A Case of Eosinophilic Granulomatosis with Polyangiitis Complicated with A IgG4 Related Disease Like Symptoms.
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ABSTRACT:
SUBMITTER: Sato S
PROVIDER: S-EPMC6332970 | biostudies-other | 2018
REPOSITORIES: biostudies-other
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Project description:The immunologic mechanisms promoting eosinophilic granulomatosis with polyangiitis (EGPA) are unclear. To characterize the mechanisms underlying pulmonary EGPA, we examined and compared EGPA paraffin-embedded lung biopsies with normal lung biopsies, using immunostaining, RNA sequencing, and RT-PCR. The results revealed novel type 2 as well as immuneregulatory features. These features included basophils and increased mast cell contents; increased immunostaining for tumor necrosis factor ligand superfamily member 14; sparse mast cell degranulation; numerous forkhead box protein P3 (FoxP3)+ regulatory T cells and IgG4 plasma cells; and abundant arachidonate 15-lipoxygenase and 25-hydroxyvitamin D-1 α hydroxylase, mitochondrial. Significantly decreased 15-hydroxyprostaglandin dehydrogenase [NAD(+)], which degrades eicosanoids, was observed in EGPA samples. In addition, there was significantly increased mRNA for chemokine (C-C motif) ligands 18 and 13 and major collagen genes, IgG4-rich immune complexes coating alveolar macrophages, and increased immunostaining for phosphorylated mothers against decapentaplegic homolog 2/SMAD2, suggesting transforming growth factor-β activation. These findings suggest a novel self-promoting mechanism of activation of alveolar macrophages by arachidonate 15-lipoxygenase-derived eicosanoids to express chemokines that recruit a combined type 2/immunoregulatory immune response, which produces these eicosanoids. These results suggest that the pulmonary EGPA immune response resembles the immune response to a tissue-invasive parasite infection.
| S-EPMC7322366 | biostudies-literature
Project description:The pathologic findings and immunologic mechanisms in eosinophilic granulomatosis with polyangiitis (EGPA) are poorly understood. To characterize pulmonary EGPA’s mechanisms, we examined EGPA paraffin-embedded lung biopsies by immunostaining, RNA sequencing, and reverse transcriptase PCR, compared to normal lung. EGPA lung infiltrates had eosinophils, alveolar macrophages, B and T cells, plasma cells, basophils, and mast cells. Mast cell degranulation was sparse. PhosphoSMAD2 immunostaining suggests TGFβ activity. Using both immunostaining and RNA-sequencing, showed significant increases for both type 2 related genes (CD209, TNFSF14 (induces TGFβ and IL-13)), immunoregulatory genes (FOXP3, CYP27B1 (makes calcitriol), ALOX15 and particularly IGHG4). Regulatory T cells and IgG4 plasma cells with IgG4-containing presumed immune complexes coating macrophages, were strikingly abundant relative to controls. HPGD (metabolizes prostaglandins and other eicosanoids) was substantially decreased. RNA studies also showed increased contents of collagen transcripts, IL13, CCL18, and CCL13. These findings suggest a novel mechanism involving alveolar macrophages, activated by ALOX15-eicosanoid products, making chemokines CCL18 and CCL13 and thus inducing a mixed type 2 plus immunoregulatory immune response. This infiltrate resembles the immune response to an invasive parasite rather than the IgE / mast cell degranulation response to luminal parasites or in asthma and other classic allergies. These findings also suggest new potential treatment targets for EGPA.
2020-01-28 | GSE144302 | GEO
Project description:BackgroundEosinophilic myocarditis (EM) is a rare and potentially life-threatening form of myocarditis, frequently (but not always) associated with eosinophilia, and presents with acute chest pain, or signs and symptoms of acute or chronic heart failure. Eosinophilic myocarditis has various aetiologies, including eosinophilic granulomatosis with polyangiitis (EGPA).Case summaryA 52-year-old female with a long-standing history of asthma, acral paraesthesia, subcutaneous nodules, and recurrent chest pain treated with anti-inflammatory drugs was admitted to our hospital with chest pain, repolarization disturbances, eosinophilia, and increased troponin levels. After an initial evaluation by coronary angiography, echocardiography and cardiac magnetic resonance, a definitive diagnosis of EM was made with the help of an endomyocardial biopsy. The aetiological diagnosis of EM as a manifestation of tissue involvement in EGPA was concluded after ruling out other possible causes of eosinophilia and with the help of other diagnostic criteria for EGPA (asthma, eosinophilia, and neuropathy). Therefore, we started with a high dosage of glucocorticoids, and attained relief of symptoms and normalization of eosinophilic count after a few days.DiscussionIn cases of myocarditis (particularly if associated with eosinophilia), EM is a manifestation of EGPA and should be considered for a prompt differential diagnosis. Endomyocardial biopsy represents the gold standard for the diagnosis of EM. The mainstay of therapy for EM is immunosuppressive drugs to help prevent its evolution to a fulminant form and chronic progression towards restrictive cardiomyopathy.
| S-EPMC8564711 | biostudies-literature
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| S-EPMC9929370 | 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: Not available
| S-EPMC7733721 | biostudies-literature
Project description:Vasculitis refers to inflammation of the systemic vessels. Eosinophilic granulomatosis with polyangiitis (EGPA) is a medium and small vessel vasculitis characterized by hypereosinophilia, pulmonary infiltrates, difficult to treat asthma and polyneuropathies. Diagnosis can often be challenging. In this article, we present a case of a young lady who was diagnosed ANCA negative EGPA.
| S-EPMC6446216 | biostudies-literature
Project description:BACKGROUND:Eosinophilic granulomatosis with polyangiitis is an eosinophilic vasculitis. Mepolizumab, an anti-interleukin-5 monoclonal antibody, reduces blood eosinophil counts and may have value in the treatment of eosinophilic granulomatosis with polyangiitis. METHODS:In this multicenter, double-blind, parallel-group, phase 3 trial, we randomly assigned participants with relapsing or refractory eosinophilic granulomatosis with polyangiitis who had received treatment for at least 4 weeks and were taking a stable prednisolone or prednisone dose to receive 300 mg of mepolizumab or placebo, administered subcutaneously every 4 weeks, plus standard care, for 52 weeks. The two primary end points were the accrued weeks of remission over a 52-week period, according to categorical quantification, and the proportion of participants in remission at both week 36 and week 48. Secondary end points included the time to first relapse and the average daily glucocorticoid dose (during weeks 48 through 52). The annualized relapse rate and safety were assessed. RESULTS:A total of 136 participants underwent randomization, with 68 participants assigned to receive mepolizumab and 68 to receive placebo. Mepolizumab treatment led to significantly more accrued weeks of remission than placebo (28% vs. 3% of the participants had ?24 weeks of accrued remission; odds ratio, 5.91; 95% confidence interval [CI], 2.68 to 13.03; P<0.001) and a higher percentage of participants in remission at both week 36 and week 48 (32% vs. 3%; odds ratio, 16.74; 95% CI, 3.61 to 77.56; P<0.001). Remission did not occur in 47% of the participants in the mepolizumab group versus 81% of those in the placebo group. The annualized relapse rate was 1.14 in the mepolizumab group, as compared with 2.27 in the placebo group (rate ratio, 0.50; 95% CI, 0.36 to 0.70; P<0.001). A total of 44% of the participants in the mepolizumab group, as compared with 7% of those in the placebo group, had an average daily dose of prednisolone or prednisone of 4.0 mg or less per day during weeks 48 through 52 (odds ratio, 0.20; 95% CI, 0.09 to 0.41; P<0.001). The safety profile of mepolizumab was similar to that observed in previous studies. CONCLUSIONS:In participants with eosinophilic granulomatosis with polyangiitis, mepolizumab resulted in significantly more weeks in remission and a higher proportion of participants in remission than did placebo, thus allowing for reduced glucocorticoid use. Even so, only approximately half the participants treated with mepolizumab had protocol-defined remission. (Funded by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT02020889 .).
| S-EPMC5548295 | biostudies-literature
Project description:Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis involving small-to-medium-sized vessels characterized by asthma, vasculitis, and peripheral eosinophilia. EGPA-associated eosinophilic myocarditis (EM) occurs rarely, yet can be fatal if left untreated. Moreover, the accurate diagnosis of EGPA-associated EM without vasculitis is exceptionally difficult because of the overlapping features with EM of other causes. We report a case of probable EGPA with subclinical neurological involvement that presented with acute EM. The constellation of peripheral eosinophilia, left ventricular dysfunction, and normal epicardial coronary arteries raised suspicion of acute EM, which was confirmed by cardiac magnetic resonance (CMR) investigation and endomyocardial biopsy (EMB). Prompt systemic administration of corticosteroids completely restored and normalized myocardial structure and function. Although the patient's history suggested the presumed hypersensitivity myocarditis, EMB revealed EM without vasculitis, not hypersensitivity, leading to a tentative diagnosis of idiopathic hypereosinophilic syndrome. Interestingly, the characteristic findings of vasculitis on CMR imaging strongly suggested EGPA-associated EM. Although the patient had no clinical neurological manifestations, a nerve conduction study confirmed mononeuritis multiplex, leading to the final diagnosis of probable EGPA. Therefore, this case highlights the diagnostic challenge associated with EGPA and the diagnostic synergy of CMR and EMB for an exploratory diagnosis of EGPA-associated EM.
| S-EPMC9300862 | biostudies-literature
Project description:Eosinophilic granulomatosis with polyangiitis (EGPA) is an extremely rare rheumatic immune disease characterized by vasculitis of small- and medium-sized blood vessels. Central nervous system (CNS) involvement frequently consists of cerebrovascular disease; a manifestation with multiple demyelinating lesions has never been reported in detail. This report describes a 38-year-old man, who presented with progressive memory deterioration and underwent microsurgery; EGPA was subsequently confirmed. Unique clinical and radiological features as well as immunohistological outcomes and DNA sequencing revealed a potential disease-associated human leukocyte antigen (HLA) type, and single-nucleotide polymorphisms (SNPs) are described for this uncommon case. Although EGPA rarely involves the CNS, this differential diagnosis should be considered when patients present with a history of nasosinusitis, elevated eosinophil percentage, clinical pulmonitis, and neurological manifestations. Microsurgery is necessary for precise diagnosis and effective treatment.
| S-EPMC6423896 | biostudies-literature