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      Use of Skin Testing Screening and Desensitization Before the First Exposure of Rituximab

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          Abstract

          Objective

          This study aimed to evaluate the incidence and severity of immediate hypersensitivity reactions (HSRs) in the first exposure to rituximab with the adoption of skin testing screening and desensitization and investigate the value of skin testing as a predictive tool for immediate HSR to rituximab.

          Methods

          This was a prospective intervention study. Patients with hematological malignancies who required rituximab were recruited. Skin testing screening with rituximab was conducted before the first infusion. Patients with positive skin testing results underwent desensitization, while those with negative results received rituximab at a standard infusion rate. All immediate HSRs were recorded, and the predictive value of positive skin testing results for immediate HSRs to rituximab was analyzed.

          Results

          In the 19 patients who adopted the novel protocol, six patients (31.6%) had immediate HSRs during the first infusion, with three mild reactions (15.8%), two moderate reactions (10.5%), and only one severe reaction (5.3%). The positive predictive value of intradermal test (IDT) with 1 mg/mL rituximab solution for immediate HSR was 100%, and the negative predictive value was 84.6%.

          Conclusion

          The protocol of skin testing screening and desensitization might have some potential to control the incidence and severity of immediate HSRs to rituximab during the first exposure. IDT result before the first infusion could become a useful predictor for immediate HSR to rituximab.

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          Most cited references17

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          Clinical features and severity grading of anaphylaxis.

          Existing grading systems for acute systemic hypersensitivity reactions vary considerably, have a number of deficiencies, and lack a consistent definition of anaphylaxis. The aims of this study were to develop a simple grading system and definition of anaphylaxis and to identify predictors of reaction severity. Case records from 1149 systemic hypersensitivity reactions presenting to an emergency department were analyzed retrospectively. Logistic regression analyses of the associations between individual reaction features and hypotension and hypoxia were used to construct a grading system. Epinephrine use, etiology, age, sex, comorbidities, and concurrent medications were then assessed for their association with reaction grade. Confusion, collapse, unconsciousness, and incontinence were strongly associated with hypotension and hypoxia and were used to define severe reactions. Diaphoresis, vomiting, presyncope, dyspnea, stridor, wheeze, chest/throat tightness, nausea, vomiting, and abdominal pain had weaker, albeit significant, associations and were used to define moderate reactions. Reactions limited to the skin (urticaria, erythema, and angioedema) were defined as mild. These grades correlated well with epinephrine usage. Older age, insect venom, and iatrogenic causes were independent predictors of severity. Preexisting lung disease was associated with an increased risk of hypoxia. This simple grading system has potential value for defining reaction severity in clinical practice and research settings. The moderate and severe grades provide a workable definition of anaphylaxis. Age, reaction precipitant, and preexisting lung disease appear to be the major determinants of reaction severity.
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            Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose.

            Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, is approved for use in colorectal cancer and squamous-cell carcinoma of the head and neck. A high prevalence of hypersensitivity reactions to cetuximab has been reported in some areas of the United States. We analyzed serum samples from four groups of subjects for IgE antibodies against cetuximab: pretreatment samples from 76 case subjects who had been treated with cetuximab at multiple centers, predominantly in Tennessee, Arkansas, and North Carolina; samples from 72 control subjects in Tennessee; samples from 49 control subjects with cancer in northern California; and samples from 341 female control subjects in Boston. Among 76 cetuximab-treated subjects, 25 had a hypersensitivity reaction to the drug. IgE antibodies against cetuximab were found in pretreatment samples from 17 of these subjects; only 1 of 51 subjects who did not have a hypersensitivity reaction had such antibodies (P<0.001). IgE antibodies against cetuximab were found in 15 of 72 samples (20.8%) from control subjects in Tennessee, in 3 of 49 samples (6.1%) from northern California, and in 2 of 341 samples (0.6%) from Boston. The IgE antibodies were shown to be specific for an oligosaccharide, galactose-alpha-1,3-galactose, which is present on the Fab portion of the cetuximab heavy chain. In most subjects who had a hypersensitivity reaction to cetuximab, IgE antibodies against cetuximab were present in serum before therapy. The antibodies were specific for galactose-alpha-1,3-galactose. Copyright 2008 Massachusetts Medical Society.
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              International Consensus on drug allergy.

              When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term ‘allergy’) are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.
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                Author and article information

                Journal
                Cancer Manag Res
                Cancer Manag Res
                cmar
                Cancer Management and Research
                Dove
                1179-1322
                22 December 2021
                2021
                : 13
                : 9319-9328
                Affiliations
                [1 ]Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment of Allergic Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases , Beijing, 100730, People’s Republic of China
                [2 ]Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing, 100730, People’s Republic of China
                Author notes
                Correspondence: Yan Zhang Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing, 100730, People’s Republic of China Tel +86-10-69151605 Email zhangyan10659@pumch.cn
                Author information
                http://orcid.org/0000-0002-1171-1858
                http://orcid.org/0000-0003-0244-218X
                Article
                339282
                10.2147/CMAR.S339282
                8710525
                1c1b3e0b-9b36-4ba4-bd9f-019c342e5f18
                © 2021 Li et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 14 September 2021
                : 07 December 2021
                Page count
                Figures: 2, Tables: 6, References: 17, Pages: 10
                Funding
                Funded by: the second Roche Oncology Research Fund of Chinese Society of Clinical Oncology;
                This work was supported by the second Roche Oncology Research Fund of Chinese Society of Clinical Oncology in 2019 [grant number Y-Roche2019/2-0066].
                Categories
                Original Research

                Oncology & Radiotherapy
                rituximab,hypersensitivity,skin testing,predictive value of tests,desensitization,lymphoma

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