- Email: [email protected]
Beta-Lactam Hypersensitivity Diagnosis, Influence of Benzylpenicillin
Abstracts S191
J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2
Characterization of Patients Sensitized to Cefuroxim B. Arnoux1, N. Soohun2, L. Rouanet-Bousquet2, P. Demoly2, P. Bousquet3; 1INSERM, Montpellier, FRANCE, 2Service des Maladies Respiratoires, University Hospital of Montpellier, FRANCE, 3Departement de la Information Medica, University Hospital of Montpellier, FRANCE. RATIONALE: Cefuroxim, which is a common beta-lactam used in France, is frequently suspected to induce hypersensitivity reactions. We report tests and characterization of sensitive patients present in our Drug Allergy and Hypersensitivity Database (DAHD). METHODS: We analysed in a historico-prospective cohort study all patients present in our DHAD (3354 patients) since 1996, for a suspected beta-lactam hypersensitivity reaction and who underwent at least skin tests to cefuroxim were included. Diagnosis (skin tests and challenges) followed the European Network on Drug allergy (ENDA) recommendations. RESULTS: 650 patients [(188, 29.1% of male), 107 (16.5%) asthmatics and 355 (54.6%) atopics] were tested. Clinical history involving cefuroxim was detected in 38 patients (5.8%). Symptoms was urticaria/angiœdema in 17 (44.7%), exanthema in 10 (26.3%) and anaphylaxis/anaphylactic shock in 6 (15.6%) patients. Only 5 (13.2%) were positive (3 skin tests and 2 oral challenges). Among those tested as an alternative treatment (612), 178 (29.2%) were positive to at least one beta-lactam. 10 (1.6%) of them were also positive to cefuroxim (3 skin tests and 7 challenges). The most common clinical presentations were urticaria/angiœdema (4, 40%) as well as anaphylaxis/anaphylactic shock (4, 40%). CONCLUSIONS: 22.2% of patient with a drug allergy to beta-lactam, were positive to cefuroxim. Among those positive to the later one, 20,8% had no history involving this drug. Funding: INSERM
733
Predictors of Mortality in Patients with Severe Cutaneous Allergic Reactions K. Leong, B. Thong, Y. Cheng, F. Chia, J. Tan, C. Tang, H. Chng; Tan Tock Seng Hospital, Singapore, SINGAPORE. RATIONALE: Severe cutaneous allergic reactions (SCARs) can lead to morbidity and mortality. We attempted to derive the clinical predictors of mortality in our patients. METHODS: We prospectively documented 1093 inhospital drug allergy events in our institution from 1997 to 2006. In this study, we defined SCAR as drug hypersensitivity syndrome (DHS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Variables in the forward stepwise logistic regression model were patient age, sex, ethnicity, type of reaction, whether the reaction developed before or during hospitalization, presence of polypharmacy (defined as concuurent use of 5 or more drugs), number of comorbidities, and types of drugs. RESULTS: There were 199 patients with SCAR, with 11 deaths (5.5%). The mean age of the patients was 55 6 19.4 years. Males constitute 47.7% of the group. Ethnically, there were Chinese (80.9%), Malay (11.1%), Indian (3.5%) and others (4.5%). There were 179 patients with DHS, 29 with SJS, 16 TEN and 10 overlap. In the multivariate model, the only statistically significant factor associated with mortality was the presence of TEN (odds ratio 2.53, p 5 0.001). CONCLUSIONS: The presence of TEN is the best clinical predictor of mortality of patients with SCARs.
734
Beta-Lactam Hypersensitivity Diagnosis, Influence of Benzylpenicillin L. Rouanet-Bousquet1, B. Arnoux2, P. Demoly1, A. Romano3, P. Bousquet4; 1Exploration des Allergies, Service des Maladies Respiratoires, University Hospital of Montpellier, FRANCE, 2INSERM, University Hos˜ di Allergologia, Complesso Intepital of Montpellier, FRANCE, 3UnitA grato Columbus, ROMA, FRANCE, 4Departement de la Information Medica, University Hospital of Montpellier, FRANCE. RATIONALE: Drug hypersensitivity to beta-lactam was often skin tested using benzyl-penicillin, major (PPL) and minor (MDM) penicillin determinants, amoxicillin, ampicillin and any other culprit beta-lactam.
However, PPL and MDM were removed from the market. The aim of the study was to assess the influence of benzylpenicillin before and after the withdrawal. METHODS: Using our Drug Allergy and Hypersensitivity Database (3354 patients recorded from Montpellier and Rome), we conducted a historico-prospective cohort study. All patients who consulted, since 1996, for a suspected beta-lactam hypersensitivity reaction and who had at least positive skin test to benzylpenicillin were included. Diagnosis and skin tests followed the ENDA recommendations. Benzylpenicillin, PPL, MDM, Ampicillin, Amoxicillin were always skin tested. RESULTS: 133 patients (48 aˆV‘‘ 36.1% men), 15 (11.3%) asthmatics and 41 (30.8%) atopics were included. 13 (9.8%) were only positive to benzylpenicillin, 32 (26.5%) were also positive for PPL and 66 (55.5%) for MDM. Without skin testing for PPL and MDM, the number of positive to benzylpenicillin increased to 20 (15.0%). No difference was observed for asthma and atopic between subjects only positive to benzylpencillin and those also positive for another penicillin (p 5 0.84 and p 5 0.34 respectively). Anaphylaxis and anaphylactic shock were more common in subjects positive to several penicillins (76 aˆV‘‘ 67.3% vs 7 aˆV‘‘ 35%, p 5 0.001). Conversely, only 26 (23.0%) vs 8 (40.0%) presented an urticaria/angiodema. CONCLUSIONS: Since the withdrawal of PPL and MDM, benzylpenicillin skin test appeared to be mandatory, 15% of the patients being only positive to this drug. This should significantly reduce oral challenges. Funding: INSERM
735
Basophil Activation Test in Immediate Allergy to Betalactams-Reviewing Stimulation Index and Positivity Criteria A. Lopes Pregal1, A. Melo2, M. Conceicxa˜o Santos2, I. Mascarenhas1, A. Spı´nola Santos1, S. Lopes Silva1, E. Pedro1, M. Pereira-Barbosa1; 1Immunoallergology Department Hospital Santa Maria, Lisbon, PORTUGAL, 2 Clinical Immunology Unit Lisbon Medical School, Lisbon, PORTUGAL. RATIONALE: Since basophil activation test (BAT) has been proposed to study allergic reactions to drugs, we evaluated its sensitivity and specificity in betalactams allergy. METHODS: 16 patients (9F/7M; 39.06 6 20.04 years-old) with immediate allergic reactions to betalactams or cephalosporins were evaluated. All patients were submitted to: 1-skin tests and BAT to PPL, MDM, penicillin G, amoxicillin, ampicillin and cephalosporins; 2-Specific IgE (sIgE) to penicillin G, penicillin V, ampicillin and amoxicillin. BAT results were considered positive with stimulation index (SI)5. Allergy was excluded with negative skin tests or provocation tests and confirmed with positive skin tests. RESULTS: Positive skin tests to at least one drug were obtained in 9 patients (56.3%). All patients with negative skin tests underwent negative provocation tests with the culprit drug. We compared sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of BAT, sIgEs and combination of both methods. BAT results were analysed both considering positive BAT with SI 5 to one or 2 among PPL, MDM, penicillin G, amoxicillin and ampicillin. BAT sensitivity (55.6%) was higher than sIgE’s (33.3%) and improved when combining both methods (88.9%). Specificity of sIgE was similar to BAT’s (85.7%) although this method had the highest PPV (83.3%). CONCLUSIONS: Establishing posititivity criteria to BAT as a minimum of 2 positive results to different drugs we improved specificity and PPV of this essay. Combining BAT and sIgE results to betalactams we obtained the most accurate in vitro evaluation. Conversely, in our population, BAT did not improve cephalosporins allergy work-up.
MONDAY
732
J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2
Characterization of Patients Sensitized to Cefuroxim B. Arnoux1, N. Soohun2, L. Rouanet-Bousquet2, P. Demoly2, P. Bousquet3; 1INSERM, Montpellier, FRANCE, 2Service des Maladies Respiratoires, University Hospital of Montpellier, FRANCE, 3Departement de la Information Medica, University Hospital of Montpellier, FRANCE. RATIONALE: Cefuroxim, which is a common beta-lactam used in France, is frequently suspected to induce hypersensitivity reactions. We report tests and characterization of sensitive patients present in our Drug Allergy and Hypersensitivity Database (DAHD). METHODS: We analysed in a historico-prospective cohort study all patients present in our DHAD (3354 patients) since 1996, for a suspected beta-lactam hypersensitivity reaction and who underwent at least skin tests to cefuroxim were included. Diagnosis (skin tests and challenges) followed the European Network on Drug allergy (ENDA) recommendations. RESULTS: 650 patients [(188, 29.1% of male), 107 (16.5%) asthmatics and 355 (54.6%) atopics] were tested. Clinical history involving cefuroxim was detected in 38 patients (5.8%). Symptoms was urticaria/angiœdema in 17 (44.7%), exanthema in 10 (26.3%) and anaphylaxis/anaphylactic shock in 6 (15.6%) patients. Only 5 (13.2%) were positive (3 skin tests and 2 oral challenges). Among those tested as an alternative treatment (612), 178 (29.2%) were positive to at least one beta-lactam. 10 (1.6%) of them were also positive to cefuroxim (3 skin tests and 7 challenges). The most common clinical presentations were urticaria/angiœdema (4, 40%) as well as anaphylaxis/anaphylactic shock (4, 40%). CONCLUSIONS: 22.2% of patient with a drug allergy to beta-lactam, were positive to cefuroxim. Among those positive to the later one, 20,8% had no history involving this drug. Funding: INSERM
733
Predictors of Mortality in Patients with Severe Cutaneous Allergic Reactions K. Leong, B. Thong, Y. Cheng, F. Chia, J. Tan, C. Tang, H. Chng; Tan Tock Seng Hospital, Singapore, SINGAPORE. RATIONALE: Severe cutaneous allergic reactions (SCARs) can lead to morbidity and mortality. We attempted to derive the clinical predictors of mortality in our patients. METHODS: We prospectively documented 1093 inhospital drug allergy events in our institution from 1997 to 2006. In this study, we defined SCAR as drug hypersensitivity syndrome (DHS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Variables in the forward stepwise logistic regression model were patient age, sex, ethnicity, type of reaction, whether the reaction developed before or during hospitalization, presence of polypharmacy (defined as concuurent use of 5 or more drugs), number of comorbidities, and types of drugs. RESULTS: There were 199 patients with SCAR, with 11 deaths (5.5%). The mean age of the patients was 55 6 19.4 years. Males constitute 47.7% of the group. Ethnically, there were Chinese (80.9%), Malay (11.1%), Indian (3.5%) and others (4.5%). There were 179 patients with DHS, 29 with SJS, 16 TEN and 10 overlap. In the multivariate model, the only statistically significant factor associated with mortality was the presence of TEN (odds ratio 2.53, p 5 0.001). CONCLUSIONS: The presence of TEN is the best clinical predictor of mortality of patients with SCARs.
734
Beta-Lactam Hypersensitivity Diagnosis, Influence of Benzylpenicillin L. Rouanet-Bousquet1, B. Arnoux2, P. Demoly1, A. Romano3, P. Bousquet4; 1Exploration des Allergies, Service des Maladies Respiratoires, University Hospital of Montpellier, FRANCE, 2INSERM, University Hos˜ di Allergologia, Complesso Intepital of Montpellier, FRANCE, 3UnitA grato Columbus, ROMA, FRANCE, 4Departement de la Information Medica, University Hospital of Montpellier, FRANCE. RATIONALE: Drug hypersensitivity to beta-lactam was often skin tested using benzyl-penicillin, major (PPL) and minor (MDM) penicillin determinants, amoxicillin, ampicillin and any other culprit beta-lactam.
However, PPL and MDM were removed from the market. The aim of the study was to assess the influence of benzylpenicillin before and after the withdrawal. METHODS: Using our Drug Allergy and Hypersensitivity Database (3354 patients recorded from Montpellier and Rome), we conducted a historico-prospective cohort study. All patients who consulted, since 1996, for a suspected beta-lactam hypersensitivity reaction and who had at least positive skin test to benzylpenicillin were included. Diagnosis and skin tests followed the ENDA recommendations. Benzylpenicillin, PPL, MDM, Ampicillin, Amoxicillin were always skin tested. RESULTS: 133 patients (48 aˆV‘‘ 36.1% men), 15 (11.3%) asthmatics and 41 (30.8%) atopics were included. 13 (9.8%) were only positive to benzylpenicillin, 32 (26.5%) were also positive for PPL and 66 (55.5%) for MDM. Without skin testing for PPL and MDM, the number of positive to benzylpenicillin increased to 20 (15.0%). No difference was observed for asthma and atopic between subjects only positive to benzylpencillin and those also positive for another penicillin (p 5 0.84 and p 5 0.34 respectively). Anaphylaxis and anaphylactic shock were more common in subjects positive to several penicillins (76 aˆV‘‘ 67.3% vs 7 aˆV‘‘ 35%, p 5 0.001). Conversely, only 26 (23.0%) vs 8 (40.0%) presented an urticaria/angiodema. CONCLUSIONS: Since the withdrawal of PPL and MDM, benzylpenicillin skin test appeared to be mandatory, 15% of the patients being only positive to this drug. This should significantly reduce oral challenges. Funding: INSERM
735
Basophil Activation Test in Immediate Allergy to Betalactams-Reviewing Stimulation Index and Positivity Criteria A. Lopes Pregal1, A. Melo2, M. Conceicxa˜o Santos2, I. Mascarenhas1, A. Spı´nola Santos1, S. Lopes Silva1, E. Pedro1, M. Pereira-Barbosa1; 1Immunoallergology Department Hospital Santa Maria, Lisbon, PORTUGAL, 2 Clinical Immunology Unit Lisbon Medical School, Lisbon, PORTUGAL. RATIONALE: Since basophil activation test (BAT) has been proposed to study allergic reactions to drugs, we evaluated its sensitivity and specificity in betalactams allergy. METHODS: 16 patients (9F/7M; 39.06 6 20.04 years-old) with immediate allergic reactions to betalactams or cephalosporins were evaluated. All patients were submitted to: 1-skin tests and BAT to PPL, MDM, penicillin G, amoxicillin, ampicillin and cephalosporins; 2-Specific IgE (sIgE) to penicillin G, penicillin V, ampicillin and amoxicillin. BAT results were considered positive with stimulation index (SI)5. Allergy was excluded with negative skin tests or provocation tests and confirmed with positive skin tests. RESULTS: Positive skin tests to at least one drug were obtained in 9 patients (56.3%). All patients with negative skin tests underwent negative provocation tests with the culprit drug. We compared sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of BAT, sIgEs and combination of both methods. BAT results were analysed both considering positive BAT with SI 5 to one or 2 among PPL, MDM, penicillin G, amoxicillin and ampicillin. BAT sensitivity (55.6%) was higher than sIgE’s (33.3%) and improved when combining both methods (88.9%). Specificity of sIgE was similar to BAT’s (85.7%) although this method had the highest PPV (83.3%). CONCLUSIONS: Establishing posititivity criteria to BAT as a minimum of 2 positive results to different drugs we improved specificity and PPV of this essay. Combining BAT and sIgE results to betalactams we obtained the most accurate in vitro evaluation. Conversely, in our population, BAT did not improve cephalosporins allergy work-up.
MONDAY
732