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Role of Dendritic Cells in Delayed-type Hypersensitivity Reactions to Iodixanol (Visipaque®)
Abstracts AB153
J ALLERGY CLIN IMMUNOL VOLUME 125, NUMBER 2
COX-2 Up-regulation After Positive Aspirin Provocation M. Silar, M. Rijavec, N. Bajrovic, M. Kosnik, P. Korosec; University Clinic of Respiratory and Allergic Diseases, Golnik, SLOVENIA. RATIONALE: Previous in-vitro observations suggest that COX-2 expression appears to be differentially regulated in aspirin-sensitive patients. METHODS: COX1 and COX-2 expression was evaluated by real-time PCR just before aspirin oral provocation and 4 hours after provocation in 13 patients suspected for aspirin intolerance. RESULTS: We found significantly higher COX-2 expression (P 5 0.007) in 4 patients who experienced positive clinical reaction to aspirin in comparison to levels before provocation. No differences were observed in 9 patients with negative testing and for COX-1 expression. CONCLUSIONS: This in-vivo finding suggests that COX-2 pathway might be involved in aspirin-induced exacerbations.
601
A Retrospective Review of Drug Challenges over 5 Years in a Pediatric Population S. Kamboj1,2, S. J. McGeady1,2, E. Yousef1,2, J. Hossain2; 1Thomas Jefferson University, Philadelphia, PA, 2Alfred I Dupont Children’s Hospital, Wilmington, DE. RATIONALE: Studies estimate that 90% of ‘‘Penicillin (PCN) allergic’’ patients can safely receive the drug. However, these patients are often treated with alternative antibiotics, leading to increased occurrence of adverse drug reactions (ADR). We report a 5-year experience in managing suspected ‘‘drug allergies’’ to PCN and alternative antibiotics in children. METHODS: Medical records of patients aged 1-21 years with ‘‘ADR’’ were reviewed for demographic data, atopy, reaction type, skin prick testing (SPT) results, and drug challenge outcomes. Continued drug avoidance was advised in patients with positive SPT or ADR during challenge RESULTS: Chart reviews identified 96 patients with ‘‘ADR’’ who subsequently underwent SPT or graded challenges to the following: PCN (n552), cephalosporins (n5 7), azithromycin (AZT) (n5 24), or clindamycin (n54). Eighty-seven patients (90.6%) tolerated drug challenges and nine patients (9.4%) were instructed to continue drug avoidance. Eight of the nine patients continued drug avoidance due to positive SPT (n54) or ADR during PCN challenge (n54). One patient continued clindamycin avoidance after positive SPT. All AZT and cephalosporin challenges passed. Patients with atopy (OR 1.70, CI 0.40, 7.24) and ADR described as hives or pruritus (OR 3.58, CI 0.70, 18.25) were found to be more likely to require continued drug avoidance. CONCLUSIONS: True ‘‘antibiotic allergy’’ by positive SPT or challenge occurs less frequently than reported ADR in the pediatric population. AZT allergy appears to be rare and AZT is seen as a safe alternative medication.
602
Role of Dendritic Cells in Delayed-type Hypersensitivity Reactions to Iodixanol (VisipaqueÒ) C. Antunez1, E. Gomez1, R. M. Gueant-Rodriguez2, A. Barbaud3, T. D. Fernandez1, I. Gastin2, J. L. Gueant2, M. Blanca1; 1Allergy Service and Research Laboratory, Carlos Haya Hospital-Fundacio´n IMABIS, Ma´laga, SPAIN, 22Department of Biochemistry-Molecular Biology-Nutrition-Metabolism, University Hospital, Nancy, FRANCE, 3Dermatology Department, Fournier Hospital, Nancy, FRANCE. RATIONALE: Delayed-type reactions to contrast media (CM) represent 2-5% of patients with adverse reactions to CM. The role of DC in drug allergy reactions has not been sufficiently studied. The aim of this study was to determine the change induced by Iodixanol on the maturational state of DC, to evaluate if immature monocyte-derived DCs (imDC) used as antigen-presenting cells improved the sensitivity of the classical lymphocyte transformation test and to analyze the in vitro cytokines produced after drug stimulation in patients with maculopapular exanthema. Method: Peripheral blood lymphocytes and imDC were obtained from 6 patients with delayed reactions to iodixanol and 6 tolerant subjects. Interactions between DC, lymphocytes and Iodixanol were analyzed by phenotypic analysis using flow cytometry, proliferation by means of H3T incorporation, and cytokine production in supernatants by 11-plex bead-based immunoassay.
RESULTS: The percentage of patients with positive LTT ranged from 17% with classical LTT (PBMC) to 83% with modified LTT (with imDC). In PBMC cultures, an increase of IL-2 and IFN-g production were induced by iodixanol. In DC cultures, in addition to IL-2 and IFNg, others cytokines involvement in the inflammatory response, such as IL-6, IL1b and TNF-a, were increased. Iodixanol induced an increase of CD80, CD83, CD86, CD40 and HLA-DR in imDC from patients with DHT but not in controls. CONCLUSION: DC play a relevant role in inducing the T-cell response in delayed reactions to Iodixanol. The use of imDC in the in vitro test may improve their sensitivity which may be useful for the diagnostic evaluation of drug reactions.
603
Suspected Allergy to Warfarin: A Management Approach Based on Experience L. Lopez, Jr, , M. Hepner, D. Doshi, C. Lauter; William Beaumont Hospital, Royal Oak, MI. RATIONALE: There are four types of cutaneous reactions with warfarin: purpura, hemorrhagic necrosis, purple toe syndrome, and urticaria. Urticarial eruptions are rarest. A previous study noted evidence of immunologic involvement. The role of IgE remains uncertain; skin testing is unavailable. No desensitization procedure has been published. METHODS: Five patients were evaluated. Based on history, examination and positive challenge, two patients underwent oral desensitization. Desensitization utilized dye-free CoumadinÒ starting with 0.005mg dose. At 15-minute intervals, the dose was advanced to 1mg. Three patients with less well documented reactions underwent graded drug challenge with dye-free CoumadinÒ. RESULTS: A 66 year-old female developed pruritic, generalized urticaria after starting on warfarin for atrial fibrillation (AF). The symptoms partially improved with MedrolÒ, but not with antihistamines. She had persistent hives for over two years with continued use. After warfarin was discontinued, her urticaria resolved. Subsequently, she needed AF ablation therapy and underwent successful desensitization with CoumadinÒ. A 30 year-old female with portal vein thrombosis received warfarin. Within hours, she developed pruritic urticaria which resolved with diphenhydramine. Warfarin intake was interrupted for INR elevation. Reintroduction resulted in diffuse urticaria and lip angioedema. She was successfully desensitized with CoumadinÒ. Three patients underwent graded drug challenge with dye-free (10mg) CoumadinÒ, starting with 0.5mg with a target dose of 5mg. They tolerated the challenge and subsequent therapy with the same product. CONCLUSIONS: Patients with warfarin allergy who require oral anticoagulation may be managed in a supervised graded drug challenge with dyefree CoumadinÒ or desensitization in a controlled setting if drug challenge is positive.
MONDAY
600
J ALLERGY CLIN IMMUNOL VOLUME 125, NUMBER 2
COX-2 Up-regulation After Positive Aspirin Provocation M. Silar, M. Rijavec, N. Bajrovic, M. Kosnik, P. Korosec; University Clinic of Respiratory and Allergic Diseases, Golnik, SLOVENIA. RATIONALE: Previous in-vitro observations suggest that COX-2 expression appears to be differentially regulated in aspirin-sensitive patients. METHODS: COX1 and COX-2 expression was evaluated by real-time PCR just before aspirin oral provocation and 4 hours after provocation in 13 patients suspected for aspirin intolerance. RESULTS: We found significantly higher COX-2 expression (P 5 0.007) in 4 patients who experienced positive clinical reaction to aspirin in comparison to levels before provocation. No differences were observed in 9 patients with negative testing and for COX-1 expression. CONCLUSIONS: This in-vivo finding suggests that COX-2 pathway might be involved in aspirin-induced exacerbations.
601
A Retrospective Review of Drug Challenges over 5 Years in a Pediatric Population S. Kamboj1,2, S. J. McGeady1,2, E. Yousef1,2, J. Hossain2; 1Thomas Jefferson University, Philadelphia, PA, 2Alfred I Dupont Children’s Hospital, Wilmington, DE. RATIONALE: Studies estimate that 90% of ‘‘Penicillin (PCN) allergic’’ patients can safely receive the drug. However, these patients are often treated with alternative antibiotics, leading to increased occurrence of adverse drug reactions (ADR). We report a 5-year experience in managing suspected ‘‘drug allergies’’ to PCN and alternative antibiotics in children. METHODS: Medical records of patients aged 1-21 years with ‘‘ADR’’ were reviewed for demographic data, atopy, reaction type, skin prick testing (SPT) results, and drug challenge outcomes. Continued drug avoidance was advised in patients with positive SPT or ADR during challenge RESULTS: Chart reviews identified 96 patients with ‘‘ADR’’ who subsequently underwent SPT or graded challenges to the following: PCN (n552), cephalosporins (n5 7), azithromycin (AZT) (n5 24), or clindamycin (n54). Eighty-seven patients (90.6%) tolerated drug challenges and nine patients (9.4%) were instructed to continue drug avoidance. Eight of the nine patients continued drug avoidance due to positive SPT (n54) or ADR during PCN challenge (n54). One patient continued clindamycin avoidance after positive SPT. All AZT and cephalosporin challenges passed. Patients with atopy (OR 1.70, CI 0.40, 7.24) and ADR described as hives or pruritus (OR 3.58, CI 0.70, 18.25) were found to be more likely to require continued drug avoidance. CONCLUSIONS: True ‘‘antibiotic allergy’’ by positive SPT or challenge occurs less frequently than reported ADR in the pediatric population. AZT allergy appears to be rare and AZT is seen as a safe alternative medication.
602
Role of Dendritic Cells in Delayed-type Hypersensitivity Reactions to Iodixanol (VisipaqueÒ) C. Antunez1, E. Gomez1, R. M. Gueant-Rodriguez2, A. Barbaud3, T. D. Fernandez1, I. Gastin2, J. L. Gueant2, M. Blanca1; 1Allergy Service and Research Laboratory, Carlos Haya Hospital-Fundacio´n IMABIS, Ma´laga, SPAIN, 22Department of Biochemistry-Molecular Biology-Nutrition-Metabolism, University Hospital, Nancy, FRANCE, 3Dermatology Department, Fournier Hospital, Nancy, FRANCE. RATIONALE: Delayed-type reactions to contrast media (CM) represent 2-5% of patients with adverse reactions to CM. The role of DC in drug allergy reactions has not been sufficiently studied. The aim of this study was to determine the change induced by Iodixanol on the maturational state of DC, to evaluate if immature monocyte-derived DCs (imDC) used as antigen-presenting cells improved the sensitivity of the classical lymphocyte transformation test and to analyze the in vitro cytokines produced after drug stimulation in patients with maculopapular exanthema. Method: Peripheral blood lymphocytes and imDC were obtained from 6 patients with delayed reactions to iodixanol and 6 tolerant subjects. Interactions between DC, lymphocytes and Iodixanol were analyzed by phenotypic analysis using flow cytometry, proliferation by means of H3T incorporation, and cytokine production in supernatants by 11-plex bead-based immunoassay.
RESULTS: The percentage of patients with positive LTT ranged from 17% with classical LTT (PBMC) to 83% with modified LTT (with imDC). In PBMC cultures, an increase of IL-2 and IFN-g production were induced by iodixanol. In DC cultures, in addition to IL-2 and IFNg, others cytokines involvement in the inflammatory response, such as IL-6, IL1b and TNF-a, were increased. Iodixanol induced an increase of CD80, CD83, CD86, CD40 and HLA-DR in imDC from patients with DHT but not in controls. CONCLUSION: DC play a relevant role in inducing the T-cell response in delayed reactions to Iodixanol. The use of imDC in the in vitro test may improve their sensitivity which may be useful for the diagnostic evaluation of drug reactions.
603
Suspected Allergy to Warfarin: A Management Approach Based on Experience L. Lopez, Jr, , M. Hepner, D. Doshi, C. Lauter; William Beaumont Hospital, Royal Oak, MI. RATIONALE: There are four types of cutaneous reactions with warfarin: purpura, hemorrhagic necrosis, purple toe syndrome, and urticaria. Urticarial eruptions are rarest. A previous study noted evidence of immunologic involvement. The role of IgE remains uncertain; skin testing is unavailable. No desensitization procedure has been published. METHODS: Five patients were evaluated. Based on history, examination and positive challenge, two patients underwent oral desensitization. Desensitization utilized dye-free CoumadinÒ starting with 0.005mg dose. At 15-minute intervals, the dose was advanced to 1mg. Three patients with less well documented reactions underwent graded drug challenge with dye-free CoumadinÒ. RESULTS: A 66 year-old female developed pruritic, generalized urticaria after starting on warfarin for atrial fibrillation (AF). The symptoms partially improved with MedrolÒ, but not with antihistamines. She had persistent hives for over two years with continued use. After warfarin was discontinued, her urticaria resolved. Subsequently, she needed AF ablation therapy and underwent successful desensitization with CoumadinÒ. A 30 year-old female with portal vein thrombosis received warfarin. Within hours, she developed pruritic urticaria which resolved with diphenhydramine. Warfarin intake was interrupted for INR elevation. Reintroduction resulted in diffuse urticaria and lip angioedema. She was successfully desensitized with CoumadinÒ. Three patients underwent graded drug challenge with dye-free (10mg) CoumadinÒ, starting with 0.5mg with a target dose of 5mg. They tolerated the challenge and subsequent therapy with the same product. CONCLUSIONS: Patients with warfarin allergy who require oral anticoagulation may be managed in a supervised graded drug challenge with dyefree CoumadinÒ or desensitization in a controlled setting if drug challenge is positive.
MONDAY
600