Seronegative Cryoglobulinemic Glomerulonephritis Coexisting With Primary Sjögren Syndrome and HBV Infection: A Diagnostic and Therapeutic Challenge

Cryoglobulinemic glomerulonephritis (CryoGN) is most often caused by mixed cryoglobulinemia, encompassing both type II and type III forms. CryoGN is commonly associated with hepatitis C virus infection or primary Sjögren syndrome (pSS). We report a rare case of serum-negative CryoGN that was associated with concomitant pSS and hepatitis B virus (HBV) infection. Kidney biopsy pathology revealed necrotizing and acute exudative proliferative glomerulonephritis with crescents, necrotizing arteritis, interstitial lymphohistiocytic inflammatory infiltrates, and organized deposits with characteristic features of cryoglobulin based on electron microscopy. The patient was first treated with entecavir for HBV suppression, followed by pulse steroids and rituximab, resulting in resolution of kidney dysfunction and proteinuria. This case underscores the importance of kidney biopsy in diagnosing CryoGN in the absence of serum positivity within the appropriate clinical context. It also highlights the role of combination therapy in targeting multiple pathogenic pathways that drive chronic immune stimulation and/or lymphoproliferation. The coexistence of pSS and HBV can trigger CryoGN. A multidisciplinary and individualized therapeutic approach (antiviral and immunosuppressive) can lead to an excellent renal response.