Basophil activation after nonsteroidal anti‐inflammatory drugs stimulation in patients with immediate hypersensitivity reactions to these drugs

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in allergic reactions of which two main types exist: IgE-mediated and crossintolerance. The diagnosis of crossintolerance reactions is often based on the drug provocation test. The potential value of the basophil activation test (BAT) was evaluated using different basophil markers in the diagnosis of patients with crossintolerance to NSAIDs and cutaneous symptoms. We studied 46 patients with crossintolerance to NSAIDs and 45 tolerant controls. BAT was performed with acetyl salicylic acid, paracetamol, diclofenac, dipyrone, naproxen, and ibuprofen at four different concentrations using CD193 and CD203c as basophil markers and CD63 as activation marker. We compared BAT results using CD193 1 or CD193 1 CD203c 1 for basophil selection and found a significant increase in the stimulation index when using CD193 1 CD203c 1 in both patients and controls (P 5 0.004 and P 5 0.017, respectively). Selection of living cells only produced an increase in basophil stimulation in patients for both CD193 1 and CD193 1 CD203c 1 (P < 0.001 for both), whereas in controls there was no change with CD193 1 and a decrease with CD193 1 CD203c 1 (P 5 0.001). We found that CD193 1 CD203c 1 increased the percentage of positive cases in patients and controls when compared with CD193 1 . When excluding dead cells, there was an increase of 21.7% in patients and 10% in controls. These results indicate that using CD193 1 CD203 1 , excluding dead cells, is the best approach for BAT although this test is not recommended for the diagnosis of patients with crossintolerance to NSAIDs owing to its low sensitivity and specificity. V C 2014 International Society for Advancement of Cytometry Key terms hypersensitivity; nonsteroidal anti-inflammatory drugs; idiosyncratic reactions; basophils; CD63; CD193; CD203c NONSTEROIDAL anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in immediate or acute hypersensitivity reactions, accounting for 20-25% of patients evaluated in allergy units, with two main mechanisms involved (1-3). One is mediated by drug-specific-IgE antibodies and reactions occur with one NSAID but there is tolerance to other nonchemically related drugs (4,5). These reactions are known as single NSAID induced hypersensitivity reactions and involve NSAIDs such as paracetamol (6), acetyl salicylic acid (ASA) (7), diclofenac (8), ketorolac (9), dipyrone (10,11), and cyclooxygenase-2 selective inhibitors (COX-2) (12). The other type of reaction is mediated by a pharmacological mechanism in which the inhibition of cyclooxygenase-1 enzyme (COX-1) leads to a decrease in the synthesis of prostaglandin E 2, which in turn hampers the production of sulphidoleukotrienes

Allergic Reactions to Metamizole: Immediate and Delayed Responses

“…We found differences comparing the time interval between the reaction and the performance of the tests in those who were negative and those who were positive. Another factor to consider that may contribute to the low sensitivity of diagnostic tests is the incomplete characterization of the chemical structures of metamizole and its metabolites [30]. Four major metamizole metabolites have been described in the literature [31]; however, we recently demonstrated the presence of arachidonoyl metabolites in patients receiving metamizole [32], and additional metabolites, such as oxalic acid derivatives, have been reported elsewhere [33].…”

Drug-Induced Anaphylaxis

“…Another in vitro option is the use of basophil activation tests. Although these have been proposed for subjects with NSAID hypersensitivity caused by cross-intolerance [83], they show a high number of false positives [84,85]. However, the basophil activation has proved to be useful for beta-lactam [86], selective reactions to pyrazolones [81,85], omeprazole [87], ranitidine [88], and other agents [89].…”

Biomarkers for evaluation of mast cell and basophil activation

“…Immediate hypersensitivity reactions involve the IgE-mediated release of histamine and other mediators from mast cells and basophils. 66 Flow cytometry-based basophil tests have been clinically used to diagnose immediate-type hypersensitivities, including anaphylaxis, AR, and other allergic diseases, as well as to confirm the sensitization of patients to foods, drugs, and insects. 57,67,68 The flow cytometric basophil activation test (BAT), based on the detection of allergen-induced CD63 expression, has been proven effective in the diagnosis of various IgE-mediated allergies.…”