Successful use of avacopan in a case of ANCA-associated vasculitis with treatment-resistant medium-sized vessel involvement

Abstract

We report the case of a 75-year-old woman who presented with fever, right back pain, paresthesia in the right extremities, erythema, purpura, and nodules. She had previously initiated dialysis due to rapidly progressive glomerulonephritis and was transferred to our hospital. Imaging studies revealed multiple cerebral and splenic infarcts and hemorrhage encapsulating the right kidney, likely due to microaneurysms in multiple renal arteries. High MPO-ANCA titers were observed, and a skin biopsy revealed granulomatous inflammation affecting medium-sized vessels, leading to a diagnosis of granulomatosis with polyangiitis (GPA) and ANCA-associated vasculitis (AAV) involving medium-sized vessels. Treatment began with intravenous pulse steroid therapy (methylprednisolone 1000 mg/day) and subsequent oral prednisolone (PSL) 40 mg (about 0.8 mg/kg) and intravenous cyclophosphamide (IVCY) at 250 mg. While her symptoms improved, she developed severe infections, including candidemia and febrile neutropenia. Consequently, we combined PSL with the C5a receptor antagonist avacopan, which allowed for PSL tapering and stabilized her disease. This case is significant as no previous reports of avacopan's efficacy in AAV with medium-sized vessel involvement suggest its potential effectiveness in such cases.

Keywords: ANCA-associated vasculitis with medium-sized vessel involvement; Avacopan; Granulomatosis with polyangiitis; Microaneurysms in renal arteries.

Fig. 1

Plain CT image of the trunk. A Reticular shadow and ground-glass opacities were observed at the bases of the lungs in the bilateral lower lung fields. B The right kidney was enlarged and there was a hyper-absorptive area on the outer side of the right kidney, suggesting hemorrhage due to capsular hemorrhage in the right kidney

Fig. 2

Contrast-enhanced CT image of the trunk. A Blood flow defect was observed in the spleen. B In the arterial phase, the contrast effect was suggestive of microaneurysms in both kidneys. C 3D image construction showed findings suggestive of microaneurysms in both kidneys

Fig. 3

Results of skin biopsy. A Arteries with diameters of 68 μm (elastica van Gieson staining, × 40) and B 250 μm (elastica van Gieson staining, × 100) are shown. C, D Granuloma with giant cells (white arrow) (hematoxylin–eosin staining, C× 200, D× 400). Skin biopsy revealed disruption of the internal elastic lamina, fibrinoid necrosis, and neutrophilic infiltration in arteries, along with granulomatous tissue in the adipose tissue

Fig. 4

MRI images of acute cerebral infarction. A DWI of the periventricular (superior) and bilateral basal ganglia (inferior) sections show high-signal findings. B Low-signal ADC in the periventricular (upper) and bilateral basal ganglia (lower) sections

Fig. 5

Peroneal nerve biopsy results. The nerve tissue showed inflammatory cell infiltration into the microvessels, myelin ovoid, and a few regenerative clusters. Myelinated nerve density showed regional differences within and between nerve bundles, consistent with polyneuritis (hematoxylin–eosin staining, × 40)

Fig. 6

Clinical course