Hypersensitivity Reactions to Taxanes: A Multicenter Study for Outcomes and Safety of Rapid Drug Desensitization.

PURPOSE: Taxanes can cause hypersensitivity reactions (HSRs), which pose a significant challenge in the treatment of malignancies. Patients who are eligible for rapid drug desensitization (RDD) can continue treatment; however, some patients experience breakthrough reactions (BTRs). Data about risk factors for BTRs during RDDs in patients with HSRs to taxanes are limited. METHODS: This was a multicenter, retrospective study of patients with immediate-HSRs to taxanes. Initial HSRs were classified as grade 1, 2, or 3 based on severity. Prick/intradermal skin tests were performed with implicated taxanes. A 12-step protocol was used during RDD. RESULTS: The study comprised 75 patients (F/M: 63/12, mean age 49.92 ± 11.72 years, 43 HSRs to paclitaxel, 32 HSRs to docetaxel). The majority of reactions (86.7%) occurred during the first or second exposure. The prevalence of drug allergy history was higher in patients with paclitaxel HSR than in those with docetaxel HSR, although it was not statistically significant (23.3% vs. 6.3%). The initial HSRs were mostly grade 2 (n = 50, 66.7%) or grade 3 (n = 22, 29.3%). Skin tests with implicated taxanes were done on 48 patients, and the rate of positive response in patients with grade 1, 2, and 3 initial HSRs were 50%, 17.6%, and 16.7%, respectively. . A total of 255 RDDs were completely performed, although BTRs occurred in 27 (grade 1, 55.6%; grade 2, 40.7%; grade 3, 3.7%). There were no statistically significant correlations between the risk of BTR and age, drug cycle, gender, positivity of skin test or atopy. The step reduction was successfully done on 9 eligible patients with mild or moderate HSRs during the 12-step RDDs. CONCLUSIONS: Our experience demonstrates a 100% success rate in completing the 255 RDDs for taxanes, affirming the safety and efficacy of the RDD within the study population.

Hypersensitivity reactions to proton pump inhibitors. An EAACI position paper.

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well-known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%-3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence-based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in-depth investigations in the topic.

Stepwise Approach in Asthma Revisited 2023: Expert Panel Opinion of Turkish Guideline of Asthma Diagnosis and Management Group.

Introduction of inhaled corticosteroids (ICS) has been the cornerstone of the long-term management of asthma. ICSs either alone or in combination with long-acting beta-2 agonists have been shown to be associated with favorable asthma outcomes. However, asthma control is still reported to be below expectations all around the world. Research in the last decades focusing on the use of ICS/formoterol both as maintenance and as needed (maintenance and reliever therapy approach) showed improved asthma outcomes. As a result of recent developments, Turkish Asthma Guidelines group aimed to revise asthma treatment recommendations. In general, we recommend physicians to consider the risk factors for poor asthma outcomes, patients' compliance and expectations and then to determine "a personalized treatment plan." Importantly, the use of short-acting beta-2 agonists alone as a symptom reliever in asthma patients not using regular ICS is no longer recommended. In stepwise treatment approach, we primarily recommend to use ICS-based controllers and initiate ICS as soon as possible. We define 2 different treatment tracks in stepwise approaches as maintenance and reliever therapy or fixed-dose therapy and equally recommend each track depending on the patient's risks as well as decision of physicians in a personalized manner. For both tracks, a strong recommendation was made in favor of using add-on treatments before initiating phenotype-specific treatment in step 5. A strong recommendation was also made in favor of using biologic agents and/or aspirin treatment after desensitization in severe asthma when indicated.

Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in adults: Beyond current classification.

BACKGROUND: Hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant clinical issue. Several classifications have been proposed to categorize these reactions, including the current European Academy of Allergy and Clinical Immunology/European Network for Drug Allergy (EAACI/ENDA) classification. This study aimed to evaluate the applicability of this classification in a real-world clinical setting. METHODS: We conducted a national multicenter study involving patients from nine hospitals in four major urban centers in Turkey. All patients had a suggestive clinical history of hypersensitivity reactions to NSAIDs. Researchers collected data using a structured form and classified reactions based on the EAACI/ENDA classification. Oral provocation tests with several NSAIDs were performed using a single-blind challenge per EAACI/ENDA guidelines. RESULTS: Our retrospective study included 966 adult patients with a history of hypersensitivity to NSAIDs. The most common triggers were Acetylsalicylic Acid (ASA), paracetamol, and metamizole. The most prevalent acute NSAID hypersensitivity group was NSAID-induced urticaria/angioedema (NIUA) (34.3%). However, 17.3% of patients did not fit neatly into the current EAACI/ENDA classification. Notably, patients with underlying asthma or allergic rhinoconjunctivitis exhibited unusual reactions, such as urticaria and/or angioedema induced by multiple chemical groups of NSAIDs, blended mixed reactions, and isolated periorbital angioedema in response to multiple chemical groups of NSAIDs. CONCLUSIONS: While the EAACI/ENDA classification system stratifies NSAID-induced hypersensitivity reactions into five distinct endotypes or phenotypes, it may not fully capture the diversity of these reactions. Our findings suggest a need for further research to refine this classification system and better accommodate patients with atypical presentations.

[The profile of severe asthmatics: Results from a specialized asthma clinic]. / Özellesmis bir astim polikliniginin agir astim verileri.

Introduction: In patients with severe asthma, individualized treatment, and appropriate phenotyping are required to achieve control. In our study, our aim was to examine the characteristics of a specific patient group in a specialized tertiary asthma outpatient clinic, which is the primary setting for evaluating severe asthma patients, with the intention of obtaining national data. Materials and Methods: In this cross-sectional observational study, sociodemographic, clinical presentations, laboratory results, and spirometry measurements of patients with severe asthma who were followed up in our specialized asthma outpatient clinic for at least one year were recorded. Patients were defined as eosinophilic if they had a blood eosinophil count of 300/µL or higher at least twice during the oral corticosteroid free-period or 150/µL or higher under oral corticosteroids as allergic if they had sensitization to at least one inhalant allergen consistent with their history. Result: Overall, 201 severe asthma patients (74.1% female) with a median disease duration of 15 (min-max= 1-49) years and a median follow-up duration of 7 (min-max= 1-40) years were analyzed. Most of the patients (56.7%) had adult-onset asthma [median age of onset was 32 (min-max= 10-62) years]. Overweight and obese patients were in the majority (31.8%, and 41.8%, respectively) and the median body mass index was 29 (min-max= 17.5-49.5). More than half of the patients (55.2%) had controlled asthma and the median Asthma Control Test score at the last visit was 23. Biologic therapies were applied to 73.1% (n= 147) of the patients [60.5% (n= 89) omalizumab, 39.5% (n= 58) mepolizumab]. Half of the group was allergic (49.3%) and three-quarters of them were eosinophilic (72.1%). Allergic patients had earlier asthma onset and had more controlled disease than nonallergic ones. Eosinophilic patients were younger and less obese than noneosinophilic patients. Obese and late-onset asthmatics had more uncontrolled disease than normal weight subjects and early onset patients. Conclusions: The high rate of disease control in the patients with severe asthma in the current study demonstrated the importance of targeted individualized therapy with accurate phenotyping in specialized asthma outpatient clinics.

[Biologics for the treatment of severe asthma: Current status report 2023]. / Agir astim tedavisinde biyolojikler: Güncel durum raporu 2023.

Severe asthma is associated with increased use of healthcare services, significant deterioration in the quality of life, and high disease and economic burden on patients and societies. Additional treatments are required for severe forms of asthma. Biological agents are recommended for the treatment of severe asthma. In this current status report, we aimed to evaluate the efficacy, effectiveness, and safety data of approved biologics; omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, in the treatment of severe asthma and appropriate patient profiles for these biologics. Pubmed and Cochrane databases based on randomized controlled trials, posthoc analyses, meta-analyses, and real-life studies examining the efficacy and effectiveness of biologics in severe asthma were searched, and the results of these studies on important asthma outcomes were reviewed. Existing studies have shown that all the approved biologic agents targeting cells, receptors, and mediators involved in type 2 inflammation in the bronchial wall in severe asthma significantly reduce asthma exacerbations, reduce the need for oral corticosteroids, and improve asthma control, quality of life, and pulmonary functions. Characterizing the asthma endotype and phenotype in patients with severe asthma and determining which treatment would be more appropriate for a particular patient is an essential step in personalized treatment.

Real-world patient-level cost-effectiveness analysis of omalizumab in patients with severe allergic asthma treated in four major medical centers in Turkey.

AIMS: To evaluate the cost-effectiveness of standard-of-care treatment (SoC) to SoC in combination with omalizumab (OML + Soc) in patients with severe asthma using real-world prospective clinical data from four major medical centers in Turkey. MATERIALS AND METHODS: Between February 2018 and November 2019, a total of 206 patients with severe asthma, including 126 of whom were in the OML + SoC group and 80 in the SoC group, were followed for 12 months to evaluate their asthma status and quality of life. Cost data for this patient-level economic evaluation were sourced from the MEDULA database of the hospitals and expressed in Turkish Lira (₺). Efficacy data were obtained by means of Turkish versions of the Asthma Control Test for asthma status, the 5-level EQ-5D-5L version (EQ-5D-5L), and the Asthma Quality of Life Scale for quality of life. A Markov model with 2-week cycles was specified, comparing costs and treatment effects of SoC vs. OML + SoC over a lifetime from the Turkish payer perspective. RESULTS: Per-patient costs were ₺23,607.08 in the SoC arm and ₺425,329.81 in the OML + Soc arm, for a difference of ₺401,722.74. Life years (LY) and quality-adjusted life years (QALY) were 13.60 and 10.08, respectively, in the SoC group; and 21.26 and 13.35, respectively, in the OML + SoC group, for differences of 7.66 LYs and 3.27 QALYs. This yielded an incremental cost-effectiveness ratio of an additional ₺52,427.04 to gain 1 LY and an incremental cost-utility ratio of an incremental ₺122,675.57 to gain 1 QALY; the latter being below the ₺156,948 willingness-to-pay threshold for Turkey referenced by WHO. One-way and multivariate sensitivity analyses confirmed the base-case results. CONCLUSION: Whereas most economic evaluations are based on aggregate data, this independent cost-effectiveness analysis using prospective real-world patient-level data suggests that omalizumab in combination with standard of care is cost-effective for severe asthma from the Turkish public payer perspective.

What is the context? Severe asthma, a subset of difficult-to-treat asthma, refers to asthma that cannot be controlled despite adherence to optimized maximal therapy and treatment of contributing factors, or asthma that worsens when high-dose therapy is reduced.Omalizumab is the first biologic therapy approved for the treatment of allergic asthma. Its main role is to prevent the release of various inflammation factors that cause severe asthma episodes.Cost-effectiveness analysis is an economic method of determining how much more a new and better treatment costs relative to the current treatment in terms of how many life years (LY) and how many quality-adjusted life years (QALY) are gained with the new treatment. Cost-effectiveness results tell us how much more money is needed over the cost of the current treatment to achieve one additional LY, regardless of the quality of life, or one additional LY with good quality of life.No cost-effectiveness data obtained from actual clinical patient data are available for Turkey. What is new? Our study found that the addition of omalizumab to the current standard of care for severe asthma increases costs but also increases life years and quality-adjusted life years. The additional cost was less than what the World Health Organization assumes is reasonable for Turkey.This study used actual clinical patient data and noted that asthma patients in the omalizumab group used fewer health services, had a better clinical course, had a better quality of life, and lived longer with their disease under control.What is the impact? In severe asthmatic patients, adding omalizumab to standard-of-care, while more costly, yields better outcomes and is therefore cost-effective.The cost-effectiveness estimates fall within the margins of being cost-responsible. The Turkish public payer should strongly consider making omalizumab available to all eligible patients. This will enable working-age patients to work, and contribute to their families, while also strengthening the Turkish economy.

Comparison of two diagnostic criteria in the diagnosis of anaphylaxis in a tertiary adult allergy clinic.

Background: Anaphylaxis is a very dynamic issue with its incidence and trigger profile changing over the years. We aimed to compile the characteristics of anaphylaxis cases diagnosed in our clinic prospectively and to make a comparison between diagnostic criteria proposed by National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) and World Allergy Organization (WAO). Method: Three-item diagnostic criteria recommended by NIAID/FAAN (2006) were used in the diagnosis of anaphylaxis. The clinical features of the cases, risk factors, etiologies, severity of anaphylaxis, and treatment approach were determined. The same patients were also classified by current WAO diagnostic criteria. Results: A total of 204 patients (158F/46 M, median age 45.3 years) were included. Drugs (65.2%), venom (9.8%) and food allergies (9.3%) were the top 3 etiologies. Among drug triggers, chemotherapeutics were the most common (17.7%), followed by antibiotics (15.3%) and non-steroidal anti-inflammatory drugs (14.2%). The patients were mostly diagnosed with the second criterion (84.8%), followed by the first criterion (11.8%) and the third criterion (3.4%) of the NIAID/FAAN criteria. In terms of WAO criteria, 82.8% of the patients were diagnosed with the first criterion, and 14.3% with the second criterion while 2.9% of the patients did not meet the WAO criteria. The severity of anaphylaxis was evaluated as grade-2, 3 and 4 in 30.9%, 64.2%, and 4.9% of the patients, respectively. Adrenaline was administered to 31.9% of the patients especially who had angioedema and bronchospasm (p = 0.04). Conclusion: Our data suggest that covering more details in patient's history may prevent possible underdiagnosis and WAO diagnostic criteria seem to be insufficient in some patients. We believe that our results will contribute to the literature on anaphylaxis and would be groundwork for future studies.

Field sting reactions in patients receiving Hymenoptera venom immunotherapy: real-life experience.

BACKGROUND: Hymenoptera stings can cause systemic allergic reactions (SARs) that are prevented by venom immunotherapy (VIT). Sting challenge tests or field stings are used to evaluate the outcome of VIT. OBJECTIVE: The aim of the study was to investigate the consequences of field stings in patients during or after completion of VIT, and to identify patients at higher risk. METHODS: Patients treated with VIT between 1995 and 2018 were retrospectively evaluated. Contacted patients were invited to the clinic and a questionnaire was conducted regarding the history of field stings. RESULTS: A total of 115 patients (F/M: 45/70, mean age: 38.5 ± 12 years) treated with VIT were included; 74/115 were contacted and asked about field stings after VIT cessation. A history of 73 field stings was reported in 38 patients, 25 of whom were treated with honeybee venom and 13 with common wasp venom. Eighteen of the reactions were SARs [8 with honeybees (1 grade-I, 6 grade-II, 1 grade-III) and 10 with common wasps (1 grade-I, 5 grade-II, 4 grade-III)]. There was no association between the severity of index reactions and field stings with either the honeybee or common wasp. The median duration of VIT was longer in patients showing no reaction than in patients with an SAR. Of the 7 patients on ACE inhibitors or beta-blockers, 1 asthmatic patient developed grade-II SAR due to field stings in the first year of VIT. CONCLUSIONS: This study confirms that VIT lasting at least 3 years is effective in preventing SARs after field stings.

Anaphylaxis is rare due to CoronaVac in a population of healthcare workers.

Background: CoronaVac, the first coronavirus disease 2019 vaccine administered in our country, was found safe in clinical trials. Objective: We aimed to reveal the rate and features of CoronaVac vaccine-associated allergic reactions among vaccinated healthcare workers (HCWs) in real-life. Methods: This study was planned as a questionnaire-based study. Participants who reported a postvaccination allergic reaction were interviewed on phone and their medical records were also checked for confirmation. Results: A total of 2,488 HCWs took part in the study and 4,054 postvaccination complete questionnaire-responses were obtained. Twenty-one HCWs (female: male, 17:4) with a mean age of 40.95 ± 10.09 stated that they had an allergic reaction after a total of 23 vaccine injections. Accordingly, the reaction rate was 0.56% among all vaccine doses. The most common reactions were systemic skin reactions (2.7%) consisting of generalized pruritus, diffuse pruritic erythema, urticaria, and maculopapular rash. That was followed by local injection site reaction (0.12%). Anaphylaxis was reported in 4 cases (0.09%) with a mean onset time of 12 ± 6 minutes. One of them had a history of anaphylaxis with 2 drugs, another had venom and food allergy. Three of the subjects had level 2 diagnostic certainty according to the Brighton Collaboration criteria and one had level 3. All anaphylaxis cases were discharged within 24 hours and none of them required intensive care. Conclusion: Our study demonstrated that allergic reactions to CoronaVac were rare and mostly mild. Although anaphylaxis was also rare, the importance of early intervention with close follow-up was once again emphasized.

Effectiveness of Low-Dose Mepolizumab in the Treatment of Eosinophilic Granulomatosis with Polyangiitis (EGPA): A Real-Life Experience.

INTRODUCTION: Data showing effectiveness of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA) are limited. METHODS: This is a single-center retrospective chart review of patients with EGPA treated with mepolizumab. Clinical, laboratory, functional parameters and asthma, rhinitis control, and quality of life scores (Asthma Control Test [ACT], Asthma Quality of Life Questionnaire [AQLQ], Rhinoconjunctivitis Quality of Life Questionnaire [RQLQ], and SinoNasal Outcome Test [SNOT]-22) were evaluated at the baseline, 6th month, and 12th month. Complete response was defined as the absence of asthma and/or ear, nasal symptoms and exacerbations with a prednisone of ≤7.5 mg/day, partial response if it was achieved with a prednisone of >7.5 mg/day. RESULTS: Overall, 25 patients (18 F/7 M) with a median age of 47 years (23-76) were enrolled. Mepolizumab 100 mg/month was administered (dose increased to 300 mg/month in 3 patients). Mepolizumab significantly decreased daily dose of oral corticosteroid (OCS) from 11.04 mg to 3.65 mg together with a significant improvement in ACT, AQLQ, RQLQ, and SNOT-22 scores and a significant reduction in asthma exacerbations and blood eosinophil count at the 6th and 12th month (all p values <0.05). The mean forced expiratory volume in 1 s increased (at baseline: 1.88 L to 2.46 L at the 12th month [p = 0.037]). Seventy-six percent of patients responded completely at the 6th month and 81.25% at the 12th month. The complete responders at the 6th and 12th month were older than partial responders and nonresponders (p = 0.030 and p = 0.057, respectively). Patients with complete response at the 6th month were on lower doses of OCS than partial responders and nonresponders (p = 0.029). CONCLUSIONS: Low-dose mepolizumab was effective in EGPA patients by improving sinonasal and asthma outcomes, while reducing the need for OCS.

Incidence and clinical course of COVID-19 in patients using omalizumab for chronic spontaneous urticaria and/or severe allergic asthma and using mepolizumab for severe eosinophilic asthma: A single center real life experience.

Introduction: To assess the incidence and course of COVID-19 in patients with severe asthma/chronic spontaneous urticaria using biological agents. Materials and Methods: A total of 202 patients (142 with asthma, and 60 with urticaria) were enrolled. The subjects were asked via face-to-face or telephone interview whether they had been diagnosed with COVID-19 and the course of the disease. Result: Study group consisted of 132 women, and 70 men (median age= 48 years). Median omalizumab dose was 300 mg/month in asthma (min-max= 150-1200 mg). The mepolizumab dose of two patients diagnosed with EGPA was 300 mg/month. Thirty one (15.3%) patients were diagnosed with COVID-19, 22 (71%) of whom were receiving omalizumab and nine (29%) were receiving mepolizumab. Asthma or chronic spontaneous urticaria diagnosis, age, sex, smoking, weight, comorbidities, atopy, and biological agent use were not statistically different between patients with or without COVID-19. Nine COVID-19 patients were hospitalized, and three of them required intensive care. Mepolizumab usage was higher in hospitalized patients (5, 55.6%), whereas omalizumab usage was higher in home-treated patients (18, 81%). The mean duration of biological use in home-treated patients was significantly higher than that of the hospitalized patients (35.64 months vs. 22.56 months, p= 0.024). Biological treatment was interrupted in 47 (23%) patients, selfinterruption due to the infection risk was the foremost reason (34%). Conclusions: The incidence of COVID-19 among patients with asthma and urticaria on mepolizumab and omalizumab was higher compared to studies from other countries. The disease course appeared mild in patients receiving long-term biological therapy.

Eosinophilic granulomatosis with polyangitis: A new target for biologicals.

Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) is a rare systemic necrotizing granulomatous vasculitis in the spectrum of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Nevertheless, EGPA has specific clinical, biological and histological properties different from other AAVs [microscopic polyangiitis (MPA) and granulomatous polyangiitis (GPA)]. Recently, thanks to the studies conducted to understand the pathophysiology of EGPA, unlike neutrophils in other AAVs, the main cells involved in EGPA have been observed to be eosinophils. The key role of eosinophils in EGPA and recent development of targeted agents to treat other eosinophil-related diseases have created new therapeutic opportunities for EGPA. Conventional treatment of EGPA relies mainly on agents that decrease inflammation. Cornerstone therapy is systemic glucocorticoids, used as monotherapy or in combination with immunosuppressive agents. However, new therapeutic approaches are needed especially for persistent asthma symptoms, refractory disease, relapses and problems associated with corticosteroid dependence. Recently, the first large-scale randomized controlled clinical trial on polyangiitis and eosinophilic granulomatosis has demonstrated the efficacy of eosinophil-targeted biotherapy anti-interleukin-5 (IL-5) mepolizumab, and is approved for the management of EGPA. This finding opens a new era for EGPA management. This review provides an overview of eosinophilic granulomatosis with polyangiitis in the light of new targeted biological therapies.

Allergen-specific immunotherapy practices and course of coronavirus disease 2019 (COVID-19) in patients during COVID-19.

BACKGROUND: Allergen-specific immunotherapy (AIT) is accepted as the only disease-modifying therapy for IgE-mediated allergic airway diseases and hymenoptera venom allergy. AIT requires repeated contact between patient and physician or nurse in the hospital. Because it is a long-term treatment, compliance is essential issue to obtain maximal efficacy. Coronavirus disease 2019 (COVID-19) pandemic reshaped doctor-patient interaction and pattern of hospital admissions. OBJECTIVE: We aimed to determine the possible changes in the administration of AIT and associated factors, in addition to the characteristics of patients diagnosed with COVID-19 infection. METHODS: Adult patients who underwent AIT for hymenoptera venom allergy, allergic rhinitis or allergic asthma between 11 March 2020 and 31 January 2021 were included in our retrospective study. Perennial and preseasonal AIT practices were evaluated. We identified patients with COVID-19 infection among the ones who received AIT. RESULTS: The mean age of 215 patients was 37.8±11.9 years and 52.1% of the patients were female. In our study, 35.4% of perennial AIT patients did not continue treatment after the COVID-19 pandemic, and the cause was patient-related in 66.7% of the cases. Compliance was 70.7% in patients receiving perennial AIT. The highest compliance rate for AIT was for venom allergy (86.5%). Thirty-four patients (15.8%) were diagnosed with COVID-19 infection. No mortality due to COVID-19 infection was observed in those who underwent AIT. CONCLUSION: COVID-19 pandemic has reduced compliance to AIT. Compliance was higher in venom immunotherapy than in aeroallergens. Severe COVID-19 infection and COVID-19 related death were not observed in patients receiving AIT.

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.

Rapid drug desensitization with platin-based chemotherapy: Analysis of risk factors for breakthrough reactions.

BACKGROUND: All platin-based chemotherapeutics can cause hypersensitivity reactions (HSRs). With rapid drug desensitization (RDD), few patients experience breakthrough reactions (BTR) during desensitization. However, data about risk factors for BTRs during RDD in patients with HSRs to platins are limited. We first aimed to describe characteristics of our platin-reactive population and to validate the Brigham and Women's Hospital's (BWH's) RDD protocol in our population along with their outcomes with RDD. Our second aim was to identify the risk factors for BTRs. METHOD: This was a retrospective chart review (2013-2020) of patients with symptoms of immediate HSRs to platins. Initial HSRs were classified as grade 1, 2, or 3 based on their severity. Skin prick tests (SPT)/intradermal tests (IDT) were performed with implicated platins. A 12-step protocol was used during RDD. RESULTS: The study comprised 65 women and seven men (mean age 57.78 ± 8.73 years). Initial HSRs to carboplatin, cisplatin, and oxaliplatin occurred in 38, 13, and 21 patients, respectively. All patients reacted at the fifth (median) recurrent infusions (min:1, max:20). The median values for carboplatin, cisplatin, and oxaliplatin were 6 (1-20), 3 (1-15), and 3 (1-11), respectively. Most initial HSRs were grade 2 (n = 40, 55.6%) and 3 (n = 27, 37.5%); only 6.9% (n = 5) were grade 1. Patients with grade 1, 2, and 3 initial HSRs had positive platin skin test results at rates of 80%, 74%, and 88%, respectively.A total of 232 RDDs were performed in 72 patients and 98.7% of these desensitizations were completed. BTRs occurred in 56 (24.1%) (grade 1 n = 14, 25%; grade 2 n = 32, 57%; grade 3 n = 10, 18%) of these desensitizations. Breakthrough reactions were more severe in patients with positive SPTs or 1:100 or 1:10 dilutions of IDT (p = 0.014). BTR was not observed during RDD in any of the patients with positive 1:1 dilutions of IDT. Positivity on prick or 1:100 or 1:10 IDT increased the risk of BTR 5.058 times. There was no significant association between the risk of BTRs and age, drug cycle, sex, comorbidities, or atopy. CONCLUSION: In our experience, 98.7% of 232 RDDs to platins were completed successfully, showing that RDD was safe and effective. Drug skin test positivity is a potential marker for identifying high-risk patients who will have BTRs during RDDs to platins.

Hypersensitivity reactions to chemotherapy: an EAACI Position Paper.

Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section.

Hypersensitivity reactions to biologicals: An EAACI position paper.

Biologicals are crucial targeted therapeutic agents in oncological, immunological, and inflammatory diseases, and their use in clinical practice is broadening. In recent years, the spread of Personalized Precision Medicine has facilitated a proliferation of new treatment options, especially biologicals. Consequently, biologicals are now among the drugs that most frequently cause hypersensitivity reactions (HSRs). Patients can develop HSRs to these agents during the first-lifetime exposure or after repeated exposure, and these HSRs can be potentially life-threatening or limit therapeutic options. Despite the relatively high prevalence, the underlying mechanisms of these HSRs remain obscure, and the optimal management pathways are still a matter of discussion. In this Position Paper, the authors will provide evidence-based recommendations for diagnosing and managing HSRs to biologicals. Additionally, the document defines unmet needs as an opportunity to shape future research.