Nonsteroidal anti-inflammatory drugs-induced hypersensitivity reactions

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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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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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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Clinical value of in vitro tests for the management of severe drug hypersensitivity reactions

Asia Pacific Allergy ◽

10.5415/apallergy.2020.10.e44 ◽

2020 ◽

Vol 10 (4) ◽

Cited By ~ 1

Author(s):

Yuttana Srinoulprasert ◽

Ticha Rerkpattanapipat ◽

Mongkhon Sompornrattanaphan ◽

Chamard Wongsa ◽

Duangjit Kanistanon

Keyword(s):

Drug Hypersensitivity ◽

In Vitro Tests ◽

Hypersensitivity Reactions ◽

Clinical Value ◽

Drug Hypersensitivity Reactions

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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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AB0273 HYPERSENSIVITY REACTIONS TO NON STEROID ANTI INFLAMMATORY DRUGS: A BOUT 87 CASES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2910 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1162.3-1162

Author(s):

K. Ksouda ◽

R. Sahnoun ◽

R. Atheymen ◽

I. Bouaziz ◽

A. Hanène ◽

...

Keyword(s):

Retrospective Study ◽

Tiaprofenic Acid ◽

Maculopapular Rash ◽

Cross Reactivity ◽

Hypersensitivity Reactions ◽

Fixed Drug Eruption ◽

Cross Reactions ◽

Immunological Mechanisms ◽

Inflammatory Drugs ◽

Anti Inflammatory

Background:Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the leading causes of hypersensitivity reactions to drugs. The pathogenesis may be immunological mechanisms (allergic reactions) or non specific immunological reactions often incriminated in cross reactivity independently of chemical structure of these molecules. Understanding of the underlying mechanism is necessary for prevention and choice of safe alternatives [1, 2].Objectives:Analyze all cases of non-steroidal anti-inflammatory drugs cutaneous eruption reported to sfax pharmacovigilance service since January 2015 to December 2020 and evaluate the possibility of cross-reactions between different molecules in this class.Methods:We conducted a retrospective study of all cases reported to sfax pharmacovigilance department. An enquiry of pharmacovigilance was performed in patients who presented side effects to AINS. The imputability study was carried out by the French method of Imputability. Medical history specifies if there is a re-administration to assess tolerance and cross-reactivity.Results:Our study included 87 patients whose average age was 45, 8 years. The sex ratio (F/M) was 1.18. lysine salicylate acetyl is the most incriminated (31%), then mefenamic acid (19.5%), diclofenac (19.5 %), ketoprofen in (9.2%), piroxicam in (6.9 %), ibuprofen in (5.4%), celocoxib in (3.4%), tiaprofenic acid in (1.1%) and naproxen in 1.1% of cases. The most common skin injury was urticaria in 29 cases (33.3%). Fixed drug eruption was observed in 17 cases. Maculopapular rash was observed in 19 cases, anaphylaxis in 5 cases and 4 cases of photosensitivity were observed. In our study we found cross-reactivity between (NSAIDs) in 8 patients.Conclusion:The diagnostic approach is often based on the controlled administration of the drug to assess tolerance and to identify safe alternatives. In cases of intolerance to COX 1 inhibitors, cross-reactions to selective cox 2 inhibitors are very rare [3].References:[1]Inmaculada Dona, Maria Salas, James R Perkins and al. Hypersensitivity Reactions to Non-Steroidal Anti-Inflammatory Drugs. Curr Pharm Des 2016; 22(45):6784-6802.[2]Flavia Angeletti, Franziska Meier, Nadja Zöller, Markus Meissner, Roland Kaufmann, Eva Maria Valesky. Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) - a retrospective study. J Dtsch Dermatol Ges 2020 Dec; 18(12):1405-1414.[3]N Blanca-López, J A Cornejo-García, M C Plaza-Serón, and al. Hypersensitivity to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Cross-Intolerance Reactions. J Investig Allergol Clin Immunol 2015; 25(4):259-69.Disclosure of Interests:None declared

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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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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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Nemszteroid gyulladáscsökkentők okozta adverz reakciók differenciáldiagnosztikája. In vitro és in vivo módszerek

Orvosi Hetilap ◽

10.1556/650.2018.31170 ◽

2018 ◽

Vol 159 (38) ◽

pp. 1556-1566

Author(s):

József Mátyás Baló-Banga ◽

Katalin Schweitzer

Keyword(s):

Plasma Membranes ◽

Mononuclear Cells ◽

In Vitro Tests ◽

Immune Mediated ◽

Release Assay ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Cox 1

Abstract: Introduction: According to the present knowledge, the effect of non-steroidal anti-inflammatory drugs (NSAIDs) depends on the inhibitory ratio of cyclooxigenase (COX)-1 to COX-2 in the plasma membranes. In addition to cardiovascular and gastrointestinal side effects, there are adverse symptoms which can be divided into cross-intolerance (non-immune mediated) and single or multiple hypersensitive (immune mediated) reactions. Due to clinical phenotypes and to in vivo aspirin reactivity, adverse effects could be further classified. Aim: The aim of these studies was a comparison of hit ratios obtained by a humoral serum test measuring specific immunglobulin E (IgE) against a rapid cellular test measuring interleukin (IL)-6 release from sensitized mononuclear cells due to various suspect NSAID after symptoms within one year. Retrospective case studies were performed in in- and out-patients of our teaching hospital in Budapest, between 2003 and 2013. Method: Specific anti-NSAID IgE levels were determined by ELISA in 55 cases. The other matching group of patients consisted of 51 patients and 9 tolerant persons. Their separated cells’ supernatants were checked for IL-6 release incubated for 20 minutes by NSAID dilutions including intraassay controls by two-step ELISA assay. Both groups have been stratified according to “new” clinical classification. Results: Results have disclosed no significant differences among the distribution of clinical symptoms between the two groups. In both groups, 9 non-steroidal anti-inflammatory drugs were tested representing all frequently used compounds with COX-1 inhibitory potential. The overall positivity rate was nearly double (65.4% against 36.9%) within the group using IL-6 release assay against that with specific IgE as the diagnostic tool. In certain cases, non-drug components of commercial preparations prompted IL-6 release as well which was paralleled by in vivo test results. Positive in vitro tests were obtained in both groups with clinically cross-intolerant as well as single or multiple sensitized cases. Conclusion: The rates of single or multiple sensitized cases exceeded in both groups that of cross-intolerant patients. In some phenotypes belonging to the latter categories, IgE type antibodies against acetylsalicylic acid could be detected as well. IL-6 release assay was the more sensitive test. In addition to pure drugs, other ingredients of medicines could also be responsible for adverse events. Orv Hetil. 2018; 159(38): 1556–1566.

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