The Great Imitator Attacks the Kidney: Syphilis-Induced Membranous Nephropathy with Lupus-Like Full-House Immunofluorescence Pattern

Introduction: Syphilis, a treatable infection caused by Treponema pallidum, is known as 'the great imitator' due to its wide range of clinical presentations. Among its rare renal presentations, membranous nephropathy is clinically significant for its potential to mimic lupus nephritis, especially when full-house immunofluorescence (IF) is present. Such overlap can result in diagnostic confusion, inappropriate immunosuppression, and preventable renal injury. Timely recognition allows for curative antibiotic therapy, highlighting the importance of differentiating syphilitic glomerulonephritis (GN) from autoimmune etiologies. We present a rare case of syphilis-induced membranous nephropathy with a full-house lupus-like IF pattern. Case Description: A 61-year-old man with hypertension, chronic kidney disease (CKD) stage IIIa, and alcohol use disorder presented with one month of generalized edema and foamy urine. Labs revealed acute kidney injury (AKI) and nephrotic-range proteinuria. Kidney biopsy showed focal proliferative exudative GN with membranous features, EXT1-positive and PLA2R-negative deposits, and a full-house IF pattern. Initial autoimmune and infectious workup, excluding syphilis, was unremarkable. The patient was empirically started on prednisone but was lost to follow up. One year later, he returned with recurrent symptoms, AKI, and persistent proteinuria. Repeat biopsy revealed EXT1-positive membranous nephropathy with a full-house IF pattern. Autoimmune serology remained negative. This time, an expanded infectious panel revealed a reactive RPR and positive T. pallidum antibodies, confirming latent syphilis. Treatment with benzathine penicillin G resulted in clinical improvement and resolution of proteinuria. Discussion: This case highlights the importance of including syphilis in the differential diagnosis of glomerular diseases with a full house pattern, especially when autoimmune serologies are negative. Although typically associated with lupus nephritis, full-house IF is not pathognomonic and may occur in infections. Misdiagnosis can result in unnecessary immunosuppression and delayed treatment. Underscoring the need for high clinical suspicion for treatable infectious mimics like syphilis in immune complex GN.