scholarly journals A Fulminant Case of Granulomatosis with Polyangiitis with Meningeal and Parenchymal Involvement

2015 ◽  
Vol 7 (1) ◽  
pp. 101-104 ◽  
Author(s):  
Ryuji Yajima ◽  
Yasuko Toyoshima ◽  
Yoko Wada ◽  
Tetsuya Takahashi ◽  
Hiroyuki Arakawa ◽  
...  
Keyword(s):  
Decompressive Craniectomy ◽  
Granulomatosis With Polyangiitis ◽  
Granulomatous Inflammation ◽  
Giant Cells ◽  
Cns Involvement ◽  
Small Vessels ◽  
Cerebrovascular Events ◽  
Brain Material ◽  
Perivascular Area ◽  
Paranasal Sinus Disease

Central nervous system (CNS) involvement, such as pachymeningitis and/or cerebrovascular events, is rare in patients with granulomatosis with polyangiitis (GPA). Furthermore, the details of pathological examinations of cases have rarely been described. We describe a case of GPA that manifested as an isolated paranasal sinus disease that invaded the subarachnoid space and caused a hemorrhagic venous infarction. We also describe the pathological characteristics of the biopsied brain material from the successful decompressive craniectomy. In particular, granulomatous inflammation with geographic necrosis and multinucleated giant cells were observed in the perivascular area of the thickened dura mater and leptomeninges. Small vessels in the meninges were involved in the granulomatous lesions, and the lumens of the veins were often occluded. In the cerebral cortices and white matter in these areas, hemorrhagic infarction was widely observed. We suggest that our findings represent a novel mechanism of CNS involvement in GPA. Moreover, we believe that the emergency decompressive craniectomy and partial lobectomy for the cerebral infarction in this patient with GPA likely contributed to his survival.

scholarly journals Granulomatous Inflammation in ANCA-Associated Vasculitis

2021 ◽  
Vol 22 (12) ◽  
pp. 6474
Author(s):  
Antje Müller ◽  
Bettina Krause ◽  
Anja Kerstein-Stähle ◽  
Sara Comdühr ◽  
Sebastian Klapa ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Granulomatosis With Polyangiitis ◽  
Local Development ◽  
Systemic Vasculitis ◽  
Kidney Tissue ◽  
Granulomatous Inflammation ◽  
Giant Cells ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Factors Affecting ◽  
Anca Associated Vasculitis

ANCA-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). While systemic vasculitis is a hallmark of all AAV, GPA is characterized by extravascular granulomatous inflammation, preferentially affecting the respiratory tract. The mechanisms underlying the emergence of neutrophilic microabscesses; the appearance of multinucleated giant cells; and subsequent granuloma formation, finally leading to scarred or destroyed tissue in GPA, are still incompletely understood. This review summarizes findings describing the presence and function of molecules and cells contributing to granulomatous inflammation in the respiratory tract and to renal inflammation observed in GPA. In addition, factors affecting or promoting the development of granulomatous inflammation such as microbial infections, the nasal microbiome, and the release of damage-associated molecular patterns (DAMP) are discussed. Further, on the basis of numerous results, we argue that, in situ, various ways of exposure linked with a high number of infiltrating proteinase 3 (PR3)- and myeloperoxidase (MPO)-expressing leukocytes lower the threshold for the presentation of an altered PR3 and possibly also of MPO, provoking the local development of ANCA autoimmune responses, aided by the formation of ectopic lymphoid structures. Although extravascular granulomatous inflammation is unique to GPA, similar molecular and cellular patterns can be found in both the respiratory tract and kidney tissue of GPA and MPA patients; for example, the antimicrobial peptide LL37, CD163+ macrophages, or regulatory T cells. Therefore, we postulate that granulomatous inflammation in GPA or PR3-AAV is intertwined with autoimmune and destructive mechanisms also seen at other sites.

Granulomatosis with Polyangiitis (Wegener's Granulomatosis): Evolving Concepts in Treatment

2018 ◽  
Vol 39 (04) ◽  
pp. 434-458 ◽  
Author(s):  
Ariis Derhovanessian ◽  
Henry Tazelaar ◽  
John Belperio ◽  
Joseph Lynch
Keyword(s):  
Respiratory Tract ◽  
Wegener’S Granulomatosis ◽  
Granulomatosis With Polyangiitis ◽  
Treatment Strategies ◽  
Granulomatous Inflammation ◽  
Wegener's Granulomatosis ◽  
Upper Respiratory Tract ◽  
Small Vessels ◽  
Successful Induction ◽  
Indolent Disease

AbstractGranulomatosis with polyangiitis (GPA), formerly termed Wegener's granulomatosis, is the most common of the pulmonary vasculitides. GPA typically involves the upper respiratory tract, lower respiratory tract (bronchi and lung), and kidney, with varying degrees of disseminated vasculitis. Cardinal histologic features include a necrotizing vasculitis involving small vessels, extensive “geographic” necrosis, and granulomatous inflammation. The spectrum and severity of the disease is heterogeneous, ranging from indolent disease involving only one site to fulminant, multiorgan vasculitis. Circulating antibodies against cytoplasmic components of neutrophils (ANCAs) play a role in the pathogenesis, and often correlate with activity of the disease. Treatment strategies are evolving. Cyclophosphamide (CYC) plus corticosteroids was the mainstay of therapy for generalized, multisystemic GPA since the 1970s. However, within the past decade, rituximab (RTX), a monoclonal antibody directed against B cells, has been shown to be at least as effective (and possibly more effective) as CYC. Furthermore, the use of RTX may reduce the need for maintenance immunosuppression. Optimal therapy for GPA remains controversial, and additional studies are required to determine the role and duration of maintenance therapy following successful induction therapy.

scholarly journals Granulomatosis with polyangiitis

2016 ◽  
Vol 9 (4) ◽  
pp. 217
Author(s):  
Zubayer Ahmad ◽  
Sadiqa Tuqan ◽  
Mirza Nazimuddin ◽  
Rama Biswas ◽  
Anindita Roy
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
High Titer ◽  
Granulomatous Inflammation ◽  
Needle Aspiration ◽  
Organ System ◽  
Lower Airway ◽  
Neurological Involvement ◽  
Cns Involvement ◽  
Intravenous Methylprednisolone ◽  
Airway Symptoms

<p>Granulomatosis with polyangiitis is a small and medium vessel vasculitis. It may affect any organ system. Neurological involvement, though less frequent, mostly manifests as peripheral neuropathy. Central nervous system (CNS) involvement as autoimmune cerebritis is rare but may be devastating. We report a patient having CNS involvement in the form of Parkinsonism long before the development of typical upper and lower airway symptoms. Granulomatosis with polyangiitis was diagnosed on the basis of cavitary lung lesions along with epistaxis, granulomatous inflammation from fine needle aspiration (FNAC) of lymph node and high titer of c-ANCA. The patient was commenced on intravenous methylprednisolone followed by mycophenolate mofetil and responded to treatment. Autoimmune cerebritis may present with subacute manifestation of diffuse CNS involvement.</p>

scholarly journals OP0054 NEW ROLE FOR PROTEINASE 3 IN IL-16 BIOACTIVITY CONTROL IN GRANULOMATOSIS WITH POLYANGIITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 28.1-29
Author(s):  
A. Kerstein-Staehle ◽  
C. Alarcin ◽  
J. Luo ◽  
G. Riemekasten ◽  
P. Lamprecht ◽  
...  
Keyword(s):  
Cell Death ◽  
Western Blot ◽  
Disease Activity ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Granulomatosis With Polyangiitis ◽  
Granulomatous Inflammation ◽  
Proteinase 3 ◽  
Sds Page

Background:The immunomodulatory cytokine IL-16 is increased in several inflammatory and autoimmune diseases1. IL-16 recruits and activates CD4+ immune cells such as T cells, dendritic cells, or monocytes. IL-16 is produced by various immune and non-immune cells, but synthesis and storage of IL-16 is regulated differentially depending on the cell type and stimulation. For its biological activity, IL-16 cleavage by caspase-3 is required1. Necrotizing granulomatous inflammation is a hallmark of granulomatosis with polyangiitis (GPA) with neutrophil dysregulation as a central driver of chronic inflammation and autoimmunity2. Earlier studies showed a correlation between increased serum IL-16 and disease parameters in AAV, including GPA3, but functional evidence for a direct link between IL-16 and neutrophils in granulomatous inflammation is missing so far.Objectives:In this study we aim to identify a functional link between increased IL-16, neutrophils, and the autoantigen proteinase 3 (PR3) with regard to chronic inflammation and autoimmunity in GPA.Methods:IL-16 was measured in sera of GPA patients (n = 40) and healthy controls (HC, n = 50) by ELISA and correlated with clinical features, such as disease activity (BVAS), creatinine, GFR, VDI and PR3-ANCA status. IL-16 protein expression was analyzed in peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) from GPA patients and HC (n = 5, each) by SDS-PAGE and western blot. Binding affinity of recombinant pro-IL-16 to native human PR3 was assessed by microscale thermophoresis. Cleavage of pro-IL-16 by active human PR3 was performed at various time points at 37°C. Cleavage products were analyzed by SDS-PAGE and western blot.Results:Circulating IL-16 was significantly increased in GPA patients compared to HC. Elevated IL-16 positively correlated with BVAS, creatinine, VDI and PR3-ANCA status and negatively correlated with GFR. In PMBC and PMN from GPA and HC we identified different expression patters of precursor and active forms of IL-16. In healthy PBMC we found high amounts of precursor (80kD), pro-IL-16 (55kD) and active IL-16 (17kD). In contrast, PBMC from GPA patients had lower amounts of pro-IL-16 and no active IL-16, indicating activation and secretion of IL-16 due to inflammatory stimulation, as shown earlier5. In GPA PMN we detected no precursor IL-16, but pro-IL-16 and its active form, in contrast to very low amounts of all IL-16 forms in healthy PMN. Processing and release of IL-16 in neutrophils has been linked to apoptosis and secondary necrosis5. By interaction studies we demonstrated direct binding of pro-IL-16 to PR3 with a Kd of 10 nM. In a subsequent cleavage assay we confirmed IL-16 processing by PR3 in a time-dependent manner.Conclusion:Correlation of serum IL-16 with clinical features of GPA suggests that IL-16 is associated with markers of disease activity, tissue damage and autoreactivity. We showed that PBMC and PMN represent a source of IL-16 in GPA. By the identification of PR3 as an additional IL-16-activating enzyme we could demonstrate a potential link between excessive PR3 expression, cell death and IL-16-dependent mechanisms, contributing to chronic granulomatous inflammation and autoimmunity in GPA.References:[1]Glass, W. G. et al. Not-so-sweet sixteen: The role of IL-16 in infectious and immune-mediated inflammatory diseases. J. Interf. Cytokine Res. 26, 511–520 (2006).[2]Millet, A. et al. Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis. J. Clin. Invest. 125, 4107–4121 (2015).[3]Yoon, T. et al. Serum interleukin-16 significantly correlates with the Vasculitis Damage Index in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Res. Ther. 22, 1–6 (2020).[4]Elssner, A. et al. IL-16 Is Constitutively Present in Peripheral Blood Monocytes and Spontaneously Released During Apoptosis. J. Immunol. 172, 7721–7725 (2004).[5]Roth, S. et al. Secondary necrotic neutrophils release interleukin-16C and macrophage migration inhibitory factor from stores in the cytosol. Cell Death Discov. 1, 15056 (2015).Disclosure of Interests:None declared

scholarly journals Atypical Granulomatosis with Polyangiitis Presenting with Meibomitis, Scleritis, Uveitis and Papillary Bladder Tumor: A Case Report and Literature Review

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 680
Author(s):  
Takashi Kojima ◽  
Murat Dogru ◽  
Eisuke Shimizu ◽  
Hiroyuki Yazu ◽  
Aya Takahashi ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Early Stage ◽  
Topical Steroid ◽  
Granulomatous Inflammation ◽  
Oral Prednisolone ◽  
Meibomian Gland ◽  
Clinical Findings ◽  
Meibomian Gland Dysfunction ◽  
Oral Steroids ◽  
Atypical Cells

Granulomatosis with polyangiitis (GPA) presents with a variety of systemic findings, sometimes with ocular findings initially, but is often difficult to diagnose at an early stage. An 85-year-old male had complaints of ocular dryness and redness and was diagnosed with meibomian gland dysfunction with meibomitis. Despite an initial treatment with topical steroid and antibiotics, the meibomitis did not improve and the left eye developed scleritis and iridocyclitis. The patient was administered topical mydriatics and oral steroids. During follow-up, the patient developed left hearing difficulty and reported a darker urine. Urinalysis revealed microscopic hematuria. A blood test showed an elevated erythrocyte sedimentation rate, positivity for perinuclear anti-neutorophil cytoplasmic antibody, and elevations in blood urea nitrogen and serum creatinine. Nasal mucosal biopsy showed a non-necrotizing granulomatous inflammation. Renal biopsy revealed focal glomerulosclerosis. Cystoscopy and bladder wash followed by a planned transurethral resection revealed atypical cells and apical papillary tumors which were resected. Iridocyclitis and scleritis responded well to oral prednisolone with 0.1% topical betamethasone and prednisolone ointment. The patient is tumor free with no recurrences 24 months after resection. GPA may present atypically with meibomian gland dysfunction without showing representative clinical findings. Early detection and treatment are essential for visual recovery.

scholarly journals Life-Threatening Subglottic Stenosis of Granulomatosis with Polyangiitis: A Case Report

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 423
Author(s):  
Jin An ◽  
Jae-Won Song
Keyword(s):  
Immunosuppressive Therapy ◽  
Granulomatosis With Polyangiitis ◽  
Granulomatous Inflammation ◽  
Subglottic Stenosis ◽  
Emergency Tracheostomy ◽  
Intralesional Steroid ◽  
Intralesional Steroid Injection ◽  
Life Threatening ◽  
Carbon Dioxide Co2 ◽  
Laryngotracheal Resection

Granulomatosis with polyangiitis (GPA) is an autoimmune disease characterized by necrotizing granulomatous inflammation. Subglottic stenosis, which is defined as narrowing of the airway below the vocal cords, has a frequency of 16–23% in GPA. Herein, we present the case of a 39-year-old woman with subglottic stenosis manifesting as life-threatening GPA, which was recurrent under systemic immunosuppressive therapy. The patient underwent an emergency tracheostomy, intratracheal intervention, such as carbon dioxide (CO2) laser surgery and intralesional steroid injection via laryngomicroscopic surgery, and laryngotracheal resection with remodeling. Severe subglottic stenosis treatment requires active intratracheal intervention, surgery, and systemic immunosuppressive therapy.

scholarly journals Hepatocellular carcinoma with regional lymphadenopathy caused by sarcoid-like reaction: a case report

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Tomoko Mizota ◽  
Masato Suzuoki ◽  
Saya Kaku ◽  
Kenichi Mizunuma ◽  
Kazuto Ohtaka ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Granulomatous Inflammation ◽  
Giant Cells ◽  
Epithelioid Cell ◽  
Imaging Modalities ◽  
Hepatoduodenal Ligament ◽  
Regional Lymph Nodes ◽  
Multiple Imaging

Abstract Background Sarcoid-like reaction (SLR) is a histological pattern of granulomatous inflammation that is clinically differentiated from sarcoidosis. Since SLR is known to occur in several neoplasias and occasionally causes lymphadenopathy and mimics metastatic malignancy, it needs to be considered whether lymphadenopathy is due to metastasis or SLR for the choice of cancer treatment. Few cases of hepatocellular carcinoma (HCC) with SLR have been reported. Here, a case of HCC with lymphadenopathy diagnosed as SLR without metastasis is presented. Case presentation A 69-year-old woman was admitted to our hospital because of upper abdominal pain. She tested positive for hepatitis C virus ribonucleic acid. Imaging modalities showed an 81 × 65-mm-sized tumor with multiple nodules in segment 3 and a 17 × 12-mm-sized tumor in segment 5 with a common HCC enhancement pattern. In addition, a lymph node in the hepatoduodenal ligament was enlarged at 13 mm in size, suggesting the metastasis of HCC. Hepatectomy of the lateral segment and segment 5 and lymph node dissection in the hepatoduodenal ligament were performed. Both tumors in segments 3 and 5 were pathologically diagnosed as HCC without vessel invasion. The tumors contained necrotic cells and epithelioid cell granulomas with multinucleated giant cells, which is typically observed in sarcoidosis. The dissected lymph nodes also contained epithelioid cell granulomas, as well as giant cells with asteroid bodies. There was no malignancy in the lymph nodes. The pathological findings suggested the coexistence of malignancy and sarcoidosis. However, since the patient did not show any typical findings of pulmonary or cardiac sarcoidosis, the case was diagnosed as HCC with SLR in the primary lesion and regional lymph nodes. Conclusions SLR needs to be considered in the differential diagnosis when a cancer patient develops lymphadenopathy. However, lymphadenopathy due to SLR is indistinguishable from that due to metastasis even when using multiple imaging modalities. Pathological examinations may be helpful for the diagnosis.

Comparison of Polymerase Chain Reaction With Histopathologic Features for Diagnosis of Tuberculosis in Formalin-Fixed, Paraffin-Embedded Histologic Specimens

2003 ◽  
Vol 127 (3) ◽  
pp. 326-330 ◽  
Author(s):  
Do Youn Park ◽  
Jee Yeon Kim ◽  
Kyung Un Choi ◽  
Jin Sook Lee ◽  
Chang Hun Lee ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Granulomatous Inflammation ◽  
Giant Cells ◽  
Caseous Necrosis ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Type Giant ◽  
Tb Pcr ◽  
Formalin Fixed ◽  
Histopathologic Features

Abstract Objective.—To investigate the relationship between various histopathologic features and the results of the tuberculosis (TB)–polymerase chain reaction (PCR) method in routinely submitted histologic specimens for the histopathologic diagnosis of TB. Design.—We used 95 formalin-fixed, paraffin-embedded tissue blocks from 81 patients who were clinically suspected of having TB. We assessed the presence of histopathologic features including well-formed granuloma, poorly formed granuloma, caseous necrosis, and Langhans-type giant cells. We performed nested PCR for IS6110 and Ziehl-Neelsen staining for acid-fast bacilli (AFB). Results.—Of the 81 patients studied, 53 patients had chronic granulomatous inflammation, whereas 28 patients had only chronic inflammation without definite granulomatous inflammation. Of the 53 cases with chronic granulomatous inflammation, 17 (32%) were AFB positive and 36 (68%) were TB-PCR positive. Among cases with chronic granulomatous inflammation, the percentage that were positive and negative by TB-PCR differed significantly with the presence of various histopathologic features. All of the 13 cases with well-formed granuloma, caseous necrosis, and Langhans-type giant cells were TB-PCR positive; however, 10 (36%) of the 28 cases with chronic inflammation without granulomatous lesions were also TB-PCR positive. Conclusions.—TB-PCR is a rapid, sensitive method for the diagnosis of TB in routinely processed formalin-fixed, paraffin-embedded histologic specimens and is readily available in histopathology laboratories. We recommend use of TB-PCR when TB is suspected clinically, especially in cases of chronic inflammation without definite evidence of granulomatous inflammation.

scholarly journals Severe course of quickly progressing glomerulonephritis in a patient with ANTSA-associated vasculitis: review and case report

2020 ◽  
Vol 7 (3) ◽  
pp. 55-62
Author(s):  
Iu. V. Lavrishcheva ◽  
Y. S. Kaledinova ◽  
A. A. Yakovenko ◽  
I. A. Artemev
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Rapidly Progressive Glomerulonephritis ◽  
Granulomatous Inflammation ◽  
Clinical Work ◽  
Chronic Hemodialysis ◽  
Complete Loss ◽  
Vascular Lesions ◽  
Upper Respiratory Tract ◽  
Delay In Diagnosis ◽  
Necrotizing Glomerulonephritis

Granulomatosis with polyangiitis is characterized by necrotizing granulomatous inflammation, vasculitis with vascular lesions of small and medium caliber and focal necrotizing glomerulonephritis. A frequent and one of the most formidable complications is kidney damage, which in a large number of cases leads to a complete loss of organ function and a switch to renal replacement therapy. Given the rare occurrence of this disease in the clinical work of practitioners, and their low awareness of this pathology, problems often arise with the diagnosis and treatment of patients with HPA. Due to the diversity and non-specific nature of the manifestations of the disease, a delay in diagnosis may occur. The presented case illustrates the manifestations of granulomatosis with polyangiitis in the form of severe damage to the upper respiratory tract and kidneys, the diagnosis of which was difficult due to the rarity of the disease and the multiple organ pathology. This article presents a clinical case of severe progression of rapidly progressive glomerulonephritis in a patient with ANCA-associated vasculitis, a brief review of the literature is given. Despite adequate therapy, the disease progressed mainly due to deterioration of renal function, which subsequently led to a complete loss of kidney function and the transition to treatment with chronic hemodialysis.

scholarly journals A Progressive Case of Eosinophilic Myocarditis Due to Eosinophilic Granulomatosis With Polyangiitis in a Caucasian Male

2020 ◽  
Vol 8 ◽  
pp. 232470962096685
Author(s):  
Valerie F. Civelli ◽  
Vishal K. Narang ◽  
Rupam Sharma ◽  
Ritika Sharma ◽  
Jessica Kim ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Inflammatory Process ◽  
Granulomatosis With Polyangiitis ◽  
Systemic Vasculitis ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Small Vessels ◽  
History Of ◽  
Eosinophilic Myocarditis ◽  
Eosinophilic Granulomatosis ◽  
Large Vessels

Vasculitis is an inflammatory process involving blood vessels of various sizes, including the small vessels in the kidneys to the large vessels, such as the aorta. This inflammatory condition is usually autoimmune in nature and is associated with involvement of many locations, such as the sinuses, lungs, kidneys, and even the heart. Specifically, eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis that may initially hide as asthma, allergic rhinitis, and/or sinusitis. However, it is known to become a lethal disease once progressed to include cardiovascular manifestations. It is important to remember EGPA as a differential for any patient with a history of asthma, allergic rhinitis, and/or sinusitis who also presents with cardiovascular complaints and eosinophilia. Treatment recommendations focus on immunosuppression in such cases. In this article, we discuss the case of a 62-year-old male, with a known history of asthma, who presented to the emergency department with concern for his chest pain and right-sided weakness. He was later diagnosed with EGPA with eosinophilic myocarditis. Diagnosis and treatment are described.

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