Acute Pancreatitis Coincided with Multiple Arteriolar Aneurysms in a Patient with Polyarteritis Nodosa

A 78-year-old man presented to our hospital with a history of 10kg weight loss within 6 months previously, and general fatigue and fever for 2 and 1 months, respectively. On hospitalization, the patient was diagnosed with polyarteritis nodosa after multiple microaneurysms were observed in the liver, kidney, pancreas, and mesenteries. He achieved remission with the administration of 1,000mg methylprednisolone for 3 days, followed by prednisolone (55mg/day). Steroids were successfully tapered with no re-elevation in inflammation. Two months after the administration of steroids, the patient complained of acute abdominal pain, and developed severe acute pancreatitis. During treatment for pancreatitis, the patient died due to septic shock and disseminated intravascular coagulation. An autopsy revealed necrotizing vasculitis in the intrapancreatic arteries and ischemia of the downstream arterioles resulting in acute pancreatitis.

Microscopic polyangiitis: Modern concepts and treatment options

The article summarizes the modern concepts of microscopic polyangiitis (MPA), a primary ANCA-associated systemic necrotizing vasculitis without immune globulin deposition (pauci-immune) that affects mainly small vessels, while granulomatous inflammation is absent. Necrotizing glomerulonephritis is very common and pulmonary capillaritis often occurs. MPA can cause rapidly progressive damage to organ systems. The modern possibilities of MPA treatment, primarily anti-B cell therapy with rituximab, are discussed.

A Case of Clinically Diagnosed ANCA Negative Granulomatosis With Polyangiitis

Significance Statement Granulomatosis with polyangitis (GPA) is a systemic necrotizing vasculitis comprising of inflammation of small and medium-sized vessels. 1 It typically presents with involvement of the upper and lower airways as well as the kidneys. If left untreated, end-organ damage may occur. Hematological investigations typically demonstrate the presence of antinuclear cytoplasmic antibodies (ANCA). 2 Here, we discuss an unusual presentation of ANCA negative GPA, presenting initially with nasal symptoms.

MO244CD47 BLOCKADE AMELIORATES AUTOIMMUNE VASCULITIS VIA THE EFFEROCYTOSIS OF NEUTROPHIL EXTRACELLULAR TRAPS*

Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by systemic necrotizing vasculitis in small vessels. The necrotic lesions consist of ANCA-mediated neutrophil extracellular traps (NETs) which represent a form of lytic cell death. The persistent NETs serve as autoantigens against ANCAs and cause organ damage in a vicious cycle. Considering dead cells are essentially cleared by phagocytic cells as a process of efferocytosis, why the NETs persist in tissue remains unclear. During efferocytosis, macrophages engulf apoptotic cells to prevent the leakage of intracellular components including toxic enzyme into the surrounding cells and these processes are regulated by the expression of CD47 as a “don’t eat me” signal. In this study, we hypothesized that ANCA-mediated NETs in AAV escape from efferocytosis via the up-regulation of CD47 and the persistent NETs amplify the disease. Method Human data: Human kidney biopsy specimens from patients with AAV and minor glomerular abnormality (MGA, as a case control) were subjected to immunohistochemistry (IHC) staining for CD47. In vitro: The expression of CD47 on neutrophils was evaluated by flow cytometry (FCM). Human neutrophils from healthy donor were treated with ANCA-IgGs from MPO-AAV patients or control IgGs. For the efferocytosis assay, macrophages were co-incubated with unstimulated, apoptotic, and ANCA-IgGs treated neutrophils in the presence of anti-CD47 monoclonal antibody (mAb) or a control antibody. The neutrophils were labeled with CFMDA cell tracker (fluorescent probe) and the efferocytosis was evaluated as neutrophil engulfed (CFMDA positive) macrophages using fluorescent microscopy. In vivo: Spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mice (8-week-old age) were treated with intraperitoneal injection of anti-CD47 mAb or a control antibody every 5 days for two weeks. The severity of glomerulonephritis was assessed by the levels of serum creatinine, haematuria, mRNA expression of pro-inflammatory genes, and histopathological findings. To address the immune response against the CD47 blockade, the titre of MPO-ANCA and the number of splenic cell subset was assessed by ELISA and FCM analysis, respectively. Results Human data: The IHC analysis of human renal specimens revealed that the positive area of CD47 of AAV was greater than that of MGA. In particular, the CD47-overexpressed cells were seen in glomeruli with necrotic crescent formation. In vitro: Mean fluorescence intensity (MFI) of CD47 in ANCA-IgGs treated neutrophils (NETs) was significantly higher than that in control IgGs treated neutrophils (ANCA-IgG; 442±21.4 a.u. vs control IgG; 402±10 a.u., p<0.05). In efferocytosis assay, apoptotic neutrophils were engulfed by macrophages (efferocytosis rate/ apoptotic neutrophil; 20.5±3.8%, live neutrophils; 0.9±0.5%). The efferocytosis rate of ANCA-induced NETs significantly decreased compared to apoptotic neutrophil, but anti-CD47 mAb improved the efferocytosis of ANCA-NETs (efferocytosis rate/ anti-CD47 mAb; 19.1±4.2%, control antibody; 7.7±2.2%, p<0.05). In vivo: the renal histopathological severity score, serum creatinine level of AAV mice treated with anti-CD47 mAb decreased compared to that of AAV mice treated with a control antibody (anti-CD47 mAb; 0.96±0.30 vs control antibody; 0.61±0.32 mg/dL). Although there was no significant difference in the number of splenic cells between anti-CD47 and control antibody treated mice, CD47 blockade therapy significantly reduced serum MPO-ANCA titre (28.5±10.4 vs 45.2±14.5 μg/mL) and renal mRNA expression (IFNα, IFNγ, MCP-1 and perforin) of AAV mice. Conclusion ANCA-mediated NETs might escape from efferocytosis through up-regulation of CD47 and provoke necrotizing vasculitis. CD47 blockade could be a potential novel therapeutic strategy for AAV.

Kawasaki Syndrome: A Special View To New Entities Like MIS-C, PIMS and Kawasaki-Like Features In Covid-19 Disease With Recommendation of Classification

Kawasaki syndrome or mucocutaneous lymph node syndrome (MCLS) is an acute, febrile, systemic illness characterized by inflammation (necrotizing vasculitis) of the small and medium-sized arteries. In addition, systemic inflammation is present in many organs. The cause is unknown; an infectious origin is suspected, favored by a hereditary basis.

Risk of Stroke in Systemic Necrotizing Vasculitis: A Nationwide Study Using the National Claims Database

ObjectiveEvidences indicate that the risk of stroke is increased in autoimmune rheumatic diseases. This study aimed to investigate the incidence of stroke in patients with systemic necrotizing vasculitis (SNV) using the national health database.MethodsData were obtained from the Korean National Claims database between 2010 and 2018 to identify incident SNV [anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and polyarteritis nodosa (PAN)] cases. The standardized incidence ratio (SIR) and incidence rate ratio (IRR) were calculated to estimate the risk of stroke in patients with SNV compared to the general population and among disease subgroups. Time-dependent Cox’s regression analysis was performed to identify risk factors for stroke.ResultsAmong 2644 incident SNV cases, 159 patients (6.0%) were affected by stroke. The overall risk of stroke was significantly higher in patients with SNV compared to the general population (SIR 8.42). Stroke event rates were the highest within the first year of SNV diagnosis (67.3%). Among disease subgroups, patients with microscopic polyangiitis (MPA) exhibited higher IRR compared to PAN (adjusted IRR 1.98). In Cox’s hazard analysis, older age and MPA were associated with higher risk of stroke [hazard ratio (HR) 1.05 and 1.88], whereas the administration of cyclophosphamide, azathioprine/mizoribine, methotrexate, and statins were protective in stroke (HR 0.26, 0.34, 0.49, and 0.50, respectively).ConclusionA considerable number of SNV patients experienced stroke, especially in the early phase of disease. Older age and MPA diagnosis were associated with elevated risk of stroke, while the administration of immunosuppressive agents and statins was beneficial in preventing stroke.

HYDRANCEPHALY : RARE ENTITY WITH INCIDENCE LESS THAN 1 IN 10000 LIVE BIRTHS

Hydranencephaly is a rare entity with incidence of 1 in 10000 live births and is characterized by near total absence of cerebral cortex and basal ganglia which are replaced by cerebrospinal fluid. Various aetiologies of hydranencephaly have been suggested which include: Infarction, leukomalacia, diffuse hypoxic-ischemic brain necrosis, intrauterine infections leading to necrotizing vasculitis. Ultrasonography, Computed Tomography and Magnetic Resonance Imaging can easily detect and diagnose hydranencephaly. We present a case of 2-month-old term infant diagnosed with hydranencephaly on computed tomography.