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International Journal of Molecular... Jun 2017Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic... (Review)
Review
Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS). DS induces a temporary hyporesponsive state by incremental escalation of sub-optimal doses of the offending drug. In vitro models have shown evidence that IgE desensitization is an antigen-specific process which blocks calcium flux, impacts antigen/IgE/FcεRI complex internalization and prevents the acute and late phase reactions as well as mast cell mediator release. Through a "bench to bedside" approach, in vitro desensitization models help elucidate the molecular pathways involved in DS, providing new insights to improved desensitization protocols for all patients. The aim of this review is to summarize up to date information on the drug HSRs, the IgE mediated mechanisms of desensitization, and their clinical applications.
Topics: Actins; Antigens; Biomarkers; Cytokines; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Immunoglobulin E; Mast Cells; Phenotype; Precision Medicine; Receptors, IgE
PubMed: 28632196
DOI: 10.3390/ijms18061316 -
PloS One 2014Previous epidemiologic studies have reported that a history of allergy is associated with reduced risk of colorectal cancer and other malignancies. However, no...
BACKGROUND
Previous epidemiologic studies have reported that a history of allergy is associated with reduced risk of colorectal cancer and other malignancies. However, no information is available for the association between allergy and the risk of lymph node metastasis. Our study was designed to determine this association in rectal cancer.
METHODS
Patients who were treated at our hospital in the period from January 2003 to June 2011, and with a pathologically hospital discharge diagnosis of rectal adencarcinoma, were included. The clinical, laboratory, and pathologic parameters were analyzed. A multivariate logistic regression model was used to determine the association. Moreover, for type of allergic drug, sub-group analysis was performed.
RESULTS
469 patients were included, including 231 with pathological lymph node metastasis (pLNM) (49.3%) and 238 without pLNM. Univariate analysis showed, compared with patients without pLNM, patients with pLNM had a younger age (60.6 ± 12.8 yr vs. 63.6 ± 12.2 yr, P = 0.012), a lower percentage of drug allergy (8.7% vs. 16.0%, P = 0.016), an increased CEA (median/interquartile-range 5.40/2.40-13.95 vs. 3.50/2.08-8.67, P = 0.009), and a lower serum sodium (141 ± 3.1 mmol/L vs. 142 ± 2.9 mmol/L, P = 0.028). Multivariate analysis showed that drug allergy was associated with a reduced risk of pLNM (OR = 0.553; 95% CI, 0.308-0.994; P = 0.048). In addition, our results showed that: (1) for tumor classification, patients with drug allergy had a higher percentage of group patients with pT1/pT2; and (2) for type of allergic drug, this inverse association was found for penicillins, not for other allergic drugs.
CONCLUSION
Drug allergy is associated with a reduced risk of pLNM in rectal cancer.
Topics: Adenocarcinoma; Age Factors; Aged; Biomarkers; Carcinoembryonic Antigen; Drug Hypersensitivity; Female; Follow-Up Studies; Humans; Logistic Models; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Penicillins; Prescription Drugs; Rectal Neoplasms; Sodium; Survival Analysis
PubMed: 25162236
DOI: 10.1371/journal.pone.0106123 -
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 Medical... Mar 2022Drug allergy alert systems (DAAS), have been considered an effective strategy to reduce preventable adverse drug events (ADEs), improving patient's safety. To date, no... (Review)
Review
BACKGROUND AND OBJECTIVE
Drug allergy alert systems (DAAS), have been considered an effective strategy to reduce preventable adverse drug events (ADEs), improving patient's safety. To date, no review has been conducted analyzing characteristics of DAAS in the hospital setting. Therefore, the aim of this study is to identify, describe and summarize the DAAS used in hospitals. The secondary objectives are to analyse drug allergy alerts (DAA) characteristics, the override rate (OvR) and the clinical consequences of alert overrides.
METHODS
Searches were conducted in Medline and Cochrane Library to identify studies describing DAAS. Systems characteristics, generated alerts, DAA, OvR, and its clinical consequences were extracted and analyzed.
RESULTS
Twenty-eight articles were included in the review. Seventeen different electronic DAAS were identified, of which 53% were commercially available. Systems differed in drug allergy information and rules for generating alerts. DAA were generally interruptive, triggered by non-exact match at drug prescribing and when ignored, an override reason was mandatory. The OvR ranged from 43.7% to 97%. The main override reason given by providers was that 'patient had previously tolerated or had taken the drug without allergic reaction'. Clinical consequences of overriding DAA were only analyzed in four studies, with an ADE incidence between 0% and 6%.
CONCLUSIONS
Different DAAS are used in hospitals with some degree of heterogeneity. Accurate and updated drug allergy information is important to generate only high value alerts. A regular review of DAAS and a standardization of alert rules, alert information and override reasons are necessary to optimize systems. Future studies should evaluate the impact of the DAAS aspects on preventing ADEs.
Topics: Decision Support Systems, Clinical; Drug Hypersensitivity; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Incidence; Medical Order Entry Systems; Medication Systems
PubMed: 34990941
DOI: 10.1016/j.ijmedinf.2021.104673 -
The Journal of Allergy and Clinical... Feb 2021Patients with multiple drug allergy labels (MDALs) present a challenging barrier to patient care.
BACKGROUND
Patients with multiple drug allergy labels (MDALs) present a challenging barrier to patient care.
OBJECTIVE
To assess the efficacy, safety, and effectiveness of removing MDALs in a single clinic visit.
METHODS
Retrospective chart review was performed from October 1, 2014, to October 31, 2018, on patients with MDALs who had electronic health record (EHR) allergy label to 2 or more drugs and who were delabeled to 1 or more drug. Our primary outcome was the number of allergy labels tested and removed, at a single or multiple visits. Postvisit surveys were administered to patients, their pharmacies, and primary care physicians for patients delabeled following an EHR transition from November 2, 2017, to October 31, 2018 (n = 184).
RESULTS
Among 536 patients meeting inclusion criteria, 916 of 943 (97.1%) tested allergy labels were removed from the EHR. Most patients, 461 of 536 (86.0%), were tested, challenged, and delabeled in a single visit, to 1 or more drug, although 134 of 536 (25%) still had evidence of 1 or more label at 1 year. In surveys, 90 of 171 (52.6%) responding pharmacies and 122 of 168 (72.6%) primary care physicians contacted had removed drug labels from the EHR as a result of the recommendations from the patient's drug allergy evaluation. Overall, 91 of 142 (64.1%) MDAL patient survey respondents were willing to take the drugs to which they had been delabeled.
CONCLUSIONS
Patients with MDALs can be safely delabeled to multiple drugs in 1 visit; however, effectiveness barriers were identified. Reinforcement of drug allergy label removal information to patients, pharmacies, and primary care providers presents a targeted area for improvement.
Topics: Ambulatory Care; Delivery of Health Care; Drug Hypersensitivity; Electronic Health Records; Humans; Retrospective Studies
PubMed: 32966878
DOI: 10.1016/j.jaip.2020.09.010 -
Current Allergy and Asthma Reports Jan 2023The purpose of this literature review was to review the latest advancements with biologics in rapid drug desensitization. Our methodology was to highlight both... (Review)
Review
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.
Topics: Humans; Drug Hypersensitivity; COVID-19; SARS-CoV-2; Antibodies, Monoclonal; Desensitization, Immunologic; Anaphylaxis; Biological Products
PubMed: 36445652
DOI: 10.1007/s11882-022-01052-z -
The Journal of Allergy and Clinical... Jan 2019Despite their low frequency, drug hypersensitivity reactions (DHRs) can be serious and result in lifelong sequelae. The diagnosis is critical to avert future reactions... (Review)
Review
Despite their low frequency, drug hypersensitivity reactions (DHRs) can be serious and result in lifelong sequelae. The diagnosis is critical to avert future reactions and should identify the culprit drug or drugs and safe alternatives. However, making the diagnosis can be complex and challenging. Reliable in vitro tests can offer the potential to improve a diagnosis of DHR and influence medical decision making. Importantly, in vitro testing is frequently not performed as a test in isolation but rather as a component of a diagnostic algorithm along with additional tests. There are several in vitro approaches for the different endotypes of DHRs. However, only few are available for routine diagnosis, and many are restricted to research laboratories. In vitro tests exhibit varying sensitivity and specificity depending on the drug involved and the clinical phenotype. In vitro tests can complement skin tests, especially in patients with negative or equivocal skin test responses inconsistent with the clinical presentation and in severe reactions in which drug provocation tests are contraindicated. The main unmet need for many in vitro tests for the diagnosis of DHRs is validation in larger studies with standardized controls that could harmonize diagnostic management between the United States, European Union, and other regions of the world.
Topics: Animals; Clinical Decision-Making; Drug Hypersensitivity; Humans; Skin Tests
PubMed: 30573343
DOI: 10.1016/j.jaci.2018.09.022 -
International Journal of Molecular... Jun 2017Drug hypersensitivity reactions have multiple implications for patient safety and health system costs, thus it is important to perform an accurate diagnosis. The... (Review)
Review
Drug hypersensitivity reactions have multiple implications for patient safety and health system costs, thus it is important to perform an accurate diagnosis. The diagnostic procedure includes a detailed clinical history, often unreliable; followed by skin tests, sometimes with low sensitivity or unavailable; and drug provocation testing, which is not risk-free for the patient, especially in severe reactions. In vitro tests could help to identify correctly the responsible agent, thus improving the diagnosis of these reactions, helping the physician to find safe alternatives, and reducing the need to perform drug provocation testing. However, it is necessary to confirm the sensitivity, specificity, negative and positive predictive values for these in vitro tests to enable their implementation in clinical practice. In this review, we have analyzed these parameters from different studies that have used in vitro test for evaluating drug hypersensitivity reactions and estimated the added value of these tests to the in vivo diagnosis.
Topics: Diagnostic Tests, Routine; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Immunoglobulin E; T-Lymphocytes
PubMed: 28590437
DOI: 10.3390/ijms18061222 -
Clinical Medicine (London, England) Dec 2016Drug allergy is defined as an adverse drug reaction with an established immunological mechanism. The National Institute for Health and Care Excellence published clinical...
Drug allergy is defined as an adverse drug reaction with an established immunological mechanism. The National Institute for Health and Care Excellence published clinical guidelines on drug allergy in 2014 and quality standards in 2015. The intention of this article is to highlight indications for referral to specialists for management of drug allergy. Accurate diagnosis of drug allergy is critical of course for patient safety, but also for better use of the drugs that we have available and to reduce unnecessary avoidance of drugs. However, there are significant limitations in terms of resource availability and also in terms of testing. There is a careful balance here in that drug allergy is very common and clearly there is neither indication nor sufficient resource in the NHS for all patients with drug allergy to be reviewed by a specialist. It is, therefore, important to highlight to general physicians and physicians of other specialties, those patients who do require referral for specialist review.
Topics: Drug Hypersensitivity; General Practitioners; Humans; Practice Guidelines as Topic; Referral and Consultation; Specialization
PubMed: 27927827
DOI: 10.7861/clinmedicine.16-6-588 -
Italian Journal of Pediatrics Jan 2020Drug Hypersensitivity Reactions (DHRs) are considered adverse effects of medications that resemble allergy symptoms. The reported positive clinical history of pediatric...
BACKGROUND AND OBJECTIVE
Drug Hypersensitivity Reactions (DHRs) are considered adverse effects of medications that resemble allergy symptoms. The reported positive clinical history of pediatric drug reactions is about 10%, however, after allergy investigations, only a small percent is confirmed as hypersensitivity. The aim of this study was to analyze the clinical history, allergy work-up results and sensitization profile of children and adolescents referred to our Allergy Unit for suspected DHRs.
METHODS
The study evaluated data related to a group of children with a positive history of drug reactions during a two-year period. The allergy work-up consisted of in vivo and in vitro tests, in accordance with the recommendations of the ENDA/EAACI guidelines.
RESULTS
Data from a group of 637 patients [348 M (54.6%); 289 F (45.4%)] were retrospectively analyzed. Beta lactams (BLs) were the most common drugs involved in the reported clinical history, followed by non-steroidal anti-inflammatory drugs (NSAIDs). Severe cutaneous adverse reactions (SCARs) were most frequently observed during BL treatment. The confirmation of BL hypersensitivity was higher for immediate reactions (IRs) [9.4%; 5.1% through positive skin tests (STs) and 5.5% through drug provocation test (DPT)] compared to non-immediate reactions (non-IRs) (8.1%; 2.2% through STs and 6.2% through DPT). A higher number of positive results was obtained for BLs and macrolides when the tests were performed within 12 months after the index reaction (p < 0.05). During DPTs with amoxicillin-clavulanic acid, four hypersensitivity reactions (including one anaphylaxis) occurred despite negative STs.
CONCLUSION
Our data demonstrated that only 9.1% of patients resulted in being positive to allergy tests which is in line with the data in literature. An allergy work-up is mandatory for excluding suspected hypersensitivity.
Topics: Adolescent; Child; Child, Preschool; Drug Hypersensitivity; Female; Hospitals, Pediatric; Humans; Immunoglobulin E; Infant; Italy; Male; Retrospective Studies; Skin Tests; Tertiary Healthcare
PubMed: 31924232
DOI: 10.1186/s13052-019-0753-4