Anaphylactic Events Research Articles

Long-term safety and efficacy of garadacimab for preventing hereditary angioedema attacks: Phase 3 open-label extension study.

Hereditary angioedema (HAE) is a chronic, unpredictable disease. Long-term prophylactic treatments that offer durable efficacy, safety, and convenience are required to assist patients in achieving complete disease control, per international guidelines. We report an interim analysis of an ongoing phase 3 (VANGUARD) open-label extension (OLE) study evaluating the long-term safety and efficacy of garadacimab for HAE prophylaxis. Adults and adolescents aged ≥12 years with HAE previously participating in phase 2 and pivotal phase 3 (VANGUARD) studies were rolled over to an OLE, alongside newly enrolled patients. Patients received garadacimab 200 mg subcutaneously, once monthly for ≥12 months. The primary endpoint was treatment-emergent adverse events (TEAEs) in patients with C1 inhibitor deficiency/dysfunction. At data cut-off (February 13, 2023; N = 161), median (interquartile range) exposure was 13.8 months (11.9-16.3). For the primary endpoint, 133/159 patients experienced ≥1 TEAE (524 events), equivalent to 0.23 events/administration and 2.84 events/patient-year. Garadacimab-related TEAEs (13% of patients, 52 events) were most commonly injection-site reactions (ISRs). No deaths occurred. One patient discontinued treatment due to garadacimab-related moderate ISR. Most TEAEs were mild/moderate; three events were serious (COVID-19, two events; abdominal HAE attack, one event) and not garadacimab related. No abnormal bleeding, thromboembolic, severe hypersensitivity, or anaphylactic events were observed. Mean HAE attack rate decreased by 95% from the run-in period; 60% of patients were attack-free. Almost all patients (93%) rated their response to garadacimab as "good" or "excellent." Garadacimab has a favorable safety profile suitable for long-term use and provides durable protection against HAE attacks.

Trends in anaphylaxis management during COVID-19

BackgroundAnaphylaxis is an acute, potentially life-threatening systemic hypersensitivity reaction that commonly occurs in the community setting and is best managed with epinephrine. ObjectiveThe purpose of this study was to examine the effects of the COVID-19 pandemic on trends in acute at home anaphylactic events including Emergency Room (ER) visits and treatment for anaphylaxis. MethodsWe used data from two sources: survey data from the Food Allergy Research & Education (FARE) Patient Registry; and electronic medical records of patients who presented to Tampa General Hospital ER with a diagnosis of anaphylaxis. We collected data from events during the Covid epidemic and before and after vaccine availability. Data was analyzed using descriptive statistics. Results190 FARE survey responses were completed. Sixty-three patients reported that the COVID-19 pandemic changed how they responded to the allergic reaction. Of these 63 patients, 71% avoided seeking medical care outside the home, 30% used self-medication more quickly than usual, and 14% delayed the use of medication. Only 87 events (46%) were treated with epinephrine. 4358 presented to TGH ER from April 1, 2018, to March 31, 2022, with an ICD-10 diagnosis code of anaphylaxis or allergic reaction. Only 718 received epinephrine in the ER. 867 patients presented 1 year prior to March 1, 2020 (before vaccine availability) and 1,833 patients presented 1 year after April 1, 2021 (after vaccine availability). ConclusionsOnly 16% of patients received epinephrine by survey and ER data capture. After COVID vaccine availability there were more ER visits for anaphylaxis among patients seen in a tertiary care teaching hospital.

Abstract PO2-12-07: Risk of anaphylaxis associated with the use of pertuzumab or other biologics with potential for use outside the hospital

Abstract BACKGROUND Intravenous (IV) pertuzumab (P) and trastuzumab (H) are approved in the US for the treatment of HER2-positive breast cancer. P and H are also approved as a fixed-dose combination for SC injection (pertuzumab, trastuzumab, and hyaluronidase-zzxf; PH FDC SC). PH FDC SC may offer the possibility of treatment outside a hospital setting by a healthcare professional. Anaphylactic reactions can be a concern with the use of biologics. PH is also frequently initiated with six to eight cycles of taxanes, which can also be associated with anaphylaxis. We used administrative claims data to evaluate the risk of anaphylaxis associated with the real-world administration of PH or other biologic drugs in the real world. Our objective was to evaluate the risk of anaphylaxis associated with the administration of P and to contextualize the risk estimate by using other biologics that can be used outside the hospital as a benchmark. METHODS Cohorts of incident users were selected using retrospective records from a US healthcare claims database (IQVIA). Patients included were privately insured in the US, aged 16 to 65 years, and initiated a treatment of interest between 2012 and 2021. Possible and severe anaphylactic events (PAEs) were identified using the algorithm developed by the US Food and Drug Administration (FDA) Sentinel Initiative and updated with ICD10 codes (PMID: 34181291). PAEs were attributed to a drug if it occurred on the day of administration or the day after. The prevalence proportion (PP) of PAE was used to approximate the risk of anaphylaxis at each cycle. A sensitivity analysis using the proportion of prior P use amongst the cases of PAE beyond cycle 1 in the H cohort was conducted to approximate how many cases of PAE could have been missed at cycle 1 of P due to a depletion of susceptibles (as P IV and H may be administered sequentially in any order, patients with a PAE from H would not receive scheduled P and thus be excluded from the P cohort). RESULTS A total of 1,919,748 patients constituted 27 cohorts. Of them, 184,414 patients initiated monoclonal antibodies (mAbs) in 12 cohorts of which 12,264 and 184 initiated P IV and PH FDC SC, respectively. In the P IV cohort, seven PAE events were observed up to cycle 6 and none after. The PP at cycle 1 of P was 1.63 per 10,000 patients (95% confidence interval [CI] = 0.45, 5.94). The risk was comparable to that of other mAbs where anaphylaxis risk is described as uncommon/rare (Table). Accounting for a potential depletion of susceptibles increased the PP at cycle 1 of P to 2.45/10,000 (95% CI = 0.83, 7.19). No PAEs were reported in patients treated with PH FDC SC. CONCLUSIONS Using one of the largest datasets available, results suggest the risk of PAE with P administration could be within the range of what is observed with other mAbs that can be administered outside of the hospital. All events were observed when patients are expected to receive treatment at the hospital due to taxane administration. No PAE events were identified for PH FDC SC, but there were few patients in this cohort. Efforts are ongoing to identify a larger cohort treated with PH FDC SC. Risk of anaphylaxis by mAb * According to summary of product characteristics. † ≥1/1,000 to <1/100. ‡ ≥1/10,000 to <1/1,000. CI = confidence interval; H = trastuzumab; IV = intravenous; P = pertuzumab; PH FDC SC = pertuzumab, trastuzumab, and hyaluronidase-zzxf. Citation Format: Thibaut Sanglier, Tom Chambers, Joanna Harton, Laurentia Wahyudi, Magali Genevray, Eleonora Restuccia, Cécile Droz-Perroteau, Chau Dang. Risk of anaphylaxis associated with the use of pertuzumab or other biologics with potential for use outside the hospital [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-07.

Cross-Reactivity of Antibodies to Rituximab with Other Therapeutic Anti-CD20 Antibodies.

One reason for a lack of response to rituximab as well as infusion-related anaphylactic adverse events is the development of antidrug Abs to rituximab. Besides rituximab, a number of other therapeutic Abs targeting CD20 are nowadays available as alternatives. In this study, we investigated the potential cross-reactivity of (human) anti-rituximab Abs to three other anti-CD20 mAbs: ofatumumab, obinutuzumab, and ocrelizumab. In 25 cases of anti-rituximab Abs, cross-reactivity was examined using both direct binding assays and inhibition immunoassays. Although no cross-reactivity was observed to ofatumumab or obinutuzumab, 8 of 25 samples also showed reactivity toward ocrelizumab in at least one of the two assays. Furthermore, in three cases of anti-ocrelizumab Abs, cross-reactivity to rituximab was observed in an inhibition immunoassay, albeit not in a direct binding assay. Our results suggest that obinutuzumab or ofatumumab are safe anti-CD20 alternatives in case of the presence of anti-rituximab Abs. It is advisable to proceed cautiously if switching from rituximab to ocrelizumab (or vice versa) is considered in case these alternatives may not be available.

ANAPHYLACTIC SHOCK DUE TO PROPHYLACTIC ANTIBIOTICS IN PLANNED SECTIO CESAREAN : A CASE REPORT

Introduction: Anaphylactic reactions during pregnancy are complex to diagnose and manage, potentially ranging from mild symptoms to life-threatening situations for both the mother and fetus. With an incidence varying from 1.44 to 2.7 cases per 100,000 births and subtle, overlapping symptoms with other obstetric emergencies, accurate identification remains a challenge. Despite being underdiagnosed, severe anaphylactic events during pregnancy share symptoms with other critical conditions, making differentiation intricate. Prior reviews and recent data underscore the necessity for guidelines and public health actions, emphasizing the importance of vigilance and specific management strategies in obstetrics. Case report: This case involves Ny. S, a 33-year-old pregnant woman undergoing an elective C-section, who developed an allergic reaction to Cefazolin, necessitating an emergency procedure and subsequent ICU admission due to anaphylactic complications. Patient at 38 weeks pregnant, encountered an unexpected allergic reaction during a planned C-section, necessitating an emergency procedure. Post-surgery, she experienced severe complications, including pulmonary and laryngeal edema, requiring intensive care. With prompt medical attention and a comprehensive treatment plan, including medications and careful monitoring, her condition stabilized over several days. By October 21, 2023, she showed significant improvement, allowing her discharge with scheduled follow-up care. Discussion: The discussion encompasses the complexity of diagnosing anaphylaxis during pregnancy, highlighting challenges in laboratory confirmation, management protocols mirroring non-pregnant guidelines, and the importance of coordinated medical care to avert adverse maternal and fetal outcomes. It emphasizes the need for standardized protocols and consensus among healthcare providers to effectively manage maternal anaphylaxis, reflecting on the rarity of this condition and the potential risks it poses to both the mother and fetus. Conclusion: Anaphylactic reaction during an elective C-section, prompting urgent medical intervention involving mechanical ventilator support and meticulous care. Patient’s subsequent recovery and discharge, along with fluctuating lab results indicating an acute immune response, underscore the complexity of diagnosing and managing maternal anaphylaxis, emphasizing the need for standardized protocols and coordinated healthcare approaches.

Safety of Cefazolin Perioperative Prophylaxis in Plastic Surgery Patients With Penicillin Allergy: A Retrospective Chart Review

Introduction: Antimicrobial prophylaxis is crucial in reducing surgical site infections (SSIs). First-generation cephalosporins are commonly first line, but issues arise when patients report a penicillin allergy. Although up to 10% of Americans report a penicillin allergy, up to 95% are not truly allergic. Even patients with true penicillin allergy likely tolerate cephalosporins due to low cross-reactivity. Nevertheless, providers are less likely to prescribe cefazolin for these patients, increasing the risk of SSI. We seek to characterize the pattern of perioperative antibiotic use and rate of reaction in plastic surgery patients who endorse a penicillin allergy. Method: This was a single-center retrospective chart review of adults who received body contouring plastic surgery from January 1, 2021 to December 31, 2021. The presence of reported penicillin allergy and administration of cefazolin versus alternative agent were evaluated, and the outcome was measured in number of anaphylactic reactions and SSI events. Results: The study included 457 patients in total; 437 (96%) were female; 106 (23%) had listed allergy to penicillin, cephalosporin, or both - 17 (16%) were listed as having anaphylaxis to penicillin, 62 (58.5%) endorsed a nonanaphylactic allergic reaction to penicillin, 8 (7.5%) endorsed an allergy without a documented reaction to penicillin, and 19 (18%) reported a prior cephalosporin allergy. All patients with a beta-lactam allergy who received cefazolin perioperatively did not have any anaphylaxis events. Three patients who received clindamycin and 1 patient who received cefazolin developed SSI postoperatively. Conclusion: Cephalosporins should be the first line for appropriate patients with a penicillin allergy, as alternative agents have increased SSI risk.

The Implementation and Evaluation of a Stock Epinephrine for Schools Program in Maricopa County, Arizona.

The increasing rate of food allergies in children, combined with the role of food as an integral part of the school day has led to the emergence of anaphylaxis as a daily threat to students, regardless of prior allergy diagnosis. Stock epinephrine-non-patient specific epinephrine auto-injectors that may be used during emergencies-is a means for schools to prepare for anaphylactic events and protect children with allergies. The Maricopa County Department of Public Health initiated the School Surveillance and Medication Program (SSMP), a data capture program, to facilitate the process of stocking epinephrine in schools. Spearheaded by the implementation efforts of the Kyah Rayne Foundation, program enrollment increased 146% between the 2020-2021 and 2021-2022 school years. The increased proportion of schools enrolled in the SSMP and the number of school personnel trained to administer epinephrine demonstrates the feasibility of school-centered stock epinephrine programs and validates strategies for increasing program uptake.

Allergic emergencies in the prehospital setting: a 5 year retrospective study.

Background. Patients with severe allergic conditions often request support from the prehospital emergency services given the rapid, unexpected and potentially life-threatening nature of the reactions, such as anaphylaxis. Studies regarding prehospital incidents for allergic conditions are scarce. This study aimed to characterize prehospitalar medical requesting assistance due to suspected hypersensitivity reactions (HSR). Methods. Retrospective study of allergic-related requesting assistances between 2017-2022 of a Portuguese emergency dispatch centre - Emergency and Resuscitation Medical Vehicle (VMER), in Coimbra University Hospital. Demographic and clinical variables were analysed, including clinical manifestations, anaphylaxis severity grading, therapeutic interventions, and post-incident allergic work-up. Regarding anaphylactic events, three diagnosis timings were compared: on-site, hospital emergency department and Investigator-diagnosis based on data reviewed. Results. Out of 12689 VMER requesting assistances, 210 (1.7%) were classified as suspected HSR reactions. After on-site medical evaluation, 127 (60.5%) cases maintained the HSR classification (median age 53 years; 56% males) and the main diagnoses included HSR to Hymenoptera venom (29.9%), food allergy (29.1%), and pharmaceutical drugs (25.5%). Anaphylaxis was assumed on-site in 44 (34.7%) cases, in the hospital emergency department in 53 cases (41.7%) and by investigators in 76 (59.8%) cases. Regarding management, epinephrine was administered on-site in 50 cases (39.4%). Conclusions. The main reason for prehospital requesting assistance was HSR to Hymenoptera venom. A high proportion of incidents met the criteria for anaphylaxis and despite the inherent difficulties of the prehospital setting, many of the on-site diagnoses agreed with the criteria. Regarding management, epinephrine was underused in this setting. Referral to specialized consultation is crucial for the management of prehospital incidents.

Reliability of patient history in determination of venom hypersensitivity in patients who underwent venom immunotherapy

Characterize the time between an index anaphylactic event and venom immunotherapy initiation in patients with venom allergy, and determine the extent to which patient history is concordant with selected venom extracts when compared to skin and blood test results.

Direct Versus Indirect Query Performance of ICD-9/-10 Coding to Identify Anaphylaxis

Anaphylaxis is an often under=diagnosed, severe allergic event for which epidemiological data are sporadic. Researchers have leveraged administrative and claims data algorithms to study large databases of anaphylactic events; however, little longitudinal data analysis is available after transition to the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM). Study longitudinal trends in anaphylaxis incidence using direct and indirect query methods. Emergency department (ED) and inpatient data were analyzed from a large state health care administration database from 2011 to 2020. Incidence was calculated using direct queries of anaphylaxis ICD-9-CM and ICD-10-CM codes and indirect queries using a symptom-based ICD-9-CM algorithm and forward mapped ICD-10-CM version to identify undiagnosed anaphylaxis episodes and to assess algorithm performance at the population level. An average of 2.4 million inpatient and 7.5 million ED observations/y were analyzed. Using the direct query method, annual ED anaphylaxis cases increased steadily from 1,454 (2011) to 4,029 (2019) then declined to 3,341 in 2020 during the coronavirus disease 2019 (COVID-19) pandemic. In contrast, inpatient cases remained relatively steady, with a slight decline after 2015 during the ICD version transition, until a significant drop occurred in 2020. Using the indirect queries, anaphylaxis cases increased markedly after the ICD transition year, especially involving drug-related anaphylaxis. Nontypical drug associations with anaphylaxis episodes using the ICD-10-CM version of the algorithm suggest poor performance with drug-related codes. Further, the increased granularity of ICD-10-CM identified potential limitations of a previously validated symptom-based ICD-9-CM algorithm used to detect undiagnosed cases.

Diagnosis and treatment of Hymenoptera venom allergy: S2k Guideline of the German Society of Allergology and Clinical Immunology (DGAKI) in collaboration with the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (ABD), the Medical Association of German Allergologists (AeDA), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNOKC), the German Society of Pediatrics and Adolescent

Diagnosis and treatment of Hymenoptera venom allergy: S2k Guideline of the German Society of Allergology and Clinical Immunology (DGAKI) in collaboration with the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (ABD), the Medical Association of German Allergologists (AeDA), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNOKC), the German Society of Pediatrics and Adolescent

Abstract 11227: A Rare Case of Echo Contrast Anaphylaxis Complicated by Acute Coronary Syndrome

Introduction: Contrast agents in echocardiography are used frequently to enhance endocardial border visualization and assessment of structural heart disease. Sulfur hexafluoride lipid type A injectable suspension is a generally well-tolerated class of contrast. Anaphylaxis to these agents is exceedingly rare. We now report the first case of acute coronary syndrome in the setting of echo contrast anaphylactic shock. Case: A 49-year-old woman was hospitalized for an ST-elevation myocardial infarction (STEMI) for which a drug-eluting stent had been placed in the left anterior descending artery (LAD). An echocardiogram was performed to evaluate for structural heart disease. Shortly after administration of echo contrast the patient developed sudden-onset tachypnea and suffered a pulseless electrical activity cardiac arrest. She was treated for anaphylactic shock with epinephrine and high-dose steroids and achieved return of spontaneous circulation. Following the arrest an electrocardiogram revealed an anterolateral STEMI. The patient immediately underwent repeat angiography which revealed a 100% in-stent thrombosis of the LAD. The occlusion was successfully revascularized with a drug eluting stent with an Impella CP (Abiomed, Danvers MA) support. Subsequent laboratory exam demonstrated an elevated blood tryptase level consistent with an anaphylactic event. Discussion: We present a unique case of anaphylactic shock with acute coronary syndrome following administration of sulfur hexafluoride echo contrast. The incidence of anaphylaxis to echo contrast is less than one per million, and therefore it may not be immediately recognized as a mechanism of shock. Any prior reactions to polyethylene glycol should be noted before using these agents as this ingredient is thought to be the cause of anaphylaxis. In our case, diagnosis of anaphylaxis was confirmed by measuring the serum tryptase level. Tryptase is released from mast cells during allergic events, so this laboratory test with high specificity for anaphylaxis can be a useful tool in challenging cases such as this. Additionally, mast cell and platelet activation secondary to anaphylaxis may be an important mechanism of acute coronary syndrome with in-stent thrombosis.

A DISCUSSION OF THE REFRACTORY PERIOD IN VENOM IMMUNOTHERAPY

<h3>Introduction</h3> Refractory periods are inconsistently observed phenomena that follow hypersensitivity reactions wherein a reaction is followed by a period of time during which additional reactions cannot be triggered. We discuss a case that challenges this theory. <h3>Case Description</h3> A 56-year-old male with Diabetes Mellitus II, Hypertension, and HIV presented with history of two prior episodes of fire ant stings leading to anaphylaxis. His baseline tryptase level was 6.1 ug/mL and sIgE to fire ant (Solenopsis invicta) was 42.3 kU/L. The patient completed the immunotherapy ultrarush induction protocol using 1:100wt/v Solenopsis invicta whole body extract (WBE) as the maintenance (1:1v/v) concentration. One hundred minutes after completion of the protocol, he developed throat tightness, nasal congestion, diffuse pruritus, and urticaria. Symptoms resolved after two injections of 0.5mL intramuscular epinephrine. One week later, he received 0.2 mL of 1:1 v/v and developed stridor, productive cough, and injected sclera 30 minutes after injection. Symptoms resolved with intramuscular epinephrine. The following week, he received another injection (decreased to 0.5 mL of 1:10 v/v) without incident. He continued weekly buildup to maintenance dose and subsequent monthly injections without additional reactions. <h3>Discussion</h3> In this case, completion of an ultrarush induction protocol and anaphylaxis failed to result in a refractory period of unresponsiveness, allowing for a second anaphylactic reaction to S. invicta WBE one week after desensitization should have been achieved. Additional research is needed to reliably identify patients experiencing a refractory period following an anaphylactic event. This would improve the accuracy of allergy testing and has the potential to make desensitization safer.

A CASE OF HEREDITARY ALPHA TRYPTASEMIA MASQUERADING AS CHEMOTHERAPY HYPERSENSITIVITY REACTION

<h3>Introduction</h3> Hereditary alpha-tryptasemia (HaT) is an established modifier of anaphylaxis and mast cell mediator-associated symptoms. We present a case of HaT diagnosed after hypersensitivity reactions to chemotherapeutic agents treated with a prolonged desensitization protocol. <h3>Case Description</h3> A 56-year-old female with high-grade serous ovarian cancer presented after a hypersensitivity reaction to paclitaxel with an event tryptase of 87.2 ng/mL. She subsequently tolerated nab-paclitaxel and was transitioned to liposomal doxorubicin therapy. During the first infusion of liposomal doxorubicin, she developed gastrointestinal pain, flushing, and hypotension. Despite re-administration via 3-bag, 13-step desensitization, the patient again experienced similar symptoms. A baseline tryptase level was elevated at >30 ng/mL. She had no symptoms in between anaphylactic events, and had previously experienced multiple insect stings without adverse reaction. A bone marrow biopsy was negative for mastocytosis. Genetic testing showed extra-allelic copies of TPSAB1 consistent with HaT. She subsequently tolerated liposomal doxorubicin via slowed 4-bag, 17-step desensitization protocol and seven days of premedication with cetirizine, cromolyn, montelukast, and famotidine. After multiple cycles, her imaging showed improvement in peritoneal carcinomatosis. However, she also developed a new reaction to iodinated contrast media which she had previously tolerated. Despite a similar premedication regimen and use of non-ionic, iso-osmolar contrast media, she experienced recurrent contrast-induced anaphylaxis. Omalizumab is being pursued as a potential treatment for preventing anaphylaxis. <h3>Discussion</h3> This patient with hypersensitivity reactions to chemotherapy agents and iodinated contrast was found to have underlying HaT. The use of a slowed desensitization protocol and multi-day premedication regimen allowed for treatment of her malignancy.

Communication of perioperative anaphylaxis under general anaesthetic to patients and within the multidisciplinary team

Background: Anaphylaxis is defined as a severe, life-threatening systemic hypersensitivity reaction. Its incidence is estimated to be 1 in 10 000 anaesthetics.1 The 6th National Audit Project (NAP6) on perioperative anaphylaxis revealed that one-third of patients experienced harm after the event, with anxiety about future anaesthetics being the most commonly reported consequence. The objective of this study is to assess the effectiveness of (1) communication of perioperative anaphylaxis and (2) emotional support provided to patients, and their consequent impacts on feelings towards future anaesthetics. This study also evaluates the current procedure for allergy referral after perioperative anaphylaxis. Methods: Thirty-four patients who experienced general anaesthetic-induced perioperative anaphylaxis in Addenbrooke’s Hospital, Cambridge between 5 January 2017 and 2 December 2020 were identified using electronic medical records. The subjective experiences of the communication of the anaphylactic event and the allergy testing results were evaluated in a telephone survey of 26 of these patients. The telephone survey also explored patients’ perception of the emotional support received after anaphylaxis and any negative impact on their feelings towards a subsequent general anaesthetic. In addition, the responsible person for making an Allergy department referral in all cases was investigated. Results: Communication of the anaphylactic event was considered excellent by 69% of patients, with a rating of 5/5 on a 1–5 rating scale. Of the 17 patients that were referred to the Allergy department for allergen testing, 16 felt communication of the test result was clear. Emotional support from hospital staff after anaphylaxis was considered excellent by 38% of patients, whereas 33% felt emotional support was poor on a 1–5 rating scale. Negative feelings towards a subsequent general anaesthetic were reported by 50% of patients. There is also a lack of consistency regarding who makes an allergy referral (surgeon or anaesthetist). Conclusions: The study data show that improvements in the process of referring patients to the Allergy department, and patient experience in terms of communication and emotional support after a traumatic anaphylactic event, should be made. This is in concordance with the findings of the NAP6 report. There need to be clearer local guidelines regarding which clinician is responsible for making an anaphylaxis referral to the Allergy department. Patients should be sent a letter explaining their anaphylaxis, the significance of it and the sources of support available if required. Anaesthetists and the Allergy department should be made aware of emotional support available to recommend to patients. We have presented our findings to the Anaesthetics and Allergy departments of Addenbrooke’s Hospital and are in the process of making changes to the practice. We will review again in 3–5 years’ time. 1.Harper NJN, Cook TM, Garcez T, et al. Br J Anaesth 2018: 121: 159–71

Allergic Reactions to COVID-19 Vaccination in High-Risk Allergic Patients: The Experience of Trieste University Hospital (North-Eastern Italy).

Background. Allergic patients may develop reactions following COVID-19 vaccination more frequently than non-allergic individuals. The aim of our study was to assess the risk of reactions in high-risk allergic patients vaccinated for COVID-19 at the University Health Agency Giuliano-Isontina (ASUGI) of Trieste (northeastern Italy). Methods. Patients were considered at high risk for allergic reactions in case of: prior anaphylactic reaction to any drug/vaccine; multiple drug allergy; intolerance to polyethylene glycol (PEG) or polysorbate 80 (PS80) containing drugs; and mast cell disorders. High-risk allergic patients were immunized in hospital by a dedicated allergy team supported by resuscitation staff. Patients were interviewed over the phone one month after vaccination to complete a structured questionnaire investigating signs and symptoms developed after immunization. Results. From March 2021 to February 2022, 269 patients with a history of severe allergic reactions were assessed, of whom 208 (77.3%) eventually received COVID-19 vaccination, 50 (18.6%) refused to be immunized, 10 (3.7%) were deferred for medical reasons and one was declared exempted due to testing positive for PS80. Mild reactions (urticaria, angioedema, rhinitis, erythema) to COVID-19 vaccines were reported by 30.3% of patients, 8.7% within 4 h and 21.6% > 4 h after immunization. No anaphylactic events were observed. Although they were 80 times (3.8%) more prevalent than in COVID-19 vaccinees from the general population (0.047%), vaccine allergic reactions in high-risk patients were mainly mild and late, more likely affecting women (OR = 3.05; 95% CI 1.22–7.65). Conclusions. High-risk allergic patients with urticaria and angioedema may experience mild flare-ups of mast cell activation-like symptoms following COVID-19 vaccination, supporting antihistamine premedication before vaccination and to be continued for one week afterwards.

Efficacy and safety of an e-consult program for COVID-19 vaccine allergy concerns.

Background: Although severe allergic reactions to coronavirus disease 2019 (COVID-19) vaccines are rare, fear of allergic reactions remains a major source of vaccine hesitancy. For concerned patients and providers alike, allergist consultation is recommended for further guidance on the risk of vaccination. The electronic consultation (e-consult) medium has the potential to make this guidance more widely accessible, thereby supporting vaccination efforts. Objective: To determine the safety and efficacy of an e-consult program for COVID-19 vaccine allergy concerns. Methods: We performed a retrospective analysis of a single-center COVID-19 vaccine allergy e-consult program. Data on demographics, allergy history, and outcomes after recommendations were gathered via review of the electronic medical record (EMR). Patients without EMR data available following the e-consult were called to inquire about vaccination status. Results: Our study included 64 patients, most of whom (51.6% [33/64]) had e-consults placed for second-dose concerns. E-consults were completed within 2 days for all patients. The most common recommendation was that patients receive any COVID-19 vaccination available (62.5%, [40/64]). Forty-one patients (64.1%) were vaccinated after receiving recommendations from an allergist, 11 of whom (26.8%) reported a vaccine reaction. Most of these reactions were nonallergic (9/11 [81.2%]). No anaphylactic events were reported. Conclusion: Results of our study suggest that e-consults were a safe and effective method of providing guidance with regard to COVID-19 vaccine risk in patients with concerns about allergic reactions. The efficiency of this medium, highlighted by the 2-day turnaround time in our study, has the potential to expand access to vaccine risk evaluations by board-certified allergist/immunologists.

Patient-reported outcomes among patients with systemic mastocytosis in routine clinical practice: Results of the TouchStone SM Patient Survey.

Systemic mastocytosis (SM) is a rare clonal neoplasm driven by KIT D816V and other mutations. Data were collected from the patient perspective on disease burden and included an SM-specific symptom assessment tool. US adults aged 18 years and older with a self-reported SM diagnosis completed an online TouchStone SM Patient Survey of 100 items, including the 12-item Short-Form Health Survey, the Indolent Systemic Mastocytosis Symptom Assessment Form, and the Work Productivity and Activity Impairment Questionnaire, as well as questions about SM diagnosis, the impact of SM on daily activities, work impairment, and health care use. The results were analyzed using descriptive statistics. Fifty-six individuals completed the survey (89% women; median age, 48 years; mean time since diagnosis, 6.7 years), reporting indolent SM (66%), aggressive SM (9%), smoldering SM (5%), and unknown SM subtype (18%). Over a 1-year recall, respondents reported seeking emergency care for anaphylaxis (30%) and taking three or more prescription medications (52%) for SM. Over one half of patients (54%) reduced their work hours because of SM, and 64% avoided leaving home because of symptoms. A majority of respondents (93%) had experienced ≥10 SM-related symptoms, noting that the most bothersome were anaphylactic episodes (18%), abdominal/stomach pain (16%), diarrhea/loose stools (13%), and fatigue (11%). Whereas an Indolent Systemic Mastocytosis Symptom Assessment Form-derived total symptom score of 28 is used to indicate moderate-to-severe symptoms, the mean total symptom score was 52.7. Mental and physical component summary scores from the 12-item Short-Form Health Survey were below population norms. Patients who were surveyed reported substantial symptom burden and unmet needs because of SM, as evidenced by seeking emergency care and reporting bothersome symptoms, poor quality of life, and reduced work hours and productivity. The objective of this research was to understand the burden and unmet needs in the rare disease of systemic mastocytosis (SM) to guide future care. Fifty-six patients completed an online survey containing questions about their diagnosis, medications, health care use, quality of life, and SM symptoms. The results demonstrated that SM is associated with severe and burdensome symptoms, anaphylactic events, emergency department visits, use of multiple medications, reduced ability to work, and poor physical and psychological quality of life. These findings suggest the need for future advances to address unmet needs in patients affected by SM.

Evaluation of the safety of 500 mg intravenous push thiamine at a tertiary academic medical center.

Background: Thiamine, also known as vitamin B1, is an essential water-soluble micronutrient. Although thiamine has minimal safety concerns, parenteral administration has been associated with rare cases of anaphylactic shock, cardiac arrest, and injection site reaction. The objective of this analysis is to evaluate the incidence of anaphylaxis and injection site reactions associated with the administration of thiamine 500 mg as an intravenous (IV) push in adult patients. Method: This single-center, retrospective analysis was performed at Brigham and Women's Hospital in Boston, Massachusetts. Electronic health records were used to identify all adult patients who were ordered for thiamine 500 mg IV push between July 1, 2020, and December 31, 2020. For the major and minor endpoints, anaphylaxis and injection site reactions were assessed, respectively. Descriptive statistics were used as appropriate. Results: A total of 463 doses of thiamine in 69 patients were evaluated. Thiamine was administered peripherally for 392 (84.7%) doses and centrally for 68 (14.7) doses. No anaphylactic reactions were observed. A total of 4 injection site reactions (0.86%) were noted with 4 unique doses. All reactions were classified as low-grade based on our institutional grading system. All injection site reactions were classified as "possible" (Naranjo score of 1-4). Conclusion: Administration of IV push 500 mg thiamine was not associated with anaphylactic events and was associated with a low rate of injection site reactions.

Pathophysiological, Cellular, and Molecular Events of the Vascular System in Anaphylaxis.

Anaphylaxis is a systemic hypersensitivity reaction that can be life threatening. Mechanistically, it results from the immune activation and release of a variety of mediators that give rise to the signs and symptoms of this pathological event. For years, most of the research in anaphylaxis has focused on the contribution of the immune component. However, approaches that shed light on the participation of other cellular and molecular agents are necessary. Among them, the vascular niche receives the various signals (e.g., histamine) that elicit the range of anaphylactic events. Cardiovascular manifestations such as increased vascular permeability, vasodilation, hypotension, vasoconstriction, and cardiac alterations are crucial in the pathophysiology of anaphylaxis and are highly involved to the development of the most severe cases. Specifically, the endothelium, vascular smooth muscle cells, and their molecular signaling outcomes play an essential role downstream of the immune reaction. Therefore, in this review, we synthesized the vascular changes observed during anaphylaxis as well as its cellular and molecular components. As the risk of anaphylaxis exists both in clinical procedures and in routine life, increasing our knowledge of the vascular physiology and their molecular mechanism will enable us to improve the clinical management and how to treat or prevent anaphylaxis.Key MessageAnaphylaxis, the most severe allergic reaction, involves a variety of immune and non-immune molecular signals that give rise to its pathophysiological manifestations. Importantly, the vascular system is engaged in processes relevant to anaphylactic events such as increased vascular permeability, vasodilation, hypotension, vasoconstriction, and decreased cardiac output. The novelty of this review focuses on the fact that new studies will greatly improve the understanding of anaphylaxis when viewed from a vascular molecular angle and specifically from the endothelium. This knowledge will improve therapeutic options to treat or prevent anaphylaxis.