Eosinophilic granulomatosis with polyangiitis with an unusual presentation

Eosinophilic granulomatosis with polyangiitis is an ANCA vasculitis characterized by asthma, rhinosinusitis and peripheral eosinophilia. The kidney is infrequently involved, usually in the form of necrotizing crescentic glomerulonephritis. We present the case of a 60-year-old man who presented with painless sudden loss of visual acuity, purpuric exanthem in his legs, asthenia and myalgia. CT-scan ruled out acute vascular and intracranial space occupant lesions. Optical coherence tomography showed signs of left central retinal artery occlusion and perfusion deficits in the right arterial retinal blood supply. Complementary study showed prominent peripheral eosinophilia (24.500 cel/uL), increased serum IgE (1260U/L) and increased C-reactive protein (10.6mg/ dl). During admission, the patient presented with acute kidney failure (serum creatinine of 4.7mg/dl) and an exceptionally high p-ANCA MPO titer (>600U/L). Eosinophilic granulomatosis with polyangiitis was diagnosed and plasmapheresis, pulse steroid therapy and intravenous cyclophosphamide were provided. Kidney biopsy showed interstitial nephritis with high eosinophil content while the glomerulus was relatively spared, with only mild endocapillary proliferation. The patient didn’t require dialysis. Kidney function was normal at discharge, although the visual deficit did not improve.

Characterization of a Rat Model of Myeloperoxidase-Anti-Neutrophil Cytoplasmic Antibody-Associated Crescentic Glomerulonephritis

<b><i>Background/Aim:</i></b> Necrotizing crescentic glomerulonephritis (GN) associated with anti-neutrophil cytoplasmic antibodies (ANCA) against myeloperoxidase (MPO) is a devastating disease that quickly progresses to kidney failure. Current therapies are broadly immunosuppressive and associated with adverse effects. We wanted to set up a model that could be suitable for testing narrowly targeted therapies. <b><i>Methods:</i></b> The model was constructed in male Wistar Kyoto rats through injections of human MPO (hMPO) and pertussis toxin, followed by a sub-nephritogenic dose of sheep anti-rat glomerular basement membrane (GBM) serum to boost the disease. Rats were monitored for 35 days. Rats given hMPO alone, saline, or human serum albumin with or without anti-GBM serum were also studied. <b><i>Results:</i></b> Rats receiving hMPO developed circulating anti-hMPO and anti-rat MPO antibodies. Challenging hMPO-immunized rats with the anti-GBM serum led to more glomerular neutrophil infiltration and MPO release, and severe haematuria, heavy proteinuria, and higher blood urea nitrogen than hMPO alone. Pauci-immune GN developed with crescents, affecting 25% of glomeruli. The majority of crescents were fibrocellular. Necrotizing lesions and Bowman capsule ruptures were detected. Cells double positive for claudin-1 (a marker of parietal epithelial cells [PECs]) and neural cell adhesion molecule (NCAM; progenitor PECs) were present in crescents. Double staining for NCAM and Ki-67 established proliferative status of progenitor PECs. Podocyte damage was associated with endothelial and GBM changes by electron microscopy. Monocyte/macrophages and CD4⁺ and CD8⁺ T cells accumulated in glomeruli and the surrounding area and in the tubulointerstitium. Lung haemorrhage also manifested. <b><i>Conclusion:</i></b> This model reflects histological lesions of human ANCA-associated rapidly progressive GN and may be useful for investigating new therapies.

Lung adenocarcinoma and sequential antineutrophil cytoplasmic antibody-associated vasculitis: a case report

The relationship between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and lung cancer remains unclear. A 66-year-old man presented with pulmonary nodules. Histological examination of a specimen from computed tomography-guided percutaneous transthoracic biopsy revealed adenocarcinoma. The patient was treated using cryoablation and systemic chemotherapy. Sixteen months later, the patient presented with fever, nasal inflammation, recurrent lung lesions, elevated serum creatinine levels, and high levels of ANCA. Histological examination of a specimen from ultrasound-guided percutaneous renal biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis. The patient responded to treatment, but granulomatosis with polyangiitis recurred and he later died. This case highlights the possibility of sequential AAV with lung cancer. Although this is relatively rare, further research is needed to better understand the association or pathophysiological link between lung cancer and AAV.

Proteinase 3-antineutrophil cytoplasmic antibody-positive necrotizing crescentic glomerulonephritis complicated by infectious endocarditis: a case report

Background Proteinase 3-antineutrophil cytoplasmic antibody has been reported to be positive in 5–10% of cases of renal injury complicated by infective endocarditis; however, histological findings have rarely been reported for these cases. Case presentation A 71-year-old Japanese man with a history of aortic valve replacement developed rapidly progressive renal dysfunction with gross hematuria and proteinuria. Blood analysis showed a high proteinase 3-antineutrophil cytoplasmic antibody (163 IU/ml) titer. Streptococcus species was detected from two separate blood culture bottles. Transesophageal echocardiography detected mitral valve vegetation. Histological evaluation of renal biopsy specimens showed necrosis and cellular crescents in glomeruli without immune complex deposition. The patient met the modified Duke criteria for definitive infective endocarditis. On the basis of these findings, the patient was diagnosed with proteinase 3-antineutrophil cytoplasmic antibody-positive necrotizing crescentic glomerulonephritis complicated by Streptococcus infective endocarditis. His renal disease improved, and his proteinase 3-antineutrophil cytoplasmic antibody titer normalized with antibiotic monotherapy. Conclusion Few case reports have described histological findings of proteinase 3-antineutrophil cytoplasmic antibody-positive renal injury complicated with infective endocarditis. We believe that an accumulation of histological findings and treatments is mandatory for establishment of optimal management for proteinase 3-antineutrophil cytoplasmic antibody-positive renal injury complicated with infective endocarditis.

A rare case of focal segmental glomerular sclerosis and subsequent necrotizing crescentic glomerulonephritis in the same patient

Background: Focal segmental glomerular sclerosis (FSGS) and necrotizing crescentic glomerulonephritis is a rare combination of diagnoses in the same patient. We report on a patient with FSGS who 10 years later developed anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis. Case Presentation: Patient is a 60-year-old female with chronic kidney disease stage 3, osteopenia and anemia. In 2007, she was positive for ANCA proteinase-3 antibody, but kidney biopsy revealed FSGS. She was treated with high-dose oral steroids with tapered dose and went into remission. In 2017, she developed acute renal failure with increased proteinuria. Despite prior FSGS diagnosis, her new kidney biopsy revealed pauci-immune necrotizing glomerulonephritis. Patient was treated with methylprednisolone 250 mg IV for three days and high dose oral steroids with tapered dose. She was also started on rituximab 375 mg/m2 IV once weekly for 4 doses. Given the extent of kidney damage, the patient decided to start peritoneal dialysis and she is also on the kidney transplant list. Conclusions: The rare concurrence of FSGS and ANCA associated glomerulonephritis has not yet been reported. The case also emphasizes the significance of screening for ANCA or obtaining kidney biopsy when indicated not only as the gold standard for diagnosis but also as prognostic value.