Revenge of the Syph: Secondary Syphilis Presenting as Nephrotic Syndrome

Introduction: A 24-year-old man presented with acute onset of bilateral lower extremity and periorbital edema. Initial labs demonstrated hypoalbuminemia (0.8 g/dL) and urinalysis portrayed significant albuminuria on dipstick testing. Nephrotic syndrome was confirmed with 7.7 g/g on spot protein-to-creatinine ratio. Patient had negative serologies for HIV, viral hepatitis, ANA, and anti-PLA2R antibody. His initial VDRL was positive. Patient elected to undergo renal biopsy while awaiting confirmatory testing for syphilis. Case Description: Renal biopsy revealed characteristic basement membrane thickening and electron-dense subepithelial deposits. On immunofluorescent staining, granular subepithelial and intramembranous immune deposits can be visualized. There was no extra-glomerular staining. Neuron-derived neurotropic factor (NDNF) staining was also positive, confirming the diagnosis of secondary membranous nephropathy due to syphilis (Figure 1). Discussion: His RPR returned reactive with a 1:32 quantitative titer confirming new diagnosis of syphilis. Due to end-organ involvement, infectious disease was asked to evaluate the patient’s case as the patient reported a history of severe penicillin allergy. Although other end-organ involvement of syphilis including the CNS, aorta, liver and myocardium necessitate penicillin desensitization, there is no consensus regarding treatment regimens for secondary membranous nephropathy due to syphilis. He was discharged with a course of doxycycline with close follow up to monitor his proteinuria. His syphilis titers will not improve until 6-12 months after treatment, and he may require penicillin desensitization if his nephrotic syndrome fails to improve.Neuron-derived neurotrophic factor (NDNF) staining confirming syphilis-associated membranous nephropathy.