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

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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Drug Allergy Profile From a National Drug Allergy Registry

Frontiers in Pharmacology ◽

10.3389/fphar.2020.555666 ◽

2021 ◽

Vol 11 ◽

Author(s):

Mona Al-Ahmad ◽

Jusufovic Edin ◽

Mosa Fardous ◽

Tito Rodriguez-Bouza

Keyword(s):

Respiratory Symptoms ◽

Drug Allergy ◽

Drug Hypersensitivity ◽

Clinical History ◽

Diagnostic Methods ◽

Skin Tests ◽

Presenting Symptoms ◽

National Drug ◽

Inflammatory Drugs ◽

Anti Inflammatory

Background: Drug hypersensitivity reactions (DHRs) are among the most frequent reasons for consultation in allergy departments and are becoming more common due to increasing prevalence and case complexity.Objective: To describe the most common drugs associated with clinical reactions, diagnostic methods used, and outcomes of allergic evaluations of a national drug allergy registry over a 12-year period were used.Methods: An observational, prospective, patient’s data registry-based study was conducted to analyze all referrals to the drug allergy outpatient clinics at Al-Rashed Allergy Center, Kuwait, between 2007 and 2019. Demographics, description of DHRs, and results of allergy tests to potential causative medications were reviewed. Diagnostic methods were focused mainly on skin tests (STs) and drug provocation test (DPT), when indicated.Results: We evaluated 1,553 patients with reported DHRs. The mean age of the population was 41.52 ± 16.93 years, and the study population consisted of 63.7% female patients. Hypersensitivity was finally confirmed in 645 (41.5%) of patients, probable in 199 (12.8%), and not confirmed/nonallergic in 709 (45.6%) patients. Anti-inflammatory drugs and analgesics contributed to 39.22% of all confirmed drug allergies, followed by antibiotics 38.1% (β-lactam antibiotics (BLs) constituted 73.98% of all antibiotics and 28.21% of all drugs), anesthetics 1.8%, and radio-contrast media 0.31%. The majority of reactions were non-immediate 51.44%. The most commonly presenting symptoms among confirmed patients were urticaria 57.80%, angioedema 42.50%, respiratory symptoms 47.60%, and erythema 33.60%. Symptoms of anaphylaxis/anaphylactic shock were reported by 284 patients (44.00%) among confirmed cases. The most common method of diagnosis was a positive clinical history (54.4% in BLs and 90.45% in nonsteroidal anti-inflammatory drugs (NSAIDs). Among confirmed allergy to BLs, a positive ST was obtained in 31.9% of patients and positive DPT in 13.7%.Conclusion: NSAIDs and antibiotics, mainly BLs, are the most commonly implicated in confirmed allergy. In both confirmed and not confirmed/nonallergic cases, BLs are the most frequently involved DHRs which are mainly immediate, and the most commonly presenting symptoms were urticaria, angioedema, and respiratory symptoms. Diagnosis was confirmed mainly by a positive clinical history and when indicated, by positive STs or a DPT.

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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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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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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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Diagnosing and Managing Patients with Reactions to Radiocontrast Media

Current Treatment Options in Allergy ◽

10.1007/s40521-021-00287-x ◽

2021 ◽

Vol 8 (3) ◽

pp. 210-221

Author(s):

Knut Brockow

Keyword(s):

Skin Testing ◽

Drug Hypersensitivity ◽

Skin Tests ◽

Hypersensitivity Reactions ◽

Positive Skin ◽

Provocation Tests ◽

Ring Molecules ◽

Allergic Skin ◽

Drug Hypersensitivity Reactions ◽

Drug Provocation Tests

Abstract Purpose of the review Iodinated radio contrast media (RCM) belong to the most common elicitors of drug hypersensitivity reactions (HR). Urticaria or anaphylaxis may occur ≤ 1(−6) hour(s) (immediate HR) and exanthems (non-immediate HR) develop > 6 h after application of RCM. Evidence for an immunologic mechanism of RCM HR against the different RCM benzene ring molecules and the benefit of allergological testing in patients with previous hypersensitivity reactions is progressively increasing. Recent findings Positive skin tests can confirm allergy in patients with previous reactions to RCM and help to select alternative better tolerated RCMs. Severe hypersensitivity reactions are mainly caused by an allergic mechanism, whereas the majority of non-severe reactions appear to be non-allergic. Skin testing is highly recommended to help identify allergic hypersensitivity reactions and to select alternatives. Using structurally different RCM is more effective than premedication for the prevention of future reactions. Drug provocation tests to RCM have been increasingly used, but are not yet standardized among different centers. Summary In patients with previous severe hypersensitivity reactions to RCM, skin testing is recommended. For future RCM-enhanced examinations in patients with previous reactions, structurally different, skin test-negative preparations should be applied. Drug provocation tests do confirm or exclude RCM hypersensitivity or may demonstrate tolerability of alternative RCMs.

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

Frontiers in Pharmacology ◽

10.3389/fphar.2020.584633 ◽

2020 ◽

Vol 11 ◽

Author(s):

Miriam Sobrino-García ◽

Esther M. Moreno ◽

Francisco J. Muñoz-Bellido ◽

Maria T. Gracia-Bara ◽

Elena Laffond ◽

...

Keyword(s):

Scientific Evidence ◽

Drug Hypersensitivity ◽

Hypersensitivity Reactions ◽

Inclusion Criteria ◽

Beta Lactams ◽

Drug Hypersensitivity Reactions ◽

Clinical Consequences ◽

Bibliographic Search ◽

Inflammatory Drugs ◽

Anti Inflammatory

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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Early Biomarkers for Severe Drug Hypersensitivity Reactions

Current Pharmaceutical Design ◽

10.2174/1381612825666191107105440 ◽

2019 ◽

Vol 25 (36) ◽

pp. 3829-3839 ◽

Cited By ~ 1

Author(s):

Adriana Ariza ◽

Maria J. Torres ◽

Carmen Moreno-Aguilar ◽

Rubén Fernández-Santamaría ◽

Tahia D. Fernández

Keyword(s):

Drug Exposure ◽

Drug Hypersensitivity ◽

Clinical Manifestations ◽

Skin Tests ◽

Time Interval ◽

Hypersensitivity Reactions ◽

Early Biomarkers ◽

Immunological Mechanisms ◽

Drug Hypersensitivity Reactions ◽

Delayed Reactions

Drug hypersensitivity reactions (DHRs) are typically classified into immediate and delayed reactions based on the time interval between drug exposure and onset of symptoms. Clinical manifestations range from mild to severe and life-threatening reactions. The most severe clinical entities are anaphylaxis and anaphylactic shock for immediate reactions, and severe cutaneous adverse reactions such as Steven Johnson Syndrome and Toxic Epidermal Necrolysis for delayed reactions. The diagnosis is complex and challenging, as drug provocation tests and even skin tests can be very risky procedures, which makes them not recommended. Therefore, it is necessary to search for useful early biomarkers to manage the diagnosis of these reactions. These biomarkers could be useful to determine the clinical entity, but not to identify the culprit drug. Some of the currently available biomarkers are few genetic associations of drug allergy with polymorphisms of human leukocyte antigen (HLA), the detection of inflammatory and lipid mediators in serum, or the detection of cytokines, chemokines, and cytotoxic markers in skin biopsies. In this literature review, it has been summarize the immunological mechanisms involved in severe reactions, both immediate and delayed, and different early biomarkers: those currently used for the diagnosis of these reactions as well as possible early biomarkers that could be useful with further studies to standardize their clinical use.

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