On the Cover

Case Description:

What is the diagnosis?

A 49-year-old male presented with lower extremity edema and a rash on his legs, torso, and back. Serum creatinine was 1.3 mg/dl, albumin was 0.9 g/dl, and the urine protein-creatinine ratio was 6 g/g. Syphilis IgG and IgM antibodies were reactive >8.0 antibody index (>1 is positive), and active infection was confirmed with a reactive rapid plasma regain test (1:64). Serum antiphospholipase A2 receptor (PLA2R) antibodies and thrombospondin type-1 domain-containing 7A (THSD7A) antibodies were negative

Image Description:

Left: Light microscopy with Jones silver stain. Normal-appearing glomerular basement membrane with no spikes or circular lucencies identified.

Center: Immunofluorescence microscopy showed 1+ IgG granular glomerular basement membrane deposition.

Right: Electron microscopy. Subepithelial electron dense deposits compatible with immune complexes. Diffusely effaced visceral epithelial cell foot processes with villous transformation of the podocytes. Glomerular basement membrane of normal thickness and contour

Teaching Points:

Findings support the diagnosis of secondarymembranous nephropathy due to secondary syphilis. The patient had no evidence of active malignancy, and his anti-PLA2R and THSD7A were negative, as were other serologies. Secondary membranous nephropathy due to secondary syphilis occurs as an antibody response mounted against Tremponema pallidum, resulting in deposition of IgG, usually in the mesangium (1), although in this case it was in the subepithelial region. Treatment with 2.4 million units of penicillin G was given prior to discharge, and at hospital follow-up, the patient’s edema and maculopapular rash had resolved. Unfortunately, he was unwilling to obtain labarotary results and subsequently was lost to follow-up.

1. Inayat F, Almas T, Bokhari SRA, Muhammad A, Sharshir MA: Membranous glomerulonephritis as an uncommon presentation of secondary syphilis: A reminder on therapeutic decision-making in clinical practice. J Investig Med High Impact Case Report 8: 1–9, 2020

(Images and text provided by Natalie Freidin, Department of Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, South Carolina; Sally Self, Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina; Romik Srivastava, Medical University of South Carolina, Charleston, South Carolina; Lauren Crowson-Hindman, Department of Pathology and LaboratoryMedicine,Medical University of SouthCarolina, Charleston, SouthCarolina; and Joshua Harbaugh, Department ofMedicine, Division of Nephrology, Medical University of South Carolina, Charleston, South Carolina.)