Nephrotic Syndrome due to Membranous Nephropathy secondary to Syphilis

We discussed a middle-aged man with risk factors including homelessness and high risk sexual behavior with idiopathic hyperkeratosis presenting with acute to subacute anasarca secondary to nephrotic syndrome ( proteinuria (>20 g per day) with hypoalbuminemia, protein gap and anasarca). He was diagnosed on kidney biopsy with Membranous Nephropathy due to Secondary Syphilis. 

Ddx for nephrotic syndrome 

  • FSGS:
    • Secondary to Infectious (HIV, Parvovirus, CMV, COVID-19); Drugs (Bisphosphonates/Heroin); Metabolic Diseases (DM, HTN, Obesity); Adaptive FSGS from hyperinfiltration injury after nephrectomy 
  • Membranous Nephropathy:
    • Subset have Phospholipase A2 Receptor on podocytes (+Ab PLA R2 is linked with MN)
    • Secondary to colon/breast/lung/hepatitis B and syphilis 
  • Minimal Change Disease
    • Malignancy (Hodgkins), drug induced (NSAID use) and mostly idiopathic MCD
  • Other
    • DM, Medications, Infection, Malignancy, SLE, Amyloid, Pre-Eclampsia 

Tests to order: ANA, dsDNA, DM, SPEP/UPEP/SPIE; HIV/CMV/Parvovirus/Syphilis; PLA-2R

Syphilis testing

  • The traditional screening algorithm
    You start off with a non treponemal test (RPR); if reactive, you confirm with a treponemal test. If the treponemal test is also reactive, you have a diagnosis of syphilis. If it is negative, you do not have syphilis or it is SO early in the infection, that you have not made antibodies. 
  • Reverse Screening algorithm
    You may start off with a treponemal test (such as EIA) for screening. If this is positive, then you reflex to a non-treponemal test (non-specific test like VDRL or RPR) to confirm syphilis. However, if you have a negative non-treponemal test, there may be 2 scenarios at play:
    1. Non treponemal tests can often seroconvert to inactive (RPR negative), so you may have late latent syphilis
    2. Early syphilis where RPR or VDRL hasn’t yet turned positive. In these cases, you order a treponemal test (like TPPA) to be a tie-breaker. If reactive, you have diagnosed syphilis. If negative, you consider your first treponemal test to be a false positive. 

Nontreponemal tests

  • Rapid plasma reagin (RPR)
  • Venereal Disease Research Laboratory (VDRL)

Treponemal tests

  • Fluorescent treponemal antibody absorption (FTA-ABS)
  • Treponema pallidum particle agglutination (TPPA)
  • T. pallidum enzyme immunoassay (TP-EIA)

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