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Allergy Feb 2022Chemotherapeutic 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...
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.
Topics: Anaphylaxis; Antineoplastic Agents; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Neoplasms; Skin Tests
PubMed: 34587281
DOI: 10.1111/all.15113 -
The Journal of Allergy and Clinical... Oct 2020The penicillin allergy label has been consistently linked with deleterious effects that span the health care spectrum, including suboptimal clinical outcomes, the... (Review)
Review
The penicillin allergy label has been consistently linked with deleterious effects that span the health care spectrum, including suboptimal clinical outcomes, the emergence of bacterial resistance, and increased health care expenditures. These risks have recently motivated professional organizations and public health institutes to advocate for the implementation of penicillin allergy delabeling initiatives; however, the burden of delabeling millions of patients is too expansive for any one discipline to bear alone. This review presents the unique perspectives and roles of various stakeholder groups involved in penicillin allergy diagnosis, assessment, and delabeling; we emphasize opportunities, barriers, and promising areas of innovation. We summarize penicillin allergy methods and tools that have proven successful in delabeling efforts. A multidisciplinary approach to delabeling patients with reported penicillin allergy, bolstered by evidence-based clinical practices, is recommended to reduce the risks that associate with the penicillin allergy label.
Topics: Anti-Bacterial Agents; Delivery of Health Care; Drug Hypersensitivity; Humans; Penicillins
PubMed: 33039010
DOI: 10.1016/j.jaip.2020.04.059 -
Clinical Reviews in Allergy & Immunology Jun 2022Hypersensitivity reactions including IgE-mediated and delayed cell-mediated reactions to aminoglycosides, clindamycin, linezolid, and metronidazole are rare. For... (Review)
Review
Hypersensitivity reactions including IgE-mediated and delayed cell-mediated reactions to aminoglycosides, clindamycin, linezolid, and metronidazole are rare. For aminoglycosides, allergic contact dermatitis is the most frequent reaction for which patch testing can be a useful step in evaluation. For clindamycin, delayed maculopapular exanthems are the most common reactions. There are case reports of clindamycin associated with drug rash with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), acute febrile neutrophilic dermatosis, and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). For linezolid, cases of hypersensitivity were exceedingly rare and included urticaria, angioedema, anaphylaxis, delayed rashes, and DRESS. For metronidazole, only rare cases were found across a broad spectrum of reactions including allergic contact dermatitis, fixed drug eruption, angioedema, anaphylaxis, serum sickness-like reaction, SJS/TEN, AGEP, SDRIFE, and a possible case of DRESS. IgE-mediated reactions and anaphylaxis to these types of antibiotics are uncommon, and reports of skin testing concentrations and desensitization protocols are largely limited to case reports and series. Non-irritating skin testing concentrations have been reported for gentamycin, tobramycin, and clindamycin. Published desensitization protocols for intravenous and inhaled tobramycin, oral clindamycin, intravenous linezolid, and oral and intravenous metronidazole have also been reported and are reviewed.
Topics: Aminoglycosides; Anaphylaxis; Angioedema; Anti-Bacterial Agents; Clindamycin; Dermatitis, Allergic Contact; Drug Eruptions; Drug Hypersensitivity; Eosinophilia; Humans; Hypersensitivity, Delayed; Immunoglobulin E; Linezolid; Metronidazole; Tobramycin
PubMed: 34910281
DOI: 10.1007/s12016-021-08878-x -
Clinical Reviews in Allergy & Immunology Jun 2022Hypersensitivity reactions (HSRs) to chemotherapy agents can present a serious challenge to treating patients with preferred or first-line therapies. Allergic reactions... (Review)
Review
Hypersensitivity reactions (HSRs) to chemotherapy agents can present a serious challenge to treating patients with preferred or first-line therapies. Allergic reactions through an immunologic mechanism have been established for platinum and taxane agents, which are used to treat a wide variety of cancers including gynecologic cancers. Platin HSRs typically occur after multiple cycles of chemotherapy, reflecting the development of drug IgE sensitization, while taxane HSRs often occur on first or second exposure. Despite observed differences between platin and taxane HSRs, drug desensitization has been an effective method to reintroduce both chemotherapeutic agents safely. Skin testing is the primary diagnostic tool used to risk-stratify patients after initial HSRs, with more widespread use for platinum agents than taxanes. Different practices exist around the use of skin testing, drug challenge, and choice of desensitization protocol. Here, we review the epidemiology, mechanism, and clinical presentation of HSRs to platinum and taxane agents, as well as key controversies in their evaluation and management.
Topics: Antineoplastic Agents; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Neoplasms; Platinum; Skin Tests; Taxoids
PubMed: 34338975
DOI: 10.1007/s12016-021-08877-y -
The Journal of Allergy and Clinical... 2019Cephalosporins are commonly used antibiotics both in hospitalized patients and in outpatients. Hypersensitivity reactions to cephalosporins are becoming increasingly... (Review)
Review
Cephalosporins are commonly used antibiotics both in hospitalized patients and in outpatients. Hypersensitivity reactions to cephalosporins are becoming increasingly common with a wide range of immunopathologic mechanisms. Cephalosporins are one of the leading causes for perioperative anaphylaxis and severe cutaneous adverse reactions. Patients allergic to cephalosporins tend to tolerate cephalosporins with disparate R1 side chains but may react to other beta-lactams with common R1 side chains. Skin testing for cephalosporins has not been well validated but appears to have a good negative predictive value for cephalosporins with disparate R1 side chains. In vitro tests including basophil activation tests have lower sensitivity when compared with skin testing. Rapid drug desensitization procedures are safe and effective and have been used successfully for immediate and some nonimmediate cephalosporin reactions. Many gaps in knowledge still exist regarding cephalosporin hypersensitivity.
Topics: Anaphylaxis; Basophil Degranulation Test; Cephalosporins; Cross Reactions; Desensitization, Immunologic; Drug Eruptions; Drug Hypersensitivity; Humans; Perioperative Period; Pharmacogenomic Variants; Serum Sickness; Skin Tests; beta-Lactams
PubMed: 31495420
DOI: 10.1016/j.jaip.2019.06.001 -
The New England Journal of Medicine Dec 2019
Review
Topics: Adult; Anaphylaxis; Anti-Bacterial Agents; Child; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Immunologic Tests; Penicillins; Skin Tests
PubMed: 31826341
DOI: 10.1056/NEJMra1807761 -
Allergy Mar 2020Nonsteroidal anti-inflammatory drugs (NSAIDs), the medications most commonly used for treating pain and inflammation, are the main triggers of drug hypersensitivity... (Review)
Review
Nonsteroidal anti-inflammatory drugs (NSAIDs), the medications most commonly used for treating pain and inflammation, are the main triggers of drug hypersensitivity reactions. The latest classification of NSAIDs hypersensitivity by the European Academy of Allergy and Clinical Immunology (EAACI) differentiates between cross-hypersensitivity reactions (CRs), associated with COX-1 inhibition, and selective reactions, associated with immunological mechanisms. Three phenotypes fill into the first group: NSAIDs-exacerbated respiratory disease, NSAIDs-exacerbated cutaneous disease and NSAIDs-induced urticaria/angioedema. Two phenotypes fill into the second one: single-NSAID-induced urticaria/angioedema/anaphylaxis and single-NSAID-induced delayed reactions. Diagnosis of NSAIDs hypersensitivity is hampered by different factors, including the lack of validated in vitro biomarkers and the uselessness of skin tests. The advances achieved over recent years recommend a re-evaluation of the EAACI classification, as it does not consider other phenotypes such as blended reactions (coexistence of cutaneous and respiratory symptoms) or food-dependent NSAID-induced anaphylaxis. In addition, it does not regard the natural evolution of phenotypes and their potential interconversion, the development of tolerance over time or the role of atopy. Here, we address these topics. A state of the art on the underlying mechanisms and on the approaches for biomarkers discovery is also provided, including genetic studies and available information on transcriptomics and metabolomics.
Topics: Angioedema; Anti-Inflammatory Agents, Non-Steroidal; Drug Hypersensitivity; Humans; Pharmaceutical Preparations; Skin Tests; Urticaria
PubMed: 31469167
DOI: 10.1111/all.14032 -
Current Opinion in Allergy and Clinical... Aug 2022
Topics: Drug Hypersensitivity; Humans
PubMed: 35852894
DOI: 10.1097/ACI.0000000000000832 -
The Journal of Allergy and Clinical... Aug 2021Drug hypersensitivity reactions (DHR) are heterogeneous in their pathomechanisms, clinical presentation, severity, and outcomes. Novel DHR mechanisms, phenotypes, and... (Review)
Review
Drug hypersensitivity reactions (DHR) are heterogeneous in their pathomechanisms, clinical presentation, severity, and outcomes. Novel DHR mechanisms, phenotypes, and endotypes have been described. The key to prevention from further exposure to the culprit drugs involves correct identification of the putative drug through a combination of in vitro and/or in vivo tests, accurate drug allergy labeling and reporting, and electronic decision support systems within electronic medical records to prevent future accidental prescribing. Prescreening and premedication, the focus of this review, may be a useful adjunct to preventive measures in certain situations. After an index immediate drug hypersensitivity reaction, prescreening may be useful in perioperative anaphylaxis, and iodinated (ICM) and gadolinium-based contrast media (GCM) where the culprit and potential alternative agents are skin tested. In certain nonimmediate DHR, pharmacogenomic prescreening may be used before prescribing high-risk drugs (eg, carbamazepine and allopurinol) where specific human-leukocyte antigen genotypes are associated with severe cutaneous adverse reactions. Premedication with antihistamine and systemic corticosteroids is another therapeutic strategy to prevent infusion reactions for certain biologicals and chemotherapeutic agents, in cases of perioperative anaphylaxis, ICM and GCM DHR, and clonal mast cell disorders. Rapid drug desensitization may also be used to induce temporary tolerance in situations where there are limited alternative drugs.
Topics: Allopurinol; Contrast Media; Drug Hypersensitivity; Humans; Premedication; Skin Tests; Stevens-Johnson Syndrome
PubMed: 34366094
DOI: 10.1016/j.jaip.2021.04.006 -
The Journal of Allergy and Clinical... May 2021Piperacillin/tazobactam is a broad-spectrum penicillin. Hypersensitivity reactions are less commonly reported than with other penicillins except in patients with cystic...
BACKGROUND
Piperacillin/tazobactam is a broad-spectrum penicillin. Hypersensitivity reactions are less commonly reported than with other penicillins except in patients with cystic fibrosis.
OBJECTIVE
Detailed clinical characterization of a patient cohort referred with suspected piperacillin-tazobactam hypersensitivity.
METHODS
Retrospective analysis of the demographic characteristics, clinical presentation, investigation, and management of 87 patients presenting to 5 European allergy centers. Patients underwent skin prick and intradermal testing with piperacillin/tazobactam, major (penicilloyl-polylysine) and minor (sodium penilloate) determinants, amoxicillin, benzylpenicillin, flucloxacillin, co-amoxiclav, clavulanic acid, and meropenem with immediate and, where appropriate, delayed reading of tests. Skin test-negative patients underwent drug provocation to piperacillin/tazobactam and/or other penicillins. A multistep protocol was used, depending on risk assessment.
RESULTS
Forty-eight of 87 (55%) patients were diagnosed with hypersensitivity to piperacillin/tazobactam with either positive skin or drug provocation test results, of whom 10 (21%) had a diagnosis of cystic fibrosis. Twenty-six (54%) patients presented with immediate and 22 (45%) with nonimmediate hypersensitivity. Patients with cystic fibrosis predominantly presented with nonimmediate hypersensitivity (70%). Reactions were severe in 52% of immediate reactors (Brown's anaphylaxis grade 3) and moderately severe (systemic involvement) in 75% of nonimmediate reactors. The number of patients with negative skin test results tolerating reintroduction was comparable in immediate (80%) and nonimmediate (88%) hypersensitivity. One-third of patients were cross-sensitized to other penicillins. The cross-sensitization pattern raised the possibility of tazobactam allergy in 3 patients. In 21 patients selectively sensitized to piperacillin/tazobactam (12 immediate, 9 nonimmediate), tolerance to other beta-lactams was demonstrated by drug provocation testing.
CONCLUSIONS
Piperacillin-tazobactam caused immediate and nonimmediate hypersensitivity with similar frequency. Most patients were selectively sensitized and tolerated other penicillins. Some patients may be allergic to the beta-lactamase inhibitor only.
Topics: Amoxicillin; Anti-Bacterial Agents; Drug Hypersensitivity; Humans; Hypersensitivity, Immediate; Penicillins; Retrospective Studies; Skin Tests
PubMed: 33444815
DOI: 10.1016/j.jaip.2020.12.051