A 64-year-old man comes to the office due to generalized edema, fatigue, and dyspnea on exertion for 2 months. The patient has a 25-year history of poorly controlled rheumatoid arthritis. Temperature is 36.9 C (98.4 F), blood pressure is 108/70 mm Hg, and pulse is 90/min. The patient is thin and appears chronically ill but is in no acute distress. There is no lymphadenopathy. Breath sounds are decreased at the lung bases. Musculoskeletal examination shows severe deformities of the hands and feet related to rheumatoid arthritis. There is pitting edema of both legs up to the knees. Peripheral pulses are normal. Urinalysis shows 4+ protein but is otherwise normal. A renal biopsy is performed. Which of the following histologic abnormalities is most likely to be seen in this patient's glomeruli?

Question

A 64-year-old man comes to the office due to generalized edema, fatigue, and dyspnea on exertion for 2 months.  The patient has a 25-year history of poorly controlled rheumatoid arthritis.  Temperature is 36.9 C (98.4 F), blood pressure is 108/70 mm Hg, and pulse is 90/min.  The patient is thin and appears chronically ill but is in no acute distress.  There is no lymphadenopathy.  Breath sounds are decreased at the lung bases.  Musculoskeletal examination shows severe deformities of the hands and feet related to rheumatoid arthritis.  There is pitting edema of both legs up to the knees.  Peripheral pulses are normal.  Urinalysis shows 4+ protein but is otherwise normal.  A renal biopsy is performed.  Which of the following histologic abnormalities is most likely to be seen in this patient's glomeruli?

Quizplus · Accepted Answer

This patient with peripheral edema and heavy proteinuria has nephrotic syndrome. Given his long-standing inflammation from poorly controlled rheumatoid arthritis (RA), the cause of his nephrotic syndrome is likely AA amyloidosis. Amyloidosis begins when native proteins (eg, light chains, beta2-microglobulin, transthyretin) misfold. This structural change in soluble precursors promotes polymerization into beta-pleated sheets that deposit as insoluble fibrils, causing organ dysfunction. Amyloid deposits appear as amorphous pink material on light microscopy with apple-green birefringence on Congo red stain under polarized light. Serum amyloid A, an acute phase reactant induced by cytokines, is excessively produced during chronic inflammatory states, resulting in AA amyloidosis. RA is the most common cause, but inflammatory bowel disease, chronic infection (eg, osteomyelitis, tuberculosis), and familial Mediterranean fever are also frequently associated. AA amyloidosis most commonly affects the kidneys, presenting as nephrotic syndrome. Hepatomegaly is frequent with splenomegaly occasionally seen. Cardiac involvement (eg, restrictive cardiomyopathy) is rare. (Choice A) Crescent formation in glomeruli occur with rapidly progressive glomerulonephritis, which can present with several conditions (eg, anti-glomerular basement membrane antibody disease). However, it rarely occurs in RA and typically presents with an active urine sediment (eg, dysmorphic hematuria, red blood cell casts). (Choice C) Diffuse hypercellular glomeruli on light microscopy are evident most often with poststreptococcal glomerulonephritis. They are also seen with membranoproliferative glomerulonephritis and lupus nephritis. In addition to proteinuria, these conditions typically have other components of nephritic syndrome (ie, hematuria, hypertension, kidney dysfunction), not nephrotic syndrome. (Choice D) IgA deposition in the glomerular mesangium is found on immunofluorescence in IgA nephropathy. IgA nephropathy only rarely causes isolated nephrotic syndrome; it typically presents as recurrent, painless hematuria (eg, nephritic syndrome) frequently provoked by upper respiratory tract infection. (Choice E) No abnormality on light microscopy in nephrotic syndrome suggests minimal change disease (MCD). The most common cause of nephrotic syndrome in children, adult MCD is sometimes associated with malignancies, drugs, or infections but not amyloidosis. Educational objective: AA amyloidosis results from excessive serum amyloid A produced in rheumatoid arthritis and other chronic inflammatory conditions. Renal disease, the most common manifestation, presents as nephrotic syndrome. Light microscopy shows amorphous pink deposits with apple-green birefringence on Congo red stain under polarized light.

A 64-Year-Old Man Comes to the Office Due to Generalized