Remimazolam-Induced Anaphylaxis and Cardiovascular Collapse: A Narrative Systematic Review of Eleven Cases.

Background and Objectives: Remimazolam, a novel benzodiazepine, is used for procedural sedation and general anesthesia due to its rapid onset and short duration of action. However, remimazolam-induced anaphylaxis (RIA) is a rare but severe complication. This study aimed to analyze RIA characteristics, focusing on cardiovascular collapse, and provide guidelines for safe remimazolam use. Methods: This study conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Research articles retrieved from PubMed on 26 May 2023, using the keywords 'remimazolam AND anaphylaxis' were evaluated based on the inclusion criteria of being written in English and aligning with the World Allergy Organization criteria for anaphylaxis, while studies not meeting these criteria were excluded. All published articles up to the search date were included without any date restrictions. The review analyzed factors such as age, sex, type of anesthesia, remimazolam dose (bolus/continuous), allergic symptoms and sign, epinephrine use, serum tryptase levels, and skin prick tests. Results: Among eleven cases, the mean age was 55.6 ± 19.6 years, with 81.8% male. Hypotension (81.8%) was the most common symptom, followed by bradycardia (54.5%) and desaturation (36.4%). Two patients experienced cardiac arrest. Serum tryptase levels confirmed anaphylaxis in ten cases. Epinephrine was the primary treatment, with intravenous doses ranging from 0.1 mg to 0.3 mg. Conclusions: Vigilance is crucial when administering remimazolam, adhering to recommended dosages, and promptly treating RIA with epinephrine. Further research is needed to understand the risk factors and refine the management strategies. Guidelines for safe remimazolam use are proposed.

Evaluation of the passive mast cell activation test for identifying allergens in perioperative anaphylaxis: a study protocol for a prospective diagnostic accuracy study.

INTRODUCTION: Perioperative anaphylaxis (POA) can lead to significant complications. Therefore, accurate identification of allergens for POA patients is critical to ensure the safety of future surgical and anaesthetic procedures. Existing perioperative allergen detection methods face challenges in sensitivity and specificity. The passive mast cell activation test (pMAT) has recently emerged as a potential diagnostic tool. Our study aims to evaluate the diagnostic efficacy of pMAT for identifying perioperative allergens, with a focus on non-depolarising neuromuscular blocking agents, the most common culprits of POA. METHODS AND ANALYSIS: This prospective diagnostic accuracy study will measure the diagnostic accuracy of pMAT in POA patients. Participants will undergo skin testing (ST), basophil activation testing (BAT) and pMAT. The diagnostic validity of pMAT will be assessed based on the results of ST and BAT. The assessment of diagnostic accuracy will include sensitivity, specificity, likelihood ratios, and false-positive and false-negative rates while measurement of the consistency rate will assess reliability. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of China-Japan Friendship Hospital (2023-KY-247). Results will be disseminated through academic presentations and peer-reviewed journal publications and will provide valuable scientific data and some new insights into the diagnostic accuracy of pMAT.

Remimazolam anaphylaxis in a patient not allergic to brotizolam: a case report and literature review.

BACKGROUND: Remimazolam is a recently developed, ultrashort-acting benzodiazepine that is used as a general anesthetic. Some cases of remimazolam anaphylaxis have been reported, but its characteristics are not fully understood. We present an interesting case report and review of the literature to better understand remimazolam anaphylaxis. CASE PRESENTATION: A 75-year-old man scheduled for robot-assisted gastrectomy was administered remimazolam for the induction of general anesthesia. After intubation, low end-expiratory CO2, high airway pressure and concurrent circulatory collapse were observed. Bronchoscopy revealed marked tracheal and bronchial edema, which we diagnosed as anaphylaxis. The patient suffered cardiac arrest after bronchoscopy but recovered immediately with intravenous adrenaline administration and chest compressions. We performed skin prick tests for the drugs used during induction except for remimazolam, considering the high risk of systemic adverse reactions to remimazolam. We diagnosed remimazolam anaphylaxis because the skin prick test results for the other drugs used during anesthesia were negative, and these drugs could have been used without allergic reactions during the subsequent surgery. Furthermore, this patient had experienced severe anaphylactic-like reactions when he underwent cardiac surgery a year earlier, in which midazolam had been used, but it was not thought to be the allergen at that time. Based on these findings, cross-reactivity to remimazolam and midazolam was suspected. However, the patient had previously received another benzodiazepine, brotizolam, to which he was not allergic, suggesting that cross-reactivity of remimazolam may vary among benzodiazepines. In this article, we reviewed the 11 cases of remimazolam anaphylaxis that have been described in the literature. CONCLUSIONS: Remimazolam is an ultrashort-acting sedative; however, it can cause life-threatening anaphylaxis. In addition, its cross-reactivity with other benzodiazepines is not fully understood. To increase the safety of this drug, further research and more experience in its use are needed.

[A CASE OF A GIRL WITH ANAPHYLAXIS INDUCED BY INHALATION OF SOYBEAN DUST].

The patient was a 3-year-old girl whose father was employed sorting and washing soybeans. She exhibited transient respiratory distress and loss of activity on the same day or the next day after her father came home wearing work clothes with soybean dust on them. One day, she developed anaphylaxis after being lifted into her father's arms while he was wearing his work clothes. Although a blood test was positive for soybean and Gly m 4-specific IgE antibodies, the girl was able to consume soy products (not including soy milk, which she had never consumed) without any issues. The father was instructed to change clothes before leaving work and bathe immediately upon returning home, and the girl has not had any further episodes of respiratory distress, loss of activity, or anaphylaxis. Though reports of anaphylaxis from soybean antigen inhalation are extremely rare, it is very likely that inhalation of soybean dust from the father's work clothes induced anaphylaxis in this case.

[PRACTICE AND TRAINING RELATED TO USING ADRENALINE AUTOINJECTORS FOR PARAMEDICS: FACTS AND ISSUES].

BACKGROUND: Although paramedics can use adrenaline autoinjectors (AAIs) during their duties, the actual conditions of their use and the challenges faced remain unclear. We investigated the actual situation and issues pertaining to creating an environment in which paramedics can operate AAIs more effectively. METHODS: A web-based survey was conducted among paramedics who participated in a web-based training session related to their latest knowledge on food allergies and emergency responses in 2022. The survey items included practice and training environments, practices of AAI administration, and regarding AAI administration. RESULTS: Seventy paramedics responded to the survey. Twenty-eight respondents (40%) had experienced cases in which they wished they had an AAI in their work to date, but only one had actually administered one. Thirty-four (49%) indicated that it would be good to have an AAI in the ambulance at all times; 48 (69%) were not concerned about the use of AAI, and the level of concern about its use was significantly related to length of service. The study also revealed that paramedics do not have an adequate training environment regarding AAI. CONCLUSION: Few paramedics have experience in administering AAI, although they are aware of the need for it. For more effective use of AAI, it is necessary to establish a training environment to familiarize paramedics with anaphylaxis and an environment that enables them to use AAI promptly in the field.

[A fish-intoxication as a rare cause of chest pain]. / Eine Fischintoxikation als seltene Ätiologie des Thoraxschmerzes.

INTRODUCTION: We describe the case of a 58-year-old patient who developed chest pain and an anaphylaktoide reaction after ingestion of contamined fish containing histamin. Histamin intoxication from food poisoning (also known as scombroid intoxication) can be mistaken for an anaphylactic reaction and occasionaly lead to cardiac symptoms, even in patients without atherosclerotic changes. This condition is called Kounis syndrom and has to be recognized as a separate syndrom with specific clinical features.

Incidence and management of the main serious adverse events reported after COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2n first appeared in Wuhan, China in 2019. Soon after, it was declared a pandemic by the World Health Organization. The health crisis imposed by a new virus and its rapid spread worldwide prompted the fast development of vaccines. For the first time in human history, two vaccines based on recombinant genetic material technology were approved for human use. These mRNA vaccines were applied in massive immunization programs around the world, followed by other vaccines based on more traditional approaches. Even though all vaccines were tested in clinical trials prior to their general administration, serious adverse events, usually of very low incidence, were mostly identified after application of millions of doses. Establishing a direct correlation (the cause-effect paradigm) between vaccination and the appearance of adverse effects has proven challenging. This review focuses on the main adverse effects observed after vaccination, including anaphylaxis, myocarditis, vaccine-induced thrombotic thrombocytopenia, Guillain-Barré syndrome, and transverse myelitis reported in the context of COVID-19 vaccination. We highlight the symptoms, laboratory tests required for an adequate diagnosis, and briefly outline the recommended treatments for these adverse effects. The aim of this work is to increase awareness among healthcare personnel about the serious adverse events that may arise post-vaccination. Regardless of the ongoing discussion about the safety of COVID-19 vaccination, these adverse effects must be identified promptly and treated effectively to reduce the risk of complications.

Anaphylaxis triggered by alpha-gal allergy. / Anafylaksi utløst av alfa-gal-allergi.

Background: Alpha-gal allergy or red meat allergy is a rare yet potentially severe allergy. Sensitisation usually occurs when alpha-gal present in the tick's saliva is transferred to humans during a tick bite, prompting the production of IgE antibodies to alpha-gal. Subsequent exposure to mammalian meat or other products containing alpha-gal can lead to allergic reactions. Case presentation: A previously healthy man in his sixties was admitted with acute anaphylaxis. A history of multiple tick bites and recent consumption of mammalian meat raised suspicion of anaphylaxis caused by alpha-gal syndrome. Interpretation: A diagnosis of alpha-gal syndrome was given based on elevated alpha-gal IgE antibodies, and further supported by medical history and clinical assessment. He was discharged with dietary instructions to eliminate food and products containing alpha-gal, and to manage allergy symptoms and anaphylaxis according to local guidelines.

Soluble antigen arrays provide increased efficacy and safety over free peptides for tolerogenic immunotherapy.

Autoantigen-specific immunotherapy using peptides offers a more targeted approach to treat autoimmune diseases, but clinical implementation has been challenging. We previously showed that multivalent delivery of peptides as soluble antigen arrays (SAgAs) efficiently protects against spontaneous autoimmune diabetes in the non-obese diabetic (NOD) mouse model. Here, we compared the efficacy, safety, and mechanisms of action of SAgAs versus free peptides. SAgAs, but not their corresponding free peptides at equivalent doses, efficiently prevented the development of diabetes. SAgAs increased the frequency of regulatory T cells among peptide-specific T cells or induce their anergy/exhaustion or deletion, depending on the type of SAgA used (hydrolysable (hSAgA) and non-hydrolysable 'click' SAgA (cSAgA)) and duration of treatment, whereas their corresponding free peptides induced a more effector phenotype following delayed clonal expansion. Over time, the peptides induced an IgE-independent anaphylactic reaction, the incidence of which was significantly delayed when peptides were in SAgA form rather than in free form. Moreover, the N-terminal modification of peptides with aminooxy or alkyne linkers, which was needed for grafting onto hyaluronic acid to make hSAgA or cSAgA variants, respectively, influenced their stimulatory potency and safety, with alkyne-functionalized peptides being more potent and less anaphylactogenic than aminooxy-functionalized peptides. Immunologic anaphylaxis occurred in NOD mice in a dose-dependent manner but not in C57BL/6 or BALB/c mice; however, its incidence did not correlate with the level of anti-peptide antibodies. We provide evidence that SAgAs significantly improve the efficacy of peptides to induce tolerance and prevent autoimmune diabetes while at the same time reducing their anaphylactogenic potential.

A Case Report and Pediatric Literature Review: Povidone as a Rare Cause of Anaphylaxis in Children.

Background: Povidone, a synthetic polymer commonly used in various products such as antiseptics, cosmetics, and medications, has been associated with allergic reactions, including anaphylaxis. Despite its widespread use, cases of povidone-induced anaphylaxis, especially in children, are under-recognized. This case report aims to highlight the importance of considering povidone allergy in pediatric patients presenting with anaphylaxis. Case Presentation: We describe a 3-year-old boy who experienced anaphylaxis following the application of povidone-iodine antiseptic solution to a leg wound. He presented with generalized urticaria, angioedema, dyspnea, and cough. Prompt diagnosis and management were initiated in the emergency department. He experienced the second anaphylaxis with povidone-containing eye drops prescribed during an ophthalmology visit. Conclusions: Povidone allergy should be considered in pediatric patients presenting with anaphylaxis, especially those with idiopathic reactions or multiple drug allergies. Clinicians should emphasize patient education on label reading and the provision of adrenaline autoinjectors to prevent life-threatening reactions associated with povidone exposure.

Perioperative anaphylactic shock caused by propofol.

Perioperative anaphylaxis is rare and the diagnosis is difficult to distinguish from normal side effects from anaesthesia. Anaesthetists should be able to diagnose anaphylaxis and treat promptly with adrenaline and fluids. Allergy investigation should be performed subsequently. This is a case report of perioperative anaphylaxis to propofol. Propofol contains refined soya oil and egg lecithin, but no connection between allergy to soy, egg or peanut and allergy to propofol has been proven, and international guidelines recommend that propofol can be used in patients with these food allergies.

Venom Hypersensitivity.

Stinging insects are a frequent cause of local and systemic hypersensitivity reactions, including anaphylaxis. For those with a history of life-threatening anaphylaxis, venom immunotherapy is effective, safe, and can be life-saving. Arachnids are a much less common source of envenomation through bites or stings and are less likely to cause a hypersensitivity reaction. However, recognizing the clinical manifestations when they do present is important for accurate diagnosis and treatment, and, when indicated, consideration of other diagnoses.

Successful rapid liposomal amphotericin B desensitization in pediatric case series.

Background: Liposomal amphotericin B (LAMB) is a crucial agent in the treatment of invasive fungal diseases caused by a wide variety of yeasts and molds. In the presence of an infection caused by a fungal agent resistant to alternative antifungal drugs, desensitization may be the only option to continue treatment. However, there is insufficient information and consensus with regard to amphotericin B desensitization protocols in the pediatric age group. Objective: We present our experience with five cases of patients in whom successful desensitization protocols were applied with LAMB, along with a review of the literature on pediatric cases. We also provide a sample desensitization protocol that we successfully applied. Methods: Pediatric patients who continued their treatment with the successful rapid desensitization protocol conducted at the Paediatric Allergy and Immunology Clinic of the Ministry of Health Ankara City Hospital between September 2019 and September 2023 were examined. Desensitization protocols were applied based on Castells' desensitization protocol. Results: Five patients ages between 5 and 12 years were referred to us due to the development of anaphylaxis during their treatment with LAMB. Anaphylaxis is diagnosed clinically, according to the European Academy of Allergy and Clinical Immunology guidelines: anaphylaxis (2021 update). A 16-step desensitization protocol was prepared by using LAMB solutions at four different dilutions (0.001, 0.01, 0.1, and 1 mg/mL). Each solution consisted of four steps, with a 15-minute infusion for each step. The patients were premedicated with 1 mg/kg/dose methylprednisolone and an antihistamine. Conclusion: The data we present on the successful application of a sample protocol to five cases, particularly in a pediatric setting, are noteworthy valuable contributions to the field, which demonstrates the feasibility and success of rapid desensitization with LAMB in pediatric patients. This can provide important insights and potentially serve as a reference for medical professionals working with similar cases in the future.

Assessment of potential adverse events following the 2022-2023 seasonal influenza vaccines among U.S. adults aged 65 years and older.

BACKGROUND: While safety of influenza vaccines is well-established, some studies have suggested potential associations between influenza vaccines and certain adverse events (AEs). This study examined the safety of the 2022-2023 influenza vaccines among U.S. adults ≥ 65 years. METHODS: A self-controlled case series compared incidence rates of anaphylaxis, encephalitis/encephalomyelitis, Guillain-Barré Syndrome (GBS), and transverse myelitis following 2022-2023 seasonal influenza vaccinations (i.e., any, high-dose or adjuvanted) in risk and control intervals among Medicare beneficiaries ≥ 65 years. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) adjusted for event-dependent observation time and seasonality. Analyses also accounted for uncertainty from outcome misclassification where feasible. For AEs with any statistically significant associations, we stratified results by concomitant vaccination status. RESULTS: Among 12.7 million vaccine recipients, we observed 76 anaphylaxis, 276 encephalitis/encephalomyelitis, 134 GBS and 75 transverse myelitis cases. Only rates of anaphylaxis were elevated in risk compared to control intervals. With all adjustments, an elevated, but non-statistically significant, anaphylaxis rate was observed following any (IRR: 2.40, 95% CI: 0.96-6.03), high-dose (IRR: 2.31, 95% CI: 0.67-7.91), and adjuvanted (IRR: 3.28, 95% CI: 0.71-15.08) influenza vaccination; anaphylaxis IRRs were 2.54 (95% CI: 0.49-13.05) and 1.64 (95% CI: 0.38-7.05) for persons with and without concomitant vaccination, respectively. CONCLUSIONS: Rates of encephalitis/encephalomyelitis, GBS, or transverse myelitis were not elevated following 2022-2023 seasonal influenza vaccinations among U.S. adults ≥ 65 years. There was an increased rate of anaphylaxis following influenza vaccination that may have been influenced by concomitant vaccination.

[EPIPEN INSTRUCTIONS FOR ANAPHYLAXIS PATIENTS DURING DISPENSING: FACTORS RELATED TO THE QUALITY OF PHARMACISTS' INSTRUCTIONS].

BACKGROUND AND AIM: We previously reported that pharmacists working in pharmacies don't have enough knowledge and enough experience teaching anaphylaxis (An) and EpiPen use. We administered a questionnaire survey to pharmacists with experience handling EpiPen prescriptions. We investigated the relationship between the questionnaire results and the factors in the pharmacists' background regarding the explanation and guidance to patients. RESULTS: The percentage of pharmacists working in pharmacies who provided guidance using visual information and demonstrations was insufficient. Moreover, this figure decreased after the second guidance session. Objective confirmation of patient understanding was also insufficient. The results indicated that self-examination and participation in drug information sessions were important background factors for pharmacists who provided detailed guidance to patients. DISCUSSION: For appropriate long-term management of their condition, An patients must master the EpiPen technique. Pharmacists' guidance plays a critical role in this regard. A support system should be established for proper instruction of pharmacy patients by improving pharmacists' self-education and other educational opportunities.

Evaluation of treatment and long-term management of anaphylaxis in pediatric departments of Greece: a 2-year nationwide survey.

BACKGROUND: Anaphylaxis proportions of incidence are increasing globally. However, limited data are available regarding anaphylaxis in the pediatric population of Greece. PURPOSE: The aim of the study was to evaluate management of anaphylaxis in Greek pediatric departments. METHODS: We performed a questionnaire-based study of children aged less than 16 years presenting with anaphylaxis in 10 national pediatric hospitals over a period of 2 years. Management of anaphylaxis was assessed prior to and after an informative intervention. RESULTS: In all, 127 cases of anaphylaxis were identified. Epinephrine was administered in almost half of all cases (51.2%), predominantly through intramuscular route (88.5%), while the majority of anaphylaxis patients were treated with antihistamines (92.9%) and corticosteroids (70.1%). Epinephrine was more likely administered by physicians if the elicitor was a drug (P < 0.003). Regarding long-term management, an epinephrine auto-injector was prescribed in 66.9% of patients. Follow-up information was available for most of the patients (92.9%), the majority of whom (76.3%) were referred to an allergist. More than half of these patients (63.6%) had a documented allergy follow-up, which identified a causative allergen in 53.3% of cases. No statistically significant differences were recorded prior to and after the intervention regarding management of anaphylaxis. CONCLUSIONS: This nationwide study highlighted the necessity of further improvement in terms of anaphylaxis treatment and secondary prevention measures. This presupposes appropriate education and training of healthcare professionals, thus contributing to proper and comprehensive care of the pediatric population.

Alpha-gal syndrome: when treatment of hypovolemic shock can lead to anaphylaxis.

Delayed anaphylaxis after ingestion of red meat because of galactose-alpha-1,3-galactose (alpha-gal) syndrome has increased in recent years. The mechanism involves an immunoglobulin E reaction to alpha-gal, a molecule found in mammalian meat, dairy products, medications and excipients containing mammalian-derived components, and tick salivary glycans. Sensitization occurs due to the bite of a lone star tick and the transmission of alpha-gal molecules into person's bloodstream. We describe a case of alpha-gal syndrome with severe food, drug, and perioperative allergy in which anaphylaxis with hypovolemic shock occurred immediately after an emergency surgical procedure, when a gelatin-containing drug was injected. This case study confirms that the clinical manifestations of alpha-gal syndrome could be different depending on the route of administration, with immediate reactions if an alpha-gal-containing drug is injected and delayed type allergic manifestations occurring several hours after oral intake. The purpose of this report is to highlight the importance of risk communication in case of exposure to medical products and surgical procedures of patients with alpha-gal syndrome and to encourage drug manufacturers to indicate clearly the origin of excipients in product literature.

Tablet allergen immunotherapy: the anaphylaxis issue.

For the first time 15 years ago, tablet allergen immunotherapy (T-AIT) formulations were approved by regulatory agencies for treating allergic rhinitis caused by grass pollen in adults and children aged >5 years. Extensive evidences existed about effectiveness and safety of AIT. However, the safety profile is particularly compelling in children. Generally, T-AIT causes local reactions, mostly in the oral cavity, that are usually mild-to-moderate and often self-resolving. However, systemic allergic reactions are also observed with T-AIT, anaphylaxis representing the most fearsome adverse event, considering that it occurs in subjects treated for allergic rhinitis. Therefore, we conducted a literature search of patients reporting anaphylaxis because of T-AIT. Nine cases of anaphylactic reactions were reported in literature. Notably, no death was reported using T-AIT. This outcome was very important as it underscored the substantial safety of T-AIT. However, T-AIT deserves careful attention, mainly in the pediatric population. In this regard, after the first report of anaphylactic reaction at the first administration of T-AIT, manufacturers recommended that the first dose should be administered in a medical facility in the presence of staff with experience in managing anaphylaxis and the patient should be observed for at least 30 min. Interestingly, reported anaphylactic reactions were due to grass pollen extracts, with no report concerning other allergen extracts. However, it is relevant to note that anaphylactic reactions because of T-AIT are not reported in recent years.