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.

EAACI/ENDA position paper on drug provocation testing.

In drug hypersensitivity, drug provocation testing (DPT), also called drug challenge, is the gold standard for investigation. In recent years, risk stratification has become an important tool for adjusting the diagnostic strategy to the perceived risk, whilst still maintaining a high level of safety for the patient. Skin tests are recommended before DPT but may be omitted in low-risk patients. The task force suggests a strict definition of such low-risk patients in children and adults. Based on experience and evidence from studies of allergy to beta-lactam antibiotics, an algorithm on how to adjust DPT to the risk, and when to omit skin tests before DPT, is presented. For other antibiotics, non-steroidal anti-inflammatory drugs and other drugs, skin tests are poorly validated and DPT is frequently necessary. We recommend performing DPT with chemotherapeutics and biologicals to avoid unnecessary desensitization procedures and DPT with skin tests negative contrast media. We suggest DPT with anesthetics only in highly specialized centers. Specifics of DPT to proton pump inhibitors, anticonvulsants and corticosteroids are discussed. This position paper provides general recommendations and guidance on optimizing use of DPT, whilst balancing benefits with patient safety and optimizing the use of the limited available resources.

Healthcare professionals' attitudes to penicillin allergy labels.

INTRODUCTION: About 10% of hospital inpatients are labelled with penicillin allergy in their electronic medical record (EMR). However, allergy is confirmed in less than 10% of these records. Consequently, 90% of patients are treated with broad-spectrum antibiotics, contributing to antimicrobial resistance. We aimed to explore experiences and practices of healthcare professionals that may explain incorrect labelling of penicillin allergy in Denmark and elucidate any consequences hereof. METHODS: An electronic survey was distributed to physicians and nurses in six hospital units in Copenhagen and via social media. The survey was active from 19 March to 1 May 2020. Data were assessed using descriptive statistics and by thematic analysis. RESULTS: The response rate was 44.6%. The survey had 369 participants; 152 physicians and 217 nurses. Half of the physicians and one in every five nurses had experienced problems treating patients with a penicillin allergy label. Physicians reported limited trust in allergy labels, and labelling practices varied. The risk that patients may be truly allergic was the main reason for not removing labels (72%), and a precautionary principle was identified related to penicillin allergy labelling. CONCLUSIONS: The penicillin allergy label is an independent factor of medication errors. Solutions to enhance patient safety may include education of physicians in allergy labelling, decision support, standardisation of the allergy registration in the various EMR systems used, and ideally also a national drug allergy register, which is accessible from all sectors. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Perioperative Hypersensitivity Evaluation and Management: A Practical Approach.

Perioperative hypersensitivity (POH) is an uncommon, potentially life-threatening event. Identification of POH can be difficult given the lack of familiarity, physiological effects of anesthesia, draping of the patient during surgery, and potential nonimmunological factors contributing to signs and symptoms. Given the unique nature and large number of medications administered in the perioperative setting, evaluation of POH can be challenging. In this paper, we present a practical approach to management with an emphasis on understanding what happens in the operating room, the overlap of signs and symptoms between nonimmunological and immunological reactions, acute management, and subsequent evaluation. In addition, we provide a strategy for further review of an initially negative evaluation and emphasize the importance of establishing management plans for the patient as well as providing recommendations to the medical, anesthesia, and surgical teams for future surgeries. A critical factor for successful management at all points in the process is a close collaboration between the anesthesia and the allergy teams.

Topical eye medications causing allergic contact dermatitis.

BACKGROUND: Allergic contact dermatitis (ACD) in the eye region caused by topical eye medications is difficult to diagnose and may be overlooked. OBJECTIVE: To study the characteristics and causative agents in patients with ACD caused by topical eye medications in a Danish tertiary dermatology department. METHODS: A retrospective study of 318 patients, patch tested between 2013 and 2021 due to suspected ACD to topical eye medications. All patients were tested with a locally developed eye medication series, some were additionally tested with suspected eye medications. Medical records were studied in patch test positive patients. RESULTS: Contact allergy to a topical eye allergen/medication was found in 12.9% (n = 41) of 318 patients, and culprit allergens were phenylephrine (6.9%), timolol (2.5%) and ketotifen (1.6%). Patch test positive patients were often previously diagnosed with cataract (29.3%) or glaucoma (24.4%), and the majority reported more than one previous reaction. Initial symptoms were oedema (56.0%), erythema (48.8%) and dermatitis (31.7%) in the eye region, and facial dermatitis was also seen. CONCLUSIONS: Patients with symptoms from the eye region who have been using topical eye medications should be patch tested with ingredients from commonly used eye medications supplemented by the products tested 'as is'.

Successful Desensitization to mRNA COVID-19 Vaccine in a Case Series of Patients With a History of Anaphylaxis to the First Vaccine Dose.

Background: Coronavirus disease 2109 (COVID-19) vaccines have recently been approved to curb the global pandemic. The risk of allergic reactions to the vaccine polyethylene glycol (PEG) component has raised significant public concern. Desensitization is suggested in cases of vaccine related hypersensitivity reactions. After comprehensive literature review on the topic, our aim was to establish a safe and effective desensitization protocol for patients with suspected or confirmed immediate type hypersensitivity reactions to the COVID-19 vaccine. Methods: Participants were referred to the McGill University Health Center (MUHC) Allergy-Immunology department for clinical evaluation following a reported reaction to their first dose of Moderna® mRNA-1273 or Pfizer-BioNTech® BNT162b2 vaccines. They underwent skin prick testing (SPT) with higher and lower molecular weight (MW) PEG and polysorbate 80, as per published protocols. Their second dose was administered following a desensitization protocol consisting of multiple dose-administration steps followed by a 60-min observation period. Results: Among a cohort of 142 patients with an increased risk for allergic reactions to the COVID-19 vaccines, six individuals were selected to undergo desensitization. All were female with allergic background including chronic spontaneous urticaria, anaphylaxis to medications, and/or vaccines. The main symptom after their first dose was difficulty swallowing with lightheadedness or immediate urticaria, angioedema, and/or dizziness. Two patients had positive skin testing. One patient was on chronic antihistamines which resulted in an inconclusive PEG skin test and the skin testing was negative for the three other patients. During the desensitization, two patients reported cutaneous symptoms of an immediate reaction and were managed with antihistamines. One of these patients also complained of ear pressure and had a drop in her systolic blood pressure, treated with intravenous fluids. Conclusion: This study suggests that some individuals with an immediate-type hypersensitivity reaction to their first dose of mRNA COVID-19 vaccine may safely receive their second dose using a desensitization protocol. The success of this desensitization protocol is a step forward in the fight against COVID-19, allowing more individuals to be immunized.

Allergies and COVID-19 vaccines: An ENDA/EAACI Position paper.

BACKGROUND: Anaphylaxis, which is rare, has been reported after COVID-19 vaccination, but its management is not standardized. METHOD: Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed. RESULTS: No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1-anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2-anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine; and 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left-over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable. CONCLUSIONS: These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated.

Allergy to polyethylene glycol and polysorbates in a patient cohort: Diagnostic work-up and decision points for vaccination during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic focus has been on polyethylene glycol (PEG) and polysorbate as these excipients are constituents in the first vaccines and possible elicitors of allergic reactions to the vaccines. We aimed to evaluate the possibility of vaccinating patients with PEG and/or polysorbate allergy against COVID-19. METHODS: Twenty-five patients with a history of an allergic reaction to drugs, vaccines and mouth hygiene products containing PEG or polysorbate and sensitization (skin test or in vitro test) or a positive challenge were included. We re-evaluated 19 of 21 patients diagnosed before 2021 and four new patients by skin prick tests (SPT) and Basophil Histamine Release (BaHR) for PEGs, polysorbates and approved COVID-19 vaccines as well as measurement of specific IgE (PEG 2000, 10,000). Patients were offered vaccination based on decision points from the primary diagnosis and re-evaluation. RESULTS: Most common primary elicitors were depot-steroids and laxatives. Most patients had experienced more than one reaction. SPT was superior to BaHR test although many SPTs became negative over time. After careful re-evaluation three patients were successfully vaccinated with the Pfizer/BioNTech vaccine. Three were vaccinated before referral. Eleven were offered the Johnson-Johnson vaccine; four were vaccinated successfully, seven abstained. Six patients could not be vaccinated with PEG or polysorbate containing vaccines. CONCLUSION: Hypersensitivity to excipients in COVID-19 vaccines constitutes a risk to patients with allergy to PEG or polysorbates. After diagnostic evaluation, a safe COVID-19 vaccine could be offered to most patients, the remainders will await new vaccines containing different excipients.

EAACI guidelines: Anaphylaxis (2021 update).

Anaphylaxis is a clinical emergency which all healthcare professionals need to be able to recognize and manage. The European Academy of Allergy and Clinical Immunology Anaphylaxis multidisciplinary Task Force has updated the 2014 guideline. The guideline was developed using the AGREE II framework and the GRADE approach. The evidence was systematically reviewed and recommendations were created by weighing up benefits and harms. The guideline was peer-reviewed by external experts and reviewed in a public consultation. The use of clinical criteria to identify anaphylaxis is suggested with blood sampling for the later measurement of tryptase. The prompt use of intramuscular adrenaline as first-line management is recommended with the availability of adrenaline autoinjectors to patients in the community. Pharmacokinetic data should be provided for adrenaline autoinjector devices. Structured, comprehensive training for people at risk of anaphylaxis is recommended. Simulation training and visual prompts for healthcare professionals are suggested to improve the management of anaphylaxis. It is suggested that school policies reflect anaphylaxis guidelines. The evidence for the management of anaphylaxis remains mostly at a very low level. There is an urgent need to prioritize clinical trials with the potential to improve the management of patients at risk of anaphylaxis.

Optimizing investigation of suspected allergy to polyethylene glycols.

BACKGROUND: Polyethylene glycols (PEGs) are polymers of varying molecular weight (MW) used widely as excipients in drugs and other products, including the mRNA vaccines against coronavirus disease 2019. Allergy to PEGs is rare. Skin testing and graded challenge carries a high risk of inducing systemic reactions. OBJECTIVE: We evaluated skin prick test (SPT) results and in vitro reactivity over time to different MW PEGs and assessed cross-sensitization patterns in PEG allergy. METHODS: Ten patients with previously diagnosed PEG allergy underwent SPT twice with PEGs 26 months apart. Lower MW (PEG 300, 3000, 6000) were tested, followed by PEG 20,000, in stepwise, increasing concentrations. Cross-sensitization to polysorbate 80 and poloxamer 407 was assessed. SPT was performed in 16 healthy controls. In vitro basophil histamine release (HR) test and passive sensitization HR test were performed in patients and controls. RESULTS: Patients previously testing positive on SPT to PEG 3000 and/or 6000 also tested positive to PEG 20,000. Patients with a longer interval since diagnosis tested negative to lower MW PEGs and positive mainly to higher concentrations of PEG 20,000. Three patients developed systemic urticaria during SPT. Eight patients showed cross-sensitization to poloxamer 407 and 3 to polysorbate 80. All controls tested negative. In vitro tests showed limited usefulness. CONCLUSIONS: Skin test reactivity to PEG can decrease over time, but titrated SPT with increasing concentrations of PEG 20,000 can be diagnostic when lower MW PEGs test negative. To avoid systemic reactions, stepwise SPT is mandatory.

Diagnosing, managing and preventing anaphylaxis: Systematic review.

BACKGROUND: This systematic review used the GRADE approach to compile evidence to inform the European Academy of Allergy and Clinical Immunology's (EAACI) anaphylaxis guideline. METHODS: We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18 449 participants: 29 randomized controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarized narratively because studies were too heterogeneous to conduct meta-analysis. RESULTS: It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. There was also insufficient evidence about the impact of most anaphylaxis management and prevention strategies. Adrenaline is regularly used for first-line emergency management of anaphylaxis but little robust research has assessed its effectiveness. Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. We searched for but found little or no comparative effectiveness evidence about strategies such as fluid replacement, oxygen, glucocorticosteroids, methylxanthines, bronchodilators, management plans, food labels, drug labels and similar. CONCLUSIONS: Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it.

[Anaphylaxis in children and adults].

In this review, we discuss anaphylaxis, which is a severe allergic condition with potentially life-threatening symptoms from airways or circulation and often associated with skin symptoms. First-line treatment is intramuscular adrenaline given by autoinjector for rapid administration. Initial dose for children less than 25 kg is 0.15 mg and for children ≥ 25 kg and adults 0.3 mg. Repeated smaller doses of adrenaline is to be preferred. Patients with severe anaphylaxis will need an IV access for fluid replacement and supplementary oxygen. Antihistamines and steroids are only second-line treatment after adrenaline administration.

[Work-up of penicillin allergy].

Up to 10% of hospitalised patients are registered as penicillin allergic. However, 80-90% will tolerate penicillin after evaluation. New Danish guidelines suggest criteria for evaluation of patients based on risk stratification according to the severity of the index reaction. The allergy label can be removed immediately, if allergy can be ruled out using the criteria presented in this review, but all other patients should be referred for evaluation in a specialist allergy department. Specific IgE measurement should only be done in adult patients with an immediate reaction (onset less-than 2 h after intake of a tablet) or urticaria.

Intradermal Tests With Drugs: An Approach to Standardization.

Background: Intradermal tests (IDTs) are performed and interpreted differently in drug allergy centers making valid comparison of results difficult. Objective: To reduce method-related and intercenter variability of IDTs by the introduction of a standardized method. Materials and methods: In 11 centers of the European Network for Drug Allergy, IDTs were prospectively performed with saline and with amoxicillin (20 mg/ml) using (1) the local method and (2) the standardized European Network in Drug Allergy (ENDA) method (0.02 ml). The diameters of the initial injection wheal (Wi) for the different volumes and sites injected obtained from each center were analyzed. Results: The most reproducible method was to fill a syringe with test solution, then expel the excess fluid to obtain exactly 0.02 ml. The median Wi diameter with 0.02 ml injection using the standardized method was 5 mm [range 2-10 mm; interquartile range (IQR) 5-5 mm; n = 1,096] for saline and 5 mm (range 2-9 mm; IQR = 4.5-5 mm; n = 240) for amoxicillin. IDT injection sites did not affect the Wi diameter. Training improved precision and reduced the variability of Wi diameters. Conclusion: Using the standardized IDT method described in this multicenter study helped to reduce variability, enabling more reliable comparison of results between individuals and centers.

Investigation of perioperative hypersensitivity reactions: an update.

PURPOSE OF REVIEW: The purpose of this review is to provide an update on how best to manage the investigation of suspected perioperative hypersensitivity reactions based on recent literature and key publications. RECENT FINDINGS: In the past two years, several very important initiatives have been taken in the field of perioperative hypersensitivity. The 6th national audit project in the United Kingdom has provided new knowledge through a series of studies, including a nationwide prospective study, and the European Academy of Allergy and Clinical Immunology has commissioned a position paper with updated recommendations for investigations. Lastly, a large international working group comprising experts in anesthesiology, allergology, and immunology, the International Suspected Perioperative Allergic Reactions group, has published a series of articles providing updates and new insights into several different key areas of perioperative hypersensitivity. SUMMARY: The investigation of perioperative hypersensitivity reactions is highly complex and aims to identify the correct culprit to ensure future avoidance but also to disprove allergy to other suspected culprits, making them available for subsequent anesthesia. To achieve this, close collaboration between anesthesiologists and allergists is called upon to ensure the best possible outcome for the patient.

Perioperative anaphylaxis: diagnostic challenges and management.

PURPOSE OF REVIEW: Perioperative hypersensitivity reactions can pose diagnostic and management challenges for the anaesthetist. Difficulties in diagnosing hypersensitivity reactions in the perioperative setting are highlighted and recommendations from recent guidelines on the acute management of life-threatening anaphylaxis are presented. RECENT FINDINGS: Anaesthetists play a key role in investigating perioperative hypersensitivity reactions. During a suspected perioperative hypersensitivity event, a serum tryptase level should be measured to help with subsequent allergy investigation. Moreover, anaesthetists can ensure that a high-quality referral is made to allergy clinics by providing thorough documentation of the events, detailing symptoms, treatments, and the chronology of drug administrations. SUMMARY: Perioperative hypersensitivity reactions are rare but can be life-threatening. A high index of suspicion should be maintained for their successful management. Whenever a perioperative hypersensitivity reaction is suspected, close collaboration between anaesthetist and the allergy team investigating the patient is paramount, in order for the patient to be appropriately investigated and have an uneventful anaesthetic in the future.

Perioperative anaphylaxis in children: Etiology, time sequence, and patterns of clinical reactivity.

BACKGROUND: Perioperative anaphylaxis (PA) in children is an uncommon but potentially life-threatening complication associated with anesthesia. Early identification and management of PA is essential to optimize clinical outcomes. METHODS: We performed a retrospective study of anesthesia records from pediatric patients with PA from centers in the United Kingdom, France, and the United States over a period of 10 years. Time sequence of clinical signs and physiological variables during PA were collected, along with results of allergy testing. RESULTS: Twenty-nine children with PA were included. Median age was 11 years. Based on the modified Ring and Messmer Grading Scale, severe reactions were seen in 25 (86%) members of this cohort, with 4 (14%) experiencing cardiac arrest. Life-threatening hypotension was the first clinical sign of PA in 59% of cases, followed by tachycardia and bronchospasm. In 16 (55%) cases, the initial signs of PA involved multiple organ systems. When the initial signs of PA were cardiovascular and/or respiratory, more epinephrine doses were administered. Average time from initial sign of PA to treatment with epinephrine was 6 minutes (SD: 6, range: 1-25). The causative allergen was identified in 15 patients. CONCLUSION: Severe hypotension is the most common presenting sign of PA in children. Initial cardiovascular and/or respiratory signs are associated with the need for increased epinephrine doses. Further studies should optimize the prediction, identification, and early management of PA in children.

Chlorhexidine Allergy: Mild Allergic Reactions Can Precede Anaphylaxis in the Healthcare Setting.

Chlorhexidine can cause severe immediate-type allergic reactions such as urticaria, anaphylactic shock or, even, cardiac arrest. We report the case of a patient who developed perioperative anaphylactic shock caused by chlorhexidine 1 year after a postoperative urticarial reaction, which was assumed not to be significant at the time. This case highlights the importance of identifying mild allergy symptoms after exposure to chlorhexidine at the pre-anaesthetic assessment to prevent more severe allergic reactions in future.