Analysis of the Costs Associated With the Elective Evaluation of Patients Labelled as Allergic to Beta-Lactams or Nonsteroidal Antiinflamatory Agents

Introduction: Being labelled as allergic to different drugs results in patients receiving other treatments, which are more toxic, less effective and more expensive. We aimed to analyze different studies of the costs of drug hypersensitivity assessment.Methods: A bibliographic search on studies regarding this issue was performed, including the available scientific evidence up to June 2020. We searched three databases with terms related to costs and allergy testing in drug hypersensitivity reactions.Results: Our search revealed 1,430 publications, of which 20 met the inclusion criteria. In the manuscript, prospective studies evaluating the costs of the evaluation of patients with suspected allergy to beta-lactams or non-steroidal anti-inflammatory drugs are analyzed. Also, comment is made on the costs associated with incorrect labeling as non-steroidal anti-inflammatory drug or penicillin hypersensitivity.Conclusions: Taking all costs into account, the study of drug hypersensitivity is not expensive, particularly considering the economic and clinical consequences of labeling a patient with hypersensitivity to drugs.

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Ipersensibilità ai FANS: intolleranza o allergia?

Medico e Bambino ◽

10.53126/meb40037 ◽

2021 ◽

Vol 40 (1) ◽

pp. 37-43

Author(s):

Laura Levantino ◽

Cristiana Corrado ◽

Laura Badina ◽

Sara Lega ◽

Egidio Barbi

Keyword(s):

Drug Hypersensitivity ◽

Clinical Manifestations ◽

Hypersensitivity Reactions ◽

Provocation Tests ◽

Immunological Mechanisms ◽

Drug Hypersensitivity Reactions ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Drug Provocation Tests ◽

Cox 1

Non-steroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity reactions in children. According to the EAACI latest classification NSAIDs hypersensitivity reactions are differentiated into cross-reactive reactions, with non-immunological mechanisms (based on COX-1 inhibition), and selective reactions, with immunological mechanisms. Paediatric clinical manifestations of NSAID hypersensitivity are typically cutaneous, but sometimes, similarly to anaphylaxis, can involve other systems, especially the respiratory one. Differentiating between NSAID intolerance and NSAID allergy through drug provocation tests is crucial for the patient because the two clinical entities require different management.

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Pharmacogenomics of Hypersensitivity to Non-steroidal Anti-inflammatory Drugs

Frontiers in Genetics ◽

10.3389/fgene.2021.647257 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hoang Kim Tu Trinh ◽

Le Duy Pham ◽

Kieu Minh Le ◽

Hae-Sim Park

Keyword(s):

Acid Metabolism ◽

Drug Hypersensitivity ◽

Methylation Status ◽

Arachidonic Acid Metabolism ◽

Hypersensitivity Reactions ◽

Lipoxygenase Pathway ◽

Drug Hypersensitivity Reactions ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Larger Sample

Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively prescribed in daily clinical practice. NSAIDs are the main cause of drug hypersensitivity reactions all over the world. The inhibition of cyclooxygenase enzymes by NSAIDs can perpetuate arachidonic acid metabolism, shunting to the 5-lipoxygenase pathway and its downstream inflammatory process. Clinical phenotypes of NSAID hypersensitivity are diverse and can be classified into cross-reactive or selective responses. Efforts have been made to understand pathogenic mechanisms, in which, genetic and epigenetic backgrounds are implicated in various processes of NSAID-induced hypersensitivity reactions. Although there were some similarities among patients, several genetic polymorphisms are distinct in those exhibiting respiratory or cutaneous symptoms. Moreover, the expression levels, as well as the methylation status of genes related to immune responses were demonstrated to be involved in NSAID-induced hypersensitivity reactions. There is still a lack of data on delayed type reactions. Further studies with a larger sample size, which integrate different genetic pathways, can help overcome current limitations of gen etic/epigenetic studies, and provide valuable information on NSAID hypersensitivity reactions.

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Discrepancies in the diagnosis and classification of nonsteroidal anti-inflammatory drug hypersensitivity reactions in children

Allergology International ◽

10.1016/j.alit.2016.10.004 ◽

2017 ◽

Vol 66 (3) ◽

pp. 418-424 ◽

Cited By ~ 19

Author(s):

Tuğba Arikoglu ◽

Gulen Aslan ◽

Didem Derici Yildirim ◽

Sehra Birgul Batmaz ◽

Semanur Kuyucu

Keyword(s):

Drug Hypersensitivity ◽

Hypersensitivity Reactions ◽

Inflammatory Drug ◽

Drug Hypersensitivity Reactions ◽

Diagnosis And Classification ◽

Anti Inflammatory

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Nonsteroidal anti-inflammatory drugs-induced hypersensitivity reactions

Romanian Neurosurgery ◽

10.33962/roneuro-2019-066 ◽

2019 ◽

pp. 411-416

Author(s):

Andrei Gheorghe Vicovan ◽

Liliana Veres ◽

Andrei Cucu ◽

Dana Turliuc ◽

Cristina Mihaela Ghiciuc

Keyword(s):

Drug Hypersensitivity ◽

Clinical Manifestations ◽

Clinical Analysis ◽

In Vitro Tests ◽

Hypersensitivity Reactions ◽

Immunological Mechanism ◽

Immunological Mechanisms ◽

Inflammatory Drugs ◽

Anti Inflammatory

The role of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in neurosurgical practice is a secondary one, however they are still constantly involved in perioperative management of pain or in nonoperative management of acute radiculopathy. Beside the well-known adverse reactions (ADRs), the neurosurgeon practitioner should also take in account the drug hypersensitivity reactions (DHRs) of NSAIDs and be able to deal with it. The aim of this paper was to review the diagnostic and management steps for NSAIDs-induced Hypersensitivity Reactions. The actual stratification of NSAIDs-induced Hypersensitivity Reactions is based on understanding of the heterogeneity of immunological/non-immunological mechanisms of reactions and complexity of clinical manifestations. Practically, this stratification allows the physician to assess suspicion of DHR, based on anamnesis and clinical analysis, and to consider further practical steps to manage and eventually confirm the diagnosis. Drug allergies are considered only the DHRs for which a definite immunological mechanism (either drug-specific antibody or T cell) is demonstrated. In conclusion, clinical analysis and anamnesis of patient with NSAIDs-induced Hypersensitivity Reactions can be realized by any physician and could be enough to diagnose, but it is not sufficient to confirm the diagnosis. In vitro tests and oral provocation challenges may be necessary to be undertaken by an allergy specialist.

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Hypersensitivity reactions to non-steroidal anti-inflammatory drugs: results of an Austrian cohort study

Allergo Journal International ◽

10.1007/s40629-020-00134-6 ◽

2020 ◽

Vol 29 (7) ◽

pp. 227-232

Author(s):

Teresa Bangerl ◽

Brigitte Zahel ◽

Andrea Lueger ◽

Emmanuella Guenova ◽

Irena Angelova-Fischer ◽

...

Keyword(s):

Skin Testing ◽

Drug Hypersensitivity ◽

Provocation Test ◽

Clinical History ◽

University Hospital ◽

Skin Tests ◽

Hypersensitivity Reactions ◽

Culprit Drug ◽

Inflammatory Drugs ◽

Anti Inflammatory

Summary Background Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of drug hypersensitivity. Despite the importance of NSAIDs in routine analgesia only few studies have systematically addressed the question of tolerability in hypersensitive patients. Methods The authors retrospectively analysed 398 patients that were treated at the Department of Dermatology, Kepler University Hospital Linz, Austria, in the period 2012–2016 with a clinical history of NSAID hypersensitivity. Skin tests (skin prick and intracutaneous tests) to common NSAIDs were performed, followed by single-blinded, placebo-controlled drug challenge with either the culprit drug or an alternative NSAID. Results A total of 361 patients were subjected to skin testing. Of these, 25 patients (6.3%) showed a positive reaction to the culprit drug. According to the severity of the reaction in the medical history, 87 patients were exposed orally to the culprit drug (oral provocation test, OPT) after negative skin test and 255 patients received OPT with alternative NSAIDs according to established protocols. OPT with the culprit drug resulted in hypersensitivity reactions in 12 patients (13.79%). In terms of alternative NSAID testing, the three most commonly tested drugs were lornoxicam (192 OPTs), acetaminophen (156 OPTs) and celecoxib (133 OPTs) with tolerability rates in respectively 88.54% (hypersensitivity reactions, 11.46%), 92.31% (hypersensitivity reactions, 7.69%) and 91.73% (hypersensitivity reactions, 8.27%) of cases. Conclusion OPT with alternative NSAIDs are useful in patients with NSAID hypersensitivity as tolerability varies between the individual substances.

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Meloxicam and/or Etoricoxib Could Be Administered Safely in Two Equal Doses during an Open Oral Challenge in Patients with Nonsteroidal Anti-Inflammatory Drug Hypersensitivity

International Archives of Allergy and Immunology ◽

10.1159/000512072 ◽

2021 ◽

pp. 1-7

Author(s):

Dolly Vanessa Rojas-Mejía ◽

Diana Lucía Silva Espinosa ◽

Diana Marcela Martínez ◽

Luis Fernando Ramírez Zuluaga ◽

Carlos Daniel Serrano Reyes

Keyword(s):

Drug Hypersensitivity ◽

Provocation Test ◽

Descriptive Study ◽

Oral Challenge ◽

Oral Drug ◽

Hypersensitivity Reactions ◽

Cross Sectional ◽

Drug Provocation Test ◽

Inflammatory Drugs ◽

Anti Inflammatory

Background: Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are common. These patients require an effective and safe analgesic alternative. Objective: The aim of the study was to demonstrate the safety of meloxicam and etoricoxib administered by open oral challenge in 2 equal steps in patients with NSAID hypersensitivity. Methods: A cross-sectional, descriptive study of patients with a diagnosis of NSAID hypersensitivity who underwent an oral drug provocation test (DPT) with meloxicam or etoricoxib between January 2011 and August 2017 was conducted. The analysis was performed from a database in BD Clinic. Results: Two hundred and twenty-eight oral provocations were performed with an alternative NSAID (203 with meloxicam and 25 with etoricoxib) in 217 patients with hypersensitivity to NSAIDs. The median age was 38 years. Ninety-eight percent of meloxicam and 100% of etoricoxib DPTs were performed in 2 steps (without previous placebo), and 52% and 64% of meloxicam and etoricoxib DPTs, respectively, were performed with 50% of the therapeutic dose in each step. Tolerance to meloxicam was demonstrated in 192 patients (94.5%) and in 100% of patients receiving etoricoxib. Conclusions: Open oral provocation with meloxicam and etoricoxib carried out in 2 steps without placebo seems to be safe and implies less costs and less time expenditure. Also, it could be performed with 2 equal doses.

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Platelet-Adherent Leukocytes Associated With Cutaneous Cross-Reactive Hypersensitivity to Nonsteroidal Anti-Inflammatory Drugs

Frontiers in Pharmacology ◽

10.3389/fphar.2020.594427 ◽

2020 ◽

Vol 11 ◽

Author(s):

Raquel Jurado-Escobar ◽

Inmaculada Doña ◽

Gador Bogas-Herrera ◽

Natalia Pérez-Sánchez ◽

María Salas ◽

...

Keyword(s):

Acute Phase ◽

Drug Hypersensitivity ◽

Arachidonic Acid Metabolism ◽

Cysteinyl Leukotriene ◽

Cyclooxygenase 1 ◽

Drug Hypersensitivity Reactions ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Underlying Mechanisms ◽

Adherent Leukocytes

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most highly consumed drugs worldwide and the main triggers of drug hypersensitivity reactions. The most frequent reaction, named cross-reactive NSAID-hypersensitivity, is due to the pharmacological activity of these drugs by blocking the cyclooxygenase-1 enzyme. Such inhibition leads to cysteinyl-leukotriene synthesis, mainly LTE4, which are responsible for the reaction. Although the complete molecular picture of the underlying mechanisms remains elusive, the participation of platelet-adherent leukocytes (CD61+) and integrins have been described for NSAID-exacerbated respiratory disease (NERD). However, there is a lack of information concerning NSAID-induced urticaria/angioedema (NIUA), by far the most frequent clinical phenotype. Here we have evaluated the potential role of CD61+ leukocytes and integrins (CD18, CD11a, CD11b, and CD11c) in patients with NIUA, and included the other two phenotypes with cutaneous involvement, NSAID-exacerbated cutaneous disease (NECD) and blended reactions (simultaneous skin and airways involvement). A group NSAID-tolerant individuals was also included. During the acute phase of the reaction, the three clinical phenotypes showed increased frequencies of CD61+ neutrophils, eosinophils, and monocytes compared to controls, which correlated with urinary LTE4 levels. However, no correlation was found between these variables at basal state. Furthermore, increased expressions of CD18 and CD11a were found in the three CD61+ leukocytes subsets in NIUA, NECD and blended reactions during the acute phase when compared with CD61−leukocyte subpopulations. During the acute phase, CD61+ neutrophils, eosinophils and monocytes showed increased CD18 and CD11a expression when compared with CD61+ leukocytes at basal state. No differences were found when comparing controls and CD61+ leukocytes at basal state. Our results support the participation of platelet-adherent leukocytes and integrins in cutaneous cross-hypersensitivity to NSAIDs and provide a link between these cells and arachidonic acid metabolism. Our findings also suggest that these reactions do not involve a systemic imbalance in the frequency of CD61+ cells/integrin expression or levels of LTE4, which represents a substantial difference to NERD. Although further studies are needed, our results shed light on the molecular basis of cutaneous cross-reactive NSAID-hypersensitivity, providing potential targets for therapy through the inhibition of platelet-leukocyte interactions.

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Short-Term Tolerability of Morniflumate in Patients with Cutaneous Hypersensitivity Reactions to Non-Steroidal Anti-Inflammatory Drugs

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463201302600126 ◽

2013 ◽

Vol 26 (1) ◽

pp. 247-250 ◽

Cited By ~ 5

Author(s):

F. Mero ◽

E. Nettis ◽

A.M. Aloia ◽

E. Di Leo ◽

A. Ferrannini ◽

...

Keyword(s):

Drug Hypersensitivity ◽

Antiinflammatory Drug ◽

Hypersensitivity Reactions ◽

Short Term ◽

Cutaneous Hypersensitivity ◽

Cutaneous Reactions ◽

Term Tolerability ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Low Incidence

Morniflumate is the morpholinoethyl ester of niflumic acid, a non-steroidal antiinflammatory drug, derived from nicotinic acid. We studied 112 patients who had experienced cutaneous reactions after using non-steroidal anti-inflammatory drugs. Only two of all the patients who underwent an oral challenge with morniflumate had a positive result to the test. By demonstrating the low incidence of reactions to morniflumate through oral challenges, we suggest that patients with non-steroidal anti-inflammatory drug hypersensitivity may tolerate this drug which would therefore be a useful alternative.

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Skin testing and drug challenge in the evaluation of drug hypersensitivity reactions

Allergy and Asthma Proceedings ◽

10.2500/aap.2021.42.200091 ◽

2021 ◽

Vol 42 (1) ◽

pp. 16-21 ◽

Cited By ~ 1

Author(s):

Anna R. Wolfson ◽

Aleena Banerji

Keyword(s):

Negative Impact ◽

Skin Testing ◽

Drug Hypersensitivity ◽

Clinical History ◽

Hypersensitivity Reactions ◽

Causative Drug ◽

Care Assessment ◽

Drug Hypersensitivity Reactions ◽

Drug Challenge ◽

Drug Challenges

Immediate hypersensitivity to drugs is characterized by symptoms such as hives, swelling, and wheezing. To prevent a negative impact on care, assessment by an allergist is important. Evaluation requires a clear clinical history, but it is often lacking or vague, which makes a diagnosis difficult. Allergists instead can use skin testing and drug challenge to evaluate drug hypersensitivity reactions, which help the patient and provider understand the causative drug(s) and, more importantly, enables the use of the exonerated drug(s). Although penicillin skin testing is standardized, well described, and widely used, skin testing for most other drugs requires the use of a nonirritating skin testing concentration that can have a low negative predictive value. Drug challenges are the criterion standard for confirming tolerance. The allergist must obtain an in-depth clinical history and then follow with skin testing and/or drug challenges when indicated to determine which drugs can be de-labelled and which should be avoided. In this review, we focused on the evaluation of drug hypersensitivity reactions to antibiotics, perioperative agents, biologics, and chemotherapeutics.

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