Membranous nephropathy associated with multicentric Castleman’s disease that was successfully treated with tocilizumab: a case report and review of the literature

Abstract

Background Multicentric Castleman’s disease is a life-threatening disorder involving a systemic inflammatory response and multiple organ failure caused by the overproduction of interleukin-6. Although renal complications of Castleman’s disease include AA amyloidosis, thrombotic microangiopathy, and membranoproliferative glomerulonephritis, membranous nephropathy is relatively rare. We experienced a case of secondary membranous nephropathy associated with Castleman’s disease. Case presentation The patient was a 43-year-old Japanese man who had shown a high zinc sulfate value in turbidity test, polyclonal hypergammaglobulinemia, anemia, and proteinuria. A physical examination revealed diffuse lymphadenopathy, an enlarged spleen and papulae of the body trunk. A skin biopsy of a papule on the patient’s back showed plasma cells in the perivascular area and he was diagnosed with multicentric Castleman’s disease, plasma cell variant. Kidney biopsy showed the appearance of bubbling in the glomerular basement membranes in Periodic acid methenamine silver stain and electron microscopy revealed electron dense deposits within and outside the glomerular basement membranes. Since immunofluorescence study showed predominant granular deposition of IgG1 and IgG2, he was diagnosed with secondary membranous nephropathy associated with Castleman’s disease. He was initially treated with prednisolone alone, however his biochemical abnormalities did not improve. After intravenous tocilizumab (700 mg every 2 weeks) was started, his C-reactive protein elevation, anemia, and polyclonal gammopathy improved. Furthermore, his urinary protein level declined from 1.58 g/gCr to 0.13 g/gCr. The prednisolone dose was gradually tapered, then discontinued. He has been stable without a recurrence of proteinuria for more than 6 months. Conclusions Tocilizumab might be a treatment option for secondary membranous nephropathy associated with Castleman’s disease.

A Case of Castleman’s Disease during the Long-Term Course of Membranous Nephropathy

“…In some cases, the immunoglobulin deposition patterns in the glomerular capillary wall have not been fully described [ 3 , 5 , 9 ], but the remaining cases demonstrated IgG deposition. In the cases with IgA and IgM staining in renal specimens, they are deposited faintly [ 6 , 7 , 14 ] or not deposited [ 11 , 13 ]. Therefore, it seems to be rare for IgG, IgA, and IgM to all be deposited as in the present case.…”

“…Therefore, it seems to be rare for IgG, IgA, and IgM to all be deposited as in the present case. Subclasses pattern of IgG in the previous cases are mostly characterized as IgG1 (+), IgG2 (+), IgG3 (−), and IgG4 (−) [ 8 , 10 , 11 , 13 ]. In the present case, only IgG4 is stained, suggesting at least the past nephrotic syndrome was primary MN and the current episode can be considered a recurrence of primary MN.…”

“…Similarly, none of the cases had any prior history of nephrotic syndrome. Most of the reports indicated that nephrotic syndrome developed at the same time as MCD, but in some cases MN was diagnosed several years after the onset of clinical signs suggestive of MCD [ 11 , 14 ]. Two cases underwent multiple renal biopsies.…”

“…Unfortunately, hypoalbuminemia was not sufciently improved, and remission of the nephrotic syndrome was not achieved, but a prompt decrease in urinary protein was achieved. We reviewed the 11 reported cases of MN with CD published between 1979 and 2021 [3,[5][6][7][8][9][10][11][12][13][14]. In some cases, the immunoglobulin deposition patterns in the glomerular capillary wall have not been fully described [3,5,9], but the remaining cases demonstrated IgG deposition.…”

“…Another case improved with corticosteroid monotherapy [4]. In most cases, improvement was achieved by tocilizumab [8,[10][11][12][13][14] or other immunosuppressive agents such as cyclophosphamide [4,7,9,13], mizoribine [14], and cyclosporine [9,14] in combination with corticosteroids. In our case, induction remission therapy with corticosteroids alone for 6 months proved efective, but it was insufcient for remission of both MN and CD, and the decision was made to add anti-IL-6 therapy in another facility.…”