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Drug hypersensitivity reaction

Juan M González-Morena, María I Montañez, Giancarlo Aldini, Francisco J Sánchez-Gómez, Dolores Pérez-Sala
Drug hypersensitivity reactions result from the activation of the immune system by drugs or their metabolites. The clinical presentations of drug hypersensitivity can range from relatively mild local manifestations to severe systemic syndromes that can be life-threatening. As in other allergic reactions, the causes are multifactorial as genetic, metabolic and concomitant factors may influence the occurrence of drug hypersensitivity. Formation of drug protein adducts is considered a key step in drug adverse reactions, and in particular in the immunological recognition in drug hypersensitivity reactions...
September 27, 2016: Current Pharmaceutical Design
José A Cornejo-García, Abderrahim Oussalah, Miguel Blanca, Rosa-María Guéant-Rodríguez, Cristobalina Mayorga, Julie Waton, Annick Barbaud, Francesco Gaeta, Antonino Romano, Jean-Louis Guéant
Our knowledge of genetic predisposing factors of drug hypersensitivity reactions (DHRs) is still scarce. The analysis of the genetic basis of these reactions may contribute to dissect the underlying mechanisms. We will outline current knowledge of the genetic predictors of most common DHRs, including reactions to betalactam antibiotics (BLs), nonsteroidal anti-inflammatory drugs (NSAIDs) and biological agents. The predictors of DHRs to BLs are mostly linked to IgE-class switching, IgE pathway and atopy (IL4R, NOD2, LGALS3) in replicated candidate gene studies, and to antigen presentation (HLA-DRA) in the single replicated GWAS performed so far...
September 27, 2016: Current Pharmaceutical Design
Patrizia Bonadonna, Massimiliano Bonifacio, Roberta Zanotti
Mastocytosis is a clonal disease characterized by proliferation and accumulation of mast cells (MC) in different tissues, preferentially skin and bone marrow, leading to a wide variety of clinical manifestations, mainly caused by the inappropriate release of MC mediators. As a consequence, patients with mastocytosis may experience symptoms due to massive MC activation and release of mediators. Anaphylaxis is the most frequent manifestation of this phenomenon.Drugs are possible triggers of anaphylaxis in patients with mastocytosis, even though the association between mastocytosis and drug anaphylaxis does not appear to be as strong as anaphylaxis after hymenoptera sting; nevertheless, MC disorders might be ruled out in cases of severe systemic reactions to drugs...
September 28, 2016: Current Pharmaceutical Design
Maren Paulmann, Maja Mockenhaupt
Severe cutaneous adverse reactions (SCAR) are known for a high morbidity and mortality. They may be life-threatening for the affected patient and difficult to accomplish for the patient's family and the treating physician. Such conditions include not only bullous reactions like toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), but also acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). Since clinical pattern, etiology, prognosis and treatment differ among these severe skin reactions, a clear diagnosis based on a comprehensive clinical examination, skin biopsy, and specific laboratory tests is necessary...
September 28, 2016: Current Pharmaceutical Design
Inmaculada Doña, María Salas, James R Perkins, Esther Barrionuevo, Francesco Gaeta, Jose A Cornejo-García, Paloma Campo, Maria José Torres
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the leading causes of hypersensitivity reactions to drugs, and they are classified in two groups: those induced by non-specific immunological mechanisms (non-allergic or cross-intolerance (CI) reactions), or by specific immunological mechanisms (allergic or selective reactions (SR)). The pathogenesis of CI is associated with their pharmacological activity (COX-1 inhibition), with symptoms due to an imbalance in the arachidonic acid pathway, independently of their chemical structure...
September 28, 2016: Current Pharmaceutical Design
Carrie C Coughlin, Melinda V Jen, Markus D Boos
Drug hypersensitivity syndrome (DHS) is a severe medication reaction involving multiple organ systems that is characterized by rash, lymphadenopathy, and laboratory aberrations, including hepatic enzyme changes. Viral reactivation in the setting of DHS can significantly affect the course of disease. We report two children in whom parvovirus infection prolonged and complicated their course of DHS. Most other DHS-complicating viruses are herpesviruses; this report broadens the scope of DHS-modifying infections to include activation of Parvoviridae...
October 25, 2016: Pediatric Dermatology
Md Nazmul Hasan, Nur Kabidul Azam, Md Nasir Ahmed, Akinori Hirashima
Snakebite is the single most important toxin-related injury, causing substantial mortality in many parts of the Africa, Asia and the Americas. Incidence of snakebite is usually recorded in young people engaged in active physical work in rural areas. The various plant parts used to treat snakebite included whole plant, leaves, barks, roots and seeds. Most bites in Bangladesh are recorded between May and October with highest number in June. Lower and upper limbs are most common sites of snakebite, but it may happen in other sites as well...
October 2016: Journal of Traditional and Complementary Medicine
Katherine C Konvinse, Elizabeth J Phillips, Katie D White, Jason A Trubiano
PURPOSE OF REVIEW: Antimicrobials are a leading cause of severe T cell-mediated adverse drug reactions (ADRs). The purpose of this review is to address the current understanding of antimicrobial cross-reactivity and the ready availability of and evidence for in-vitro, in-vivo, and ex-vivo diagnostics for T cell-mediated ADRs. RECENT FINDINGS: Recent literature has evaluated the efficacy of traditional antibiotic allergy management, including patch testing, skin prick testing, intradermal testing, and oral challenge...
October 7, 2016: Current Opinion in Infectious Diseases
Meghan MacKenzie, Richard Hall
PURPOSE: Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU. SOURCE: We selected relevant literature to illustrate the important concepts contained within. PRINCIPAL FINDINGS: Two main approaches have been used to identify genetic abnormalities - the candidate gene approach and the genome-wide approach...
October 17, 2016: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
Tara F Carr
OBJECTIVE: The aim of this paper was to review the classification of adverse drug reactions, highlight the known pathophysiology of immediate hypersensitivity reactions, and discuss the utility of diagnostic testing for immunologically mediated immediate reactions to gadolinium-based contrast agents (GBCAs). METHODS: Current literature on immediate reactions to GBCA was reviewed and summarized. RESULTS: Adverse drug reactions to GBCA are rare, and can be attributed to physiologic, immunologic, and nonimmunologic processes...
June 29, 2016: Topics in Magnetic Resonance Imaging: TMRI
James R Costello, Bobby Kalb, Diego R Martin
Since their clinical introduction in 1988, gadolinium-based contrast agents (GBCAs) have demonstrated an excellent safety profile with a reported acute adverse reaction rate ranging from 0.01% to 2%. By comparison, the acute adverse reaction rate of low osmolar nonionic computed tomography contrast agents (CTCs) ranges from 0.7% to 3.1%. Many of the risk factors associated with CTC reactions (drug allergies, asthma, atopy, prior contrast reaction) also point toward an increased incidence of acute adverse events to GBCAs...
June 29, 2016: Topics in Magnetic Resonance Imaging: TMRI
Marc D Cohen, Edward Keystone
Rituximab is a chimeric monoclonal antibody directed at the CD20 molecule on the surfaces of some but not all B cells. It depletes almost all peripheral B cells, but other niches of B cells are variably depleted, including synovium. Its mechanism of action in rheumatoid arthritis (RA) is only partially understood. Rituximab was efficacious in clinical trials of patients with RA, including those who are methotrexate naïve, those with an incomplete response to methotrexate, and those with an incomplete response to tumor necrosis factor inhibitors...
December 2015: Rheumatol Ther
Gemma Amo, José A Cornejo-García, Jesus M García-Menaya, Concepcion Cordobes, M J Torres, Gara Esguevillas, Cristobalina Mayorga, Carmen Martinez, Natalia Blanca-Lopez, Gabriela Canto, Alfonso Ramos, Miguel Blanca, José A G Agúndez, Elena García-Martín
The high-affinity IgE receptor (Fcε RI) is a heterotetramer of three subunits: Fcε RIα, Fcε RIβ, and Fcε RIγ (αβγ2) encoded by three genes designated as FCER1A, FCER1B (MS4A2), and FCER1G, respectively. Recent evidence points to FCERI gene variability as a relevant factor in the risk of developing allergic diseases. Because Fcε RI plays a key role in the events downstream of the triggering factors in immunological response, we hypothesized that FCERI gene variants might be related with the risk of, or with the clinical response to, selective (IgE mediated) non-steroidal anti-inflammatory (NSAID) hypersensitivity...
2016: Frontiers in Pharmacology
Thomas Schluep, Jason Lickliter, James Hamilton, David L Lewis, Ching-Lung Lai, Johnson Yn Lau, Stephen A Locarnini, Robert G Gish, Bruce D Given
ARC-520 Injection, an RNA interference drug for the treatment of hepatitis B that targets cccDNA-derived viral mRNA transcripts with high specificity, effectively reduces the production of viral proteins and HBV DNA. In this phase I, randomized, double-blind, placebo-controlled study, 54 healthy volunteers (half male, half female) received a single, intravenous dose of 0.01-4.0 mg/kg ARC-520 Injection (N = 36) or placebo (N = 18). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (cytokines and complement)...
October 14, 2016: Clinical Pharmacology in Drug Development
G Cortellini, A Romano, A Santucci, A Barbaud, S Bavbek, D Bignardi, M Blanca, P Bonadonna, M T Costantino, J J Laguna, C Lombardo, L Losappio, J Makowska, A Nakonechna, O Quercia, E A Pastorello, V Patella, I Terreehorst, S Testi, J R Cernadas, J Dionicio Elera, D Lippolis, S Voltolini, D Grosseto
BACKGROUND: Hypersensitivity to acetylsalicylic acid (ASA) constitutes a serious problem for subjects with coronary artery disease. In such subjects, physicians have to choose the more appropriate procedure between challenge and desensitization. As the literature on this issue is sparse, the present study aims to establish in these subjects clinical criteria for eligibility for an ASA challenge and/or desensitization. METHODS: Collection and analysis of data on ASA challenges and desensitizations from 10 allergy centers, as well as consensus among the related physicians and an expert panel...
October 12, 2016: Allergy
Jiwon Lee, Eu Gene Park, Munhyang Lee, Jeehun Lee
BACKGROUND AND PURPOSE: Antiepileptic drug (AED)-associated cutaneous adverse drug reactions can lead to the discontinuation of medications. The aim of this study was to determine the long-term efficacy and safety of performing desensitization to oxcarbazepine. METHODS: This study involved 20 patients who exhibited cutaneous adverse drug reactions associated with oxcarbazepine use between July 2009 and March 2016 at Samsung Medical Center. All of the participants had to discontinue oxcarbazepine despite presenting initially positive responses...
October 7, 2016: Journal of Clinical Neurology
Yanbing Zu, Min-Han Tan, Chee Ren Ee, Jackie Y Ying
A number of human leukocyte antigen (HLA) gene alleles have been found to be genetic risk markers for immunologically mediated drug hypersensitivity. Clinical adoption of HLA pharmacogenomics requires facile and accurate allele screening assays. As HLA genes are highly polymorphic, currently available methods are usually labor-intensive and liable to generate false positives. Herein we report a general strategy for screening HLA alleles with nanoparticle probes. Specific HLA alleles can be identified by gauging three to five sequence variants...
October 5, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
David A Khan
Adverse drug reactions (ADRs) are a relatively common cause of morbidity and mortality. Many factors can contribute to ADRs, including genetics. The degree to which genetics contributes to ADRs is not entirely clear and varies by drug, as well as the type of ADR. Pharmacogenetics and, more recently, pharmacogenomics have been applied to the field of ADRs for both predictable ADRs and hypersensitivity drug reactions. Evaluations for glucose-6-phosphate dehydrogenase and thiopurine S-methyltransferase are commonplace clinical tests to reduce hematologic problems associated with drugs, such as dapsone and azathioprine, respectively...
October 2016: Journal of Allergy and Clinical Immunology
Tatiana Duarte, Sara Gonçalves, Catarina Sá, Rita Marinheiro, Rita Rodrigues, Filipe Seixo, Elza Tomas, Rui Caria
Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs are common and five types of reactions have been defined. The prevalence of such reactions in patients with myocardial infarction is unclear, and so antiplatelet therapy in this population is a challenge. Various desensitization protocols have been developed but there are no specific guidelines for their use. The authors present the case of a patient with acute coronary syndrome and aspirin hypersensitivity referred for urgent coronary angiography...
October 4, 2016: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
Adam N Williams
Aspirin-exacerbated respiratory disease (AERD) is a distinct clinical condition characterized by chronic sinusitis with nasal polyps, asthma, and hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Distinguishing AERD from other forms of chronic sinusitis, asthma, and NSAID reactivity has important clinical implications for management. The clinical history is helpful, but not adequate for confirming the diagnosis of AERD, in most cases. Diagnostic provocation challenge remains the only way to confirm or exclude the diagnosis of AERD...
November 2016: Immunology and Allergy Clinics of North America
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