A 68-year-old woman comes to the office due to recurrent bacterial sinusitis, pneumonia, and urinary tract infections over the past several months. The patient has no prior medical conditions or history of severe infections in childhood. She does not use tobacco, alcohol, or illicit drugs. Temperature is 36.6 C (97.9 F), blood pressure is 130/76 mm Hg, and pulse is 72/min. On physical examination, the lungs are clear to auscultation, heart sounds are normal, and the abdomen is soft and nontender with no hepatosplenomegaly. Laboratory testing reveals normocytic normochromic anemia. Bone marrow aspirate shows an increased number of cells, as shown below. Which of the following is the most likely cause of this patient's increased susceptibility to infections?

Question

A 68-year-old woman comes to the office due to recurrent bacterial sinusitis, pneumonia, and urinary tract infections over the past several months.  The patient has no prior medical conditions or history of severe infections in childhood.  She does not use tobacco, alcohol, or illicit drugs.  Temperature is 36.6 C (97.9 F), blood pressure is 130/76 mm Hg, and pulse is 72/min.  On physical examination, the lungs are clear to auscultation, heart sounds are normal, and the abdomen is soft and nontender with no hepatosplenomegaly.  Laboratory testing reveals normocytic normochromic anemia.  Bone marrow aspirate shows an increased number of cells, as shown below.  Which of the following is the most likely cause of this patient's increased susceptibility to infections?

Quizplus · Accepted Answer

11ec160b_37ce_bea5_9249_29574ecf8283_MD0001_00 This patient's bone marrow aspirate has numerous plasma cells, which are distinguished by the presence of abundant basophilic cytoplasm, perinuclear paleness (large Golgi apparatus), and nuclei with "clock-face" (peripheral) chromatin. The presence of >10% plasma cells in the bone marrow raises strong suspicion for multiple myeloma (MM). In MM, neoplastic plasma cells crowd the bone marrow, leading to impairments in normal hematopoiesis. B-cell development is particularly affected, which reduces plasma cell diversity and limits the generation of targeted immunoglobulins against infectious agents. Therefore, patients with MM have increased risk of recurrent bacterial infections, particularly of the urinary tract, lungs, and sinuses. Although patients with MM have high levels of circulating monoclonal immunoglobulin, monoclonal immunoglobulin does not provide immunity against a diverse range of pathogens. MM is also associated with normocytic anemia (due to ineffective erythropoiesis), bone pain (due to osteolytic lesions), hypercalcemia, and renal insufficiency (due to clogging of the tubules with immunoglobulin light chains). (Choice A) Chediak-Higashi syndrome is a rare autosomal recessive disorder that causes abnormal lysosomal fusion and transport. Although it is associated with recurrent bacterial infections and hematologic malignancies, most cases are identified in early childhood, and patients generally have hypopigmentation and progressive neurologic dysfunction. (Choice C) Leukocyte adhesion deficiency is an inherited disorder associated with defective adhesion and transmigration of leukocytes from the vasculature to tissues. Patients typically have recurrent bacterial infections that begin in early childhood. It is not associated with excessive plasma cells in the bone marrow. (Choice D) Terminal complement deficiency (C5-C9) prevents the formation of the membrane attack complex and dramatically increases the risk of recurrent infection with Neisseria species; patients are usually healthy otherwise and have no abnormalities in the bone marrow. (Choice E) Chronic granulomatous disease is a genetic disorder associated with severe bacterial and fungal infections due to impaired ability of phagocytes to generate reactive oxygen species (oxidative burst). Most cases present in early childhood, and plasma cell effacement of the bone marrow would not be seen. Educational objective: Multiple myeloma is associated with the clonal proliferation of plasma cells in the bone marrow. This prevents normal B-cell lymphogenesis and increases the risk of bacterial infection due to decreased production of normal immunoglobulins.

A 68-Year-Old Woman Comes to the Office Due to Recurrent