Periodic fever syndrome with relapsing glomerulonephritis: a case report and teaching points

Abstract

We report a case of relapsing mesangial and endocapillary proliferative glomerulonephritis (GN) associated with a periodic fever syndrome. The patient presented 11 times in >4 years with acute febrile episode followed in 1-3 days by hematuria, thrombocytopenia and other symptoms of acute GN with variable severity of acute kidney injury. In three episodes, the patient required renal replacement therapy for 7, 10 and 2 treatments, respectively. Shortly after the acute symptoms of the febrile episode had resolved each time, the kidney function would recover and the serum creatinine would return to baseline. Two kidney biopsies obtained during separate episodes showed acute tubular injury along with morphological changes resembling post-infectious GN but with no clinical evidence to support an infectious etiology. Multiple treatment regimens were unable to control the disease. Symptoms were alleviated by rituximab but did not completely remit. Stable remission of the periodic fever and GN was finally achieved after anakinra therapy was initiated 18 months ago. Since then, the patient had several episodes of documented infection without high fever and nephritic kidney manifestations. His kidney function remained stable with normal serum creatinine.

Keywords: autoinflammatory reactions; glomerulonephritis; periodic fever.

Fig. 1.

Kidney biopsy during Episode 1 (E1): (a) periodic acid-Schiff stain, ×400; (b, c) Silver methenamine stain, ×400; (d, e) electron microscopy. The glomeruli show both mesangial and endocapillary proliferation with focally increased numbers of glomerular neutrophils. There is increased interstitial edema accompanied by a mild mixed inflammatory cell infiltrate. Focal mild fibrosis is also present. The tubules show epithelial cell attenuation and occasional tubules contain intra-luminal red blood cell casts. Large sub-endothelial hump-like deposits were ultrastructurally seen on EM along with 70–80% epithelial cell foot process effacement with microvillous transformation and cytoplasmic vacuolization. Immunofluorescent histology showed a very faint focal mesangial and capillary wall staining for IgG and a speckled mesangial and capillary wall staining for C3 (1–2+). There was a minimal mesangial staining for kappa light chain. Stains for IgA, IgM, C1q and lambda were negative (not shown). Morphological diagnoses: (i) acute post-infectious GN. (ii) Acute tubular injury.

Fig. 2.

Kidney biopsy during Episode 2 (E2). (a, b) Hematoxylin and eosin stain, ×100; (c) periodic acid-Schiff stain, ×200. (d) Silver methenamine stain, ×400. The glomeruli show both mesangial and endocapillary proliferation. A few glomeruli appear ischemic with capillary wrinkling and moderate periglomerular fibrosis. There is patchy interstitial fibrosis accompanied by collections of interstitial inflammatory cells, a few atrophic tubules and focal tubule dropout. Focal fibrosis is also present. Immunofluorescent staining showed an irregular, speckled capillary wall and mesangial staining for IgG (trace), C3 (1+) and C1q (trace). There was a faint cast staining for IgA (trace). Stains for IgM, kappa and lambda all were negative (not shown). Electron microscopy revealed hump-shaped sub-epithelial deposits with near-complete visceral epithelial cell foot process effacement (not shown). Morphological diagnoses: (i) acute post-infectious GN with focal global glomerulosclerosis, glomerular ischemic change and interstitial fibrosis. (ii) Acute tubular injury. (iii) Arteriosclerosis, minimal to mild.

Fig. 3.

Hospital course during PFS-related GN, Episode 4 (E4).