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The Korean Journal of Internal Medicine Feb 2022Drug desensitization is the temporary induction of tolerance to a sensitized drug by administering slow increments of the drug, starting from a very small amount to a... (Review)
Review
Drug desensitization is the temporary induction of tolerance to a sensitized drug by administering slow increments of the drug, starting from a very small amount to a full therapeutic dose. It can be used as a therapeutic strategy for patients with drug hypersensitivity when no comparable alternatives are available. Desensitization has been recommended for immunoglobulin E (IgE)-mediated immediate hypersensitivity; however, its indications have recently been expanded to include non-IgE-mediated, non-immunological, or delayed T cell-mediated reactions. Currently, the mechanism of desensitization is not fully understood. However, the attenuation of various intracellular signals in target cells is an area of active research, such as high-affinity IgE receptor (FcεRI) internalization, anti-drug IgG4 blocking antibody, altered signaling pathways in mast cells and basophils, and reduced Ca2+ influx. Agents commonly requiring desensitization include antineoplastic agents, antibiotics, antituberculous agents, and aspirin/nonsteroidal antiinflammatory drugs. Various desensitization protocols (rapid or slow, multi-bag or one-bag, with different target doses) have been proposed for each drug. An appropriate protocol should be selected with the appropriate concentration, dosage, dosing interval, and route of administration. In addition, the protocol should be adjusted with consideration of the severity of the initial reaction, the characteristics of the drug itself, as well as the frequency, pattern, and degree of breakthrough reactions.
Topics: Antineoplastic Agents; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Immunoglobulin E; Mast Cells
PubMed: 35123386
DOI: 10.3904/kjim.2021.438 -
JAMA Network Open May 2024β-lactam (BL) allergies are the most common drug allergy worldwide, but most are reported in error. BL allergies are also well-established risk factors for adverse drug...
IMPORTANCE
β-lactam (BL) allergies are the most common drug allergy worldwide, but most are reported in error. BL allergies are also well-established risk factors for adverse drug events and antibiotic-resistant infections during inpatient health care encounters, but the understanding of the long-term outcomes of patients with BL allergies remains limited.
OBJECTIVE
To evaluate the long-term clinical outcomes of patients with BL allergies.
DESIGN, SETTING, AND PARTICIPANTS
This longitudinal retrospective cohort study was conducted at a single regional health care system in western Pennsylvania. Electronic health records were analyzed for patients who had an index encounter with a diagnosis of sepsis, pneumonia, or urinary tract infection between 2007 and 2008. Patients were followed-up until death or the end of 2018. Data analysis was performed from January 2022 to January 2024.
EXPOSURE
The presence of any BL class antibiotic in the allergy section of a patient's electronic health record, evaluated at the earliest occurring observed health care encounter.
MAIN OUTCOMES AND MEASURES
The primary outcome was all-cause mortality, derived from the Social Security Death Index. Secondary outcomes were defined using laboratory and microbiology results and included infection with methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, or vancomycin-resistant Enterococcus (VRE) and severity and occurrence of acute kidney injury (AKI). Generalized estimating equations with a patient-level panel variable and time exposure offset were used to evaluate the odds of occurrence of each outcome between allergy groups.
RESULTS
A total of 20 092 patients (mean [SD] age, 62.9 [19.7] years; 12 231 female [60.9%]), of whom 4211 (21.0%) had BL documented allergy and 15 881 (79.0%) did not, met the inclusion criteria. A total of 3513 patients (17.5%) were Black, 15 358 (76.4%) were White, and 1221 (6.0%) were another race. Using generalized estimating equations, documented BL allergies were not significantly associated with the odds of mortality (odds ratio [OR], 1.02; 95% CI, 0.96-1.09). BL allergies were associated with increased odds of MRSA infection (OR, 1.44; 95% CI, 1.36-1.53), VRE infection (OR, 1.18; 95% CI, 1.05-1.32), and the pooled rate of the 3 evaluated antibiotic-resistant infections (OR, 1.33; 95% CI, 1.30-1.36) but were not associated with C difficile infection (OR, 1.04; 95% CI, 0.94-1.16), stage 2 and 3 AKI (OR, 1.02; 95% CI, 0.96-1.10), or stage 3 AKI (OR, 1.06; 95% CI, 0.98-1.14).
CONCLUSIONS AND RELEVANCE
Documented BL allergies were not associated with the long-term odds of mortality but were associated with antibiotic-resistant infections. Health systems should emphasize accurate allergy documentation and reduce unnecessary BL avoidance.
Topics: Humans; Drug Hypersensitivity; Female; Male; beta-Lactams; Retrospective Studies; Middle Aged; Aged; Anti-Bacterial Agents; Longitudinal Studies; Pennsylvania; Adult; Urinary Tract Infections; Risk Factors; Electronic Health Records
PubMed: 38758551
DOI: 10.1001/jamanetworkopen.2024.12313 -
Acta Bio-medica : Atenei Parmensis Sep 2020Drug hypersensitivity reactions (DHRs) are adverse reactions to a drug. In children, most common drugs inducing such reactions include beta-lactams (BLs) and...
Drug hypersensitivity reactions (DHRs) are adverse reactions to a drug. In children, most common drugs inducing such reactions include beta-lactams (BLs) and non-steroidal anti-inflammatory drugs (NSAIDs). The aim of the present work was to provide current knowledge on the management of DHRs in the pediatric population, focusing on BLs and NSAIDs hypersensitivity. The clinical feature of DHRs include immediate and non-immediate (delayed and accelerated) reactions, that may be severe or non-severe. A systematic approach to the patient based on the reported clinical history is essential to organize a safe and adapted allergy work-up. Skin tests are the first step to assess a possible DHRs, especially in immediate reactions to BLs. Drugs concentrations for these tests are standardized and validated. The drug provocation test remains the gold standard to reach a firm diagnosis. In selected cases, a therapeutic desensitization protocol may be proposed in children with a confirmed diagnosis of drug hypersensitivity. Clinicians should be aware of the diagnostic and therapeutic options, to provide the best management in children having experienced a history of DHR.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Child; Drug Hypersensitivity; Humans; Skin Tests; beta-Lactams
PubMed: 33004778
DOI: 10.23750/abm.v91i11-S.10312 -
Ugeskrift For Laeger Jul 2020Up to 10% of hospitalised patients are registered as penicillin allergic. However, 80-90% will tolerate penicillin after evaluation. New Danish guidelines suggest... (Review)
Review
Up to 10% of hospitalised patients are registered as penicillin allergic. However, 80-90% will tolerate penicillin after evaluation. New Danish guidelines suggest criteria for evaluation of patients based on risk stratification according to the severity of the index reaction. The allergy label can be removed immediately, if allergy can be ruled out using the criteria presented in this review, but all other patients should be referred for evaluation in a specialist allergy department. Specific IgE measurement should only be done in adult patients with an immediate reaction (onset less-than 2 h after intake of a tablet) or urticaria.
Topics: Adult; Anti-Bacterial Agents; Drug Hypersensitivity; Humans; Penicillins
PubMed: 32734861
DOI: No ID Found -
Allergy Feb 2022Drug hypersensitivity reactions (DHR) are heterogeneous and unusual immune reactions with rather unique clinical presentations. Accumulating evidence indicates that... (Review)
Review
Drug hypersensitivity reactions (DHR) are heterogeneous and unusual immune reactions with rather unique clinical presentations. Accumulating evidence indicates that certain non-covalent drug-protein interactions are able to elicit exclusively effector functions of antibody reactions or complete T-cell reactions which contribute substantially to DHR. Here, we discuss three key interactions; (a) mimicry: whereby soluble, non-covalent drug-protein complexes ("fake antigens") mimic covalent drug-protein adducts; (b) increased antibody affinity: for example, in quinine-type immune thrombocytopenia where the drug gets trapped between antibody and membrane-bound glycoprotein; and (c) p-i-stimulation: where naïve and memory T cells are activated by direct binding of drugs to the human leukocyte antigen and/or T-cell receptors. This transient drug-immune receptor interaction initiates a polyclonal T-cell response with mild-to-severe DHR symptoms. Notable complications arising from p-i DHR can include viral reactivations, autoimmunity, and multiple drug hypersensitivity. In conclusion, DHR is characterized by abnormal immune stimulation driven by non-covalent drug-protein interactions. This contrasts DHR from "normal" immunity, which relies on antigen-formation by covalent hapten-protein adducts and predominantly results in asymptomatic immunity.
Topics: Drug Hypersensitivity; HLA Antigens; Haptens; Humans; Receptors, Antigen, T-Cell; Receptors, Immunologic
PubMed: 34037262
DOI: 10.1111/all.14962 -
Annals of Allergy, Asthma & Immunology... Jun 2021To review type 1 hypersensitivity reactions and anaphylaxis to checkpoint inhibitor-monoclonal antibodies and its management with drug desensitization. (Review)
Review
OBJECTIVE
To review type 1 hypersensitivity reactions and anaphylaxis to checkpoint inhibitor-monoclonal antibodies and its management with drug desensitization.
DATA SOURCES
English-language literature on MEDLINE regarding hypersensitivity, anaphylaxis, and checkpoint inhibitor-monoclonal antibodies.
STUDY SELECTIONS
References were selected based on relevance, novelty, robustness, and applicability.
RESULTS
There are well-known tissue toxicities associated to checkpoint inhibitors, but hypersensitivity reactions and anaphylaxis have been underreported. The presentation of these reactions is based on clinical phenotypes with underlying endotypes identified by specific biomarkers. Drug desensitizations have been successfully applied to checkpoint inhibitor drugs to allow patients with cancer to receive first-line therapies. This review provides current best practices for the recognition and diagnosis of hypersensitivity reactions and anaphylaxis to checkpoint inhibitors and their management using drug desensitization.
CONCLUSION
Hypersensitivity reactions and anaphylaxis have been identified as potential adverse effects induced by checkpoint inhibitor-monoclonal antibodies. Drug desensitization is a safe and effective treatment option for patients who experience hypersensitivity reactions in need of these monoclonal antibodies to improve cancer outcomes.
Topics: Anaphylaxis; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Autoimmune Diseases; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Immune Checkpoint Inhibitors
PubMed: 33781937
DOI: 10.1016/j.anai.2021.03.008 -
Infectious Diseases in Obstetrics and... 2022To examine the relationship between documented -lactam allergy and cesarean delivery (CD) surgical site infection (SSI). . We conducted a retrospective cohort analysis...
OBJECTIVE
To examine the relationship between documented -lactam allergy and cesarean delivery (CD) surgical site infection (SSI). . We conducted a retrospective cohort analysis of women who underwent CD at Ben Taub Hospital and Texas Children's Pavilion for Women (Houston, TX) from August 1, 2011, to December 31, 2019. The primary exposure was a documented -lactam allergy, and the second exposure of interest was the type of perioperative antibiotic received. The primary outcome was the prevalence of SSI. Maternal characteristics were stratified by the presence or absence of a documented -lactam allergy, and significance was evaluated using Pearson's chi-squared test for categorical variables and -test for continuous variables. A logistic regression model estimated odds of SSI after adjusting for possible confounders.
RESULTS
Of the 12,954 women included, 929 (7.2%) had a documented -lactam allergy while 12,025 (92.8%) did not. Among the 929 women with a -lactam allergy, 495 (53.3%) received non--lactam perioperative prophylaxis. SSI occurred in 38 (4.1%) of women who had a -lactam allergy versus 238 (2.0%) who did not ( ≤ 0.001). -Lactam allergy was associated with higher odds of SSI compared to no allergy (adjusted odds ratio (aOR) = 1.97; 95%confidence interval (CI) = 1.24-3.14; = 0.004) after controlling for age, race, ethnicity, insurance status, delivery body mass index (BMI), tobacco use, intra-amniotic infection in labor, duration of membrane rupture, preterm delivery, delivery indication, diabetes, hypertension, group B Streptococcus colonization, and type of perioperative antibiotic received.
CONCLUSION
The presence of a -lactam allergy is associated with increased odds of developing a CD SSI after controlling for possible confounders, including the type of perioperative antibiotic received.
Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Child; Drug Hypersensitivity; Female; Humans; Infant, Newborn; Pregnancy; Retrospective Studies; Surgical Wound Infection; beta-Lactams
PubMed: 35281850
DOI: 10.1155/2022/5313948 -
Hospital Pediatrics Apr 2023Penicillin (PCN) allergy labels are widely recognized to be highly inaccurate. Little is known about parental perceptions of the PCN allergy evaluation and removal...
BACKGROUND
Penicillin (PCN) allergy labels are widely recognized to be highly inaccurate. Little is known about parental perceptions of the PCN allergy evaluation and removal process, especially in the hospital setting.
METHODS
Focus groups were held with parents of children and adolescents with a PCN allergy label discharged from a large academic children's hospital between January 1, 2019, and April 15, 2020. The open-ended, semistructured moderator guide included questions about PCN allergy testing and evaluation, accuracy of the PCN allergy diagnosis, amoxicillin oral challenges, delabeling process, and preferred setting for PCN allergy delabeling evaluation (outpatient clinic, hospital, etc). Study investigators coded the transcripts and identified underlying themes using inductive and deductive thematic analysis.
RESULTS
A total of 21 parents and 2 adolescents participated across 4 focus groups. We developed a theoretical framework depicting key elements of parents' and adolescents' experiences with PCN allergies, consisting of 4 major interconnected themes: (1) family context; (2) the invitation to delabel; (3) decision context; and (4) the PCN delabeling outcome. PCN allergies remained a concern for families even if their children passed an oral challenge. Some parents preferred testing to be performed in the hospital and felt this was a safer location for the procedure.
CONCLUSIONS
Parents are amenable to hospital based PCN allergy evaluation and delabeling. Further studies should incorporate parental and patient preferences to implement safe and effective PCN allergy delabeling processes in the hospital setting.
Topics: Child; Adolescent; Humans; Penicillins; Drug Hypersensitivity; Amoxicillin; Risk Assessment; Hypersensitivity; Anti-Bacterial Agents
PubMed: 36919441
DOI: 10.1542/hpeds.2022-006737 -
Hong Kong Medical Journal = Xianggang... Jun 2021Adverse drug reactions are more common in geriatric patients than in younger patients, but there have been insufficient studies concerning the epidemiology or burden of...
INTRODUCTION
Adverse drug reactions are more common in geriatric patients than in younger patients, but there have been insufficient studies concerning the epidemiology or burden of drug allergy labels in geriatric patients. We prospectively investigated the prevalence and outcomes of geriatric patients with drug allergy labels in a cohort of hospitalised patients.
METHODS
Patients admitted to a regional hospital over a 6-month period were recruited for this study. All patients with drug allergy labels were prospectively followed until discharge; clinical data were anonymously extracted for analyses. Patients were categorised into either geriatric (aged ≥65 years) or non-geriatric (aged <65 years) groups. Demographic characteristics, clinical outcomes, and prevalences of drug allergy labels were compared between groups.
RESULTS
There were 4361 admissions involving 3641 patients during the 6-month study period. Overall, 492 patients (13.5%) had drug allergy labels, consisting of 151 non-geriatric patients (30.7%) and 341 geriatric patients (69.3%). The prevalence of drug allergy labels did not significantly differ between geriatric and non-geriatric patients (13.5% vs 13.5%, P=0.976). Significantly more patients in the geriatric group had drug allergy labels to cardiovascular system drugs (15.5% vs 4.6%, P=0.001). Geriatric patients had a significantly lower rate of direct discharge from the hospital (73.0% vs 88.1%, P<0.001) and required transfers to convalescent or rehabilitation care for further management.
CONCLUSIONS
More than 13% of hospitalised geriatric patients had drug allergy labels. The leading causes of drug allergy labels were similar between geriatric and non-geriatric patients. Geriatric patients with drug allergy labels had significantly more labelled allergies to cardiovascular system drugs and adverse clinical outcomes.
Topics: Aged; Delivery of Health Care; Drug Hypersensitivity; Hong Kong; Hospitalization; Humans; Prevalence
PubMed: 34168086
DOI: 10.12809/hkmj208716 -
International Journal of Molecular... Aug 2023Drug hypersensitivity reactions are a serious concern in clinical practice because they can be severe and result in lifelong sequelae. An accurate diagnosis and... (Review)
Review
Drug hypersensitivity reactions are a serious concern in clinical practice because they can be severe and result in lifelong sequelae. An accurate diagnosis and identification of the culprit drug is essential to prevent future reactions as well as for the identification of safe treatment alternatives. Nonetheless, the diagnosis can be challenging. In vivo and in vitro tests can be helpful, although none are conclusive; therefore, the tests are not usually performed in isolation but as part of a diagnostic algorithm. In addition, some in vitro tests are only available in research laboratories, and standardization has not been fully accomplished. Collaborating research is needed to improve drug hypersensitivity reaction diagnosis. In this review, we update the current available in vivo and in vitro tools with their pros and cons and propose an algorithm to integrate them into clinical practice.
Topics: Humans; Algorithms; Causality; Disease Progression; Drug Hypersensitivity; Hypersensitivity
PubMed: 37628756
DOI: 10.3390/ijms241612577