Showing papers by "Michael J. Rieder published in 2022"

Drug reaction with eosinophilia and systemic symptoms (DRESS): A tertiary care centre retrospective study

Abstract: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, drug‐induced severe adverse reaction that usually occurs 3–6 weeks after initial exposure to certain drugs. It affects mainly adults and children to a lesser extent. Clinical features include fever, facial oedema, generalized skin rash, lymphadenopathy, haematological abnormalities and internal organ involvement. The objective was to investigate the clinical and laboratory features of patients with DRESS in our centre.

War exposure, post-traumatic stress symptoms and hair cortisol concentrations in Syrian refugee children

Abstract: Abstract Altered secretion of cortisol, the primary effector of the hypothalamus–pituitary–adrenal axis, has been proposed as a means by which traumatic experiences compromise later mental health. However, despite the popularity of cortisol as a potential biomarker for stress and adversity, findings are inconsistent, and little is known about the impact of war-related trauma on stress physiology of children and adolescents. Here we aimed to evaluate the relationships between war exposure, current living conditions, hair cortisol concentrations (HCC) and post-traumatic stress disorder (PTSD) symptoms in a large cohort of Syrian refugee children and adolescents (6–18 years) and their caregiver. This longitudinal observational study assessed Syrian refugee children and adolescents in two waves, 1 year apart, within informal tented settlements in Lebanon. The relationships between war exposure, time since leaving Syria, PTSD symptoms and HCC were investigated using linear mixed-model regression utilising both waves of data collected (Y1: N = 1574, Y2: N = 923). Hair cortisol concentration was positively, but weakly associated with the number of war-related events experienced. This was limited to those who were at least 12 years old at the time of war exposure. Conversely, HCC decreased with time since leaving Syria. HCC was also associated with PTSD symptoms but not with the quality of their current living conditions. This study revealed that changes to hypothalamic-pituitary-adrenal axis activity may accompany both earlier war exposure and current PTSD symptoms in children and adolescents. Additionally, early adolescence may be a particularly sensitive time in terms of trauma-related changes to the hypothalamic-pituitary-adrenal axis.

Genetic markers of drug hypersensitivity in pediatrics: current state and promise

Abstract: ABSTRACT Introduction Drug hypersensitivity reactions (DHRs) represent a great challenge to clinicians due to their unpredictability and severity, notably being potentially fatal. Genetic markers for DHRs have been emerging as potential valuable clinical tools for prediction and diagnosis of DHRs. Dedicated pediatric studies in this field are scarce and many published studies lack key data in this regard. Area covered This review briefly covers the current status of the use and validation of genetic markers for drug hypersensitivity in pediatrics. Classification, epidemiology and pathophysiology of DHRs are also briefly described. We searched PubMed, Ovid Medline, Web of Science, Scopus and Google Scholar literature databases for all relevant articles published from their date of commencement to March 2022. We summarized the current existing evidence and discussed the role and potential of pharmacogenomic testing in management of DHRs in pediatrics. Expert opinion Several genetic markers for DHRs in children have been identified and proven to be useful tools for prediction, diagnosis, and management of these adverse reactions. However, data in pediatric populations is still limited and confined to specific drugs in specific ethnic groups. Further research is needed to identify and validate more genetic markers to help guide drug therapy in children.

Pathophysiology of Drug Hypersensitivity.

Abstract: Drug Hypersensitivity reactions (DHRs) are type B adverse drug reactions (ADRs) traditionally defined as unpredictable, dose independent and not related to the drug pharmacology. DHRs, also called drug allergy if the immune system involvement is confirmed, represent around one-sixth of all ADRs and can cause major clinical problems due to their vague clinical presentation and irregular time course. Understanding the underlying pathophysiology of DHRs is very important for their diagnosis and management. Multiple layers of evidence exist pointing to the involvement of the immune system in DHRs. Recent data have led to a paradigm shift in our understanding of the exact pathophysiology of these reactions. Numerous hypotheses proposing explanation on how a low molecular weight drug molecule can elicit an immune reaction have been proposed. In addition to the classical 'hapten' hypothesis, the reactive metabolite hypothesis, the pharmacological interaction with the immune system (p-i) concept, the danger/injury hypothesis, and the altered peptide repertoire hypothesis have been proposed. We here introduce the inflammasome activation hypothesis and the cross-reactivity hypothesis as an additional models explaining the pathophysiology of DHRs. Available data supporting these hypotheses are briefly summarized and discussed. We also introduced the cross-reactivity model, which may provide a platform to appreciate the potential role played by other factors leading to the activation of the immune system. We believe that although the drug in question could be the trigger of the reaction, the components of the immune system mediating the reaction do not act in isolation but rather affected by the proinflammatory milieu occurring at the time of the reaction. This review attempts at summarizing the available evidence to further illustrate the pathophysiology of DHRs.

Bridging the gap between bench and clinic: the importance of understanding the mechanism of iodinated contrast media hypersensitivity.

Abstract: Since the advent of computed tomography (CT), iodinated contract media (ICM) has become one of the most regularly administered intravenous medications in clinical settings. Although considered generally safe, ICM is one of the most common causes of adverse drug reactions in clinical practice, accounting for more than two million adverse reactions worldwide. Currently, there are few useful tools to diagnose patient hypersensitivity, with the major limitation being the lack of consensus regarding the mechanisms of hypersensitivity to ICM. While there is an overwhelming abundance of literature pertaining to clinical features including incidence, symptomatology, and risk, few studies have further investigated the underlying mechanisms behind their clinical observations. Of the available literature discussing pathophysiology, most primary studies were completed over twenty years ago, since which the molecular characteristics of ICM have changed. Furthermore, many reviews mentioning pathophysiology fail to adequately emphasize the clinical importance of understanding the molecular pathways involved in hypersensitivity. In this review we aim to emphasize the clinical relevance of pathophysiology as it relates to the prediction and diagnosis of hypersensitivity reactions to ICM. To this end, we will first briefly characterize hypersensitivity reactions to ICM with respect to epidemiology and clinical presentation. We will then present the existing evidence supporting various proposed mechanisms of hypersensitivity, highlighting the gaps that remain in the mechanistic delineation of both immediate and delayed reactions. Finally, we discuss the possibility of in vitro testing as a way to predict and diagnose hypersensitivity reactions, pending a more complete elucidation of mechanisms.

The role of in vitro testing in pharmacovigilance for ß-lactam-induced serum sickness-like reaction: A pilot study

Abstract: Background: Current pharmacovigilance (PV) methods for detection of adverse drug reactions (ADRs) fail to capture rare immune-mediated drug hypersensitivity reactions (DHRs) due to their scarcity and the lack of clear diagnostic criteria. Drug-induced serum sickness-like reactions (SSLRs) are rare type of DHRs that occur in susceptible patients 1–3 weeks after exposure to the culprit drug with ß-lactam antibiotics being the most associated drugs. The diagnosis of drug induced SSLR is difficult due to the lack of safe and reliable diagnostic tests for identifying the culprit drug. The lymphocyte toxicity assay (LTA) is an in vitro test used as a diagnostic tool for drug hypersensitivity reactions (DHRs). Objective: To evaluate the role of the LTA test for diagnosing and capturing SSLR due to ß-lactam antibiotics in a cohort of patients. Methods: Patients were recruited from patients referred to the Drug Hypersensitivity Clinic at Clinic at London Health Science Centre with suspicion of drug allergy. Twenty patients (10 males and 10 females) were selected to be tested to confirm diagnosis. Demographic data was collected form the patents and blood samples were withdrawn from all patients and from 20 healthy controls. The LTA test was performed on all subjects and data is expressed as percentage increase in cell death compared to control (vehicle without the drug). Results: In the result of LTA tests performed on samples from the selected 20 patients. There was a significant (p < 0.05) concentration-dependent increase in cell death in cells isolated from patients as compared to cells from healthy controls when incubated with the drug in the presence of phenobarbitone-induced rat liver microsomes. Conclusion: Giving its safety and good predictive value the LTA test has very strong potential to be a useful diagnostic tool for ß-lactam-induced SSLR. The test procedure is relatively simple and not overly costly. Further studies including other drug classes are needed to evaluate the utility of the LTA test for SSLR due to other drugs.