Nonallergic Hypersensitivity Reactions Research Articles

Penilloic acid is the chief culprit involved in non-IgE mediated, immediate penicillin-induced hypersensitivity reactions in mice.

Metabolites/impurities (MIs) of penicillin are normally considered to be the main substances inducing immediate hypersensitivity reactions in penicillin treatment. Our previous research found that penicillin can cause non-allergic hypersensitivity reactions (NAHRs) by directly triggering vascular hyperpermeability and exudative inflammation. However, the chief culprits and underlying mechanisms involved in penicillin-induced NAHRs have not yet been fully elucidated. In this study, we used a combination of approaches including a mouse non-allergic hypersensitivity reaction model, UPLC-MS/MS analyses of arachidonic acid metabolites (AAMs), immunoblotting technique, and molecular docking, etc to investigate the culprits involved in penicillin-induced hypersensitivity reactions. We found penilloic acid, one of the main MIs of penicillin, could trigger NAHRs via inducing increased vascular permeability, while the other MIs did no exhibit similar effect. Penilloic acid-induced reactions were not IgE-dependent. Significantly increased arachidonic acids and cascade metabolites in lungs, and activation of RhoA/ROCK signaling pathway in the ears and lungs of mice were noticed after once administration of penilloic acid. This study revealed that penilloic acid was the chief culprit involved in penicillin-induced immediate NAHRs in mice, which mainly associated with direct stimulation of vascular hyperpermeability and exudative inflammation. The activations of AAMs and RhoA/ROCK signaling pathway played important roles in these reactions.

Skin Tests for the Exploration of Hypersensitivity Reactions Associated with Iodinated Contrast Media.

Iodinated contrast media (ICM) are responsible for multiple side effects, especially hypersensitivity reactions. These reactions can either be authentic allergies or non-allergic hypersensitivity reactions. Skin tests (prick and intradermal tests) are simple to perform and can be of great help, especially if the ICM needs to be re-used. The aim of the study was to assess the characteristics of the patients in whom skin tests were performed and the results of these tests. This is a retrospective study from June 2014 to June 2019. All included patients had at least one episode of hypersensitivity reaction to ICM and underwent skin tests. We included 35 patients aged 18 to 85 years. The iopromide was the most implicated ICM. The reactions were mainly cutaneous (n=30) and immediate (n=27). The skin tests were negative, except for two patients. The re-use of ICM occurred in 11 patients: 9 with an ICM other than the one suspected and two patients with the same ICM. Among these patients, 5 did not have any premedication. Two of them had a second hypersensitivity reaction, the first with another ICM and the second with the same ICM. One of the main pillars of allergic exploration is ICM skin testing, not only to prevent a recurrence, but also to allow patients to benefit from ICM re-use, which are sometimes essential.

Assessment of immediate and non-immediate hypersensitivity contrast reactions by skin tests and provocation tests: A review.

Introduction:Allergic and nonallergic hypersensitivity reactions to iodinated contrast media (ICM) and gadolinium-based contrast media are classified as immediate or non-immediate hypersensitivity reactions (IHR and NIHR), respectively. Skin tests and provocation tests are recommended for the evaluation of hypersensitivity reactions to contrast agents; however provocations are not common in clinical practice.Methods:A MEDLINE search was conducted to investigate studies comprising both skin tests and provocation tests that evaluated hypersensitivity reactions to ICM.Results:Nineteen studies were identified that reported on skin tests, followed by provocations. In the case of IHR to ICM, 65/69 (94%) patients with a positive skin test for the culprit media tolerated a challenge with a skin-test-negative alternative ICM. In IHR to ICM with a negative skin test for the culprit media, provocations were positive in 3.2%–9.1% patients. In the case of a NIHR to ICM with a positive skin test, provocation with a skin-test-negative agent was tolerated in 75/105 (71%) of cases. In NIHR with a negative skin test for the culprit agent, re-exposure to the culprit or an alternative was positive in 0%–34.6% patients. Provocations with the same ICM in skin test positive patients with IHR or NIHR were positive for a majority of the patients, although such provocation tests were rarely performed. Data on hypersensitivity reactions, skin tests and provocations with gadolinium-based contrast media were limited; however, they exhibited a pattern similar to that observed in ICM.Conclusion:In both ICM and gadolinium-based contrast media, the risk of an immediate repeat reaction is low when skin tests are negative. In contrast, a provocation with a skin-test-positive contrast medium showed a high risk of an immediate repeat hypersensitivity reaction. Therefore, a thorough medical history is necessary, followed by skin tests. A provocation is recommended, for diagnostic work-up, when the diagnosis is uncertain.

Prevention of nonsteroidal inflammatory drug-induced urticaria and/or angioedema

BackgroundUrticaria and/or angioedema (U/AE) are the most frequent and less severe forms of nonallergic hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Management of NSAID-induced U/AE includes (1) the avoidance of the culprit drug and of cyclooxygenase (COX) 1 inhibitors, (2) the use of weak COX-2 inhibitors, and/or (3) desensitization to aspirin. Because these possibilities may have drawbacks, we tested the possibility of preventing NSAID-induced U/AE by the administration of antihistamines and/or a combination of antihistamines and leukotriene antagonists. ObjectiveTo test the preventive effect of antihistamines and/or leukotriene antagonists on the development of U/AE in patients with a history of NSAID hypersensitivity confirmed by a positive challenge result. MethodsA single, placebo-controlled, oral challenge using the culprit NSAID was applied to 65 patients with a history of NSAID-induced U/AE. In the case of recurrence of the symptoms, another oral challenge was performed under premedication with antihistamines alone or combined antihistamines and leukotriene antagonists. ResultsA total of 59 of 65 patients (90%) tolerated a normal dose of NSAID, confirming previous data on the poor reproducibility of nonallergic hypersensitivity reactions to NSAIDs on challenge. Of the 6 patients who experienced recurrence of the U/AE on NSAID challenge, antihistamines and combined antihistamines and leukotriene antagonists prevented the hypersensitivity reactions in 2 and 3 of them, respectively. Only 1 patient still developed a moderate NSAID-induced urticaria despite the double premedication. ConclusionTreatment with NSAIDs at normal doses is possible and well tolerated in patients who have experienced NSAID-induced U/AE, which could be prevented by the concomitant use of antihistamines and leukotriene antagonists.

Diagnosis and management of drug hypersensitivity reactions

The present article addresses the advances in the diagnosis and management of drug hypersensitivity reactions that were discussed in the 4th Drug Hypersensitivity Meeting held in Rome in April 2010. Such reactions can be classified as immediate or nonimmediate according to the time interval between the last drug administration and onset. Immediate reactions occur within 1 hour, and nonimmediate reactions occur after more than 1 hour. Clinical and immunologic studies suggest that type-I (IgE-mediated) and type-IV (T cell-mediated) pathogenic mechanisms are involved in most immediate and nonimmediate reactions, respectively. In diagnosis prick, patch, and intradermal tests are the most readily available tools. Determination of specific IgE levels is still the most common in vitro method for diagnosing immediate reactions. New diagnostic tools, such as the basophil activation test, the lymphocyte activation test, and enzyme-linked immunospot assays for analysis of the frequency of antigen-specific, cytokine-producing cells, have been developed for evaluating either immediate or nonimmediate reactions. The sensitivity of allergologic tests is not 100%; therefore in selected cases provocation tests are necessary. In the diagnosis of nonallergic hypersensitivity reactions to nonsteroidal anti-inflammatory drugs, the provocation test with the suspected drug still represents the "gold standard." However, there was no consensus regarding the use of this test in subjects with histories of hypersensitivity reactions to 1 (single reactors) or more (multiple reactors) nonsteroidal anti-inflammatory drugs. With regard to management, desensitization allows patients to be treated with irreplaceable chemotherapy agents, such as taxanes, platinum salts, and mAbs, to which they have presented hypersensitivity reactions. Desensitization also permits the use of aspirin in aspirin-sensitive patients undergoing revascularization and in subjects with aspirin-exacerbated respiratory disease.

Allergic and nonallergic hypersensitivity reactions to silicone: a report of one case

AllergyVolume 64, Issue 10 p. 1555-1556 Allergic and nonallergic hypersensitivity reactions to silicone: a report of one case A. Rubio, Corresponding Author A. Rubio *Université de Nice Sophia AntipolisPôle Enfant Adolescent, CHU de NiceHôpital Archet 2133 Route de Saint Antoine de Ginestière, 06200 Nice (France)Tel.: 00 33 (0)4 92 03 64 71Fax: 00 33 (0)4 92 03 59 51E-mail: [email protected]Search for more papers by this authorC. Ponvert, C. PonvertSearch for more papers by this authorO. Goulet, O. GouletSearch for more papers by this authorP. Scheinmann, P. ScheinmannSearch for more papers by this authorJ. De Blic, J. De BlicSearch for more papers by this author A. Rubio, Corresponding Author A. Rubio *Université de Nice Sophia AntipolisPôle Enfant Adolescent, CHU de NiceHôpital Archet 2133 Route de Saint Antoine de Ginestière, 06200 Nice (France)Tel.: 00 33 (0)4 92 03 64 71Fax: 00 33 (0)4 92 03 59 51E-mail: [email protected]Search for more papers by this authorC. Ponvert, C. PonvertSearch for more papers by this authorO. Goulet, O. GouletSearch for more papers by this authorP. Scheinmann, P. ScheinmannSearch for more papers by this authorJ. De Blic, J. De BlicSearch for more papers by this author First published: 15 September 2009 https://doi.org/10.1111/j.1398-9995.2009.02086.xCitations: 5 We report the case of a child with suspected immediate-type allergy to latex and/or silicone. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume64, Issue10October 2009Pages 1555-1556 RelatedInformation

Aspirin sensitivity and desensitization for asthma and sinusitis

NSAIDs-including aspirin (ASA)-that inhibit cyclooxygenase (COX)-1 induce nonallergic hypersensitivity reactions consisting of attacks of rhinitis and asthma. Such reactions occur exclusively in a subset of asthmatic patients who also have underlying nasal polyps and chronic hyperplastic eosinophilic sinusitis. We now refer to their underlying inflammatory disease of the entire respiratory tract as aspirin-exacerbated respiratory disease. This review focuses on descriptions of these patients; methods available to diagnose ASA-exacerbated respiratory disease; the unique ability of all NSAIDs that inhibit COX-1 to cross-react with ASA; lack of cross-reactivity with selective COX-2 inhibitors; an update on pathogenesis; and current thoughts about treatment, including ASA desensitization and daily ingestion of ASA itself.

Hypersensitivity Reactions to Paracetamol in Children: A Study of 25 Cases

Purpose of the Study. Reports of paracetamol (acetaminophen) allergic and nonallergic hypersensitivity reactions are rare. However, urticaria, angioedema, dyspnea, and allergic and nonallergic anaphylactic reactions have been reported in both children and adults in association with paracetamol administration. Most reactions to paracetamol occur in patients with a nonallergic hypersensitivity to nonsteroidal antiinflammatory drugs (NSAIDs). Alternatively, reactions may result from an allergic hypersensitivity to paracetamol, with tolerance of NSAIDs. This study reports an investigation of 25 children with suspected paracetamol hypersensitivity. Study Population. Twenty-five children, aged 8 months to 15 years, with a history of adverse reactions associated with paracetamol administration. In 12 of the 25 children studied, paracetamol adverse reactions were associated with concurrent administration of other medications or biological agents. Methods. Diagnosis of paracetamol hypersensitivity was based on either clinical history or the results of an oral challenge test. Reported reactions included urticaria, angioedema, conjunctivitis, dyspnea, and a maculopapular rash. Oral challenge tests with paracetamol were performed in the hospital setting. Paracetamol dosing was initiated at 1 mg and gradually increased until the appropriate cumulative dose for age and weight was achieved. An oral challenge with acetylsalicylic acid was performed in 1 child with a history highly suggestive of paracetamol hypersensitivity. Results. Paracetamol hypersensitivity was diagnosed in 1 patient (4%) on the basis of clinical history. The child reported accelerated reactions on 2 occasions, including facial angioedema, conjunctivitis, and dyspnea with wheezing, after isolated intake of paracetamol. Oral challenge to acetylsalicylic acid in this patient induced urticaria and angioedema. Oral challenges to paracetamol in the 24 other children studied were tolerated. Conclusions. Results of this study of 25 children with suspected paracetamol hypersensitivity concur with those of previous reports: paracetamol hypersensitivity is rare and is associated with hypersensitivity reactions to antiinflammatory medications. Reviewer Comments. Adverse reactions temporally associated with paracetamol may result from reactions to other medications or the underlying conditions for which these medications have been prescribed. Diagnostic evaluation of suspected paracetamol hypersensitivity is complicated further by the lack of validated, available skin or in vitro testing. Adverse reactions to paracetamol can be both allergic and nonallergic in nature. The results of this study underscore the need for careful evaluation for both paracetamol and NSAID hypersensitivity in children with a history suggestive of adverse reactions to paracetamol.

Cross-reactivity among drugs: clinical problems

Cross-reactivity among drugs is either mediated by immunologic mechanisms or not. The former kind is usually explained by the presence of common antigenic determinants in the cross-reacting drugs. In the case of compounds provoking non-allergic hypersensitivity reactions, cross-reactivity is explained by a common pharmacological characteristic, such as the inhibitory effect of non-steroidal anti-inflammatory drugs on cyclooxygenase-1 and the capability of muscle relaxants or contrast media to release histamine through a non-immunologic mechanism. The main clinical problem deriving from cross-reactivity among drugs is the compelling need to choose a potentially cross-reactive compound and, therefore, to assess cross-reactivity by diagnostic tests. In choosing alternative compounds, skin testing has been used in evaluating IgE-mediated cross-reactivity between penicillins and cephalosporins, as well as among muscle relaxants. In assessing T cell-mediated cross-reactivity among contrast media, corticosteroids, anticonvulsants and heparins, delayed-reading intradermal tests and patch tests, together with lymphocyte transformation tests, can be performed. Because of the limited sensitivity of in vivo and in vitro testing, the most prudent way of establishing the tolerability of a compound of the same group in patients who especially require one is a graded challenge when other allergologic tests are negative.