Rivaroxaban-Associated Bullous Pemphigoid in a Patient With Atrial Fibrillation.
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ABSTRACT:
SUBMITTER: Liang JC
PROVIDER: S-EPMC8636228 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The direct factor Xa inhibitor rivaroxaban was the first within the group of orally available direct factor Xa inhibitors to gain clinical approval for oral anticoagulation in patients with nonvalvular atrial fibrillation in 2011. The -xabans, as drugs from the group of oral direct factor Xa inhibitors are often referred to, comprise currently three drugs (apixaban, edoxaban, and rivaroxaban) with clinical approval for a variety of clinical indications that require oral anticoagulation therapy. The number of patients with nonvalvular atrial fibrillation requiring long-term oral anticoagulation therapy for the prevention of stroke and systemic embolism is predicted to increase up to five times by 2050. Many of these patients will be within the elderly and aging population that is at a higher risk of stroke and also at a higher risk for bleeding events. This requires novel options for efficient and safe oral anticoagulation, and rivaroxaban is one of the novel oral anticoagulants that have been shown to be at least as effective as vitamin K antagonists in patients with nonvalvular atrial fibrillation. Furthermore, like all of the novel oral anticoagulants, rivaroxaban provides a significant reduction in intracerebral hemorrhage compared with vitamin K antagonists such as warfarin. The clinical utility of oral anticoagulation with rivaroxaban in patients with nonvalvular atrial fibrillation is discussed here, along with special patient considerations, including impaired renal function, switching from a vitamin K antagonist, and patients with concomitant acute coronary syndrome.
| S-EPMC3938442 | biostudies-literature
Project description:BACKGROUND:Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the West. Oral steroids are the standard treatment.This is an update of the review published in 2005. OBJECTIVES:To assess treatments for bullous pemphigoid. SEARCH STRATEGY:In August 2010 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials), MEDLINE, EMBASE, and the Ongoing Trials registers. SELECTION CRITERIA:Randomised controlled trials of treatments for participants with immunofluorescence-confirmed bullous pemphigoid. DATA COLLECTION AND ANALYSIS:At least two authors evaluated the studies for the inclusion criteria, and extracted data independently. MAIN RESULTS:We included 10 randomised controlled trials (with a total of 1049 participants) of moderate to high risk of bias. All studies involved different comparisons, none had a placebo group. In 1 trial plasma exchange plus prednisone gave significantly better disease control at 1 month (0.3 mg/kg: RR 18.78, 95% CI 1.20 to 293.70) than prednisone alone (1.0 mg/kg: RR 1.79, 95% CI 1.11 to 2.90), while another trial showed no difference in disease control at 6 months.No differences in disease control were seen for different doses or formulations of prednisolone (one trial each), for azathioprine plus prednisone compared with prednisone alone (one trial), for prednisolone plus azathioprine compared with prednisolone plus plasma exchange (one trial), for prednisolone plus mycophenolate mofetil or plus azathioprine (one trial), for tetracycline plus nicotinamide compared with prednisolone (one trial). Chinese traditional medicine plus prednisone was not effective in one trial.There were no significant differences in healing in a comparison of a standard regimen of topical steroids (clobetasol) with a milder regimen (RR 1.00, 95% 0.97 to 1.03) in one trial. In another trial, clobetasol showed significantly more disease control than oral prednisolone in people with extensive and moderate disease (RR 1.09, 95% CI 1.02 to 1.17), with significantly reduced mortality and adverse events (RR 1.06, 95% CI 1.00 to 1.12). AUTHORS' CONCLUSIONS:Very potent topical steroids are effective and safe treatments for BP, but their use in extensive disease may be limited by side-effects and practical factors. Milder regimens (using lower doses of steroids) are safe and effective in moderate BP. Starting doses of prednisolone greater than 0.75 mg/kg/day do not give additional benefit, lower doses may be adequate to control disease and reduce the incidence and severity of adverse reactions. The effectiveness of adding plasma exchange, azathioprine or mycophenolate mofetil to corticosteroids, and combination treatment with tetracycline and nicotinamide needs further investigation.
| S-EPMC7138251 | biostudies-literature
Project description:Total knee arthroplasty is one of the safest and most routinely performed orthopedic procedures. As the volume of cases is expected to rise each year, so too will the incidence of uncommon complications. We describe a rare case of bullous pemphigoid, an autoimmune skin blistering disorder, that occurred after total knee arthroplasty in an otherwise healthy patient and led to hospital readmission. Early diagnosis and treatment of this condition may limit its spread and help to avoid comorbid sequelae.
| S-EPMC8141602 | biostudies-literature
Project description:Bullous pemphigoid (BP) is a rare autoimmune skin blistering disease, characterized by the presence of autoantibodies against hemidesmosomal autoantigens. Cytokine expression is altered in BP patients, and several of these differently expressed cytokines, including IL-1α, IL-1β, IL-8, and TNF-α, contribute to disease pathogenesis. Since genetic polymorphisms in the genes of these cytokines might be implicated in susceptibility to BP disease, we aimed at testing this implication in susceptibility to BP in an Iranian cohort. Blood samples were collected from the subjects and genomic DNA was extracted. To detect the single nucleotide polymorphisms (SNPs), IL-1α (rs1800587), IL-1β (rs1143627, rs16944, rs1143634), IL-8 (rs4073), and TNF-α (rs1799964, rs1800630, rs1799724, and rs361525) genes were genotyped in BP patients and healthy controls as well as IL-8 (rs4073) in pemphigus vulgaris (PV) patients. Quantitative gene expression was evaluated by RT-PCR analysis. A significant difference was observed in the distribution of genotypes or alleles of IL-8 SNP between the BP patients and controls. The A-allele of IL-8 SNP is significantly more prevalent in the control individuals compared to the BP patient. To further validate this observation, we included PV patients as an additional control. Again, the A-allele of IL-8 SNP is significantly more prevalent in the PV compared to the BP patients. While we observed a trend toward significant differences regarding alleles of TNF-α rs1799724 as well as alleles of TNF-α rs1799964, this difference was, however, not evident after correction for multiple analysis. There was no significant difference in all other studied SNPs. In contrast to IL-1α, IL-1β, and TNF-α, IL-8 gene expression levels were significantly higher in the patients than that of controls. The minor allele in IL-8 SNP might play a protective role in susceptibility to BP in Iranian patients. Although higher expression levels of IL-8 gene was found in the patients compared with healthy controls, these levels, however, suggest no association with the examined polymorphism. Moreover, further investigation revealed an elevation in gene expression between wild and polymorphic genotypes of IL-1α rs1800587 and TNF-α rs361525 in the patient group and these SNPs are therefore associated with altering the levels of gene expression.
| S-EPMC6455081 | biostudies-literature
Project description:Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology.
| S-EPMC6883920 | biostudies-literature
Project description:Pemphigus and bullous pemphigoid are autoantibody-mediated blistering skin diseases. In pemphigus, keratinocytes in epidermis and mucous membranes lose cell-cell adhesion, and in pemphigoid, the basal keratinocytes lose adhesion to the basement membrane. Pemphigus lesions are mediated directly by the autoantibodies, whereas the autoantibodies in pemphigoid fix complement and mediate inflammation. In both diseases, the autoantigens have been cloned and characterized; pemphigus antigens are desmogleins (cell adhesion molecules in desmosomes), and pemphigoid antigens are found in hemidesmosomes (which mediate adhesion to the basement membrane). This knowledge has enabled diagnostic testing for these diseases by enzyme-linked immunosorbent assays and dissection of various pathophysiological mechanisms, including direct inhibition of cell adhesion, antibody-induced internalization of antigen, and cell signaling. Understanding these mechanisms of disease has led to rational targeted therapeutic strategies.
| S-EPMC5560122 | biostudies-other
Project description:BackgroundTH17/IL-23 immune axis is considered to be involved in the pathogenesis of autoimmune and chronic inflammatory diseases. Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease, characterized by the presence of autoantibodies against the components of the dermal-epidermal junction. Animal studies and characterization of patient samples point toward a contribution of TH17 cells in BP pathogenesis. However, genetic polymorphisms in the genes of TH17/IL-23 cytokines have not yet been well investigated in BP.MethodsDetection of polymorphisms in IL-17A (rs2275913 and rs3819025), IL-17F (rs2397084 and rs763780), IL-17RA (rs2229151), and IL-23R (rs2201841, rs7530511, rs11209026, and rs10889677) genes were performed following the collection of blood samples and DNA extraction from BP patients and controls. Gene expression of IL-23R was determined by quantitative RT-PCR analysis.ResultsThe prevalence of IL-23R rs7530511 genotypes and alleles, as well as IL-23R rs2201841 alleles, is significantly different between the BP patients and controls. While the minor C-allele of IL-23R rs7530511 is highly present in the patients, the G-allele distribution of IL-23R rs2201841 is significantly more prevalent in the control individuals compared to the BP patients. Genotypes and alleles of other SNPs in IL-17A, IL-17F, and IL-17RA were similarly distributed in patients and controls.ConclusionsNo alteration was found in the gene expression between wild and polymorphic genotypes of IL-23R (rs2201841 and rs7530511) variations, indicating they do not contribute to altering the levels of gene expression in blood. In summary, our data show that the alleles of two SNPs in IL-23R rs2201841 and rs7530511 are associated with BP.
| S-EPMC7767565 | biostudies-literature
Project description:Atrial fibrillation (AF) is the most common cardiac arrhythmia in the developed world and is associated with a fivefold increase in the risk of stroke, accounting for up to 15% of strokes in the general population. The European Society of Cardiology now recommends direct oral anticoagulants, such as rivaroxaban, apixaban, and dabigatran, in preference to vitamin K antagonist therapy for the prevention of stroke in patients with A F. This review focuses on the direct Factor Xa inhibitor rivaroxaban, summarizing the properties that make rivaroxaban appropriate for anticoagulant therapy in this indication (including its predictable pharmacokinetic and pharmacodynamic profile and once-daily dosing regimen) and describing data from the Phase III ROCKET AF trial, which showed once-daily rivaroxaban to be noninferior to warfarin for the prevention of stroke in patients with nonvalvular AF. In this trial, similar rates of major and nonmajor clinically relevant bleeding were observed; however, when compared with warfarin, rivaroxaban was associated with clinically significant reductions in intracranial and fatal bleeding. On the basis of these results, rivaroxaban was approved in both the United States and the European Union for the prevention of stroke and systemic embolism in patients with nonvalvular AF. Subanalyses of ROCKET AF data showed rivaroxaban to have consistent efficacy and safety across a wide range of patients, and studies to confirm these results in real-world settings are underway. This review also describes practical considerations for treatment with rivaroxaban in clinical practice (including dose reductions in specific high-risk patients, eg, those with renal impairment), recommendations for the transition from vitamin K antagonists to rivaroxaban, the management of bleeding events, and the measurement of rivaroxaban exposure.
| S-EPMC3968084 | biostudies-other
Project description:Objectives: The clinical outcome of bullous pemphigoid appears worse in patients with infectious complications, and assessment of the prevalence and risk factors of infectious complications could be necessary to plan preventative strategies and to instruct the treatment plans. We sought to determine the risk factors of infection and compare associated factors in inpatients and outpatients with different system infections. Design: This is a single-centered retrospective study on the medical records of 252 patients from 2010 to 2018 at the dermatology department, Peking Union Medical College. Medical profiles of medical history, diagnosis, infectious complications, and treatment plans were analyzed. The associated factors were compared between the subgroups, including inpatients and outpatients, different body sites of infection. Results: Of the total 252 patients with bullous pemphigoid (BP), 81 patients (81/252, 32.1%) had infectious complications. Forty-eight patients died from pulmonary infections (11/48, 22.9%), cardiovascular diseases (6/48, 12.5%), and other diseases. Infections were most frequently found in skin/mucosa (44/252, 17.5%), respiratory system (32/252, 12.7%), and blood (10/252, 4.0%). On multivariate analysis, risk factors of infections in BP were maximal control dose of corticosteroids (OR 2.539, 95% CI 1.456-4.430, p = 0.001), low serum albumin level (OR 2.557, 95% CI 1.283, 5.092, p = 0.007), hospitalization (OR 4.025, 95% CI 2.289, 7.079, p < 0.001), comorbidities including respiratory disease (OR 4.060, 95% CI, 1.861, 8.858, p < 0.001), eye disease (OR 4.431, 95% CI 1.864, 10.532, p < 0.001), and diabetes (OR 2.667, 95% CI 1.437, 4.949, p = 0.002). The rate of infection was significantly higher in inpatients compared to that in outpatients (54.0 vs. 20.6%, p < 0.001), with diverse risk factors. Mucocutaneous infections were associated with a maximal control dose of corticosteroid and other dermatoses. Respiratory infections were related to respiratory disease and old age, and hematologic infection was associated with low serum hemoglobin levels and mucosal involvement of BP. Both of them were associated with mucosal involvement of BP and high titer anti-BP180 antibody. Conclusions: Infectious complications of bullous pemphigoid are common and are associated with mucosal involvement of BP, more comorbidities, the higher dose of corticosteroids, and the lower level of serum albumin.
| S-EPMC7390841 | biostudies-literature
Project description:Dabigatran and rivaroxaban are new oral anticoagulants that are eliminated through the kidneys. Their use in dialysis patients is discouraged because these drugs can bioaccumulate to precipitate inadvertent bleeding. We wanted to determine whether prescription of dabigatran or rivaroxaban was occurring in the dialysis population and whether these practices were safe.Prevalence plots were used to describe the point prevalence (monthly) of dabigatran and rivaroxaban use among 29977 hemodialysis patients with atrial fibrillation. Poisson regression compared the rate of bleeding, stroke, and arterial embolism in patients who started dabigatran, rivaroxaban, or warfarin. The first record of dabigatran prescription among hemodialysis patients occurred 45 days after the drug became available in the United States. Since then, dabigatran and rivaroxaban use in the atrial fibrillation-end-stage renal disease population has steadily risen where 5.9% of anticoagulated dialysis patients are started on dabigatrian or rivaroxaban. In covariate adjusted Poisson regression, dabigatran (rate ratio, 1.48; 95% confidence interval, 1.21-1.81; P=0.0001) and rivaroxaban (rate ratio, 1.38; 95% confidence interval, 1.03-1.83; P=0.04) associated with a higher risk of hospitalization or death from bleeding when compared with warfarin. The risk of hemorrhagic death was even larger with dabigatran (rate ratio, 1.78; 95% confidence interval, 1.18-2.68; P=0.006) and rivaroxaban (rate ratio, 1.71; 95% confidence interval, 0.94-3.12; P=0.07) relative to warfarin. There were too few events in the study to detect meaningful differences in stroke and arterial embolism between the drug groups.More dialysis patients are being started on dabigatran and rivaroxaban, even when their use is contraindicated and there are no studies to support that the benefits outweigh the risks of these drugs in end-stage renal disease.
| S-EPMC4363265 | biostudies-literature