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Rationale: At present, there is still insufficient understanding of the progression from persistent allergic reactions to severe reactions. Adrenaline remains the preferred medication for severe allergic reactions, and intramuscular injection of adrenaline can also be considered for patients with grade I reactions that are difficult to alleviate gastrointestinal symptoms. It is worth further discussing whether it is possible to break the conventional intramuscular injection recommended by the guidelines when the effect of intramuscular injection is not ideal for persistent grade I severe allergic reactions., Patient Concerns: A young male, 20 years of age, was admitted to emergency department because of repeated rash for 3 days and abdominal pain for 6 hours after taking traditional Chinese medicine. After hormone therapy, the rash continued to recur and secondary gastrointestinal symptoms occurred on the 3th day. Adrenaline intramuscular injection was given to temporarily relieve the rash and abdominal pain, but symptoms still persisted., Diagnosis: The patient was diagnosed with persistent severe allergic reaction (grade I)., Interventions: Continuous intravenous infusion of low-dose adrenaline under electrocardiographic monitoring, real-time monitoring of heart rate and blood pressure, and routine treatment with methylprednisolone, diphenhydramine, calcium gluconate, and cetirizine. During this period, adrenaline intramuscular injection is temporarily added when abdominal pain symptoms are obvious. The entire treatment process used a total of 6.8 mg of adrenaline., Outcomes: During the entire period of adrenaline intervention, the patient did not experience any new discomfort, and there were no abnormal fluctuations in heart rate, rhythm, or blood pressure. The symptoms of rash and abdominal pain gradually improved., Lessons: For patients with persistent grade I severe allergic reactions, intravenous administration of low-dose adrenaline under close vital sign monitoring is safe, feasible, and highly effective in preventing biphasic, persistent, or worsening allergic reactions., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: To understand the current global scale of drug hypersensitivity (DH) and drug allergy (DA), and to identify possible strategies to increase the accuracy of epidemiological data., Recent Findings: Global patterns of DH/DA seem to be changing and increasing worldwide, but there are still great challenges in capturing quality DH/DA mortality and morbidity statistics (MMS). DH/DA MMS may gain new perspectives with the global implementation of the International Classification of Diseases (ICD)-11. Improving the quality of epidemiological data related to DH/DA should clarify areas of uncertainty, which would lead to better strategies to reduce the burden of these conditions., Summary: DH/DA remains a complex and unaddressed problem globally that often deprives patients of optimal medication choices and places them at risk for life-threatening reactions. DH/DA labels should contribute to people well being, by protecting true allergic individuals from being re-exposed to their allergic drugs and providing needed medications to individuals wrongly labeled as allergic or who have lost allergic sensitivity. The true rate of DH/DA is in fact unknown due to a number of factors, such as misdiagnosis, miscoding and under- and over-notification, among others. Moreover, there is lack of data about DH/DA epidemiology in many countries. Difficulties on collecting accurate and comparable data should be acknowledged, with great impact in the correct labeling DH/DA in electronic health records and official statistics. More accurate definitions, classification and coding may contribute to a better-quality MMS thanks to the ICD-11, under implementation worldwide. Improving the quality of epidemiological data related to DH/DA should clarify areas of uncertainty, which would lead to better strategies to reduce the burden of these conditions. As knowledge derived from populations is key information for more realistic decision-making, the construction of the new section addressed to DH/DA in the ICD-11 will allow the collection of more accurate epidemiological data to support quality management of patients, and facilitate healthcare planning to implement public health measures to prevent and reduce the morbidity and mortality attributable to these conditions., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Perioperative hypersensitivity reactions are rare but potentially catastrophic events. This review acts to summarize recent recommendations for both immediate and poststabilization management of suspected reactions, alongside practical advice for anaesthetists who may be faced with these events., Recent Findings: Prompt treatment is essential but may be hampered by delay in recognition. This can occur because there are multiple differential diagnoses for the observed clinical signs as well as variations in clinical presentation. Resuscitation is dependent on the use of adrenaline and fluids. Adrenaline should be administered in small, titrated intravenous boluses. Low-dose infusions should be commenced early if the response to boluses is poor. Large volume fluid resuscitation may be required to maintain adequate circulating volume. Chest compressions are recommended when there is evidence of inadequate perfusion, rather than waiting until cardiac arrest is confirmed. Antihistamines and corticosteroids are no longer recommended in the immediate management phase. Once the patient has been stabilized, it is important to obtain serial tryptase concentrations to aid the subsequent clinic investigation. The decision to proceed or abandon surgery will be based on an individual risk-benefit analysis. All cases of suspected perioperative hypersensitivity, including fatal cases, must be referred for formal investigation., Summary: There have been recent updates to management guidelines in perioperative hypersensitivity. Treatment algorithms, treatment packs and referral packs can all help the anaesthetist manage these complex cases, aid the subsequent investigation and ensure patient safety in the future., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Drug allergy is responsible for a huge burden on public healthcare systems, representing in some instances a threat for patient's life. Diagnosis is complex due to the heterogeneity of clinical phenotypes and mechanisms involved, the limitations of in vitro tests, and the associated risk to in vivo tests. Predictive models, including those using recent advances in artificial intelligence, may circumvent these drawbacks, leading to an appropriate classification of patients and improving their management in clinical settings., Recent Findings: Scores and predictive models to assess drug allergy development, including patient risk stratification, are scarce and usually apply logistic regression analysis. Over recent years, different methods encompassed under the general umbrella of artificial intelligence, including machine and deep learning, and artificial neural networks, are emerging as powerful tools to provide reliable and optimal models for clinical diagnosis, prediction, and precision medicine in different types of drug allergy., Summary: This review provides general concepts and current evidence supporting the potential utility of predictive models and artificial intelligence branches in drug allergy diagnosis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Patients with mast cell disorders frequently experience symptoms from excessive mediator release like histamine and tryptase, ranging from mild flushing to severe anaphylactic responses. Hypersensitivity reactions (HRs) to drugs are a major cause of anaphylaxis in these patients, who often worry about triggering mast cell degranulation when taking medications. The aim of this review is to explore the complex interactions between mast cell disorders and drug HRs, focusing on the clinical challenges of managing these conditions effectively to enhance understanding and guide safer clinical practices., Recent Findings: Among the drugs most commonly associated with hypersensitivity reactions in patients with mast cell disorders are non-steroidal anti-inflammatory drugs, antibiotics, and perioperative agents. Recent studies have highlighted the role of Mas-related G-protein coupled receptor member X2 (MRGPRX2) - a receptor involved in non-immunoglobulin E mediated mast cell degranulation - in exacerbating HRs. Investigations reveal varied drug tolerance among patients, underscoring the need for individual risk assessments., Summary: Tailored diagnostic approaches are crucial for confirming drug allergies and assessing tolerance in patients with mastocytosis, preventing unnecessary medication avoidance and ensuring safety before acute situations arise., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The author declares no conflict of interest.

Competing Interests: The authors declare no conflicts of interest.

Rationale: Although rare, systemic hypersensitivity reactions to nedaplatin chemotherapy arise rapidly and can be life-threatening. The causes are unclear, and multiple potential mechanisms exist. Here, we report a case of systemic hypersensitivity reaction to nedaplatin and review the literature to establish a recommended protocol., Patient Concerns: A 62-year-old man was being treated for squamous lung cancer with multiple metastases. On the first day of chemotherapy, 5 minutes after nedaplatin infusion, he developed panic, shortness of breath, and dyspnea with rapid heart rate, reduced oxygen saturation, and elevated blood pressure., Diagnoses: The symptoms indicated that the patient had developed a severe hypersensitivity reaction to nedaplatin, which could be life-threatening without immediate intervention., Intervention: Nedaplatin was discontinued, and he was treated with oxygen, ECG monitoring, finger pulse oximeter monitoring, 10 mg dexamethasone sodium phosphate injected intravenously, 20 mg diphenhydramine hydrochloride injected intramuscularly, and 40 mg methylprednisolone sodium succinate injected intravenously., Outcome: His allergic symptoms resolved, and once his vital signs stabilized, he was given 5 mg oral desloratadine once daily and 10 mg oral ebastine once daily to alleviate the effects of the allergic reaction. Once his vital signs remained stable without any special supportive treatment, he was discharged from the hospital. His chemotherapy regimen was discontinued, with no plan for a follow-up treatment due to the possibility of cross-allergic reactions between platinum-based drugs., Lessons: Clinical use of nedaplatin should be monitored and managed intensively for prevention and treatment of hypersensitivity reactions. Care should be taken to control the titration rate during infusion while closely monitoring vital signs. Clinical staff should be prepared to treat allergic symptoms as soon as they appear. The acute phase should involve immediate discontinuation of the drug; intravenous saline infusion for volume expansion; rapid assessment of circulation, airway, respiration, state of consciousness, and skin condition; and administration of oxygen, antihistamines, and epinephrine as appropriate for anaphylaxis. More randomized clinical trials are needed to elucidate appropriate preventative and management strategies to improve patient safety and support their successful completion of clinical treatment programs., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: Many systemic medications have been observed to cause ocular toxicity. A subset of these reactions is thought to involve immunomodulation or a hypersensitivity reaction. As new medications are developed, ocular adverse effects are becoming increasingly prevalent. Herein we review immune-mediated drug reactions affecting they eye with special attention to the hypersensitivity mechanisms leading to ocular toxicity., Recent Findings: Recent work has focused on mechanisms and risk of immune-mediated ocular adverse drug reactions including genetic susceptibility and loss of ocular immune privilege., Summary: Given the consequences of immune-mediated ocular adverse drug reactions, clinicians must be aware of these to facilitate early recognition and management. The prompt involvement of an ophthalmologist for diagnosis and management is often essential to preserve vision and avoid long-term morbidity., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Perioperative anaphylaxis (POA) is rare but is associated with significant morbidity and mortality. Patients are referred to the allergist to identify the mechanism of the reaction, the causative agent and make recommendations regarding subsequent anaesthesia. Despite a well conducted allergological evaluation, the causative agent is not found in 30-60% of these reactions, leaving patients without a well established diagnosis., Recent Findings: Several mechanisms can induce POA. In addition to the well known IgE-mediated reactions, IgG-mediated reaction, MRGPR-X2-related reaction or nonspecific histamine release may be involved. These situations are not easily assessed by the allergological workup., Summary: When the allergological workup is negative, the situation should be reassessed with the team present at the time of the reaction to confirm the reality of the hypersensitivity reaction and to search for a possible differential diagnosis. If POA is confirmed, the allergological evaluation should be repeated, ensuring proper execution according to current guidelines and including the search for hidden allergens. Specific IgE assays or basophil activation tests may be of interest. In case of negative results, a closely monitored drug challenge test, in coordination with the anaesthesia teams, may be useful to avoid the exclusion of any drug injected during the reaction., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Serum tryptase, a mast cell marker, provides clues for the mechanism, severity, and management of drug hypersensitivity induced by immunoglobulin E dependent or independent mast cell activation., Recent Findings: The interpretation of serum tryptase levels has been challenged during the last 2 years by major advances in tryptase genetics and their rapid incorporation into clinical practice. On the contrary, new pathophysiological insight into nonmast cell-dependent immediate hypersensitivity has been gained., Summary: This review provides up-to-date information on the pathophysiology and recommended use and interpretation of tryptase in the context of drug hypersensitivity reactions as a function of their endotype., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The aim of this study was to review the practice of general practitioners (GPs) in regard to the diagnosis and management of drug hypersensitivity reactions (DHRs) to identify major challenges and to facilitate the development of decision support tools to GPs confronted with DHRs patients., Recent Findings: DHRs are still a challenge in the GPs clinical practice, which implies difficulties in clinical decisions and referral to allergy specialists., Summary: DHRs can range from mild to severe and even life-threatening. Drugs are the main cause of anaphylaxis deaths in most countries. Most DHRs are firstly seen by GPs, paediatricians or emergency doctors. However, our systematic review demonstrated difficulties in differentiating DHRs from other drug side effects. Most DHRs epidemiological data are from hospital and emergency departments, which may not reflect the real-life experience in primary care. GPs should be aware of the alert signs of DHRs: the involvement of other systems beyond the skin and/or atypical skin/ mucosal involvement, which mandated immediate referral to an emergency department. Data still stress difficulties in the recognition of DHRs clinical manifestations and highlight the need for decision aids to support their management by GPs. Structured clinical history and clinical examination are key diagnostic tools. Reasons for referring to allergy specialists based on the literature are to investigate cause, to undergo specific procedure, such as desensitization and to identify well tolerated, alternative drugs., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chlorhexidine generally has a good safety profile. However, allergic reactions are reported with increasing frequency. In China, it is rarely reported, and its characteristics are unknown. The purpose of this study was to summarize the experience of a Chinese allergy center with chlorhexidine allergy., Methods: The authors retrospectively reviewed all patients who underwent chlorhexidine allergy testing in the Allergy Center of West China Hospital, Sichuan University (Chengdu, China), in the period February 2018 to May 2022 (n = 43 patients) and included the patients diagnosed with chlorhexidine allergy for analysis., Results: Ten patients who were diagnosed by skin prick and serum-specific immunoglobulin E tests were included. They experienced a total of 30 allergic reactions to chlorhexidine (mean ± SD, 3.0 ± 1.3). Five patients experienced six allergic reactions (6 of 30, 20%) during general or local anesthesia, and they may have been exposed to chlorhexidine via different routes. Only one allergic reaction (1 of 30, 3%) was recorded with exposure via a mouthwash. The other 23 allergic reactions (23 of 30, 77%) were caused via a skin disinfectant; the route of exposure was IV cannulation in 22 allergic reactions (22 of 23, 96%) and broken skin in one allergic reaction (1 of 23, 4%). The symptoms included a quick onset and great severity. Two patients (2 of 10, 20%) had been accidentally re-exposed to chlorhexidine after diagnosis., Conclusions: This study conducted in China showed that the majority of reactions to chlorhexidine were attributed to skin disinfectants, and IV cannulation was the most common exposure route; in general, however, chlorhexidine allergy was easily overlooked. The potential allergenicity of chlorhexidine used for skin preparation before IV cannulation or should be considered in patients who develop allergic reactions perioperatively., (Copyright © 2023, the American Society of Anesthesiologists. All Rights Reserved.)

Introduction: Drug hypersensitivity syndrome (DHS) induced by sulfasalazine is a serious systemic delayed adverse drug reaction, which is associated with significant morbidity and mortality., Patient Concerns: A 52-year-old man was hospitalized for developing a rash after 3 weeks of sulfasalazine treatment for ulcerative colitis (UC)., Diagnosis: The patient was diagnosed with DHS based on his drug history, clinical manifestations, and laboratory test results., Interventions: The patient was administered intravenous glucocorticoids. The patient's condition improved after treatment with human immunoglobulin and antihistamines., Outcomes: Combination therapy of glucocorticoid and gamma globulin, the whole-body pruritus disappeared, and no new rash appeared. The whole-body rash subsided or turned dark red., Conclusion: This article describes the diagnosis and treatment process of a case of sulfasalazine-induced DHS and reviews the relevant literature to improve clinician understanding and avoid misdiagnosis and missed diagnosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: There is a broad spectrum of chemotherapy-induced adverse reactions. Hypersensitivity reactions are being extensively studied as they can affect the ideal treatment. The goal of this review is to describe the current management of adverse reactions to chemotherapy, focusing on hypersensitivity events., Recent Findings: The range of possible desensitization protocols is increasing, as well as the delabeling algorithms and diagnostic tools. One-bag desensitization protocols, omalizumab use in immediate hypersensitivity reactions, slow desensitization protocols in nonimmediate hypersensitivity reactions and standardization of skin tests for platinum drugs, are some examples., Summary: The handling of adverse reactions to chemotherapy is evolving, with the increasing identification of hypersensitivity reactions and the development of strategies for their management, to maintain the culprit drug., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Drug desensitization is the only therapeutic option for patients with drug allergies who need to receive the drugs they are allergic to, and it is especially critical in patients with an urgent need for chemotherapy, biologics, or antibiotics, where equally effective alternatives might not be available. However, drug desensitization is not a cookbook where anyone with no experience or specific training can find a general recipe. This review article will approach the singularities that make personalized and highly specialized care essential in this field., Recent Findings: Drug desensitization needs to be personalized for each individual patient bearing in mind countless factors. Recent articles have tried to define the optimal resources and the most important factors to account for in personalization. However, drug desensitization is only a tool within the wider management pathway, and we will discuss recent findings in allergy delabelling in chemotherapy, biologics, and antibiotics., Summary: Risk-assessment, delabelling, and desensitization protocols, as a part of wider management pathways, can be adapted locally along with comprehensive and multifactorial risk-management strategies. These high-complexity and high-risk procedures, such as drug desensitization, need to be managed by expert allergists who can provide personalization, innovation, continuous improvement, research, and teaching in expert centres., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

Background: The epidemiology of hospital adverse reactions (ARs), particularly allergic reactions, or hypersensitivity reactions (HSRs), is poorly defined. To determine priorities for allergy safety in healthcare, we identified and described safety reports of allergic reactions., Methods: We searched the safety report database of a large academic medical center from April 2006 to March 2016 using 101 complete, truncated, and/or misspelled key words related to allergic symptoms, treatments, and culprits (e.g., medications, foods). Patient and event data were summarized for ARs and two types of ARs, HSRs and side effects/toxicities., Results: Among 9111 key word search-identified events, 876 (10%) were ARs, of which 436 (5%) were HSRs and the remaining 440 (5%) were side effect reactions or toxicities. Whereas the most common HSRs were simple cutaneous reactions (83%), the following severe immediate HSRs were also identified: shortness of breath (16%), anaphylaxis (14%), and angioedema (12%). Most HSRs were caused by drugs (81%), with antibiotics (26%), particularly β-lactams (11%), and vancomycin (8%), commonly implicated. Other causes of drug HSRs included contrast agents (24%), chemotherapeutics (7%), and opioids (6%). Nondrug HSRs were from blood products (8%), latex (3%), and devices (3%). Food reactions were rarely identified (1%)., Conclusions: We identified ARs, HSRs, and side effects/toxicities, contained in a decade of safety reports at an academic medical center. Allergy safety in the healthcare setting should target approaches to common and severe reactions, with a focus on the safe administration of β-lactams, vancomycin, contrast agents, chemotherapeutics, and opioids. Priority nondrug HSR culprits include blood products, latex, and devices., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The goal of this article is to provide an updated understanding and evidence-based approach where possible for antifungal hypersensitivity. This includes recognition of clinical phenotype, implications for cross-reactivity and diagnostic, and management strategy for immediate and delayed hypersensitivity reactions., Recent Findings: Antifungal hypersensitivity reactions can be classified according to their latency (immediate or delayed) and clinical phenotype. The majority of the cases described in the literature are delayed T-cell mediated reactions of various severities but immediate reactions consistent with non-Immunoglobulin E (IgE)-mediated mast cell activation and IgE-mediated reactions have also been described. Ancillary information such as skin testing, drug challenge and ex vivo experimental approaches can aid causality assessments and inform antifungal class cross-reactivity, which help optimize antifungal prescribing and stewardship., Summary: This review will update the clinician on mechanisms of drug hypersensitivity as well as providing a structured approach to the recognition, diagnosis and management of antifungal hypersensitivity reaction., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Children with mitochondrial disease undergo anesthesia for a wide array of surgical procedures. However, multiple medications used for their perioperative care can affect mitochondrial function. Defects in function of the mitochondrial electron transport chain (ETC) can lead to a profound hypersensitivity to sevoflurane in children. We studied the sensitivities to sevoflurane, during mask induction and maintenance of general anesthesia, in children presenting for muscle biopsies for diagnosis of mitochondrial disease., Methods: In this multicenter study, 91 children, aged 6 months to 16 years, presented to the operating room for diagnostic muscle biopsy for presumptive mitochondrial disease. General anesthesia was induced by a slow increase of inhaled sevoflurane concentration. The primary end point, end-tidal (ET) sevoflurane necessary to achieve a bispectral index (BIS) of 60, was recorded. Secondary end points were maximal sevoflurane used to maintain a BIS between 40 and 60 during the case, and maximum and minimum heart rate and blood pressures. After induction, general anesthesia was maintained according to the preferences of the providers directing the cases. Primary data were analyzed comparing data from patients with complex I deficiencies to other groups using nonparametric statistics in SPSS v.27., Results: The median sevoflurane concentration to reach BIS of 60 during inductions (ET sevoflurane % [BIS = 60]) was significantly lower for patients with complex I defects (0.98%; 95% confidence interval [CI], 0.5-1.4) compared to complex II (1.95%; 95% CI, 1.2-2.7; P < .001), complex III (2.0%; 95% CI, 0.7-3.5; P < .001), complex IV (2.0%; 95% CI, 1.7-3.2; P < .001), and normal groups (2.2%; 95% CI, 1.8-3.0; P < .001). The sevoflurane sensitivities of complex I patients did not reach significance when compared to patients diagnosed with mitochondrial disease but without an identifiable ETC abnormality (P = .172). Correlation of complex I activity with ET sevoflurane % (BIS = 60) gave a Spearman's coefficient of 0.505 (P < .001). The differences in sensitivities between groups were less during the maintenance of the anesthetic than during induction., Conclusions: The data indicate that patients with complex I dysfunction are hypersensitive to sevoflurane compared to normal patients. Hypersensitivity was less common in patients presenting with other mitochondrial defects or without a mitochondrial diagnosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)