Cryoglobulinemic Glomerulonephritis in Sjogren Syndrome

Introduction: We report a case of seronegative cryoglobulinemic glomerulonephritis (GN) in the setting of Sjogren’s Syndrome. Case Description: A 64-year-old female with a history of hypertension and rheumatoid arthritis was admitted with a 2-month history of persistent nausea, emesis, and 24-pound weight loss. She was also found to have an elevated sCr of 1.8 mg/dL (unknown baseline), microscopic hematuria, and nephrotic syndrome with a UPCR of 5.4 g/g. Serologic work-up obtained showed +ANA (1:320; speckled nuclear pattern), +SSA (>8 u), +SSB (>8 u), elevated CRP (5.13 mg/dL), +rheumatoid factor (68.2 IU/mL), decreased C3 (61 mg/dL) and C4 (2 mg/dL), +IgM kappa M protein (0.022 g/dL) with free light chain ratio of 1.4. Pertinent negatives included cryoglobulin, HCV antibody, ANCA, PLA2R, dsDNA. Kidney biopsy showed membranoproliferative GN with diffuse and global endocapillary hypercellularity. Two glomeruli had cellular crescents and few glomeruli showed intraluminal Periodic Acid Schiff positive pseudo-thrombi consistent with cryoplugs. Immunofluorescence showed IgM dominant diffuse global granular mesangial and capillary loop staining with slight clonal shift (kappa > lambda) on both frozen and paraffin-embedded tissues. Electron microscopy on paraffin-embedded tissue showed possible subendothelial deposits with short fibrillary substructures. Given concerns for crescentic cryoglobulinemic GN, the patient received pulse-dose steroids. Further investigations were negative for cyclic citrullinated peptide, MYD88 gene mutation, and blood and urine cultures. CT chest/abdomen/pelvis was negative for lymphadenopathy. Esophagogastroduodenoscopy showed moderate chronic gastritis with immunohistochemical stain negative for lymphoma. Bone marrow biopsy was negative for malignancies or plasma cell dyscrasias. The patient was diagnosed with type II cryoglobulinemic GN in the setting of Sjogren’s Syndrome and was treated with steroid taper and rituximab infusion. While hospitalized, patient’s sCr peaked to 3.7 and downtrended, discharged with a sCr of 1.4. Discussion: Sjogren’s Syndrome has variable renal manifestations including interstitial nephritis, renal tubular acidosis, GN, and nephrolithiasis. In cases of mixed cryoglobulinemic GN, it is important to exclude active infections, lymphomas, and plasma cell dyscrasias.