicillin G (8 cases) and other betalactams in the remaining cases. The most frequent reactions were anaphylaxis (25 cases) and urticaria (14 cases). All patients had negative intradermal tests with aztreonam and all patients tolerated the intramuscular graded challenge. Intradermal tests with aztreonam showed to have a negative predictive value of 100% in betalactam-allergic patients. CONCLUSIONS: Our data confirm the lack of cross-reactivity between betalactams and aztreonam. Immediate-type skin tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in betalactam-allergic patients who urgently need this drug.
J ALLERGY CLIN IMMUNOL FEBRUARY 2008
262
Successful Implementation of a Standardized Rapid Drug Desensitization Protocol for Chemotherapy and Rituximab in 413 Cases H. Legere, N. M. Tennant, D. E. Sloane, N. Barrett, D. Hong, F. I. Hsu, T. M. Laidlaw, S. Nallamshetty, R. I. Palis, J. Rao, M. C. Castells; Brigham and Women’s Hospital, Boston, MA. RATIONALE: Temporary tolerance to chemotherapeutic drugs, including monoclonal antibodies, has been acheived at our institution with a standardized rapid desensitization protocol. We evaluated the safety and efficacy of this protocol. METHODS: 98 patients (97 with solid tumors, 1 with polymyositis) with hypersensitivity reactions (HSRs) to chemotherapeutic agents received rapid desensitization to carboplatin, cisplatin, oxaliplatin, paclitaxel, pegylated doxorubicin, adriamycin, or rituximab according to a standardized 12-step protocol, via either the intravenous or intraperitoneal route. The inclusion criteria were: 1) age 18 years; 2) ability to provide informed consent; and 3) HSR to a chemotherapeutic drug or monoclonal antibody occurring during the infusion or shortly after (within 48 hours). Patients with delayed reactions, serum sickness, Stevens-Johnson syndrome, or toxic epidermal necrolysis were excluded. Initial desensitizations occurred in the Medical Intensive Care Unit and most subsequent infusions in the outpatient setting. Data on the safety and efficacy of the protocol were obtained by review of treatment records. RESULTS: 413 desensitizations were performed, 94% of which induced limited or no side effects. During desensitizations, no life-threatening HSRs or deaths occurred, and all patients received their full target dose. For patients who were desensitized multiple times, most reactions occurred during the first desensitization. During any given desensitization, most reactions occurred at the last step of the protocol. The protocol was equally effective intravenously and intraperitoneally. CONCLUSIONS: Rapid drug desensitization using our standardized 12step protocol is safe and effective. This approach should be the standard of care in treating patients with HSRs to chemotherapeutic drugs, including monoclonal antibodies. Funding: Ovations For The Cure
263
Differences in the Clinical Presentation of Anaphylaxis in Patients with Indolent Systemic Mastocytosis (ISM) versus Idiopathic Anaphylaxis (IA) A. P. Koterba1, C. Akin2; 1University of Michigan, Department of Medicine, Ann Arbor, MI, 2University of Michigan, Department of Medicine, Division of Allergy & Immunology, Ann Arbor, MI. RATIONALE: Recurrent anaphylaxis is a common clinical feature of ISM and IA. We sought to investigate the clinical presentation of anaphylaxis in patients with ISM compared to IA. METHODS: Thirty consecutive patients referred for evaluation of mastocytosis underwent bone marrow biopsy. Symptoms/signs of anaphylaxis were tabulated and tryptase, IgE levels, and hematologic parameters were compared. RESULTS: Fifteen patients (8 female/7 male, ages 25-58) had confirmed ISM according to WHO criteria. Fifteen patients (12 female/3 male, ages 17-54) who did not fit criteria were designated with IA. Tryptase levels were significantly elevated with ISM compared to IA (71.5 vs 7.6 ng/ml, p < 0.001). Conversely, those with IA had significantly higher IgE levels (109.6 vs 43.3 IU/ml, p < 0.05). Hematologic parameters did not significantly differ between groups. Notably, no patients with ISM endorsed urticaria during anaphylactic episodes. Urticaria was reported more frequently with IA versus ISM (33% vs 0%, p < 0.005). GI symptoms (60% ISM, 73% IA), flushing (80% ISM, 67% IA), hypotension (40% ISM, 47% IA), and syncope (67% ISM, 67% IA) were commonly reported amongst both groups, however no significant intergroup difference was observed. Angioedema was noted in 2/15 with ISM and 4/15 with IA. 4/15 with ISM and 3/15 with IA reported bronchospasm. CONCLUSIONS: Urticaria is a negative clinical indicator for the presence of mast cell disease in patients with anaphylaxis. Other clinical features of anaphylaxis in patients with mast cell disease were similar to