Sustained silencing peanut allergy by xanthopurpurin is associated with suppression of peripheral and bone marrow IgE-producing B cell.

Introduction: Peanut allergy is an immunoglobulin E (IgE) mediated food allergy. Rubia cordifolia L. (R. cordifolia), a Chinese herbal medicine, protects against peanut-induced anaphylaxis by suppressing IgE production in vivo. This study aims to identify IgE-inhibitory compounds from the water extract of R. cordifolia and investigate the underlying mechanisms using in vitro and in vivo models. Methods: Compounds were isolated from R. cordifolia water extract and their bioactivity on IgE production was assessed using a human myeloma U266 cell line. The purified active compound, xanthopurpurin (XPP), was identified by LC-MS and NMR. Peanut-allergic C3H/HeJ mice were orally administered with or without XPP at 200µg or 400µg per mouse per day for 4 weeks. Serum peanut-specific IgE levels, symptom scores, body temperatures, and plasma histamine levels were measured at challenge. Cytokines in splenocyte cultures were determined by ELISA, and IgE + B cells were analyzed by flow cytometry. Acute and sub-chronic toxicity were evaluated. IL-4 promoter DNA methylation, RNA-Seq, and qPCR analysis were performed to determine the regulatory mechanisms of XPP. Results: XPP significantly and dose-dependently suppressed the IgE production in U266 cells. XPP significantly reduced peanut-specific IgE (>80%, p <0.01), and plasma histamine levels and protected the mice against peanut-allergic reactions in both early and late treatment experiments (p < 0.05, n=9). XPP showed a strong protective effect even 5 weeks after discontinuing the treatment. XPP significantly reduced the IL-4 level without affecting IgG or IgA and IFN-γ production. Flow cytometry data showed that XPP reduced peripheral and bone marrow IgE + B cells compared to the untreated group. XPP increased IL-4 promoter methylation. RNA-Seq and RT-PCR experiments revealed that XPP regulated the gene expression of CCND1, DUSP4, SDC1, ETS1, PTPRC, and IL6R, which are related to plasma cell IgE production. All safety testing results were in the normal range. Conclusions: XPP successfully protected peanut-allergic mice against peanut anaphylaxis by suppressing IgE production. XPP suppresses murine IgE-producing B cell numbers and inhibits IgE production and associated genes in human plasma cells. XPP may be a potential therapy for IgE-mediated food allergy.

Examining cefazolin utilization and perioperative anaphylaxis in patients with and without a penicillin allergy label: A cross-sectional study.

STUDY OBJECTIVE: To compare the occurrence of cefazolin perioperative anaphylaxis (POA) in patients with and without a penicillin allergy label (PAL) to determine whether the prevalence of cefazolin POA differs based on the presence of a PAL. DESIGN: Cross-sectional study. SETTING: A large U.S. healthcare system in the Baltimore-D.C. region, July 2017 to July 2020. PATIENTS: 112,817 surgical encounters across inpatient and outpatient settings in various specialties, involving 90,089 patients. Of these, 4876 (4.3%) encounters had a PAL. INTERVENTIONS: Perioperative cefazolin administration within 4 h before surgery to 4 h after the procedure began. MEASUREMENTS: The primary outcome was cefazolin POA in patients with and without PALs. Potential POA cases were identified based on tryptase orders or diphenhydramine administrations within the initial cefazolin administration to 6 h postoperatively. Verification included two validation steps. The first checked for hypersensitivity reaction (HSR) documentation, and the second, led by Allergy specialists, identified POA and the probable culprit. The secondary outcome looked at cefazolin use trends in patients with a PAL, stratified by setting and specialty. MAIN RESULTS: Of 112,817 encounters, 1421 (1.3%) had possible cefazolin HSRs. Of these, 22 (1.5%) had POA, resulting in a 0.02% prevalence. Of these, 13 (59.1%) were linked to cefazolin and 9 (40.9%) attributed to other drugs. Only one cefazolin POA case had a PAL, indicating no significant difference in cefazolin POA prevalence between patients with and without PALs (p = 0.437). Perioperative cefazolin use in patients with PALs steadily increased from 2.6% to 6.0% between 2017 and 2020, specifically in academic settings. CONCLUSIONS: The prevalence of cefazolin POA does not exhibit significant differences between patients with and without PALs, and notably, the incidence remains remarkably low. Based on these findings, it is advisable to view cefazolin as an acceptable choice for prophylaxis in patients carrying a PAL.

Anaphylaxis: A 2023 practice parameter update.

This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.

Reducing unnecessary premedication prior to parenteral iron therapy: A quality improvement project.

BACKGROUND: Intravenous (IV) iron carries risks of mild, self-limiting, tryptase-negative Fishbane and complement activation-related pseudo-allergy reactions, with rare reports of anaphylaxis. Historically, high-molecular-weight iron dextran (HMWID) was associated with a higher incidence of anaphylaxis and empiric premedication with antihistamines/corticosteroids have been used to mitigate this risk. HMWID is no longer available and the risk of hypersensitivity reactions with newer IV iron formulations is low. Therefore, the use of routine prophylactic premedication in all patients is not justified but should be considered in high-risk patients. STUDY DESIGN AND METHODS: Our primary aim was to reduce inappropriate premedication before IV iron administration by 50% so that our institution's hematology providers only prescribe premedications to patients at high risk of having a severe reaction. Interventions included a multidisciplinary education initiative to highlight current evidence against universal administration of premedications and revision of the IV iron informed consent form and electronic order set. RESULTS: We measured the success of our intervention by comparing data collected during a 6-month pre-intervention period (837 infusions) to a 6-month post-intervention period (947 infusions). Inappropriate administration of premedications decreased from 79% in the pre-intervention period compared to 65% in the post-intervention period. We found no significant difference in the number of Fishbane reactions, severe reactions, and emergency room admissions, despite this reduction in premedication use. DISCUSSION: Although we did not reach our goal of a 50% reduction in inappropriate premedication use, opportunities for process improvements were uncovered and are being explored in the next cycle of this quality improvement project.

Characteristics and management of hypersensitivity reactions with rabbit anti-thymocyte globulin in pediatric patients.

Background: Anti-thymocyte globulin (ATG) has been successfully used for decades to prevent graft versus host disease before hematopoietic stem cell transplantation (HSCT) as a part of conditioning regimen. However, sometimes hypersensitivity reactions may limit its use. Objective: To evaluate hypersensitivity reactions experienced during rabbit-ATG infusion among children and present successful desensitization protocol. Methods: The medical records of pediatric patients who were given rabbit-ATG treatment at our tertiary center hospital HSCT unit between 2019 and 2022 were reviewed retrospectively. Diagnosis of the patients, age at the time of HSCT, gender, presence of hypersensitivity reaction to rabbit-ATG, and management were evaluated. Characteristics of the reaction and presence of hypersensitivity reaction to other drugs were also noted. If performed, desensitization protocols were evaluated retrospectively. Results: We evaluated 81 patients; 66.6% of them (n = 54) were boys. The mean age of the patients was 8.78 ± 5.48 years. Hypersensitivity to rabbit-ATG was seen in six patients (7.4%). Four of them (4.9%) had anaphylaxis; two (2.4%) had urticaria. Intradermal test performed to every patient before the first dose of ATG infusion was detected a positive result in 1 patient (1.2%) . None of these seven patients had allergic reactions to other drugs before. Successful ATG desensitization was performed in five patients by using a 12-16 step protocol due to patients' reaction severity. Conclusion: This study aimed to evaluate hypersensitivity reactions with rabbit-ATG in children. A successful desensitization protocol with rabbit-ATG is presented. Desensitization must be performed with an experienced team very carefully in the absence of alternative drug.

A phase II study of Bruton's tyrosine kinase inhibition for the prevention of anaphylaxis.

BACKGROUNDIgE-mediated anaphylaxis is a potentially fatal systemic allergic reaction for which there are no currently FDA-approved preventative therapies. Bruton's tyrosine kinase (BTK) is an essential enzyme for IgE-mediated signaling pathways and is an ideal pharmacologic target to prevent allergic reactions. In this open-label trial, we evaluated the safety and efficacy of acalabrutinib, a BTK inhibitor that is FDA approved to treat some B cell malignancies, in preventing clinical reactivity to peanut in adults with peanut allergy.METHODSAfter undergoing graded oral peanut challenge to establish their baseline level of clinical reactivity, 10 patients had a 6-week rest period, then received 4 standard doses of 100 mg acalabrutinib twice daily and underwent repeat food challenge. The primary endpoint was the change in patients' threshold dose of peanut protein to elicit an objective clinical reaction.RESULTSAt baseline, patients tolerated a median of 29 mg of peanut protein before objective clinical reaction. During subsequent food challenge on acalabrutinib, patients' median tolerated dose significantly increased to 4,044 mg (range 444-4,044 mg). 7 patients tolerated the maximum protocol amount (4,044 mg) of peanut protein with no clinical reaction, and the other 3 patients' peanut tolerance increased between 32- and 217-fold. 3 patients experienced a total of 4 adverse events that were considered to be possibly related to acalabrutinib; all events were transient and nonserious.CONCLUSIONAcalabrutinib pretreatment achieved clinically relevant increases in patients' tolerance to their food allergen, thereby supporting the need for larger, placebo-controlled trials.TRIAL REGISTRATIONClinicalTrials.gov NCT05038904FUNDINGAstraZeneca Pharmaceuticals, the Johns Hopkins Institute for Clinical and Translational Research, the Ludwig Family Foundation, and NIH grants AI143965 and AI106043.

Research Advances in Mast Cell Biology and Their Translation Into Novel Therapies for Anaphylaxis.

Anaphylaxis is an acute, potentially life-threatening systemic allergic reaction for which there are no known reliable preventative therapies. Its primary cell mediator, the mast cell, has several pathophysiologic roles and functions in IgE-mediated reactions that continue to be poorly understood. Recent advances in the understanding of allergic mechanisms have identified novel targets for inhibiting mast cell function and activation. The prevention of anaphylaxis is within reach with new drugs that could modulate immune tolerance, mast cell proliferation and differentiation, and IgE regulation and production. Several US Food and Drug Administration-approved drugs for chronic urticaria, mastocytosis, and cancer are also being repurposed to prevent anaphylaxis. New therapeutics have not only shown promise in potential efficacy for preventing IgE-mediated reactions, but in some cases, they are able to inform us about mast cell mechanisms in vivo. This review summarizes the most recent advances in the treatment of anaphylaxis that have arisen from new pharmacologic tools and our current understanding of mast cell biology.

Do Children With an Allergic Transfusion Reaction Require Premedication For All Blood Products?

BACKGROUND: Children with a history of allergic transfusion reactions (ATRs) receive antihistamine premedication with or without hydrocortisone to prevent subsequent reactions. We aim to examine the frequency of developing ATRs to subsequent different blood product type transfusions. METHODS: A retrospective chart review of children who received blood product transfusions (packed red blood cells, platelets, frozen plasma, intravenous immunoglobin, albumin, and cryoprecipitate) and developed ATRs. Cases were identified through Transfusion Transmitted Injuries Surveillance System- Ontario database with a complementary chart review. Demographics and subsequent transfusions records were described. RESULTS: During this period, 35,925 blood products were transfused to 4153 patients. Thirty-eight ATRs were reported in 30 patients. All ATRs were minor except 1 anaphylaxis to albumin transfusion. Seven patients (23%) developed multiple ATRs, and all of them were of the same blood product type. A total of 60 subsequent different blood product types were transfused to the 7 patients who had multiple ATRs; none of those transfusions caused ATR. CONCLUSION: In children with a history of ATR, developing a reaction to a different blood product type is rare. Hence, premedicating those transfusions is not warranted.

Development and Evaluation of a Mobile Web-based Food Allergy and Anaphylaxis Management Educational Program for Parents of School-aged Children with Food Allergy: A Randomized Controlled Trial.

PURPOSE: This study aimed to develop a mobile web-based food allergy (FA) and anaphylaxis management educational program for parents of school-aged children with food allergies and evaluate its effectiveness. METHODS: A mobile program was developed based on a web-based teaching-learning system model. Its effectiveness was subsequently evaluated using a parallel, randomized controlled pre- and post-test design. This study included 73 parents of school-aged children with food allergies. These parents were randomly assigned to either the experimental (n = 37) or control (n = 36) groups. The experimental group participated in a 2-week mobile web-based educational program that covered major topics in FA and anaphylaxis management. These topics included an understanding of food allergies and anaphylaxis, learning techniques for using an epinephrine auto-injector, and developing an emergency action plan. An educational booklet was provided to the control group. Participants completed a pre-test and two post-test questionnaires to evaluate the impact of the program. The assessment tools were the Food Allergy Knowledge Test, Food Allergy Self-Efficacy for Parents, and Food Management and Adaptation Scale. The data were analyzed using descriptive statistics, a test of homogeneity for the pre-test, an independent t-test, and repeated measures ANOVA. RESULTS: The experimental group experienced greater improvement in the knowledge of FA (post-intervention t = 14.51, p < .001; 2 weeks post-intervention, t = 16.15, p < .001), FA self-efficacy (post-intervention t = 77.99, p < .001; 2 weeks post-intervention, t = 76.09, p < .001), and practice behavior in FA management (post-intervention t = 28.10, p < .001; 2 weeks post-intervention, t = 27.98, p < .001) after web-based FA education. CONCLUSION: This study revealed improvements in the knowledge, self-efficacy, and practice behaviors of parents regarding FA and anaphylaxis management. Therefore, the mobile web-based educational program can contribute to the effective management of food allergies and anaphylaxis for parents of school-aged children. CRIS registration: KCT0007491.

Could Artificial Intelligence Prevent Intraoperative Anaphylaxis? Reference Review and Proof of Concept.

Drugs and various medical substances have been used for many decades to diagnose or treat diseases. Procedures like surgery and anesthesia (either local or general) use different pharmacological products during these events. In most of the cases, the procedure is safe and the physician performs the technique without incidents. Although they are safe for use, these substances (including drugs) may have adverse effects, varying from mild ones to life-threatening reactions in a minority of patients. Artificial intelligence may be a useful tool in approximating the risk of anaphylaxis before undertaking a medical procedure. This material presents these undesirable responses produced by medical products from a multidisciplinary point of view. Moreover, we present a proof of concept for using artificial intelligence as a possible guardship against intraoperative anaphylaxis.

[Updates in diagnosis, treatment, and prevention of anaphylaxis to neuromuscular blocking agents and their antagonists].

Anaphylaxis to perioperative drugs has an insidious and rapid onset, can be life-threatening, and often results in the suspension of surgery. Neuromuscular blocking agents (NMBAs) are currently considered to be the most common cause of anaphylactic reactions among anesthetic drugs. With the increasing amount of anesthesia and surgery in the world, there are more and more NMBAs use, and the corresponding allergic risk is also increasing. With the use of NMBAs, their antagonists, such as neostigmine and sugammadex, are often used too, which have more and more allergy reports in clinical practice. Due to the complex mechanism of allergy caused by NMBAs and their antagonists, it is difficult to find out the culprit drug. The cross-reactivity between NMBAs is common, so it is often difficult to choose alternative drugs. This article summarized the epidemiology, pathological mechanisms, diagnostic methods and procedures, immediate treatment, and prevention strategies of anaphylaxis caused by these drugs.

Global patterns of drug allergy-induced fatalities: a wake-up call to prevent avoidable deaths.

PURPOSE OF REVIEW: To identify patterns and key issues though a systematic review in order to support prevention strategies and reduce avoidable deaths related to drug-induced anaphylaxis (DAF). RECENT FINDINGS: DAF rate has been estimated by 0.13-0.53/106 population/year. General global trends of DAF are increasing over time, mostly occurring at healthcare settings (62%) with a similar gender distribution and an average age of 53 years. Antibiotics, anaesthetics, radio-contrast media and NSAIDs were the most frequently implicated agents. Main comorbidities were personal history of drug allergy, cardiovascular diseases and asthma. Main manifestations were cardiovascular and respiratory commitments. Use of adrenaline is mentioned in only 29% of the articles. SUMMARY: DAF is increasing worldwide and most cases are iatrogenic. This first systematic review of DAF identified key gaps and served as a wake-up call to prevent avoidable deaths. Phenotype at risk for DAF was represented by patients aged more than 54 years, with personal history of drug allergy/hypersensitivity with no or incomplete allergological work-up, cardiovascular disease and/or asthma with need of hospitalization and/or frequent healthcare assistance. Additional risk for those who need frequent use of intravenous antibiotics and/or undergoing surgery or image investigation with radiocontrast media.

Food Allergy Education and Management in Schools: A Scoping Review on Current Practices and Gaps.

Currently, no synthesis of in-school policies, practices and teachers and school staff's food allergy-related knowledge exists. We aimed to conduct a scoping review on in-school food allergy management, and perceived gaps or barriers in these systems. We conducted a PRISMA-ScR-guided search for eligible English or French language articles from North America, Europe, or Australia published in OVID-MedLine, Scopus, and PsycINFO databases. Two reviewers screened 2010 articles' titles/abstracts, with 77 full-text screened. Reviewers differed by language. Results were reported descriptively and thematically. We included 12 studies. Among teachers and school staff, food allergy experiences, training, and knowledge varied widely. Food allergy experience was reported in 10/12 studies (83.4%); 20.0-88.0% had received previous training (4/10 studies; 40.0%) and 43.0-72.2% never had training (2/10 studies; 20.0%). In-school policies including epinephrine auto-injector (EAI) and emergency anaphylaxis plans (EAP) were described in 5/12 studies (41.7%). Educational interventions (8/12 studies; 66.7%) increased participants' knowledge, attitudes, beliefs, and confidence to manage food allergy and anaphylaxis vs. baseline. Teachers and school staff have more food allergy-related experiences than training and knowledge to manage emergencies. Mandatory, standardized training including EAI use and evaluation, and the provision of available EAI and EAPs may increase school staff emergency preparedness.

Combining failure modes and effects analysis and cause-effect analysis: a novel method of risk analysis to reduce anaphylaxis due to contrast media.

BACKGROUND: Contrast media agents are essential for computed tomography (CT)-based diagnoses. However, they can cause fatal adverse effects such as anaphylaxis in patients. Although it is rare, the chances of anaphylaxis increase with the number of examinations. OBJECTIVE: We aimed to design a quality improvement initiative to reduce patient risk to contrast media agents. METHODS: We analysed CT processes using contrast iodine in a tertiary-care academic hospital that performs approximately 14 000 CT scans per year in Japan. We applied a combination of failure modes and effects analysis (FMEA) and cause-effect analysis to reduce the risk of patients developing allergic reactions to iodine-based contrast agents during CT imaging. RESULTS: Our multidisciplinary team comprising seven professionals analysed the data and designed a 56-process flowchart of CT imaging with iodine. We obtained 177 failure modes, of which 15 had a risk-probability number higher than 100. We identified the two riskiest processes and developed cause-and-effect diagrams for both: one was related to the exchange of information between the radiation and hospital information system regarding the patient's allergy, the other was due to education and structural deficiencies in observation following the exam. CONCLUSION: The combined method of FMEA and cause-and-effect analysis reveals high-risk processes and suggests measures to reduce these risks. FMEA is not well-known in healthcare but has significant potential for improving patient safety. Our findings emphasise the importance of adopting new techniques to reduce patient risk and carry out best practices in radiology.

Perioperative Anaphylaxis: Evaluation and Management.

Perioperative anaphylaxis (PA) is a rare but life-threatening condition that poses diagnostic and management challenges in the operating room. The incidence of severe perioperative reactions is estimated to be approximately 1:7000-10,000. Management involves both immediate stabilization of the patient and identifying the culprit agent. Identification is essential to prevent recurrence of the event in subsequent surgeries and to avoid unnecessary labeling of drug allergy. Identifying all possible exposures including medications, disinfectants, latex, and dyes and choosing the appropriate tests are essential for proper evaluation. To identify the culprit, primary testing modalities include tryptase at the time of the reaction with subsequent levels and skin testing with nonirritating concentrations to the medications and substances utilized during the procedure and those potentially used as alternates. This strategy provides guidance for future surgeries and procedures. Close collaboration between the allergy, anesthesiology, and surgery teams is essential for appropriate management of these patients at the time of the reaction, during the post event evaluation and in preparation for subsequent surgeries.

Influenza.

Seasonal influenza epidemics of variable severity pose challenges to public health. Annual vaccination is the primary way to prevent influenza, and a wide range of vaccines are available, including inactivated or live attenuated standard-dose, recombinant vaccines, as well as adjuvanted or high-dose vaccines for persons aged 65 years or older. Persons at increased risk for influenza complications include young children, persons with underlying medical conditions, and older adults. Prompt diagnosis of influenza can facilitate early initiation of antiviral treatment that provides the greatest clinical benefit. This article summarizes recommendations for providers on influenza vaccination, diagnostic testing, and antiviral treatment.

Drug Desensitizations for Chemotherapy: Safety and Efficacy in Preventing Anaphylaxis.

Hypersensitivity reactions (HSRs) to antineoplastic drugs are increasing due to the expanding use of classical and new drugs in a wide variety of malignancies. PURPOSE OF REVIEW: The goal of this review is to provide current best practices in the diagnosis and management of HSRs based on data and evidence. RECENT FINDINGS: A plethora of studies have provided evidence of the safety and efficacy of rapid drug desensitizations (RDD) to allow for the reintroduction of antineoplastic drugs following an HSR, based on risk stratification. Recently described biomarkers such as basophil activation test, total IgE, BRCA genotyping, and serum IL-6 can aid in guiding improved precision desensitization protocols. Personalized premedication regimens and protocols have improved RDD safety and outcomes. RDD allows for the continued use of chemotherapeutic drugs without impaired drug efficacy. RDD represents the best approach to maintain cancer patients on their most effective treatments.

Stem Cell Factor Neutralization Protects From Severe Anaphylaxis in a Murine Model of Food Allergy.

Food allergy is a growing public health problem with ~15 million people affected in the United States. In allergic food disease, IgE on mast cells bind to ingested antigens leading to the activation and degranulation of mast cells. Stem cell factor (SCF) is mast cell growth and activation factor that is required for peripheral tissue mast cells. We targeted a specific isoform of SCF, the larger 248 amino acid form, that drives peripheral tissue mast cell differentiation using a specific monoclonal antibody in a model of food allergy. Ovalbumin sensitized and intragastrically challenged mice were monitored for symptoms of anaphylaxis including respiratory distress, diarrhea, and a reduction in body temperature. During the second week of challenges, allergic mice were injected with an antibody to block SCF248 or given IgG control. Mice treated with α-SCF248 had a decreased incidence of diarrhea and no reduction in body temperature suggesting a reduction in anaphylaxis compared to IgG control treated animals. Re-stimulated mesenteric lymph nodes indicated that α-SCF248 treated mice had decreased OVA-specific Th2 cytokine production compared to IgG control treated allergic animals. The reduction of food induced anaphylaxis was accompanied by a significant reduction in gut leak. The mesenteric lymph node cells were analyzed by flow cytometry and showed a decrease in the number of type 2 innate lymphoid cells in mice injected with α-SCF248. Morphometric enumeration of esterase+ mast cells demonstrated a significant reduction throughout the small intestine. Using a more chronic model of persistent food-induced anaphylaxis, short term therapeutic treatment with α-SCF248 during established disease effectively blocked food induced anaphylaxis. Together, these data suggest that therapeutically blocking SCF248 in food allergic animals can reduce the severity of food allergy by reducing mast cell mediated disease activation.

Hypersensitivity reactions and anaphylaxis to checkpoint inhibitor-monoclonal antibodies and desensitization.

OBJECTIVE: To review type 1 hypersensitivity reactions and anaphylaxis to checkpoint inhibitor-monoclonal antibodies and its management with drug desensitization. DATA SOURCES: English-language literature on MEDLINE regarding hypersensitivity, anaphylaxis, and checkpoint inhibitor-monoclonal antibodies. STUDY SELECTIONS: References were selected based on relevance, novelty, robustness, and applicability. RESULTS: There are well-known tissue toxicities associated to checkpoint inhibitors, but hypersensitivity reactions and anaphylaxis have been underreported. The presentation of these reactions is based on clinical phenotypes with underlying endotypes identified by specific biomarkers. Drug desensitizations have been successfully applied to checkpoint inhibitor drugs to allow patients with cancer to receive first-line therapies. This review provides current best practices for the recognition and diagnosis of hypersensitivity reactions and anaphylaxis to checkpoint inhibitors and their management using drug desensitization. CONCLUSION: Hypersensitivity reactions and anaphylaxis have been identified as potential adverse effects induced by checkpoint inhibitor-monoclonal antibodies. Drug desensitization is a safe and effective treatment option for patients who experience hypersensitivity reactions in need of these monoclonal antibodies to improve cancer outcomes.

Anti-type I allergic effects of Jing-Fang powder extracts via PI3K/Akt pathway in vitro and in vivo.

Jing-Fang powder (Schizonepeta tenuifolia Briq. and Saposhnikovia divaricata (Turcz.) Schischk.) was used to treat chronic bronchitis, asthma and chronic urticaria. Based on the preliminary results of screening research on the antiallergic effective parts of Jing-Fang powder, its ethyl acetate extract fractions (JFEE) and isolate D (JFEE-D) showed the best anti-allergic effect. RBL-2H3 cell activation degranulation model and mice passive cutaneous anaphylaxis (PCA) reaction model were used to investigate the effects and mechanisms of JFEE and JFEE-D on IgE-mediated type I allergic reactions. LC-MS was utilized to determine the composition of JFEE and JFEE-D. We found that JFEE and JFEE-D significantly reduced ß-HEX, histamine, IL-4, IL-6 levels in cell supernatants, and improved the degree and morphology of cell degranulation. JFEE and JFEE-D significantly inhibited the increase of ear vascular permeability and abnormal increase of serum IgE, TNF-α, IL-6 levels. JFEE and JFEE-D inhibited mRNA expression of PI3K and Akt and down-regulated protein expression of PI3K, Akt, p-Akt, and PLCγ1 in sensitized RBL-2H3 cells. The combined use of JFEE and JFEE-D with pathway inhibitor Wortmannin revealed synergistic down-regulation of PI3K, Akt, and p-Akt protein expression. The combined use of pathway agonist IGF-1, JFEE and JFEE-D down-regulated increase of p-Akt/Akt protein expression. Moreover, JFEE and JFEE-D significantly inhibited protein expression of PI3K, p-Akt and PLCγ1 in PCA model mice. These results show that JFEE and JFEE-D inhibit type I allergic reactions by inhibiting PI3K/Akt signaling pathway.