A 33 y.o. male presents with leg swelling(and Oh, by the way, a rash on the penis)

Why are his legs swelling?

Our patient had nephrotic syndrome from membranous glomerulonephropathy caused  by syphilis.

Membranous nephropathy can be caused by hep B, HIV,  hep C, NSAIDS, Li,  and gold salts.  It is also caused by autoimmune diseases like lupus and occasionally can be caused by solid cancers.  In the case of our patient, all other causes were ruled out and he improved with penicillin alone. 

pathologic findings of membranous glomerulonephropathy

Renal disease is also caused by heroin and cocaine.  7 of 8 heroin addicts that present with nephrotic syndrome have membronoproliferative glomerulonephritis in one study.  Blacks are 3-7 times more likely to suffer renal disease. 

Cocaine releases endothelins which induce endogenous angiotensin converting enzyme causing vasoconstriction.   This can result in renal infarct, endothelial injury  or acute rhabdo from muscle breakdown.  These effects can be  partially blocked by ACE inhibitors. The final common pathway of endothelins is to cause fibrosis and renal failure.

Crowe A, Howse M, Bell G, Henry J. Substance abuse and the kidney  2000 QJM 93:147-152.

Van Assen S, Bakker S. Did syphilis truly strike the kidneys this times. 2005. Nephrology, dialysis transplantation Vol. 20 Issue 6 1029-1031.

Zhang Z, Hever A, Bhasin N, et al. Secondary syphilis associated with membranous nephropathy. 2018 Perin J. 22:17-062.