Dec 1, 1997 - METHODS: Peripheral NK cells from 10 patients with a non immediate reactin to AX and 10 healthy controls were isolated by using magnetic.
Abstracts S189
J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Are Not Just Severe Cutaneous Adverse Reactions F. L. Chia, B. Y. H. Thong, K. P. Leong, Y. K. Cheng, J. W. Tan, C. Y. Tang, H. H. Chng; Tan Tock Seng Hospital, Singapore, SINGAPORE. RATIONALE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two of the main severe cutaneous adverse reactions (SCAR) defined based on the type and extent of skin involvement without inclusion of systemic manifestations. The aim of this study was to describe the systemic manifestations of patients with SJS and TEN in a prospective study. METHODS: Consecutive patients with SJS, TEN and SJS-TEN overlap reported using an electronic allergist-verified inpatient drug allergy (DA) reporting system during the study period 1st December 1997 to 31st December 2006. RESULTS: A total of 1093 episodes of DA were reported of which 108 (9.9%) patients developed SJS, TEN, or SJS-TEN overlap. Among these patients, systemic features were present in 35 (32.4%) patients including 29/82 (35.4%) patients with SJS, 3/16 (18.8%) TEN, and 3/10 (30%) SJSTEN overlap. The most common initial cutaneous manifestation was maculopapular exanthem (80%) and erythema multiforme (28.6%) before progression of rash or skin denudation. The most common systemic manifestations were hepatitis (85.7%), fever (65.7%), leukocytosis/eosinophilia (54.3%) and acute renal insufficiency (31.4%). CONCLUSION: Concomitant systemic manifestations were present in 32.4% of patients with SJS, TEN or SJS/TEN overlap. Physicians should be aware that SJS and TEN may not be purely cutaneous reactions and look out for these systemic features.
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Lymphocyte Transformation Test Using Dendritic Cells as Antigen Presenting Cells In Delayed-Type Hypersensitivity Reactions To Heparins M. J. Torres1, N. Blanca-Lopez2, S. Lopez1, C. Mayorga3, G. Canto2, P. Chaves3, C. Rondon1, I. Bravo1, M. Blanca1; 1Carlos Haya Hospital, Ma´laga, SPAIN, 212 de Octubre Hospital, Madrid, SPAIN, 3Fundacion IMABIS, Ma´laga, SPAIN. RATIONALE: In vitro tests are not useful for diagnosing delayed type hypersensitivity (DTH) reactions to heparins since the lymphocyte transformation test (LTT) may give false negatives. The aim of this study was to improve the LTT with heparins using dendritic cells (DC) as antigen-presenting cells. METHODS: Patients with DTH to heparins (N 5 7) and controls (N 5 9) were studied. For the LTT, either monocytes and B cells (classical LTT) or immature DC (obtained from peripheral monocytes after incubation with rhGM-CSF and rhIL-4) were used as antigen presenting cells (APC). The heparins tested were: Sodium Heparin, Dalteparin, Bemiparin, Nadroparin, Tinzaparin, Enoxaparin, Sulodexide, Fondaparinux and Lepirudin. Results, expressed as stimulation index (SI), were considered positive when >3. LTT was repeated in 3 patients one year after the reaction. RESULTS: Patients were diagnosed by skin testing (N 5 6) or drug provocation tests (N 5 1). In six patients, including the one who was skin test negative, LTT was positive to most of the heparins tested with both monocytes/B cells and DC, but showed a higher SI when using DC. In those patients where LTT were repeated after one year, proliferation to the culprit drug was only detected when DC were used as APC. All LTT were negative in controls. CONCLUSIONS: Autologous monocyte-derived dendritic cells used as APC may improve the in vitro lymphocyte responses in patients with delayed allergic reactions to heparins, increasing and prolonging the specific proliferative responses, especially to the culprit heparin. Funding: FIS PI052290 and PAI CTS 570
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NK Activation and Cytotoxicity in Patients with Allergy to Beta-Lactams P. Chaves1, C. Mayorga1, C. Antunez1, T. D. Fernandez1, S. Lopez1, J. A. Cornejo-Garcia1, J. L. Rodriguez-Bada1, M. Blanca2, M. J. Torres2; 1 Carlos Haya Hospital-Fundacion IMABIS, Ma´laga, SPAIN, 2Carlos Haya Hospital, Ma´laga, SPAIN. RATIONALE: Betalactams are the more frequent cause of allergic reactions mediated by either IgE or T-lymphocytes. NK cells act in innate immunological reactions by lysing target cells by direct interaction with molecules present in pathogens and in damaged cells. There are limited knowledge about how small molecular compounds, like betalactams, interact with NK. This interaction may lead in a release of cytotoxic factors. The objective of this work was to analyze the effect of amoxicillin (AX) on NK in patients allergic to AX compared to healthy donors. METHODS: Peripheral NK cells from 10 patients with a non immediate reactin to AX and 10 healthy controls were isolated by using magnetic beads. These cells were then cultured in absence or presence of different stimuli (IL121IL15, AX, anti-IL121anti-IL15) for determining their cytotoxic phenotype (CD69, Perforin Granzyme-B, TNFa and IFNg) and cocultured with K562 (NK-sensitive) for their cytotoxic function (propidium iodide (PI) and annexin) by flow cytometry. RESULTS: Cytotoxic phenotype studies showed an increase in CD69, TNFa and IFNg with IL121IL15 and a decrease in these markers with anti-IL121anti-IL15 in both patients and controls. AX induced an increase in these markers in 50% of patients but not in controls. With respect to cytotoxic function, we observed that IL121IL15 increased annexin but not PI, this was blocked with anti-IL121anti-IL15 in both patients and controls. AX induced increase in PI only in those patients where a cytotoxic phenotype was detected. CONCLUSIONS: Amoxicillin enhance the NK cells activity in patients with a non immediate reaction to this drug. Funding: FIS PI061561
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One-year Descriptive Analysis of Non Steroidal Antinflammatory Drugs Hypersensitivity In Our Allergy Department I. Don˜a Dı´az, G. Requena, M. Torres, F. Guijarro, P. Campo, C. Rondo´n, M. del Prado, M. Blanca; Carlos Haya Hospital, Ma´laga, SPAIN. RATIONALE: Non steroidal antiinflammatory drugs (NSAID) are the most frequent cause of allergic reactions to drugs followed by betalactams, and its prevalence is increasing. The aim of the study was to evaluate the clinical characteristics of confirmed NSAIDs hypersensitivity reactions in our Allergy Department during a one year period (2004-2005). METHODS: Descriptive analysis from our database of cases of NSAIDs hypersensitivity, whether selective or cross-intolerance, confirmed by skin testing or drug provocation test was performed. Age, sex, atopy, culprit drug, concomitant diseases, reaction type, time interval between drug intake and reaction, number of episodes and NSAIDs tolerance after the last reaction were recorded. RESULTS: One-hundred and eighty seven patients were diagnosed of NSAIDs allergy (61% female), mean age 38 6 22 years. Drugs more frequently involved were metamizol (30%), ibuprofen (27%), aspirin (25%) and diclofenac (7%), most of them administered by oral route (92%). Time intervals were less than 1 hour in 61%, between 1 and 6 hours in 33% and over 24-48 hours in 6%. Severe reactions occurred in 61% of patients. Selective hypersensitivity was confirmed in 28% of patients and cross-intolerance to different NSAIDs in 72%. CONCLUSIONS: NSAIDs are a common cause of drug hypersensitivity in our area, being the cross-intolerance the most frequent diagnosis. Metamizol is still the most frequent drug involved although ibuprofen and aspirin are also involved in many cases.
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