A 56-year-old woman comes to the office due to worsening fatigue and edema of the bilateral lower extremities for the past several months. She also reports that her legs feel tight. The patient has no prior medical conditions and takes no medications. Family history is significant for hypothyroidism in her sister. The patient does not use tobacco, alcohol, or illicit drugs. Temperature is 37 C (98.6 F), blood pressure is 112/64 mm Hg, and pulse is 86/min and regular. Physical examination reveals normal heart and lung sounds, mild hepatomegaly, and pitting edema of the bilateral lower extremities. Other examination findings are shown in the exhibit. Laboratory studies are as follows: Which of the following is the most likely cause of this patient's current condition?

Question

A 56-year-old woman comes to the office due to worsening fatigue and edema of the bilateral lower extremities for the past several months.  She also reports that her legs feel tight.  The patient has no prior medical conditions and takes no medications.  Family history is significant for hypothyroidism in her sister.  The patient does not use tobacco, alcohol, or illicit drugs.  Temperature is 37 C (98.6 F), blood pressure is 112/64 mm Hg, and pulse is 86/min and regular.  Physical examination reveals normal heart and lung sounds, mild hepatomegaly, and pitting edema of the bilateral lower extremities.  Other examination findings are shown in the exhibit.  Laboratory studies are as follows:  Which of the following is the most likely cause of this patient's current condition?

Quizplus · Accepted Answer

11ec25c8_d47a_fe88_bc81_433936109aca_MD0003_00 This patient with nephrotic syndrome, hepatomegaly, periorbital purpura, and waxy skin changes likely has AL amyloidosis. The unifying feature of amyloidoses (eg, AL, AA, age-related, and hereditary amyloidosis) is misfolded precursor proteins that deposit in extracellular tissues as fibrils, causing organ dysfunction. AL amyloidosis results from excess immunoglobulin light chains produced in plasma cell dyscrasias (eg, multiple myeloma, Waldenström macroglobulinemia). Although some overlap exists between the different amyloidoses, the organs involved vary with the type of precursor protein. AL amyloidosis commonly presents with kidney involvement manifesting as nephrotic syndrome (eg, 4+ proteinuria, low albumin, pitting edema). Also prominent are hepatomegaly and restrictive cardiomyopathy. The deposits can lead to waxy, tight skin (epidermal deposits); macroglossia; and peripheral neuropathy. Periorbital purpura is a rare but very characteristic finding that may reflect protein infiltration causing a bleeding diathesis (eg, due to factor X sequestration in the liver) and weakening of vessel walls leading to hemorrhage. Because of potential response to chemotherapy, AL amyloidosis requires differentiation from the other types of systemic amyloidosis. The presence of a clonal plasma cell disorder is confirmed by serum or urine protein electrophoresis, free light chain assay, or bone marrow biopsy. (Choice B) Dermatomyositis is an inflammatory myopathy with cutaneous manifestations. Heliotrope eruption (violaceous erythema) of the eyelids is a pathognomonic sign. Although this finding may be confused with purpura, progressive proximal muscle weakness would be the predominant manifestation, and nephrotic syndrome is atypical. Heliotrope eruption (Choice C) Hashimoto thyroiditis results from autoimmune thyroid destruction and causes hypothyroidism. Fatigue is common, and lower extremity edema can occur but is typically nonpitting (myxedema, reflecting glycosaminoglycan infiltration). Periorbital edema is sometimes present, but purpura is not characteristic. Hepatomegaly and nephrotic syndrome are rare. myxedema (Choice D) Sarcoidosis can affect any organ but most frequently presents with lung involvement. Granulomatous infiltration on biopsy of the liver and kidney is common; however, hepatomegaly and nephrotic syndrome are uncommon. Skin lesions are variable and usually present as papules, nodules, or plaques rather than purpura. (Choice E) Systemic sclerosis causes progressive skin and internal organ fibrosis. Although patients with edema can feel skin tightness, scleroderma denotes visible thickening and hardening that is not pitting and typically involves the hands and face. Periorbital purpura, nephrotic syndrome, and hepatomegaly are not typically present. Educational objective: AL amyloidosis most commonly presents as nephrotic syndrome. Hepatomegaly and restrictive cardiomyopathy are frequent manifestations. Periorbital purpura is a rare but highly characteristic skin finding.

A 56-Year-Old Woman Comes to the Office Due to Worsening