A 24-year-old woman comes to the office for the evaluation of joint pain, fatigue, edema, and weight gain for the past four weeks. She has no previous medical conditions except for recurrent oral ulcers. The patient takes no medications and does not use tobacco, alcohol, or illicit drugs. Blood pressure is 130/80 mm Hg and pulse is 80/min. Examination shows oral mucosal ulcers, facial puffiness, and 3+ peripheral edema. Swelling, erythema, and tenderness are noted over the bilateral metacarpophalangeal and proximal interphalangeal joints. Cardiopulmonary examination reveals no abnormalities. Twenty-four-hour urine protein excretion is 4.5 g. Serum antinuclear antibodies are present. Kidney biopsy shows glomerular capillary wall thickening with no increase in cellularity. When the sample is stained with methenamine silver, irregular spikes protruding from the glomerular basement membrane are seen. This patient most likely has which of the following conditions?

Question

A 24-year-old woman comes to the office for the evaluation of joint pain, fatigue, edema, and weight gain for the past four weeks.  She has no previous medical conditions except for recurrent oral ulcers.  The patient takes no medications and does not use tobacco, alcohol, or illicit drugs.  Blood pressure is 130/80 mm Hg and pulse is 80/min.  Examination shows oral mucosal ulcers, facial puffiness, and 3+ peripheral edema.  Swelling, erythema, and tenderness are noted over the bilateral metacarpophalangeal and proximal interphalangeal joints.  Cardiopulmonary examination reveals no abnormalities.  Twenty-four-hour urine protein excretion is 4.5 g.  Serum antinuclear antibodies are present.  Kidney biopsy shows glomerular capillary wall thickening with no increase in cellularity.  When the sample is stained with methenamine silver, irregular spikes protruding from the glomerular basement membrane are seen.  This patient most likely has which of the following conditions?

Quizplus · Accepted Answer

This patient has nephrotic syndrome (ie, generalized edema, marked proteinuria). In conjunction with the characteristic biopsy findings, this presentation suggests membranous glomerulopathy (MG). MG is caused by immune-complex deposition in the subepithelial portion of the glomerular capillary wall. Light microscopy shows diffuse thickening of the glomerular basement membrane (GBM) without an increase in glomerular cellularity. Immunofluorescence reveals granular deposits of IgG and C3 along the GBM. Electron microscopy demonstrates irregular, electron-dense immune deposits located between the GBM and epithelial cells. Protrusion of the GBM through the deposits resemble spikes and domes when stained with a silver stain. MG is a common cause of nephrotic syndrome in adults. Most cases are idiopathic, with the remainder due to chronic infection (eg, viral hepatitis, syphilis), solid tumors (eg, lung, colon), or systemic lupus erythematous (SLE). This patient with inflammatory arthritis, oral ulcers, and antinuclear antibodies likely has MG secondary to SLE (which leads to renal disease from anti-double-stranded DNA immune-complex formation). (Choices A and B) Anti-GBM disease (ie, Goodpasture disease) and antineutrophil cytoplasmic antibody-associated glomerulonephritis (eg, granulomatosis with polyangiitis) cause rapidly progressive crescentic disease, characterized by glomerular hypercellularity with crescent formation (composed of fibrin and proliferating cells). These diseases cause nephritic syndrome (eg, hematuria, red blood cell casts), not isolated proteinuria. (Choice C) Diffuse proliferative nephritis, another common renal manifestation of SLE, is characterized by proliferation of lymphocytes and endothelial cells within the capillary loops. Diffuse "wire-loop" deposits are often seen. (Choice D) Focal segmental glomerulosclerosis also causes nephrotic syndrome but is characterized by sclerosis in some (but not all) glomeruli (focal) and some portions of the glomerulus. It is commonly associated with drug use (eg, heroin) and viruses (eg, HIV). (Choice E) Membranoproliferative glomerulonephritis is often associated with hepatitis B or C. It is characterized by thickening of the GBM, but, unlike MG, large hypercellular glomeruli are also seen. (Choice G) Postinfectious glomerulonephritis occurs more commonly in children and causes a nephritic (not nephrotic) syndrome, typically two to four weeks after a group A streptococcal infection. Light microscopy demonstrates enlarged, diffusely hypercellular glomeruli. Educational objective: Membranous glomerulopathy is a common cause of nephrotic syndrome in adults and can occur in association with solid malignancy, viral hepatitis, and systemic lupus erythematosus. Immune-complex deposition in the subepithelial portion of the glomerular capillary wall causes diffuse thickening of the glomerular basement membrane (without increased cellularity); these deposits have a "spike and dome" appearance when stained with silver stains. __________ References: The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. (http://www.ncbi.nlm.nih.gov/pubmed/21068142)

A 24-Year-Old Woman Comes to the Office for the Evaluation