ANCA-Negative Vasculitis in Eosinophilic Granulomatosis with Polyangiitis Complicated with Membranous Nephropathy: A Case Report and Brief Literature Review

Abstract

Renal involvement in eosinophilic granulomatosis with polyangiitis (EGPA) typically occurs in anti-neutrophil cytoplasmic autoantibody (ANCA)-positive cases presenting with rapidly progressive renal insufficiency and urinary abnormalities induced by primarily necrotizing crescentic glomerulonephritis (NCGN). Recently, ANCA-negative EGPA has also been reported to manifest with renal involvement, such as NCGN or non-NCGN, including membranous nephropathy (MN). Herein, we report a 70-year-old female who presented with purpura on the lower legs, upper limb numbness, renal dysfunction (eGFR, 20.5 ml/min/1.73 m²), and eosinophilia (eosinophils, 37,570/μl). MPO-and PR3-ANCA were negative, and urinalysis revealed urine protein (0.63 g/day) but without red blood cells in the urine sediment. Thus, she was diagnosed with ANCA-negative EGPA with rapidly progressive renal dysfunction. A renal biopsy revealed vasculitis in the interlobular arteries without NCGN, with the vasculitis being complicated by MN. Micrograph findings on fluorescence immunostaining contained both primary and secondary characteristics of MN (dominance of IgG subclass 4 more than subclass 1 vs. negativity of PLA2R and THSD7A). After treatment with prednisolone, her eosinophil counts normalized, and renal dysfunction improved. Furthermore, urine protein did not increase above 1.0 g/day during the clinical course. This is a rare case of ANCA-negative EGPA presenting with acute renal dysfunction without NCGN and subclinical MN with unknown etiology. It is important to recognize that EGPA pathology varies widely throughout the disease course, and the clinical course of subclinical MN should be carefully assessed in further follow-ups.

Figure 1

Histological findings of the renal specimen. Light microscopy image showing infiltration of inflammatory cells in the interstitial area and a severe degree of interstitial fibrosis and tubular atrophy (about 60%) but without granulomas ((a): PAS staining, original magnification ×100). Among the interlobular arteries, some show inflammatory cell infiltration in the lumen ((b): black arrow, hematoxylin and eosin staining, original magnification ×400), fibrin deposition in the vascular wall, and rupture of the elastic fibers ((c): white arrow, PAS staining, original magnification ×400). There are no significant abnormal findings in the glomerulus, including membrane changes ((d): periodic acid-methenamine silver staining, original magnification ×400). As shown in the micrograph of fluorescence immunostaining ((e): original magnification ×400), glomerular capillary deposits are dominant in IgG4. PLA2R and THSD7A are negative, suspicious of a secondary pathology. Electron microscopy image ((f): original magnification ×3000) showing subepithelial electron-dense deposits (EDDs) and a thickened basement membrane with spike formation (arrow). EDDs are limited to the subepithelium and are relatively uniform in size and distribution, which is not a finding of a secondary pathology.