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
- 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
- DM, Medications, Infection, Malignancy, SLE, Amyloid, Pre-Eclampsia
Tests to order: ANA, dsDNA, DM, SPEP/UPEP/SPIE; HIV/CMV/Parvovirus/Syphilis; PLA-2R
- 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:
- Non treponemal tests can often seroconvert to inactive (RPR negative), so you may have late latent syphilis
- 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.
- Rapid plasma reagin (RPR)
- Venereal Disease Research Laboratory (VDRL)
- Fluorescent treponemal antibody absorption (FTA-ABS)
- Treponema pallidum particle agglutination (TPPA)
- T. pallidum enzyme immunoassay (TP-EIA)