Maintaining Safety with SARS-CoV-2 Vaccines Castells, Mariana C; Phillips, Elizabeth J
The New England journal of medicine,
02/2021, Letnik:
384, Številka:
7
Journal Article
Penicillin Allergy Castells, Mariana; Khan, David A; Phillips, Elizabeth J
The New England journal of medicine,
12/2019, Letnik:
381, Številka:
24
Journal Article
The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 presents with a spectrum of clinical manifestations from asymptomatic or mild, self-limited ...constitutional symptoms to a hyperinflammatory state ("cytokine storm") followed by acute respiratory distress syndrome and death. The objective of this study was to provide an evidence-based review of the associated pathways and potential treatment of the hyperinflammatory state associated with severe acute respiratory syndrome coronavirus 2 infection. Dysregulated immune responses have been reported to occur in a smaller subset of those infected with severe acute respiratory syndrome coronavirus 2, leading to clinical deterioration 7 to 10 days after initial presentation. A hyperinflammatory state referred to as cytokine storm in its severest form has been marked by elevation of IL-6, IL-10, TNF-α, and other cytokines and severe CD4
and CD8
T-cell lymphopenia and coagulopathy. Recognition of at-risk patients could permit early institution of aggressive intensive care and antiviral and immune treatment to reduce the complications related to this proinflammatory state. Several reports and ongoing clinical trials provide hope that available immunomodulatory therapies could have therapeutic potential in these severe cases. This review highlights our current state of knowledge of immune mechanisms and targeted immunomodulatory treatment options for the current coronavirus disease 2019 pandemic.
Antibiotic allergy Blumenthal, Kimberly G; Peter, Jonny G; Trubiano, Jason A ...
The Lancet,
01/2019, Letnik:
393, Številka:
10167
Journal Article
Recenzirano
Odprti dostop
Antibiotics are the commonest cause of life-threatening immune-mediated drug reactions that are considered off-target, including anaphylaxis, and organ-specific and severe cutaneous adverse ...reactions. However, many antibiotic reactions documented as allergies were unknown or not remembered by the patient, cutaneous reactions unrelated to drug hypersensitivity, drug-infection interactions, or drug intolerances. Although such reactions pose negligible risk to patients, they currently represent a global threat to public health. Antibiotic allergy labels result in displacement of first-line therapies for antibiotic prophylaxis and treatment. A penicillin allergy label, in particular, is associated with increased use of broad-spectrum and non-β-lactam antibiotics, which results in increased adverse events and antibiotic resistance. Most patients labelled as allergic to penicillins are not allergic when appropriately stratified for risk, tested, and re-challenged. Given the public health importance of penicillin allergy, this Review provides a global update on antibiotic allergy epidemiology, classification, mechanisms, and management.
The evolution of human immunodeficiency virus (HIV) treatment has improved our understanding and management of complex pharmacological issues that have driven improved outcomes and quality of life of ...the HIV‐infected patient. These issues include adherence, long‐ and short‐term toxicities, pharmacoenhancement, pharmacogenomics, therapeutic drug monitoring, differential penetration of drugs into sanctuary sites, such as the central nervous system, genital tract and small bowel, and drug–drug and drug–food interactions related to cytochrome P450 drug‐metabolizing enzymes, uridine diphosphate glucuronyltransferases and drug transporters, to name a few. There is future promise, as an increased understanding of the immunopathogenesis of HIV and global public health initiatives are driving novel treatment approaches with goals to prevent, control and, ultimately, eradicate HIV.
Immune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy. We ...report the cases of two patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab. In both patients, there was development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with a robust presence of T-cell and macrophage infiltrates. Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumors and skeletal muscle. Pharmacovigilance studies show that myocarditis occurred in 0.27% of patients treated with a combination of ipilimumab and nivolumab, which suggests that our patients were having a rare, potentially fatal, T-cell-driven drug reaction. (Funded by Vanderbilt-Ingram Cancer Center Ambassadors and others.).
Immune‐mediated adverse reactions to vaccines Stone, Cosby A.; Rukasin, Christine R.F.; Beachkofsky, Thomas M. ...
British journal of clinical pharmacology,
December 2019, Letnik:
85, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Vaccination continues to be the single most important and successful public health intervention, due to its prevention of morbidity and mortality from prevalent infectious diseases. Severe ...immunologically mediated reactions are rare and less common with the vaccine than the true infection. However, these events can cause public fearfulness and loss of confidence in the safety of vaccination. In this paper, we perform a systematic literature search and narrative review of immune‐mediated vaccine adverse events and their known and proposed mechanisms, and outline directions for future research. Improving our knowledge base of severe immunologically mediated vaccine reactions and their management drives better vaccine safety and efficacy outcomes.
The overlabeling of pediatric antibiotic allergy represents a huge burden in society. Given that up to 10% of the US population is labeled as penicillin allergic, it can be estimated that at least 5 ...million children in this country are labeled with penicillin allergy. We now understand that most of the cutaneous symptoms that are interpreted as drug allergy are likely viral induced or due to a drug-virus interaction, and they usually do not represent a long-lasting, drug-specific, adaptive immune response to the antibiotic that a child received. Because most antibiotic allergy labels acquired in childhood are carried into adulthood, the overlabeling of antibiotic allergy is a liability that leads to unnecessary long-term health care risks, costs, and antibiotic resistance. Fortunately, awareness of this growing burden is increasing and leading to more emphasis on antibiotic allergy delabeling strategies in the adult population. There is growing literature that is used to support the safe and efficacious use of tools such as skin testing and drug challenge to evaluate and manage children with antibiotic allergy labels. In addition, there is an increasing understanding of antibiotic reactivity within classes and side-chain reactions. In summary, a better overall understanding of the current tools available for the diagnosis and management of adverse drug reactions is likely to change how pediatric primary care providers evaluate and treat patients with such diagnoses and prevent the unnecessary avoidance of antibiotics, particularly penicillins.
The variant allele HLA‐B*15:02 is strongly associated with greater risk of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients treated with carbamazepine or oxcarbazepine. ...The variant allele HLA‐A*31:01 is associated with greater risk of maculopapular exanthema, drug reaction with eosinophilia and systemic symptoms, and SJS/TEN in patients treated with carbamazepine. We summarize evidence from the published literature supporting these associations and provide recommendations for carbamazepine and oxcarbazepine use based on HLA genotypes.
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