- Email: [email protected]
Successful Desensitization to Infliximab in 14 Subjects
Abstracts S237
J ALLERGY CLIN IMMUNOL VOLUME 123, NUMBER 2
Antibiotic Allergy: Relationship to Age and Gender E. Macy1, K. T. Poon2; 1SCPMG-Kaiser Permanente San Diego, San Diego, CA, 2Kaiser Permanente Southern California, Pasadena, CA. RATIONALE: Data from large outpatient populations on the effect of age and gender on the prevalence of reported antibiotic allergy is rare. METHODS: Demographic and drug allergy data was extracted from the electronic health records of the 411,543 patients cared for by Kaiser Permanente in San Diego County who had 1 outpatient visit during 2007. RESULTS: The most commonly reported antibiotic allergy for females was penicillin (11.0% of the population) followed by sulfa (7.9%), macrolides (1.9%), others (1.7%), cephalosporins (1.7%), tetracyclines (1.5%), and quinolones (0.8%). For males it was penicillin (6.5%) followed by sulfa (2.4%), cephalosporins (0.8%), macrolides (0.6%), others (0.5%), tetracyclines (0.5%), and quinolones (0.3%). Antibiotic allergy was more common in females for all antibiotic classes evaluated and for all decades of life compared to males. Antibiotic allergy was more common in both males and females as age increased. Antibiotic allergy accounted for 54.2% of all drug allergy reports. Other significant drug classes that account for most of the rest of the drug allergy reported included narcotics (13.9%), NSAIDs (7.7%), ACE inhibitors (3.1%), non-ACE-inhibitor anti-hypertension medications (2.9%), radiographic contrast materials (2.3%), anti-cholesterol medications (1.7%), therapeutic proteins (0.8%), and local anesthetics (0.5%). One drug allergy was reported by 13.9% of the population and 8.5% reported more than one drug allergy. CONCLUSIONS: Antibiotic allergy accounts for more than half of all drug allergies reported. Antibiotic allergy is significantly associated with females and the elderly. Antibiotic allergy is rarely undiagnosed and reported allergies appear to accumulate with age based on antibiotic utilization.
916
Azithromycin Allergy: How Common in Pediatrics? S. Kamboj, E. Yousef; A.I. Dupont Hospital for Children, Wilmington, DE. RATIONALE: The discontinuation of commercial drug testing for penicillin (PCNs) in 2004 left no method for formal testing to PCN allergy. Many practitioners have explored alternative drug therapy regimens with different drug classes, such as the macrolides specifically Azithromycin. This study describes a 2-year experience with suspected ‘‘Azithromycin allergy’’ in PCN allergic patients. METHODS: The medical records of 350 children aged 1-18 years with ICD-9 code of ‘‘adverse reaction to medications’’ were reviewed. Diagnosis of ‘‘Azithromycin allergy’’ was based on clinical history. Chart reviews identified 16 pediatric patients with ‘‘Azithromycin allergy’’ who underwent Azithromycin drug challenges. RESULTS: All patients had a previously documented adverse reaction to Azithromycin. No patients had history of Stevens Johnson Syndrome or anaphylaxis with Azithromycin. In 15 of 16 patients (93.7%) there was previously documented adverse reactions to PCNs and/or cephalosporins. Overall, 15 of 16 patients (93.7%) underwent a 3 dose incremental challenge of Azithromycin in the office with a cumulative dose of 10 mg/kg, max dose being 500 mg. 1 of 16 patients (6.2%) was prescribed Azithromycin by their PMD and observed closely. All patients (100%) had sucessful oral challenges. CONCLUSIONS: The data suggests an extremely rare occurrence of Azithromycin allergy. This antibiotic is therefore a safe alternative to PCNs and/or cephalosporins in patients allergic to these two drugs.
917
Successful Desensitization to Infliximab in 14 Subjects Y. Yilmaz-Demirdag, A. M. Casillas, S. L. Bahna; Louisiana State University Health Sciences Center, Shreveport, LA. RATIONALE: Systemic reactions to infliximab (Remicade; Centocor, Inc.) often lead to its permanent discontinuation. We tested the safety and effectiveness of a desensitization protocol, we had developed, on 14 patients who had systemic reactions to this drug. METHODS: The protocol utilizes 3 concentrations of infliximab (0.1, 1.0, and 2.5 mg/ml), starting at 0.01 mg dose and increasing every 15 min until the total therapeutic dose (350-600 mg) is reached over 4-6 hours. We applied it to 14 patients (20-76 years): 9 Crohn’s disease, 2 rheumatoid arthritis, 2 psoriatic arthritis, and 1 ankylosing spondylitis. Their initial adverse reactions included: flushing in 6, dyspnea/chest tightness in 5, itching without rash in 4, rash in 3, chills in 3, lip swelling in2, body ache in 2, nausea in 1, and wheezing in 1; and occurred during their 1st to 3rd infusions. RESULTS: Out of 13 patients tested, SPT (5 mg/ml) and ID test (1 mcg & 5 mcg/ml) were negative in all but one. By using our protocol, 102 infusions at 4-8 weeks intervals were administered to the 14 patients without premedication, except in 3 (diphenhydramine, acetaminophen, and prednisone). Some developed mild reactions: flushing (8), itching without rash (7), chills (5), nausea (4), rash (1), and headache, responding well to symptomatic treatment. No serious reactions occurred during or after these infusions. CONCLUSIONS: Although such systemic reactions to infliximab may have multiple mechanisms, our desensitization protocol has been safe and effective, and may be applied to similar cases.
918
Role of TLR Agonist in Allergic Reactions to Drugs E. Gomez1, C. Mayorga1, C. Antunez1, T. D. Fernandez1, S. 1 Lopez , M. J. Torres2, P. Chaves1, M. Blanca1; 1Fundacion IMABIS-Carlos Haya Hospital, Ma´laga, Spain, 2Carlos Haya Hospital, Ma´laga, Spain. RATIONALE: Lymphocyte transformation tests (LTT) is currently the only in vitro test available for diagnosing non-immediate allergic reactions (NIR) to drugs despite its low sensitivity. Dendritic cells (DC) have been used by our group to improve LTT sensitivity although it is still not optimal with some drugs probably because DC do not achieve a complete maturation. In these cases, a concomitant stimulation by TLR similar to the one that takes place in viral infections may contribute to a complete DC maturation and therefore a higher LTT. The aim of this work was to study how the interaction of drugs and agonist with TLR of DC induce changes in DC maturation and lymphocyte proliferation. METHODS: DC maturation was analyzed by flow cytometry and T cell proliferation to the drugs by LTT in presence or absence of TLR-7/8 agonist in subjects with a confirmed maculopapular exanthema (MPE) induced either by drugs or by virus and in healthy controls. RESULTS: Data showed an increase of DC maturational markers (HLADR, CD80 and CD86) compared to basal conditions in patients with MPE induced by drugs or viral infection. LTT was only positive (SI > 3) to the drug responsible of the reaction and when TLR agonist was present in the culture. In healthy controls no DC maturation was observed and LTT were negative. CONCLUSIONS: The presence of virus epitopes that interact with TLR from DC may increase LTT sensitivity in the evaluation of allergic reactions to drugs that occurred concomitantly to a viral infection.
TUESDAY
915
J ALLERGY CLIN IMMUNOL VOLUME 123, NUMBER 2
Antibiotic Allergy: Relationship to Age and Gender E. Macy1, K. T. Poon2; 1SCPMG-Kaiser Permanente San Diego, San Diego, CA, 2Kaiser Permanente Southern California, Pasadena, CA. RATIONALE: Data from large outpatient populations on the effect of age and gender on the prevalence of reported antibiotic allergy is rare. METHODS: Demographic and drug allergy data was extracted from the electronic health records of the 411,543 patients cared for by Kaiser Permanente in San Diego County who had 1 outpatient visit during 2007. RESULTS: The most commonly reported antibiotic allergy for females was penicillin (11.0% of the population) followed by sulfa (7.9%), macrolides (1.9%), others (1.7%), cephalosporins (1.7%), tetracyclines (1.5%), and quinolones (0.8%). For males it was penicillin (6.5%) followed by sulfa (2.4%), cephalosporins (0.8%), macrolides (0.6%), others (0.5%), tetracyclines (0.5%), and quinolones (0.3%). Antibiotic allergy was more common in females for all antibiotic classes evaluated and for all decades of life compared to males. Antibiotic allergy was more common in both males and females as age increased. Antibiotic allergy accounted for 54.2% of all drug allergy reports. Other significant drug classes that account for most of the rest of the drug allergy reported included narcotics (13.9%), NSAIDs (7.7%), ACE inhibitors (3.1%), non-ACE-inhibitor anti-hypertension medications (2.9%), radiographic contrast materials (2.3%), anti-cholesterol medications (1.7%), therapeutic proteins (0.8%), and local anesthetics (0.5%). One drug allergy was reported by 13.9% of the population and 8.5% reported more than one drug allergy. CONCLUSIONS: Antibiotic allergy accounts for more than half of all drug allergies reported. Antibiotic allergy is significantly associated with females and the elderly. Antibiotic allergy is rarely undiagnosed and reported allergies appear to accumulate with age based on antibiotic utilization.
916
Azithromycin Allergy: How Common in Pediatrics? S. Kamboj, E. Yousef; A.I. Dupont Hospital for Children, Wilmington, DE. RATIONALE: The discontinuation of commercial drug testing for penicillin (PCNs) in 2004 left no method for formal testing to PCN allergy. Many practitioners have explored alternative drug therapy regimens with different drug classes, such as the macrolides specifically Azithromycin. This study describes a 2-year experience with suspected ‘‘Azithromycin allergy’’ in PCN allergic patients. METHODS: The medical records of 350 children aged 1-18 years with ICD-9 code of ‘‘adverse reaction to medications’’ were reviewed. Diagnosis of ‘‘Azithromycin allergy’’ was based on clinical history. Chart reviews identified 16 pediatric patients with ‘‘Azithromycin allergy’’ who underwent Azithromycin drug challenges. RESULTS: All patients had a previously documented adverse reaction to Azithromycin. No patients had history of Stevens Johnson Syndrome or anaphylaxis with Azithromycin. In 15 of 16 patients (93.7%) there was previously documented adverse reactions to PCNs and/or cephalosporins. Overall, 15 of 16 patients (93.7%) underwent a 3 dose incremental challenge of Azithromycin in the office with a cumulative dose of 10 mg/kg, max dose being 500 mg. 1 of 16 patients (6.2%) was prescribed Azithromycin by their PMD and observed closely. All patients (100%) had sucessful oral challenges. CONCLUSIONS: The data suggests an extremely rare occurrence of Azithromycin allergy. This antibiotic is therefore a safe alternative to PCNs and/or cephalosporins in patients allergic to these two drugs.
917
Successful Desensitization to Infliximab in 14 Subjects Y. Yilmaz-Demirdag, A. M. Casillas, S. L. Bahna; Louisiana State University Health Sciences Center, Shreveport, LA. RATIONALE: Systemic reactions to infliximab (Remicade; Centocor, Inc.) often lead to its permanent discontinuation. We tested the safety and effectiveness of a desensitization protocol, we had developed, on 14 patients who had systemic reactions to this drug. METHODS: The protocol utilizes 3 concentrations of infliximab (0.1, 1.0, and 2.5 mg/ml), starting at 0.01 mg dose and increasing every 15 min until the total therapeutic dose (350-600 mg) is reached over 4-6 hours. We applied it to 14 patients (20-76 years): 9 Crohn’s disease, 2 rheumatoid arthritis, 2 psoriatic arthritis, and 1 ankylosing spondylitis. Their initial adverse reactions included: flushing in 6, dyspnea/chest tightness in 5, itching without rash in 4, rash in 3, chills in 3, lip swelling in2, body ache in 2, nausea in 1, and wheezing in 1; and occurred during their 1st to 3rd infusions. RESULTS: Out of 13 patients tested, SPT (5 mg/ml) and ID test (1 mcg & 5 mcg/ml) were negative in all but one. By using our protocol, 102 infusions at 4-8 weeks intervals were administered to the 14 patients without premedication, except in 3 (diphenhydramine, acetaminophen, and prednisone). Some developed mild reactions: flushing (8), itching without rash (7), chills (5), nausea (4), rash (1), and headache, responding well to symptomatic treatment. No serious reactions occurred during or after these infusions. CONCLUSIONS: Although such systemic reactions to infliximab may have multiple mechanisms, our desensitization protocol has been safe and effective, and may be applied to similar cases.
918
Role of TLR Agonist in Allergic Reactions to Drugs E. Gomez1, C. Mayorga1, C. Antunez1, T. D. Fernandez1, S. 1 Lopez , M. J. Torres2, P. Chaves1, M. Blanca1; 1Fundacion IMABIS-Carlos Haya Hospital, Ma´laga, Spain, 2Carlos Haya Hospital, Ma´laga, Spain. RATIONALE: Lymphocyte transformation tests (LTT) is currently the only in vitro test available for diagnosing non-immediate allergic reactions (NIR) to drugs despite its low sensitivity. Dendritic cells (DC) have been used by our group to improve LTT sensitivity although it is still not optimal with some drugs probably because DC do not achieve a complete maturation. In these cases, a concomitant stimulation by TLR similar to the one that takes place in viral infections may contribute to a complete DC maturation and therefore a higher LTT. The aim of this work was to study how the interaction of drugs and agonist with TLR of DC induce changes in DC maturation and lymphocyte proliferation. METHODS: DC maturation was analyzed by flow cytometry and T cell proliferation to the drugs by LTT in presence or absence of TLR-7/8 agonist in subjects with a confirmed maculopapular exanthema (MPE) induced either by drugs or by virus and in healthy controls. RESULTS: Data showed an increase of DC maturational markers (HLADR, CD80 and CD86) compared to basal conditions in patients with MPE induced by drugs or viral infection. LTT was only positive (SI > 3) to the drug responsible of the reaction and when TLR agonist was present in the culture. In healthy controls no DC maturation was observed and LTT were negative. CONCLUSIONS: The presence of virus epitopes that interact with TLR from DC may increase LTT sensitivity in the evaluation of allergic reactions to drugs that occurred concomitantly to a viral infection.
TUESDAY
915