Immediate Hypersensitivity Reactions Research Articles

Involvement of autologous myeloid dendritic cells in the evaluation of immediate hypersensitivity reactions to betalactams

BackgroundAmoxicillin (AX) and clavulanic acid (CLV) are the betalactam antibiotics (BLs) most used to treat bacterial infections, although they can trigger immediate hypersensitivity reactions (IDHRs). The maturation analysis of monocyte-derived dendritic cells (moDCs) and their capacity to induce proliferative response of lymphocytes are useful to test the sensitisation to a drug, although without optimal sensitivity. Nevertheless, this can be improved using directly isolated DCs such as myeloid DCs (mDCs). MethodsmDCs and moDCs were obtained from 28 allergic patients (AP), 14 to AX, 14 to CLV and from 10 healthy controls (HC). The expression of CCR7, CD40, CD80, CD83, and CD86 was analysed after stimulation with both BLs. We measured the capacity of these pre-primed DCs to induce drug-specific activation of different lymphocyte subpopulations, CD3+, CD4+, CD8+, CD4+Th1, and CD4+Th2, by flow cytometry. ResultsHigher expression of CCR7, CD40, CD80, CD83, and CD86 was observed on mDCs compared to moDCs from AP after stimulating with the culprit BL. Similarly, mDCs induced higher proliferative response, mainly of CD4+Th2 cells, compared to moDCs, reaching up to 67% of positive results with AX, whereas of only 25% with CLV. ConclusionsmDCs from selective AP efficiently recognise the culprit drug which trigger the IDHR. mDCs also trigger proliferation of lymphocytes, mainly those with a Th2 cytokine pattern, although these responses depend on the nature of the drug, mimicking the patient's reaction.

Development of anti-PEG IgG/IgM/IgE ELISA assays for profiling anti-PEG immunoglobulin response in PEG-sensitized individuals and patients with alpha-gal allergy

Polyethylene glycol (PEG) is frequently used in various protein and nanomedicine therapeutics. However, various studies have shown that select PEGylated therapeutics can induce production of anti-PEG antibodies (APA), potentially culminating in rapid clearance from the systemic circulation, loss of efficacy and possibly increased risks of allergic reactions. Although IgE is a frequent cause of immediate hypersensitivity reactions (IHR), the role of IgE APA in PEG-related IHR is not well understood, due in part to a lack of standardized assays for measuring IgE APA. Here, we developed a rigorous competitive ELISA method to measure the concentrations of various APA isotypes, including IgE, with picomolar sensitivities. In a small number of serum samples from patients with known PEG allergy, the assay allowed us to detect a strong correlation between IgG and IgE APA in individuals with history of allergic reactions to PEG or PEGylated drugs, but not between IgM and IgE APA. We detected appreciable levels of IgG and IgM APA in individuals with history of alpha-gal allergy, however, they were not elevated relative to those detected in other healthy controls, and we found no pre-existing IgE APA. While preliminary and should be further investigated, these results suggest that differences in the route and mechanism of PEG exposure may drive variability in APA response.

Effectiveness of Carboplatin-Prescreening Intradermal Skin Tests to Reduce Unanticipated Immediate Hypersensitivity Reactions: A Comparative Study

BackgroundCarboplatin administration poses a risk of immediate hypersensitivity reactions (IHRs) that tend to increase with repeated administration and are mostly IgE-mediated. ObjectiveThis study evaluated the usefulness of carboplatin-prescreening intradermal skin tests (IDTs). MethodsCarboplatin-prescreening IDTs were routinely conducted in patients with a history of receiving six or more carboplatin cycles from January 2021. The primary objective was to assess disparities in the incidence of unanticipated IHRs to carboplatin administration. Comparisons were made between patients in the intervention group (period: 2021–2022) and those who did not undergo prescreening IDTs under the same conditions (pre-intervention group; period: 2019–2020). The secondary objectives included evaluating the sensitivity and specificity of the prescreening IDT and the incidence of carboplatin IHR according to the number of infusion cycles. ResultsThe intervention group comprised 67 patients who were administered 347 carboplatin cycles, whereas the pre-intervention group included 96 patients who were administered 464 carboplatin cycles. The risk of unanticipated carboplatin IHRs decreased by 83.2% in the intervention group compared to the pre-intervention group (pre-intervention group: 3.45%, N=16 vs. intervention group: 0.58%, N=2; p=0.005). The prescreening IDT showed a sensitivity and specificity of 77.78% and 99.41%, respectively. The risk of newly developed IHRs based on the number of carboplatin cycles was <1% (cycle 1-5), 2.11% (cycle 6), 3.90% (cycle 7-12), 2.90% (cycle 13-18), and 0.74% (cycle ≥ 19), respectively. ConclusionsInitiating carboplatin-prescreening IDTs from the seventh cycle significantly reduced the risk of unanticipated IHRs.

Skin Test–Guided Strategy to Select Alternative Iodinated Contrast Media in Patients With Immediate Hypersensitivity Reaction: A Prospective Confirmative Study

Iodinated contrast media (ICM) are a common cause of drug-induced immediate hypersensitivity reaction (IHR). Repeated use of ICM is often necessary; therefore, a standardized protocol to prevent recurrence of IHR is required. We aimed to propose an intradermal skin test (IDT)-guided strategy for previous reactors to prevent recurrence of IHR. We conducted a prospective multicenter study from May 2018 to December 2020 and recruited patients who had experienced IHR to ICM. Once enrolled, the participants underwent IDT with a causative ICM. The alternatives for reexposure were selected using the following protocol: (1) if the IDT with the culprit ICM was positive, further skin tests with other available ICM were conducted to choose IDT-negative agents as alternatives, and (2) if the IDT with the culprit ICM was negative, a randomly changed ICM was used without additional skin tests. The recurrence and severity of hypersensitivity were assessed in subsequent computed tomography examinations. Premedication was administered according to the severity of the index event in all cases. A total of 496 participants were enrolled, and 299 were reexposed to ICM. Among 269 participants who followed the protocol, 228 (84.8%) completed computed tomography examinations without adverse reactions, and IHR recurred in 16 of 30 participants (53.3%) who did not follow the protocol (P < .001). In addition, application of the protocol reduced the severity of IHR in recurred cases (P= 0.003). Our IDT-guided strategy not only reduced recurrence of IHR to ICM but also mitigated the severity in recurred cases. This provides evidence for recommending an IDT to diagnose ICM allergy and find safe alternatives.

Clinical validation of the basophil activation test in immediate hypersensitivity reactions to gadolinium-based contrast agents.

Gadolinium based contrast agents (GBCAs) are safe compounds globally used in magnetic resonance imaging (MRI). However, in last years it has been detected an increase of immediate hypersensitivity reactions (IHRs) to them. Diagnosis of IHRs to GBCAs is based on clinical symptoms, skin tests (STs) and drug provocation test (DPT). But DPTs are not without risks, thus it is important to implement an in vitro alternative method such as the basophil activation test (BAT). We described the clinical validation of the BAT using ROC curves from a control population formed by 40 healthy individuals without previous reactions to any contrast agents and 5 patients suffering from IHRs to GBCAs. Four patients presented IHRs to gadoteric acid (GA) as the culprit agent and another one to gadobutrol (G). Basophil reactivity was measured in percentage of CD63 expression and in stimulation index (SI). The optimal cut-off with the highest sensitivity (S) and specificity (E) for the GA was of 4.6% at 1:100 dilution (S=80% and E=85%; AUC=0.880, p=0.006). For the SI with GA, the cut-off of highest sensitivity and specificity was of 2.79 at 1:100 dilution (S=80% and E=100%; AUC=0.920, p=0.002). Sensitivity did not show differences between STs regarding the BAT (p<0.05). Moreover, the BAT was able to detect one case with IHR to GA which had negative STs. Therefore, the BAT is a useful method in diagnosis of IHRs to GBCAs.

Characteristics of immediate hypersensitivity reaction to paclitaxel-based chemotherapy in gynecologic cancer patients.

Immediate hypersensitivity reactions (IHRs) are commonly found in patients receiving paclitaxel. Effects of paclitaxel vary because of variable co-therapy or re-challenge with paclitaxel. Our objective was to investigate the incidence, patterns, and risk factors for paclitaxel-related IHRs and management of IHRs in gynecologic malignancy patients. This retrospective study was performed in gynecologic cancer patients receiving paclitaxel-based regimens at Siriraj hospital from January 2012 to December 2017. 416 subjects were included and received ranitidine 50 mg, dexamethasone 20 mg, ondansetron 16 mg intravenously and diphenhydramine 50 mg orally 30 minutes before starting chemotherapy. The incidence of IHRs was 17.79%. IHRs occurring on first exposure to paclitaxel was 81.1% and occurred within 30 minutes after starting paclitaxel. The most commonly found presentation of IHRs were skin reactions (86.5%). In multivariate analysis, age < 54.5 years, stage of cancer < 2, and leukocyte cell count < 7.735 × 109/L were significantly associated with IHRs. Seventy-two out of 74 patients that recovered from IHRs were reintroduced paclitaxel. Forty-seven patients (97.92%) of 48 patients with mild reactions were successfully reintroduced to paclitaxel after treatment with chlorpheniramine or other interventions. The incidence of paclitaxel-related IHRs was about one in five. Skin reactions were the most commonly occurring reactions. Younger age, stage of cancer < 2, and leukocytes < 7.735 × 109/L were significant risk factors for IHRs. Patients with IHRs recovered without the use of dexamethasone and antihistamines before the reintroduction of paclitaxel.

Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunization Stress-Related Responses With COVID-19 mRNA Vaccine

BackgroundWith the implementation of mass vaccination campaigns against COVID-19, the safety of vaccine needs to be evaluated.ObjectiveWe aimed to assess the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunization stress–related responses (ISRR) with the Moderna COVID-19 vaccine.MethodsThis nested case-control study included recipients who received the Moderna vaccine at a mass vaccination center, Japan. Recipients with IHSR and ISRR were designated as cases 1 and 2, respectively. Controls 1 and 2 were selected from recipients without IHSR or ISRR and matched (1 case: 4 controls) with cases 1 and cases 2, respectively. Conditional logistic regression analysis was used to identify risk factors associated with IHSR and ISRR.ResultsOf the 614,151 vaccine recipients who received 1,201,688 vaccine doses, 306 recipients (cases 1) and 2478 recipients (cases 2) showed 318 events of IHSR and 2558 events of ISRR, respectively. The incidence rates per million doses were estimated as IHSR: 266 cases, ISRR: 2129 cases, anaphylaxis: 2 cases, and vasovagal syncope: 72 cases. Risk factors associated with IHSR included female, asthma, atopic dermatitis, thyroid diseases, and a history of allergy; for ISRR, the risk factors were younger age, female, asthma, thyroid diseases, mental disorders, and a history of allergy and vasovagal reflex.ConclusionIn the mass vaccination settings, the Moderna vaccine can be used safely owing to the low incidence rates of IHSR and anaphylaxis. However, providers should be aware of the occurrence of ISRR. Although recipients with risk factors are associated with slightly increased risks of IHSR and ISRR, this is not of sufficient magnitude to warrant special measures regarding their vaccination.

COVID-19 Vaccination Safety and Tolerability in Patients Allegedly at High Risk for Immediate Hypersensitivity Reactions.

The reported incidence of immediate hypersensitivity reactions (IHR) including anaphylaxis after COVID-19 vaccination is 10-fold higher than for other vaccines. Several patient groups are theorized to be at particular risk. Since specific vaccination guidelines for these patients are based on expert opinion, we performed a retrospective monocentric analysis of the tolerability of adenoviral vector and mRNA-based COVID-19 vaccines in a cohort of patients allegedly at high risk of IHR. Reactions were assessed immediately on-site by allergists during a monitored vaccination protocol and after 3–7 days through telephone interviews. The cohort included 196 patients (aged 12–84 years) with primary mast cell disease (pMCD, 50.5%), idiopathic anaphylaxis (IA, 19.9%), hereditary angioedema (HAE, 5.1%) or miscellaneous indications (24.5%). Twenty-five immediate reactions were observed in 221 vaccine doses (11.3%). Most occurred in IA or miscellaneous patients. None fulfilled anaphylaxis criteria and most were mild and self-limiting. Reaction occurrence was significantly associated with female sex. In total, 13.5% of pMCD patients reported mast cell activation-like symptoms within 72 h post-vaccination. All pediatric pMCD patients (n = 9, 12–18 years) tolerated both mRNA-based vaccine doses. In summary, adenoviral vector and mRNA-based COVID-19 vaccines were safe and well-tolerated in patients with pMCD, HAE, and IA. No anaphylaxis was observed. The mild and subjective nature of most reactions suggests a nocebo effect associated with vaccination in a medicalized setting. Patients with pMCD could experience mild flare-ups of mast cell activation-like symptoms, supporting antihistamine premedication.

Compound Kushen Injection Induces Immediate Hypersensitivity Reaction Through Promoting the Production of Platelet-Activating Factor via de Novo Pathway.

Compound Kushen Injection (CKI) is a bis-herbal formulation extracted from Kushen (Radix Sophorae Flavescentis) and Baituling (Rhizoma Heterosmilacis Yunnanensis). Clinically, it is used as the adjuvant treatment of cancer. However, with the increased application, the cases of immediate hypersensitivity reactions (IHRs) also gradually rise. In this study, we investigated the underlying mechanism(s) and active constituent(s) for CKI-induced IHRs in experimental models. The obtained results showed that CKI did not elevate serum total IgE (tIgE) and mouse mast cell protease 1 (MMCP1) after consecutive immunization for 5 weeks, but could induce Evans blue extravasation (local) and cause obvious hypothermia (systemic) after a single injection. Further study showed that alkaloids in Kushen, especially matrine, were responsible for CKI-induced IHRs. Mechanism study showed that various platelet-activating factor (PAF) receptor antagonists could significantly counter CKI-induced IHRs locally or systemically. In cell system, CKI was able to promote PAF production in a non-cell-selective manner. In cell lysate, the effect of CKI on PAF production became stronger and could be abolished by blocking de novo pathway. In conclusion, our study identifies, for the first time, that CKI is a PAF inducer. It causes non-immunologic IHRs, rather than IgE-dependent IHRs, by promoting PAF production through de novo pathway. Alkaloids in Kushen, especially matrine, are the prime culprits for IHRs. Our findings may provide a potential approach for preventing and treating CKI-induced IHRs.

Immediate-Type Systemic Hypersensitivity Reactions After the Inactivated SARS-CoV-2 Vaccine in Healthcare Workers

The vaccines developed for Coronavirus disease 2019 (COVID-19) not only brought hope to the struggle against the pandemic but also raised questions about hypersensitivity reactions that might occur. Although some studies regarding these concerns with mRNA COVID-19 vaccines have been published, these data on inactivated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccine are not available. The objective of this study was to determine the safety of the inactivated SARS-CoV-2 vaccine manufactured by Sinovac by evaluating the reported systemic immediate hypersensitivity reactions (IHRs) after the administration of the vaccine to healthcare workers (HCWs). This was a retrospective analysis of inactivated SARS-CoV-2 vaccine recipients in all HCWs vaccinated at our center. Relevant data of all patients who received the vaccine were collected from the electronic medical records available at our center’s database. A statistical analysis of subjects who reported acute adverse reactions was conducted. Of the 3354 HCWs vaccinated with the first dose (female 59.9%, pre-existing allergic disorder 2.4%), four acute adverse reactions (0.12%) met the definition of a systemic IHRs were reported, and only one was confirmed to be anaphylaxis. One out of these four cases received her second dose through graded administration. For the second dose, no systemic reaction was reported in our study population. Inactivated SARS-CoV-2 vaccine appears to be well tolerated in HCWs without any pre-existing allergic disorders.

Cross-reactive hypersensitivity to NSAIDs: Experience of a Tunisian allergology center

BackgroundThe accurate diagnosis of cross-reactive reactions (CRR) to nonsteroidal anti-inflammatory drugs (NSAIDs) depends on a careful history and oral drug challenge. In this study, we report the result of a new procedure implemented in Tunisian allergology center to explore CRR to NASIDs in patients with immediate hypersensitivity (IHS) to NSAIDs. MethodsOur structured protocol using oral provocation tests (OPTs) was based on the latest advances in the literature. This protocol was tested in patients with a clinical history of IHS reactions to one or more NSAIDs and referred to the pharmacology department of Sfax (Tunisia) between 2012 and 2018. Patients were classified into 5 subgroups: an ASA subgroup, a multiple NSAIDs subgroup, a single non-selective NSAID subgroup, a paracetamol subgroup, and a celecoxib subgroup. ResultsA total of 34 patients were enrolled. Personal history of atopy was found in 26 (76.5%). A diagnosis of CRR to NSAIDs was made in 24 patients (70.6%): 6 patients in the ASA subgroup, 12 patients in the multiple NSAIDs subgroup, 4 patients in the single non-selective NSAID subgroup, 1 patient in the paracetamol subgroup and 1 patient in the celecoxib subgroup. Regarding safe alternatives in patients with CRR to NSAIDs (n=24), prevalence of cross-reactivity to paracetamol or celecoxib was found in 20% and 27.3% of patients with confirmed CRR to NSAIDs, respectively. ConclusionOur structured protocol based on standardized oral provocation tests helps physicians to prescribe a suitable drug in patients with a history of IHS reactions to NSAIDs.

Penicillin and cephalosporin cross-reactivity: role of side chain and synthetic cefadroxil epitopes

BackgroundAnalysis of cross-reactivity is necessary for prescribing safe cephalosporins for penicillin allergic patients. Amoxicillin (AX) is the betalactam most often involved in immediate hypersensitivity reactions (IHRs), and cefadroxil (CX) the most likely cephalosporin to cross-react with AX, since they share the same R1 side chain, unlike cefuroxime (CO), with a structurally different R1. We aimed to analyse cross-reactivity with CX and CO in patients with confirmed IHRs to AX, including sIgE recognition to AX, CX, CO, and novel synthetic determinants of CX.MethodsFifty-four patients with confirmed IHRs to AX based on skin test (ST) and/or drug provocation test (DPT) were included. Serum sIgE to AX and benzylpenicillin was determined by Radioallergosorbent test (RAST). Two potential determinants of CX, involving intact or modified R1 structure, with open betalactam ring, were synthesised and sIgE evaluated by RAST inhibition assay.ResultsTolerance to CX (Group A) was observed in 64.8% cases and cross-reactivity in 35.2% cases (Group B). Cross-reactivity with CO was only found in 1.8% cases from Group B. ST to CX showed a negative predictive value of 94.6%. RAST inhibition assays showed higher recognition to CX as well as to both synthetic determinants (66% of positive cases) in Group B.ConclusionsCross-reactivity with CX in AX allergic patients is 35%, being ST not enough for prediction. R1, although critical for recognition, is not the unique factor. The synthetic determinants of CX, 1-(HOPhG-Ser-Bu) and 2-(pyrazinone) are promising tools for determining in vitro cross-reactivity to CX in AX allergic patients.

Insights into hypersensitivity reactions in dentistry

Abstract Hypersensitivity reactions are an important hazard in healthcare. Modern dentistry depends on the use of drugs and materials widely known to elicit them. Such reactions are either immediate or nonimmediate – the former carries the risk of anaphylaxis, whereas the latter includes potentially fatal severe cutaneous adverse reactions. Apart from well-established immunoglobulin E–mediated immediate hypersensitivity reactions (IHRs), recent advances have shed light on the pathophysiology of other IHRs, suggesting a role for MRGPRX2-induced mast cell activation. Hypersensitivity to both drugs and metals may come as a challenge to dentists, often requiring changing to infrequently used compounds. Local anesthetics are cause for concern, but are a rare cause for IHRs. The opposite occurs with antimicrobials, as antibacterials frequently cause hypersensitivity reactions. Nonsteroidal anti-inflammatory drugs are another common cause, especially in patients suffering from asthma and/or chronic spontaneous urticaria. General anesthetics are a common cause for immediate hypersensitivity, whereas most drugs used for conscious sedation are rare elicitors. Chlorhexidine is a remarkable cause for anaphylaxis, nowadays, despite rare reports linked to rinsed formulations. Preservatives, flavors, and other compounds present in dentifrices cause both irritative and allergic contact dermatitis/mucositis. Metals, notably nickel and cobalt, are a very common cause for hypersensitivity in dentistry. Acrylates may induce contact mucositis, due to lack of proper polymerization of residuals, being an important cause for contact stomatitis and a dentistry occupational hazard. Acute reactions require a prompt treatment, especially in the presence of anaphylaxis, which should be treated using intramuscular epinephrine. Delayed type reactions with fever should be referred to tertiary urgent care facilities. Suspicion of hypersensitivity in dentistry requires a thorough allergological study and referral is mandatory in all cases.

Penicillin causes non-allergic anaphylaxis by activating the contact system

Immediate hypersensitivity reaction (IHR) can be divided into allergic- and non-allergic-mediated, while “anaphylaxis” is reserved for severe IHR. Clinically, true penicillin allergy is rare and most reported penicillin allergy is “spurious”. Penicillin-initiated anaphylaxis is possible to occur in skin test- and specific IgE-negative patients. The contact system is a plasma protease cascade initiated by activation of factor XII (FXII). Many agents with negative ion surface can activate FXII to drive contact system. Our data showed that penicillin significantly induced hypothermia in propranolol- or pertussis toxin-pretreated mice. It also caused a rapid and reversible drop in rat blood pressure, which did not overlap with IgE-mediated hypotension. These effects could be countered by a bradykinin-B2 receptor antagonist icatibant, and consistently, penicillin indeed increased rat plasma bradykinin. Moreover, penicillin not only directly activated contact system FXII-dependently, but also promoted bradykinin release in plasma incubated-human umbilical vein endothelial cells. In fact, besides penicillin, other beta-lactams also activated the contact system in vitro. Since the autoactivation of FXII can be affected by multiple-factors, plasma from different healthy individuals showed vastly different amidolytic activity in response to penicillin, suggesting the necessity of determining the potency of penicillin to induce individual plasma FXII activation. These results clarify that penicillin-initiated non-allergic anaphylaxis is attributed to contact system activation, which might bring more effective diagnosis options for predicting penicillin-induced fatal risk and avoiding costly and inappropriate treatment clinically.

Immediate Hypersensitivity Reactions Caused by Drug Excipients: A Literature Review.

The European Medicines Agency defines excipients as the constituents of a pharmaceutical form apart from the active substance. Immediate hypersensitivity reactions (IHRs) caused by excipients contained in the formulation of medications have been described. However, there are no data on the prevalence of IHRs due to drug excipients. Clinical manifestations of allergy to excipients can range from skin disorders to life-threatening systemic reactions. The aim of this study was to review the literature on allergy to pharmaceutical excipients and to record the IHRs described with various types of medications, specifically reactions due to the excipients contained in their formulations. The cases reported were sorted alphabetically by type of medication and excipient in order to obtain a list of the excipients most frequently involved for each type of medication.

Reduced iodinated contrast media dose and injection speed for CT: how much does this decrease the risk of a hypersensitivity reactions?

Adverse reactions developing after administration of iodinated contrast media (ICM) can either constitute hypersensitivity reactions, toxic reactions, or even events unrelated to ICM exposure, such as acute spontaneous or infection-induced urticaria (1). Toxicity-related reactions (also called “physiologic” or “chemotoxic” reactions) are more common than hypersensitivity reactions and often manifest with mild unspecific symptoms, such as pruritus, heat sensation, transient erythema, dizziness, nausea, sneezing, chest tightness, arrhythmia, hypertension, and vasovagal signs (i.e., hypotension and bradycardia). Immediate hypersensitivity reactions (IHR) (acute hypersensitivity reactions) occur within 1 hour after ICM administration and either present with full anaphylaxis, involving skin, gastrointestinal, respiratory and/or cardiovascular organ systems simultaneously, sometimes with bronchospasm and/or hypotension, but may also manifest as fractions of anaphylaxis, such as urticaria, or angioedema only (2,3). Fatalities do occur (4). Among IHR, there is growing evidence that particularly severe reactions may be immunoglobulin E (IgE)-mediated and skin test- positive, whereas mild to moderate hypersensitivity reactions are mostly non-allergic (5-7). IHR have been reported in a frequency of about 0.3–3% of ICM injections (1).

Qing-Kai-Ling Injection Induces Immediate Hypersensitivity Reaction via the Activation of Anaphylatoxin C3.

Background and Objective: Qing-Kai-Ling (QKL) is derived from a famous ancient Chinese patent medicine Angong Niuhuang pills (ANP) which has been used across Asia, especially in China, for the treatment of “febrile disease,” such as stroke, encephalitis and meningitis for hundreds of years. As an extract of ANP without heavy metal, the clinical applicability of QKL is more intensive, of which its injection is commonly used in acute and serious diseases. This study aims to clarify the potential mechanisms of immediate hypersensitivity reaction (IHR) induced by QKL injection (QKLI). Methods: β-hexosaminidase release assay was performed on the human mast cell line LAD2 and mouse peritoneal mast cells. T helper 2 (Th2) immunity-amplified mice were prepared by aluminum adjuvant. Anaphylactic shock was detected by measuring rectal thermometry in propranolol-pretreated mice. For evaluating microvascular permeability, Evans Blue extravasation assay was used. Serum total IgE (tIgE) and the activated complement-derived anaphylatoxin C3 (C3a) levels were measured by ELISA. Results: QKLI was unable to elevate serum tIgE level in the Th2 immunity-amplified mice, but can increase vasopermeability and trigger anaphylaxis after the first injection. By screening seven fractions of QKLI, only the extract of Isatidis Radix (Isatis tinctoria L.) induced hindpaw Evans Blue extravasation, which was disappeared in Isatidis Radix-free QKLI. Mechanism study indicated that QKLI or Isatidis Radix-caused IHR could be blocked by the antagonists for histamine or C3a, rather than PAF or C5a. Consistently, QKLI and Isatidis Radix could also directly activate human serum complement-derived anaphylatoxin 3 (C3) in vitro with the half effective concentration values of 0.69% and 218.6 μg/ml, respectively. Conclusion: QKLI-IHR is complement activation-related pseudoallergy, rather than an IgE-mediated allergy. QKLI activates C3 and might consequently provoke mast cells to release histamine, which is a principal effector of its IHR. The pseudoallergic reaction induced by QKLI was attributed to the extract of Isatidis Radix. This study suggests a potential therapeutic strategy for the prophylaxis and treatment of QKLI-IHR.

Immediate-hypersensitivity reactions to proton pump inhibitors: Experience in a medical department

Immediate-hypersensitivity reactions to proton pump inhibitors: Experience in a medical department

In Vitro Diagnosis of Immediate Drug Hypersensitivity During Anesthesia: A Review of the Literature

Quantification of specific IgE (sIgE) antibodies constitutes an important measure to document anesthesia-related immediate hypersensitivity reactions (IHRs). However, only a few drug-specific assays are available and their predictive value is not known. In cases of non-IgE mediated IHRs, diagnosis might benefit from cellular tests such as basophil mediator release tests and basophil activation tests (BATs). To review the potential and limitations of quantification of sIgE, mediator release, and BAT in anesthesia-related IHRs, a literature search was conducted using the key words allergy, basophil activation, CD63, CD203c, diagnosis, drugs, hypersensitivity, flow cytometry, MRGPRX2, specific IgE antibodies, leukotrienes, histamine, and tryptase; this was complemented by the authors' experience. The drugs and compounds that have predominantly been studied are neuromuscular blocking agents (NMBAs), β-lactams, latex, and chlorhexidine. For sIgE NMBA, sensitivity and specificity varies between 38.5% to 92% and 92% to 100%, respectively. For sIgE β-lactams, sensitivity varies between 0% to 85% and specificity between 52% to 100%. sIgE to morphine should not be used in isolation to diagnose IHRs to NMBAs or opiates. sIgE for latex, and, in difficult cases, molecular diagnosis with quantification of sIgE to Hevea components constitute reliable diagnostics. For drugs, the sensitivity of BAT varies between 50% and 60% and specificity reaches 80% to 90%. Basophil mediator release tests seem to be abandoned and supplanted by BATs.

P26: THE UTILITY OF BASOPHIL ACTIVATION TEST IN THE DIAGNOSIS OF TYPE 1 HYPERSENSITIVITY REACTIONS MEDIATED BY CEPHALOSPORINS: SELECTIVE AND CROSS REACTIVE RESPONSES

Lack of understanding of the antigenic determinants generated by cephalosporins have hindered the development of sensitive in vitro tests for the detection of cephalosporin mediated immediate hypersensitivity reactions (IHRs) and the in vivo tests are risky. Hence, the aim of this study was to investigate the utility of the basophil activation test (BAT) to diagnose cephalosporin mediated IHR. 16 patients with at least one manifestation consistent with IHRs to cephalosporins (recent history, intra-dermal skin testing (ST) and/or DPT) and 10 non-allergic negative controls were included. The BAT was conducted using a spectrum of beta-lactams including the culprit cephalosporin. Basophils were gated using CD45+/CD123+/HLA-DR-/±CD193+ and the CD63 up-regulation (>10% as compared with the baseline) was used as the activation marker. Cross reactivity were tested using 3–8 different beta-lactams in 15 patients. The sensitivity and specificity of the BAT was compared to the findings from the clinical diagnosis. A total of 26 individuals were recruited, including 16 with at least 1 manifestation consistent with a cephalosporin mediated IHR and 10 non-allergic controls. 270 and 220 BAT were performed with various beta-lactams in the patient and non-patient group. 6/16 subjects were deemed clinically allergic and BAT was positive in four of them, resulting in a sensitivity of the BAT of 66.6% and specificity of 100%. There was minimal cross-reactivity demonstrated between different Cephalosporins and BAT was concordant with the DPT outcomes in all of the subjects where results were comparable. Similar profile was seen in subjects tested for penicillins. BAT is a useful adjunct in testing patients with Cephalosporin allergies. It can help choose a safe alternative drug and avoid the need for performing multiple drug provocation tests to rule out cross-reactivity.