Management and treatment of perioperative hypersensitivity.

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.

Mast cell conditions and drug allergy: when to suspect and how to manage.

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.

A successful desensitization in an adult patient with ARA-C infusion reaction.

INTRODUCTION: Cytarabine (ARA-C) is an antimetabolite agent used especially in the treatment of hematologic malignancies. Infusion reactions have an important place among the side effects that may occur due to treatment. Clinical findings of infusion reactions resemble allergic reactions. CASE REPORT: 47-year-old male patient with a diagnosis of B-cell Acute Lymphoblastic Leukaemia developed infusion reaction during ARA-C treatment. MANAGEMENT & OUTCOME: There was no alternative treatment option for his existing malignant disease, we decided ARA-C desensitization. DISCUSSION: We would like to describe a successful desensitization protocol in an adult patient who experienced a reaction during ARA-C infusion.

[Does aspirin therapy after desensitization still have a role in treatment of chronic rhinosinusitis with nasal polyposis in the era of biologics?] / Hat die ASS-Desaktivierung in Zeiten von Biologika noch einen Stellenwert bei chronischer Rhinosinusitis mit nasaler Polyposis?

The prevalence of analgesic intolerance syndrome (AIS), internationally known as NSAID-exacerbated respiratory disease (NERD), is reported to be 0.5-5.7% in the general population. The disease often begins with nasal symptoms, which are later joined by chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and respiratory hypersensitivity reactions following use of nonsteroidal anti-inflammatory drugs (NSAIDs). In the setting of chronic respiratory disease, the type 2 inflammatory endotype is predominant in approximately 80% of patients with CRSwNP, rendering biologics directed against interleukin (IL)-4, IL­5, IL-13, and IgE of high clinical interest, particularly in patients with severe CRSwNP and NERD. NERD is often associated with CRSwNP and asthma. Patients with CRSwNP and NERD have been treated, among other therapies, with aspirin therapy after desensitization (ATAD). With the approval of monoclonal antibodies for CRSwNP and asthma, the question arises as to what extent ATAD, which is associated with undesirable side effects, is still useful in the treatment of CRSwNP. In this manuscript, the use of ATAD in CRSwNP patients is discussed from different medical and socioeconomic points of view, both alternatively to or in combination with monoclonal antibodies. Accordingly, both ATAD and biologics continue to play a supporting role in modern treatment of CRSwNP in NERD patients, and should be used judiciously to complement each other.

Successful desensitization in a patient with recurrent anaplastic oligodendroglioma presenting with procarbazine-mediated anaphylaxis.

INTRODUCTION: Procarbazine is an oral chemotherapeutic agent used in the treatment of brain malignancies and is associated with hypersensitivity reactions. In case of grade 4 reactions, rechallenge should be avoided, and the agent should be replaced, unless the treatment is curative, in which case the application of a desensitization protocol should be considered. We present a successful case of desensitization in procarbazine anaphylaxis. CASE REPORT: A 53-year-old male patient was diagnosed with recurrent anaplastic oligodendroglioblastoma. The patient received three cycles of procarbazine, lomustine, and vincristine chemotherapy for malignancy recurrence. In the fourth cycle, on the 12th day of procarbazine treatment, the patient developed anaphylaxis. Procarbazine was given together with premedication as part of the 12-step desensitization process, and the fourth cycle was successfully completed. MANAGEMENT AND OUTCOME: Procarbazine hypersensitivity reactions are observed less frequently than reactions to other chemotherapeutics. We presented a case of procarbazine-associated severe anaphylaxis that was able to continue procarbazine chemotherapy with successful desensitization. This case is important in terms of confirming the procarbazine desensitization protocol. DISCUSSION: In literature there is only one protocol developed was successfully applied in one patient with procarbazine anaphylaxis. In the current case, we took this protocol into consideration in the management of our patient. Following the use of this protocol, the patient was able to continue procarbazine chemotherapy successfully. Procarbazine anaphylaxis is rare, and more cases are needed to be reported to confirm the desensitization protocol and when to continue procarbazine treatment.

One-Bag 8-Step Ferric Carboxymaltose Desensitization Protocol for Patients with a History of Hypersensitivity Reactions to Iron Preparations.

INTRODUCTION: Iron deficiency is the most common cause of anemia in both sexes, although it is more common in women. Intravenous (IV) iron replacement is preferred in patients who cannot tolerate oral treatment or when iron stores need to be replenished rapidly. In this study, we wanted to share the ferric carboxymaltose (FCM) desensitization protocol that we self-created and successfully applied. METHODS: This retrospective cross-sectional study included patients with a history of hypersensitivity reactions (HSRs) to IV or oral iron replacement and patients who were planned to receive IV iron replacement but were referred to the allergy clinic because of have risk factors (atopic diseases, history of HSR to other drugs, high serum tryptase levels, etc.) for HSRs. Before desensitization, some of the patients underwent skin tests (skin prick test and intradermal test) with FCM, and the results were recorded. Skin tests were not performed in patients with a history of drug use (antihistamine, systemic steroid, omalizumab, etc.) that affected the results of skin tests. All patients underwent a one-bag 8-step desensitization protocol with 500 mg FCM and were observed for 2 h after desensitization. RESULTS: A total of 15 patients (14 females and 1 male) with a mean age of 41.13 ± 11.18 years were included in the study. When the patients were evaluated in terms of the risk of allergic reactions according to their clinical history, 8 patients had a history of anaphylaxis with iron preparations (FCM, n = 4; ferric hydroxide sucrose, n = 2; iron [II] glycine sulfate, n = 1; and iron [III] hydroxide polymaltose, n = 1), and 7 patients had a history of HSR other than anaphylaxis with iron preparations (urticaria, n = 6 [FCM, n = 2; iron (II) glycine sulfate, n = 2; and iron (III) hydroxide polymaltose, n = 2] and urticaria + angioedema [ferric hydroxide sucrose, n = 1]). Desensitization was successfully completed in all patients. No HSR was observed during or after the procedure in any of the patients. CONCLUSION: IV iron replacement is a very effective method, especially in cases where iron stores need to be replenished more rapidly. In patients with a history of iron HSR or at risk of developing HSR, replacement can be safely performed without an allergic reaction with successful desensitization protocols.

Local Anesthetic Hypersensitivity Reactions in Pediatric Patients: Recognition and Management.

Local anesthetics (LAs) are commonly used in all medical specialties, particularly in association with surgery, obstetrics, dentistry, and emergency departments. Most individuals, starting from young children, are exposed to LAs during life. LA hardly induces adverse events when used in recommended doses and with proper injection techniques. However, immediate anaphylactic reactions to LA injections may be a rare but life-threatening manifestation. A comprehensive report of the event and performing a specialist examination are crucial to prevent further episodes. The diagnosis should be based on history, medical records, skin and challenge tests.

Differential presentation of hypersensitivity reactions to carboplatin and oxaliplatin: Phenotypes, endotypes, and management with desensitization.

BACKGROUND: Drug hypersensitivity reactions (DHRs) to platinum-based drugs are heterogenous and restrict their access, and drug desensitization (DD) has provided a ground-breaking procedure for their re-introduction, although the response is heterogeneous. We aimed to identify the phenotypes, endotypes, and biomarkers of reactions to carboplatin and oxaliplatin and their response to DD. METHODS: Seventy-nine patients presenting with DHRs to oxaliplatin (N = 46) and carboplatin (N = 33) were evaluated at the Allergy Departments of two tertiary care hospitals in Spain. Patient symptoms, skin testing, biomarkers, and outcomes of 267 DDs were retrospectively analyzed. RESULTS: Oxaliplatin-reactive patients presented with type I (74%), cytokine release reaction (CRR) (11%), and mixed (Mx) (15%) phenotypes. In contrast, carboplatin reactive patients presented with predominantly type I (85%) and Mx (15%) but no CRRs. Out of 267 DDs, breakthrough reactions (BTRs) to oxaliplatin occurred twice as frequently as carboplatin (32% vs. 15%; p < .05). Phenotype switching from type I to another phenotype was observed in 46% of oxaliplatin DDs compared to 21% of carboplatin DDs. Tryptase was elevated in type I and Mx reactions, and IL-6 in CRR and Mx, indicating different mechanisms and endotypes. CONCLUSION: Carboplatin and oxaliplatin induced three different types of reactions with defined phenotypes and endotypes amendable to DD. Although most of the initial reactions for both were type I, oxaliplatin presented with unique CRR reactions. During DD, carboplatin reactive patients presented mostly type I BTR, while oxaliplatin-reactive patients frequently switched from type I to CRR, providing a critical difference and the need for personalized DD protocols.

Hypersensitivity Reaction and Rapid Drug Desensitization with Chemotherapeutics: A Tertiary Reference Center Experiences.

INTRODUCTION: Chemotherapy drugs have been in our lives for a long time, and all agents have the potential to develop hypersensitivity. Rapid drug desensitization is an option when hypersensitivity develops. The aim of this study was to examine the characteristics, diagnostic processes, and treatment results of patients with chemotherapeutic agent hypersensitivity who applied to our tertiary reference center. METHODS: Patients who applied to our tertiary allergy outpatient clinic between January 2016 and September 2022 due to chemotherapy-induced drug hypersensitivity were examined. Demographic data of the patients, cancer diagnoses, chemotherapy regimens, skin tests, premedication scheme, desensitization cycle were evaluated. We applied a 16-step desensitization in patients with index reaction anaphylaxis or positive skin tests. If the index reaction was not anaphylaxis or skin tests were negative, we applied a 12-step desensitization. If the prick test with chemotherapeutic drugs was negative especially with taxanes, premedication was administered. We used the montelukast, cetirizine, and methylprednisolone for premedication. RESULTS: Fifty-one patients were evaluated; 35 (68.6%) were female. The most common malignancy was colorectal cancer in 17 (33.3%) patients. The most common agent responsible for hypersensitivity was oxaliplatin in 17 (33.3%) patients, followed by paclitaxel in 13 (25.4%). When the symptoms of immediate reaction to chemotherapeutic drugs were analyzed as described in the EAACI position paper, only skin and mucosal involvement was seen in 24 (46.8%) patients; only respiratory system involvement or back pain was seen in 3 (6.2%) patients; multisystem involvement meeting the criteria for anaphylaxis was seen in 24 (47%) patients. Skin test was positive in 17 (56.6%) of 30 patients who developed a reaction with platin. Prolonged anaphylaxis was developed in 1 patient, and desensitization was not performed again. Fifty of 51 patients were able to receive the target chemotherapy dose by desensitization. In total, a 172-step desensitization was applied to 51 patients. CONCLUSION: If completing the cycle is considered a treatment success, this was achieved in 98% (50/51) patients with rapid drug desensitization. This gives us the opportunity to use first-line chemotherapy agents.

Oxaliplatin-induced hypersensitivity reactions: risk factors and management.

OBJECTIVE: Chemotherapy-related adverse reactions have been steadily increasing in recent years. In patients who develop oxaliplatin-induced hypersensitivity reactions (HSRs), prognosis and quality of life are adversely affected. Proper management of cancer patients enables them to safely receive first-line treatments. This study aimed to assess the risk factors in oxaliplatin-induced HSRs and the effectiveness of the rapid desensitization protocol. PATIENTS AND METHODS: In the study, 57 patients treated with oxaliplatin between October 2019 and August 2020 in the Medical Oncology Department of Elazig City Hospital were retrospectively evaluated. We analyzed patients' clinical histories to reveal any associations with the development of oxaliplatin-induced HSRs. Moreover, we re-evaluated 11 patients with oxaliplatin-induced HSRs through infusion time or desensitization procedures. RESULTS: Of 57 patients treated with oxaliplatin, 11 (19.3%) had HSRs. Patients with HSRs were younger and had higher peripheral blood eosinophil counts than those without HSRs (p=0.004, p=0.020, respectively). Prolongation of the infusion time was effective in the re-administration of oxaliplatin in six of the hypersensitive patients. Rapid desensitization protocol was performed for a total of 11 cycles in four patients with recurrent HSRs, and their chemotherapy regimens were successfully completed. CONCLUSIONS: This retrospective study has revealed that younger ages and higher peripheral eosinophil counts could be predictive for oxaliplatin-induced HSR. Furthermore, the study confirms that prolongation of the infusion time and rapid desensitization protocol are effective in patients with HSRs.

Pearls for practice from the 2022 joint task force drug allergy practice parameter.

PURPOSE OF REVIEW: To review updated recommendations in the 2022 Drug Allergy Practice Parameters for the evaluation and management of drug hypersensitivity reactions. RECENT FINDINGS: Adverse drug reactions have become increasingly prominent with the advent of new and emerging pharmacologic therapies. Hypersensitivity reactions encompass a significant proportion of adverse drug reactions and negatively impact both the individual patient and overall health system. Reactions are heterogeneous in presentation and may be immediate (onset of symptoms ≤6 h) or delayed (onset of symptoms >6 h to months) after drug exposure. The 2022 Drug Allergy Practice Parameter provides consensus-based statements for evaluation of hypersensitivity reactions to antibiotics, NSAIDs, cancer chemotherapies, immune checkpoint inhibitors, biologics, and excipients. In general, the guideline highlights the importance of patient history in elucidating the phenotype and severity of the index reaction. Drug challenge remains the gold standard for diagnosis and is increasingly favored over skin testing in patients with nonsevere, nonanaphylactic drug reaction histories. SUMMARY: The 2022 Drug Allergy Practice Parameter provides an updated framework for physicians to reference in clinical practice when managing patients with drug hypersensitivity reactions.

Utilizing Biologics in Drug Desensitization.

PURPOSE OF REVIEW: The purpose of this literature review was to review the latest advancements with biologics in rapid drug desensitization. Our methodology was to highlight both desensitization to biologics themselves and the use of biologics in desensitization to both biologic and nonbiologic drugs. RECENT FINDINGS: Biologics are a vast category of drugs that include monoclonal antibodies, nanobodies, modern vaccinations, and even hormones. Desensitization to biologics can be safely performed through standardized procedure. Biomarkers are used both in vitro and in vivo to help identify and classify hypersensitivity reactions. Hypersensitivity reactions to the mRNA vaccinations against SARS-CoV-2 present their own unique challenges to management. There are specific excipients in monoclonal antibodies that are thought to be responsible for many of their hypersensitivity reactions. Certain biologics can even be used to assist in desensitization to other drugs. Rapid drug desensitization is a standardized procedure that may be able to help many patients who have experienced hypersensitivity reactions to biologics and would best be treated with them to continue to receive them. Biologic drugs have opened a new era in medicine for the prevention and treatment of infectious diseases, cancer, and inflammatory diseases. Hypersensitivity reactions to biologics are quite common. This literature review presents the latest advancements in our understanding of hypersensitivity reactions to biologics, how rapid drug desensitization can be used to continue therapy despite history of hypersensitivity, and how biologics themselves can be used to aid in desensitization itself.

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.

Hypersensitivity reactions to biologics in children.

INTRODUCTION: Hypersensitivity reactions (HSRs) have been observed with the use of biologics in children. The management of HSRs in children is mainly based on experiences from the adult population. Recently, data from different centers experienced in managing these reactions, including desensitization in children, have been published, allowing clinicians to have an appropriate global overview and compare results. AREAS COVERED: This review highlights the published data on hypersensitivity reactions to biologics in children and drug desensitization protocols adapted to the pediatric population. EXPERT OPINION: With regard to HSRs to biologics in children, few data are available. Compared with the adult population, there is a lack of knowledge in the endophenotypes, management and the standardization of protocols including premedication regimens in children. An international consensus is needed to provide clinicians with new insight on how to apply personalized management and to perform tailored desensitization protocols in pediatric populations. Various specialists including allergists, pediatricians, oncologists, hematologists, rheumatologists, and pharmacists, should build a multidisciplinary management team to keep pediatric patients on their best treatment options in the safest manner.

Drug-induced Anaphylaxis.

Drug hypersensitivity is increasing worldwide as the consumption of drug is increasing. Many clinical presentations of drug hypersensitivity are complex and take place in the setting of illness and/or polypharmacotherapy. To review the most recent findings in the diagnosis and management of immediate drug hypersensitivity reactions. Studies were selected based on their relevance, originality and date of publication. The understanding of endotypes, biomarkers and phenotypes has improved the categorization of immediate hypersensitivity reactions. In this review, we discussed the short- and long-term management of anaphylaxis with a special focus on in vivo and in vitro diagnostic methods. Moreover, the clinical management of drug-induced anaphylaxis, the role of hidden allergens and the importance of delabeling are discussed. Endophenotyping is crucial to correctly diagnose and treat patients with immediate drug hypersensitivity reactions, preventing future episodes through drug desensitization.

Toxicity management and efficacy of carboplatin desensitization therapy for recurrent epithelial ovarian carcinoma: A real-world study.

Epithelial Ovarian cancer (EOC) is the most lethal gynecologic cancer worldwide. Carboplatin (CP) is the main chemotherapeutic agent in the treatment of ovarian cancer. However, the development of a hypersensitivity reaction (HSR) in 10% to 15% of patients with EOC is an important limiting factor for the clinical use of CP. Herein, we aimed to investigate the efficacy and safety of CP-desensitization (CP-D) therapy in the treatment of recurrent patients with EOC. Forty-seven ovarian cancer cases treated with CP-desensitization at the Istanbul University Oncology Institute were retrospectively analyzed between 01.01.2017 and 01.01.2022. The decision for CP-D was based on the patients' history of HSR and/or a positive skin test. For all patients, a 6-hour 12-step rapid drug desensitization protocol with a 30-minutes premedication regimen was used. Forty-seven patients were included in this study, and the median age at diagnosis was 53 years (range; 27-80). Twenty-one (43.7%) patients had 1 or more comorbid diseases, and 12.7% had a previous history of drug allergy. On average, HSR due to carboplatin was identified after 9 (7-16) cycles, and carboplatin was administered n = 11 (range, 3-36) times to patients. The overall survival from the first desensitization procedure (0S2) was 42.2 months (range: 25.3-59.1), and the 1-, 2-, and 5-years survival rates were 92.6%, 75.6%, and 47.2%, respectively. The objective response rate (ORR) was 78.5%. Cumulatively, 496 CP-D procedures were performed, of which 478 (96.3%) were successfully completed. None of the patients included in this study developed severe (grade 3-4) HSR during CP administration (no adrenaline was used, no need for intensive care). No deaths due to CP-D were noted. CP-D is a beneficial and safe method in treating platinum-sensitive recurrent EOC patients with CP-induced HSR.