Reliability of Early and Late Testing for Suspected Perioperative Hypersensitivity.

BACKGROUND: The optimal timing of diagnostic testing for perioperative hypersensitivity (POH) remains unknown. It has been recommended that investigation is best carried out at least 4 to 6 weeks after the event. On the other hand, guidelines discourage the use of in vitro tests later than 3 years after the index reaction. OBJECTIVE: This retrospective study aimed to assess the reliability of early and late skin tests (STs). It also attempted to verify whether discouraging late ex vivo and in vitro tests is substantiated. METHODS: For the first aim, patients were stratified over three epochs: an early timing group, with investigations performed within 6 weeks; a recommended timing group, with tests performed between 6 weeks and 6 months; and a late timing group, tested later than 6 months after the event. For the second study purpose, we studied the reliability of specific IgE quantification and basophil activation test rocuronium within 6 weeks and after 3 years in patients who experienced an ST-proven POH to rocuronium. RESULTS: A total of 677 patients were included. Based on a positive ST result, a causative agent was found in 74.2% of the early timing group, 62.6% of the recommended timing group, and 50% of the late timing group. A positive specific IgE for rocuronium or morphine was found in 80% of patients tested within 6 weeks, 63% of patients tested between 6 weeks and 3 years, and 50% of patients tested more than 3 years after the event. A positive basophil activation test was found in 83.3%, 51%, and 20%, respectively, of patients. CONCLUSIONS: Our data confirm that evaluation of drug allergy for suspected POH can be performed before 6 weeks after the event, and there is no maximal upper time limit disclosing ex vivo and in vitro testing.

Serum specific IgE antibodies in immediate drug hypersensitivity.

Immediate drug hypersensitivity reactions (IDHRs) constitute a significant health problem that may be compounded by consequences of diagnostic error. In daily practice, IDHR diagnostic work up starts with drug-specific skin testing and/or quantification of specific IgE (sigE) antibodies in serum. Here we critically review the performance, i.e. potential and limitations of sIgE to ß-lactam antibiotics (ß-LABs), curarizing neuromuscular blocking agents (NMBAs), opiates and (semi)synthetic opioids, fluoroquinolones (FQs), poppy seed (papaver somniferum), chlorhexidine and finally Hevea latex. Quintessence of these studies is clear. Quantification of these drug-specific sIgE should not be used in isolation to document or exclude diagnosis of an IDHR. False negative results entail the risk for subsequent potentially life-threatening anaphylaxis upon re-exposure. False positive results lead to erroneous avoidance and unnecessary substitutions and fails to identify the true etiology.

Flow cytometric basophil activation tests: Staining of exteriorized basophil granule matrix by fluorescent avidin versus appearance of CD63.

BACKGROUND: Staining of exteriorized basophil granule matrix by fluorescent avidin might be a reliable technique to monitor basophil degranulation. This study compares the avidin-based technique with the upregulation of CD203c and appearance of CD63 in response to various stimuli. METHODS: Fourteen individuals responsive to anti-IgE, nine healthy controls, and five birch pollen-allergic patients, and five nonresponders were studied. Activation experiments included anti-IgE, fMLP, interleukin-(IL)-3, and birch pollen allergen. Basophil activation/degranulation was analyzed by flow cytometry and microscopy using anti-CD63, anti-CD203c, and avidin. RESULTS: Stimulation with anti-IgE, fMLP, and relevant allergen results in upregulation of CD203c, CD63 appearance, and an increase in avidin binding. In response to anti-IgE and allergen, upregulation of CD203c peaks within 10 min, CD63 and avidin binding reach a plateau after 10-20 min. CD63 staining leads to a bimodal distribution, avidin staining causes a unimodal shift with a less clear discrimination between degranulating and nondegranulating cells. In response to fMLP, upregulation of CD203c and CD63 and avidin binding are maximal after 2.5 min. Following incubation with anti-IgE and fMLP, percentages of CD203c+ cells are higher than those of CD63+ and avidin+ cells, pointing to a dissociation between activation and degranulation. Percentages of CD63+ cells are systemically higher than those of avidin+ cells. Incubated with IL-3 only upregulates CD203c, while no CD63 or avidin binding is observed. CONCLUSIONS: Staining of exteriorized proteoglycans by avidin is a reliable technique to quantify basophil degranulation but offers no added value when compared to traditional assays that use CD63 as a readout.

The Limited Value of Prolonged Drug Challenges in Nonimmediate Amoxicillin (Clavulanic Acid) Hypersensitivity.

BACKGROUND: Misdiagnosis of amoxicillin (clavulanic acid) (AX(/CL)) hypersensitivity has serious consequences. A drug challenge (DC) is the final diagnostic to affirm or infirm AX(/CL) hypersensitivity. However, uncertainties remain whether a prolonged drug challenge (pDC) should benefit the diagnosis of a nonimmediate AX(/CL) hypersensitivity. OBJECTIVE: To assess the added value of a standardized 7-day pDC in the diagnosis of nonimmediate or unclear penicillin hypersensitivity. METHODS: A total of 132 patients with a history of a nonimmediate hypersensitivity reaction or an unclear reaction to AX(/CL) or an undefined penicillin with a negative diagnostic workup including a single-day DC (DC) with AX(/CL) were selected. In all these patients, an additional pDC with AX(/CL) was planned. Thirteen patients started the pDC immediately after the DC. To ensure that hypersensitivity symptoms manifesting during the pDC course do not result from the DC, in the remaining 119 patients, the pDC was scheduled after a washout of 1 week. RESULTS: A total of 128 patients (12 without washout, 116 with washout) completed the pDC. Three patients reacted with a mild maculopapular exanthema. However, the value of a pDC was evidenced in only 1 patient who reacted during her pDC after an uneventful washout. In 2 patients pDC was cancelled because they reacted during the washout. CONCLUSIONS: A pDC is of limited added value to the diagnostic algorithms of nonimmediate hypersensitivity reaction or unclear hypersensitivity reactions to AX(/CL). In our hands, the traditionally recommended diagnostic algorithm that offers a 1-day DC as a final diagnostic in patients with negative workup for AX(/CL) is appropriate.

Acute Management, Diagnosis, and Follow-Up of Suspected Perioperative Hypersensitivity Reactions in Flanders 2001-2018.

BACKGROUND: Despite numerous efforts to describe the clinical manifestations and the epidemiology of perioperative hypersensitivity (POH), there remains room to increase awareness among anesthetists and immunologists/allergists. OBJECTIVE: To report the findings of a 17-year survey of suspected POH in Antwerp, Belgium. METHODS: We analyzed clinical and diagnostic data from 715 patients referred because of a suspected POH reaction, between January 1, 2001, and May 31, 2018. A total of 456 patients demonstrating a POH could be queried about subsequent anesthesia. RESULTS: A total of 608 cases formed the final dataset; 208 had a non-life-threatening reaction and 400 a life-threatening reaction. In life-threatening reactions, hypotension was predominating. In the non-life-threatening reactions, 83.9% of the patients displayed cutaneous manifestations. In life-threatening reactions, intravenous adrenaline and fluids were administered in 75.7% and 31%, respectively, and 41.3% had their intervention abandoned. Mast cell activation (MCA) was mainly, but not exclusively, observed in severe grades but did not predict the mechanistic process nor the culprit. A cause was identified in 77.8% of severe and 48.6% of milder cases. Main culprits were neuromuscular blocking agents, latex, cefazolin, and dyes. A total of 156 cases had uneventful anesthesia, except 1 patient who was inadvertently re-exposed to hidden chlorhexidine. CONCLUSIONS: This study highlights that there is room for an improved acute management and an optimized diagnostic workup that should not be restricted to patients with severe reactions and/or showing MCA.