Granulomatosis with polyangiitis (Wegener's) complicated by splenic rupture and severe acute respiratory distress syndrome: A case report.
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SUBMITTER: Ahmad Y
PROVIDER: S-EPMC8271247 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC8071825 | biostudies-literature
Project description:ObjectiveTo determine whether disease processes related to granulomatosis with polyangiitis (Wegener's) (GPA) are reflected in gene expression profiles of the nasal mucosa.MethodsNasal brushings of the inferior turbinate were obtained from 32 patients with GPA (10 with active nasal disease, 13 with prior nasal disease, and 9 with no history of nasal disease) and a composite comparator group with and without inflammatory nasal disease (12 healthy people, 15 with sarcoidosis, and 8 with allergic rhinitis). Differential gene expression was assessed between subgroups of GPA and comparators.ResultsA total of 339 genes were differentially expressed between the GPA and comparator groups (absolute fold change >1.5; false discovery rate <0.05). Top canonical pathways up-regulated in nasal brushings from patients with GPA included granulocyte adhesion and diapedesis (P = 8.6(-22) ), agranulocyte adhesion and diapedesis (P = 1.3(-14) ), IL10 signaling (P = 3.0(-11) ), LXR/RXR activation (P = 4.3(-11) ), and TREM1 signaling (P = 9.0(-11) ). A set of genes differentially expressed in GPA independently of nasal disease activity status included genes related to epithelial barrier integrity (fibronectin 1, desmosomal proteins) and several matricellular proteins (e.g., osteonectin, osteopontin). Significant overlap of differentially expressed genes was observed between active and prior nasal disease GPA subgroups. Peripheral blood neutrophil and mononuclear gene expression levels associated with GPA were similarly altered in the nasal gene expression profiles of patients with active or prior nasal disease.ConclusionProfiling the nasal transcriptome in GPA reveals gene expression signatures related to innate immunity, inflammatory cell chemotaxis, extracellular matrix composition, and epithelial barrier integrity. Thus, airway-based expression profiling is feasible and informative in GPA.
| S-EPMC4519398 | biostudies-literature
Project description:Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) is a multisystem autoimmune condition associated with anti-neutrophil cytoplasm antibodies. Management of GPA can be complex, owing to the sometimes fulminant and multisystem nature of the presentation, the age demographics of the affected population, and a significant incidence of disease relapse. In this paper, we discuss how some of the challenges in the management of GPA have been and continue to be addressed including: reducing the toxicity of induction therapy; developing biomarkers to determine who can safely stop maintenance immunosuppression; improving the efficacy of maintenance therapy for relapsing patients; managing localized disease; and management of disease and treatment-associated comorbidity. Consideration is also given to emerging therapeutics in the treatment of GPA.
| S-EPMC4000246 | biostudies-literature
Project description:ObjectivesTo determine the safety and efficacy of abatacept in non-severe relapsing granulomatosis with polyangiitis (Wegener's)(GPA).MethodsAn open-label trial of intravenous abatacept was conducted in 20 patients with non-severe relapsing GPA. Prednisone up to 30 mg daily was permitted within the first 2 months, and patients on methotrexate, azathioprine, or mycophenolate mofetil continued these agents. Patients remained on study until common closing or early termination.ResultsOf the 20 patients, 18 (90%) had disease improvement, 16 (80%) achieved remission (BVAS/WG=0) at a median of 1.9 months, and 14 (70%) reached common closing. Six patients (30%) met criteria for early termination due to increased disease activity; 3 of 6 achieved remission and relapsed at a median of 8.6 months. The median duration of remission before common closing was 14.4 months, with the median duration of time on study for all patients being 12.3 months (range 2-35 months). Eleven of the 15 (73%) patients on prednisone reached 0 mg. Nine severe adverse events occurred in 7 patients, including 7 infections that were successfully treated.ConclusionsIn this study of patients with non-severe relapsing GPA, abatacept was well tolerated and was associated with a high frequency of disease remission and prednisone discontinuation.
| S-EPMC4149903 | biostudies-literature
Project description:BackgroundEosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare multisystem disease characterized by asthma, rhinosinusitis, and eosinophilia. Cardiac involvement, present in half the patients, may be life threatening.Case summaryA young woman with long-standing asthma and nasal polyposis was admitted with new-onset dyspnoea, sinus tachycardia, and eosinophilia. She had severe biventricular thrombosis and severe tricuspid regurgitation (TR) on echocardiography, with preserved ejection fraction of both ventricles. Cardiac magnetic resonance (CMR) imaging showed diffuse subendocardial late gadolinium enhancement (LGE). She had a positive test for perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) confirming the diagnosis of ANCA positive EGPA. She was treated with anticoagulation, high-dose corticosteroids, cyclophosphamide, and rituximab with gradual resolution of her symptoms. Follow-up echocardiography showed significant improvement in ventricular thrombi and TR but could not reliably exclude residual ventricular thrombus. Repeat CMR at 11 months confirmed complete resolution of both ventricular thrombi and near complete resolution of LGE.DiscussionCardiac involvement in EGPA, a rare cause of heart failure, can manifest as severe biventricular thrombosis and severe TR, resulting in heart failure with preserved ejection fraction. Combined immunosuppression and anticoagulation can lead to complete remission within a year. CMR is instrumental for both diagnosis and follow-up of EGPA, allowing for safe discontinuation of oral anticoagulation.
| S-EPMC7793161 | biostudies-literature
Project description:ObjectiveGranulomatosis with polyangiitis (Wegener's) (GPA) is a type of antineutrophil cytoplasmic antibody-associated vasculitis that often entails severe end-organ damage and treatment-related complications that frequently lead to hospitalization and death. Nationwide trends in hospitalizations and in-hospital mortality over the past 2 decades are unknown and were evaluated in this study.MethodsUsing the National Inpatient Sample, the largest all-payer inpatient database in the US, trends in hospitalizations with a discharge diagnosis of GPA (formerly Wegener's granulomatosis; International Classification of Disease, Ninth Revision, Clinical Modification code 446.4) between 1993 and 2011 were studied. Analyses were performed using hospital-level sampling weights to obtain US national estimates.ResultsFrom 1993 to 2011, the annual hospitalization rate for patients with a principal diagnosis of GPA increased by 24%, from 5.1 to 6.3 per 1 million US persons (P?<?0.0001 for trend); however, in-hospital deaths in this group declined by 73%, from 9.1% to 2.5% (P?<?0.0001 for trend), resulting in a 66% net reduction in the annual in-hospital mortality rate. The median length of stay declined by 20%, from 6.9 days in 1993 to 5.5 days in 2011 (P?=?0.0002 for trend). Infection was the most common principal discharge diagnosis when GPA was a secondary diagnosis, including among those who died during hospitalization.ConclusionThe findings from these nationally representative, contemporary inpatient data indicate that the in-hospital mortality of GPA has declined substantially over the past 2 decades, while the overall hospitalization rate for GPA increased slightly. Infection remains a common principal hospitalization diagnosis among GPA patients, including hospitalizations resulting in mortality.
| S-EPMC5219862 | biostudies-literature
Project description:Acute respiratory distress syndrome has not been a described complication of hypothermia. Causes of hypothermia are commonly associated with alcohol abuse and infection, both of which could lead to acute respiratory distress syndrome. We present a case of severe hypothermia complicated by acute respiratory distress syndrome in a young immunocompetent male treated successfully with mechanical intubation and venovenous extracorpeal membrane oxygenation. Risk factors for known causes of acute respiratory distress syndrome included a witnessed aspiration event and RSV pneumonia. On review of the literature, severe hypothermia has been found to cause pulmonary edema in post-mortem studies, but acute respiratory distress syndrome has not yet been recognized as a known complication. Our case highlights that acute respiratory distress syndrome may be multifactorial in etiology and related to complications of severe hypothermia.
| S-EPMC6554481 | biostudies-literature
Project description:The objective of this study is to assess the relationship between inflammatory disease in granulomatosis with polyangiitis (GPA, Wegener's) and the development of subclinical atherosclerosis. A total of 46 adult patients with GPA were enrolled. Disease status was measured by Birmingham vasculitis assessment scores as modified for GPA, vasculitis damage index, disease duration, and number of relapses. Classic atherosclerotic risk factors, platelet aggregation responses, and circulating microparticle (MP) levels were recorded. All patients underwent carotid artery intima-media thickness (IMT) measurement as outcome for subclinical atherosclerosis. In univariate analyses, systolic and diastolic blood pressure, creatinine, and age were significantly associated with higher IMT (ρ values 0.37, 0.38, 0.35, and 0.054, respectively [P < 0.02 for all]). In a multiple regression model, greater number of relapses, older age at the onset of disease, and higher diastolic blood pressure were found to be associated with higher IMT (P values 0.003, <0.001, and 0.031, respectively). MP counts and platelet reactivity correlated well with disease activity in GPA. Furthermore, MPs were found to activate vascular endothelial cells and platelets in vitro. The cumulative burden of systemic inflammation in GPA correlated with the development of subclinical atherosclerosis. The correlation with subclinical atherosclerosis could be because of glucocorticoid use and not the inflammatory process in GPA, giving the inherent bias that exits with the use of glucocorticoid with each relapse. The findings of increased levels of circulating leukocyte-derived MPs and enhanced platelet reactivity during relapse suggest possible roles for MPs and platelets in disease pathogenesis and support a growing literature that links inflammation, atherosclerosis, and platelet activation. This hypothesis is further substantiated by our demonstration that MPs isolated from plasma of GPA patients can activate platelets and vascular endothelial cells.
| S-EPMC4862201 | biostudies-literature
Project description:ObjectiveTo assess a generic measure of health-related quality of life (HRQOL) as an outcome measure in granulomatosis with polyangiitis (Wegener's) (GPA).MethodsSubjects were participants in the Wegener's Granulomatosis Etanercept Trial (WGET) or the Vasculitis Clinical Research Consortium Longitudinal Study (VCRC-LS). HRQOL was assessed with the Short Form 36 (SF-36) health survey that includes physical and mental component summary scores (PCS and MCS, respectively). Disease activity was assessed with the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG).ResultsThe data from 180 subjects in the WGET (median followup 2.3 years, mean number of visits 10) and 237 subjects in the VCRC-LS (median followup 2.0 years, mean number of visits 8) were analyzed. A 1 unit increase in the BVAS/WG corresponded to a 1.15 unit (95% confidence interval [95% CI] 1.02, 1.29) decrease for the PCS and a 0.93 (95% CI 0.78, 1.07) decrease for the MCS in the WGET, and to a 1.16 unit decrease for the PCS (95% CI 0.94, 1.39) and a 0.79 unit decrease for the MCS (95% CI 0.51, 1.39) in the VCRC-LS. In both arms of the WGET study, SF-36 measures improved rapidly during the first 6 weeks of treatment followed by gradual improvement among patients achieving sustained remission (0.5 improvement in PCS per 3 months), but worsened slightly (0.03 decrease in PCS every 3 months) among patients not achieving sustained remission (P = 0.005).ConclusionHRQOL, as measured by the SF-36, is reduced among patients with GPA. SF-36 measures are modestly associated with other disease outcomes and discriminate between disease states of importance in GPA.
| S-EPMC3250569 | biostudies-literature
Project description:To examine the association of previously identified autoimmune disease susceptibility loci with granulomatosis with polyangiitis (Wegener's) (GPA), and to determine whether the genetic susceptibility profiles of other autoimmune diseases are associated with those of GPA.Genetic data from 2 cohorts were meta-analyzed. Genotypes for 168 previously identified single-nucleotide polymorphisms (SNPs) associated with susceptibility to different autoimmune diseases were ascertained in a total of 880 patients with GPA and 1,969 control subjects of European descent. Single-marker associations were identified using additive logistic regression models. Associations of multiple SNPs with GPA were assessed using genetic risk scores based on susceptibility loci for Crohn's disease, type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis (RA), celiac disease, and ulcerative colitis. Adjustment for population substructure was performed in all analyses, using ancestry-informative markers and principal components analysis.Genetic polymorphisms in CTLA4 were significantly associated with GPA in the single-marker meta-analysis (odds ratio [OR] 0.79, 95% confidence interval [95% CI] 0.70-0.89, P = 9.8 × 10(-5) ). The genetic risk score for RA susceptibility markers was significantly associated with GPA (OR 1.05 per 1-unit increase in genetic risk score, 95% CI 1.02-1.08, P = 5.1 × 10(-5) ).RA and GPA may arise from a similar genetic predisposition. Aside from CTLA4, other loci previously found to be associated with common autoimmune diseases were not statistically significantly associated with GPA in this study.
| S-EPMC3425721 | biostudies-literature