Early Biomarkers for Severe Drug Hypersensitivity Reactions

2019 ◽  
Vol 25 (36) ◽  
pp. 3829-3839 ◽  
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.

scholarly journals Converter Phenotype: A New Profile That Is Not Exclusive to Taxanes

2022 ◽  
Vol 2 ◽  
Author(s):  
Teodorikez Wilfox Jimenez-Rodriguez ◽  
Francisco Manuel Marco de la Calle ◽  
Inmaculada Lozano-Cubo ◽  
Rosa Ana Montoyo-Anton ◽  
Victor Soriano-Gomis ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Drug Exposure ◽  
Drug Hypersensitivity ◽  
Skin Tests ◽  
Hypersensitivity Reactions ◽  
Test Results ◽  
Drug Reactions ◽  
Immediate Hypersensitivity ◽  
Drug Hypersensitivity Reactions ◽  
Median Interval

Introduction: Phenotype I hypersensitivity reactions are the most commonly reported drug reactions; however, precision medicine has made it possible to characterize new phenotypes. A recent communication proposed the existence of a “converter phenotype,” which would affect patients who present non-immediate hypersensitivity reactions and in subsequent exposures develop immediate hypersensitivity reactions. This study aimed to describe the clinical characteristics of converter phenotype reactions and their evolution during desensitization to chemotherapeutic drugs and monoclonal antibodies.Methods: We retrospectively reviewed our database of patients undergoing desensitization to chemotherapy or biological agents and selected those with a converter phenotype. Demographic and clinical characteristics of the patients, the results of skin tests, tryptase and IL-6 levels, and desensitization outcomes were assessed.Results: Of 116 patients evaluated, 12 (10.3%) were identified as having a converter phenotype. The median interval between drug exposure and reaction was 90.6 h (range 8-288 h). After the conversion, phenotype I was the most frequent (58.3%), followed by cytokine release reactions (33.3%). Fifty-one desensitizations were undertaken and all treatments completed, with 10 (19.6%) breakthrough reactions. No new changes in the phenotype were detected.Conclusions: The symptoms of non-immediate drug hypersensitivity reactions may indicate the need for an early allergological evaluation to assess the risk of future immediate drug reactions. Clinical characteristics, skin test results, and biomarkers can help predict responses to rapid drug desensitization, guiding clinicians on how to optimize therapy delivery while maintaining patient safety.

Ipersensibilità ai FANS: intolleranza o allergia?

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.

scholarly journals INVESTIGATION OF MEDICALLY INDUCED SKIN REACTIONS BASED ON THE ANALYSIS OF REPORTS OF ADVERSE DRUG REACTIONS IN THE REPUBLIC OF CRIMEA (FROM 2009 TO 2016)

2019 ◽  
Vol 7 (1) ◽  
pp. 32-41 ◽  
Author(s):  
A. V. Matveev ◽  
А. E. Krasheninnikov ◽  
E. A. Egorova ◽  
Е. I. Konyaeva
Keyword(s):  
Adverse Reactions ◽  
Drug Hypersensitivity ◽  
Clinical Manifestations ◽  
World Health ◽  
Report Cards ◽  
Hypersensitivity Reactions ◽  
Drug Reactions ◽  
Skin Reactions ◽  
Drug Hypersensitivity Reactions ◽  
The Republic

Drug hypersensitivity reactions are among the most important problems that arise when using drugs. The occurrence of such reactions in the population is at least 7% and tends to a constant increase. The most frequent manifestations of drug hypersensitivity reactions are medically induced skin lesions.The aimof this research was to study and analyze the cases of development of skin drug reactions on the basis of the reports on the adverse reactions (ADRs) of the drugs, registered in the Republic of Crimea in the period from 2009 to 2016.Materials and methods.The objects of the research were report cards about the adverse reactions, registered in the regional base (registry) of spontaneous messages called ARCADe (Adverse Reactions in Crimea, Autonomic Database) for the period from 2009 to 2016. During the analysis of the report cards, 2,698 cases of the development of skin drug reactions arising in response to the use of drugs in patients were selected. The study of the frequency of occurrence of skin drug reactions in the application of various groups of drugs was carried out taking into account the codes of the Anatomical Therapeutic Chemical (ATC) Сlassification System of drugs of the World Health Organization (WHO).Results.Of the study showed that the development of skin drug reactions was most often associated with the use of antimicrobial agents for internal use, nonsteroidal anti-inflammatory drugs (NSAIDs), drugs for the treatment of diseases of the gastrointestinal tract and agents that affect the nervous system. Among the clinical manifestations of skin drug reactions, generalized and localized rashes prevailed, and itching and hyperemia of the skin were much less common in patients. The analysis of age categories showed that the most frequently medically induced reactions occurred in children from birth to 3 years, as well as in the age group of patients from 46 to 60 years. The risk factors identified in the course of the analysis, were female gender, early childhood and old age, as well as the presence of aggravated drug allergy history.Conclusion.Drug hypersensitivity reactions create certain difficulties in clinical practice related to the diagnosis, treatment and prophylaxis, and may also cause danger to health or life of patients. In this connection, the study of such adverse reactions is the most important task of practical health care and requires direct participation of doctors of all specialties.

scholarly journals Non-immediate drug hypersensitivity reactions secondary to intravitreal anti-vascular endothelial growth factors

2021 ◽  
Author(s):  
E. Moret ◽  
A. Ambresin ◽  
C. Gianniou ◽  
J. Bijon ◽  
C. Besse-Hayat ◽  
...  
Keyword(s):  
Growth Factors ◽  
Drug Hypersensitivity ◽  
Clinical Manifestations ◽  
Drug Discontinuation ◽  
Vascular Endothelial Growth Factors ◽  
Vascular Endothelial ◽  
Hypersensitivity Reactions ◽  
Anti Vegf ◽  
Drug Hypersensitivity Reactions ◽  
Endothelial Growth Factors

Abstract Purpose To describe a series of non-immediate drug hypersensitivity reactions after intravitreal anti-vascular endothelial growth factors (anti-VEGFs). Patients and methods Retrospective report of 6 patients with cutaneous non-immediate drug hypersensitivity reactions following intravitreal anti-VEGF injections, 4 after ranibizumab, 1 after bevacizumab and 1 after aflibercept. Results Clinical manifestations ranged from mild maculopapular rash, purpura to severe generalized erythroderma, with or without systemic involvement such as microscopic hematuria and proteinuria or fever. In two out of the six patients, reintroduction of either the same or an alternative anti-VEGF drug did induce a recurrence of the drug hypersensitivity reaction, while 4 patients showed no recurrence. Conclusion Cutaneous non-immediate drug hypersensitivity reactions secondary to intravitreal anti-VEGF may occur. Continuation of the same drug or switch to another anti-VEGF may either induce recurrence or be well supported by the patient. The decision of drug discontinuation should be guided by the severity of the disease.

scholarly journals ANAMNESTIC, CLINICAL AND LABORATORY DATA ANALYSIS OF PATIENTS FOR DRUG HYPERSENSITIVITY REACTIONS

2021 ◽  
pp. 5-13
Author(s):  
Svitlana Zubchenko ◽  
Iryna Kril ◽  
Marta Lomikovska ◽  
Anna Havrylyuk ◽  
Kristina Lischuk-Yakymovych ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Drug Hypersensitivity ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Basophil Activation Test ◽  
Progressive Increase ◽  
Hypersensitivity Reactions ◽  
Treatment Protocols ◽  
Test Execution ◽  
Drug Hypersensitivity Reactions

The current development of the pharmaceutical industry in the synthesis of new chemical compounds, standardized treatment protocols, and disease prevention can lead to a progressive increase in drug hypersensitivity reactions, which often have serious consequences for human health. Increasing evidence of involvement of infections, including Herpesviridae viruses, in the development of drug hypersensitivity reactions is known.The method of flow cytometry can be used, in particular, the basophil activation test to diagnose drug hypersensitivity reactions. The anamnestic, clinical, andlaboratory data of 368 people were analyzed for the selection of patients at risk of drug hypersensitivity for the basophil degranulation test execution. It was found that among patients hypersensitivity reactions were most often detected to antibiotics (50.0%), radiopaque substances (27.7%), perioperative drugs, local anesthetics - 13.6% each. Clinical manifestations of these reactions were urticaria with angioneurotic edema (40.6%), urticaria (28.1%), anaphylaxis (21.9%), obstructive bronchitis chenges (9.37%). According to anamnestic and clinical-laboratory data, patients with a high risk of drug hypersensitivity reactions revealed frequent manifestations of herpesvirus infection HSV1 (34.4%), active chronic persistence of EBV (59.4%), accompanied by manifestations of EBV-associated secondary immune disorders and prevalence of chronic EBV infection in all patients.

scholarly journals Use of Rapid Drug Desensitization in Delayed Hypersensitivity Reactions to Chemotherapy and Monoclonal Antibodies

2022 ◽  
Vol 2 ◽  
Author(s):  
Arantza Vega ◽  
M. Isabel Peña ◽  
Inés Torrado
Keyword(s):  
Monoclonal Antibodies ◽  
Drug Hypersensitivity ◽  
Hypersensitivity Reactions ◽  
Short Period ◽  
Drug Hypersensitivity Reactions ◽  
Facial Edema ◽  
Delayed Reactions ◽  
Hospital Visits ◽  
To Receive ◽  
Maculopapular Exanthema

Background:Rapid drug desensitization (RDD) allows first-line therapies in patients with immediate drug hypersensitivity reactions (DHR) to chemotherapeutic drugs (ChD) and monoclonal antibodies (mAb). Desensitization in delayed drug reactions has traditionally used slow protocols extending up to several weeks; RDD protocols have been scarcely reported.Patients and Method:We retrospectively analyzed the patients referred to the Allergy Department, who had experienced a delayed DHR (> 6 h) related to a ChD or mAb and underwent an RDD protocol. The rate of successful administration of the offending drug and the presence of adverse reactions were evaluated.Results:A total of 93 RDDs were performed in 11 patients (including 6 men and 5 women, with a median age of 61 years). The primary DHR were maculopapular exanthema (MPE) (8), generalized delayed urticaria (1), MPE with pustulosis and facial edema (1), and facial edema with desquamative eczema (1). The meantime for the onset of symptoms was 3 days (range 1–16 days). RDD was performed using a protocol involving 8–13 steps, with temozolomide (25), bendamustine (4), rituximab (9), infliximab (24), gemcitabine (23), and docetaxel (8), within 4.6–6.5 h. Sixteen breakthrough reactions were reported during the RDD (17.2 %) in 5 patients; all were mild reactions including 11 delayed and 5 immediate reactions. All patients completed their treatment.Conclusions:RDD is a potentially safe and effective procedure in patients suffering from delayed reactions to ChD and mAb. It allows them to receive full treatment in a short period, thereby reducing time and hospital visits.

scholarly journals Nonsteroidal anti-inflammatory drugs-induced hypersensitivity reactions

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.

scholarly journals Diagnosing and Managing Patients with Reactions to Radiocontrast Media

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.

scholarly journals Mild to moderate hypersensitivity reactions to beta-lactams in children: a single-centre retrospective review

2019 ◽  
Vol 3 (1) ◽  
pp. e000435 ◽  
Author(s):  
Leticia Vila ◽  
Vanesa Garcia ◽  
Oihana Martinez Azcona ◽  
Loreley Pineiro ◽  
Angela Meijide ◽  
...  
Keyword(s):  
Drug Hypersensitivity ◽  
Skin Tests ◽  
Penicillin G ◽  
Hypersensitivity Reactions ◽  
Beta Lactam ◽  
Patch Tests ◽  
Provocation Tests ◽  
Delayed Reactions ◽  
Diagnostic Work ◽  
Low Sensitivity

ObjectiveBeta-lactam (BL) antibiotics are the most reported drugs in hypersensitivity reactions in children. More than 90% of these children tolerate the suspected drug after diagnostic work-up. Skin tests (STs) show low sensitivity. Our aim was to assess the performance of drug provocation tests (DPTs) without previous ST in mild and moderate delayed reactions and to propose a new DPT protocol.Design of the studyCharts from 213 children under 15 years of age referred for suspected BL allergy from 2011 to 1013 were reviewed. Prick, intradermal and patch tests were performed with major determinant penicilloyl-polylysine, minor determinant mixture, amoxicillin (AMX), cefuroxime, penicillin G and AMX–clavulamate. Children with negative skin tests underwent DPT. After an initial full dose of antibiotic, DPT was carried on for 3 days at home in patients reacting within the first 3 days of treatment. If the reaction took place from day 4 on of treatment, patients took the antibiotic for 5 days.ResultsWe included 108 girls and 105 boys. Mean age at the time of reaction was 3.66±3.06 years. 195 patients (91.5%) reacted to one BL. 154 reactions (67.2%) were non-immediate. Mild to moderate skin manifestations were most frequently reported. AMX–clavulanate was the most frequently involved (63.4%). DPT confirmed the diagnosis of drug hypersensitivity in 17 (7.3%) cases. These 17 patients had negative ST.ConclusionIn mild and moderate cases of BL hypersensitivity, diagnosis can be performed by DPT without previous ST

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