A 45-year-old man comes to the office due to 3 months of exertional fatigue and weight loss. He is sexually active with multiple male partners. Temperature is 37.9 C (100.2 F), blood pressure is 110/70 mm Hg, pulse is 84/min, and respirations are 13/min. BMI is 20 kg/m². The patient appears chronically ill and has mucosal pallor. There are thick, white plaques over the buccal mucosa and soft palate. Anterior and posterior cervical lymphadenopathy is present. The lungs are clear to auscultation. The abdomen is soft and nontender. There is no organomegaly. Laboratory results are as follows: Which of the following is the most likely underlying cause of this patient's anemia?

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11ec160b_3aed_d896_9249_7fed333860e7_MD0001_00 This patient's high-risk sexual history, weight loss, lymphadenopathy, chronically ill appearance, and oral candidiasis (white buccal/soft palate plaques) suggest undiagnosed HIV infection. Patients with chronic infections such as HIV often develop anemia of chronic disease (ACD) due to high circulating levels of inflammatory cytokines, which cause maladaptive changes to iron utilization. Although ACD is mediated by a wide range of inflammatory cytokines (eg, IL-1, IL-6, tumor necrosis factor-alpha, interferon gamma), the major player is hepcidin, a small peptide released by the liver in response to inflammation. Hepcidin binds to and inhibits iron channels on enterocytes and reticuloendothelial macrophages, leading to reduced iron absorption in the gut and reduced iron recycling in the reticuloendothelial system (the site of senescent erythrocyte destruction). This significantly reduces circulating serum iron, which limits iron availability for erythropoiesis. Patients with ACD typically develop normocytic or slightly microcytic anemia with a low reticulocyte response. Total iron-binding capacity is generally reduced due to cytokine-mediated suppression of transferrin. Treatment of the underlying condition (eg, antiretroviral therapy) often ameliorates or resolves ACD. (Choice B) Decreased synthesis of globin chains is seen in thalassemia, a genetic disorder that presents with microcytic anemia and reduced erythrocyte life span. Serum iron levels tend to be high with thalassemia due to increased erythropoiesis to compensate for the anemia. (Choice C) Fibrin deposition in the microvasculature is seen in disseminated intravascular coagulation, a consumptive coagulopathy marked by microangiopathic hemolytic anemia and significant thrombocytopenia. Patients typically have normocytic (not microcytic) anemia and normal or high serum iron levels. (Choice D) Iron deficiency anemia (eg, gastrointestinal bleeding) also typically causes microcytic anemia with low serum iron. However, unlike ACD, iron deficiency anemia is typically associated with a high iron-binding capacity due to increased circulating transferrin levels. (Choice E) Porphyria is a genetic disorder caused by deficiency of heme synthesis enzymes. Patients typically develop neurovisceral (eg, abdominal pain) or cutaneous (eg, blistering) manifestations. Microcytic anemia with low serum iron would be atypical. Educational objective: Anemia of chronic disease is caused by chronic elevations in inflammatory cytokines, which lead to reduced iron absorption and increased iron retention in the reticuloendothelial system. This impairs iron availability and causes a normocytic or slightly microcytic anemia with low serum iron and low total iron-binding capacity.

A 45-Year-Old Man Comes to the Office Due to 3