A 35-year-old woman comes to the office for evaluation of fatigue and exertional dyspnea. She has a history of systemic lupus erythematosus and is noncompliant with therapy. The patient takes naproxen as needed for joint pains. Vital signs are within normal limits. Examination shows mild pallor. The remainder of the examination shows no abnormalities. Laboratory results are as follows: Which of the following is the most likely underlying cause of her current condition?

Question

A 35-year-old woman comes to the office for evaluation of fatigue and exertional dyspnea.  She has a history of systemic lupus erythematosus and is noncompliant with therapy.  The patient takes naproxen as needed for joint pains.  Vital signs are within normal limits.  Examination shows mild pallor.  The remainder of the examination shows no abnormalities.  Laboratory results are as follows:  Which of the following is the most likely underlying cause of her current condition?

Quizplus · Accepted Answer

11ec160b_3aec_a012_9249_1ff3cd0828b3_MD0001_00 This patient with untreated systemic lupus erythematosus (SLE) has normocytic anemia with low serum iron and low total iron-binding capacity, raising strong suspicion for anemia of chronic disease (ACD). Most cases arise in those with chronic elevation of inflammatory cytokines due to underlying rheumatologic disease (eg, SLE), chronic infection, or malignancy. Although a number of inflammatory cytokines contribute to the development of ACD, the primary mediator is hepcidin, a small peptide released by the liver in response to inflammation. Hepcidin binds to and inactivates iron channels (ferroportin) on enterocytes and reticuloendothelial macrophages, which results in reduced iron absorption in the gut and increased iron sequestration in the reticuloendothelial system. Because reticuloendothelial macrophages recycle senescent erythrocytes and provide >95% of daily iron for erythrocytosis, sequestration of iron in the reticuloendothelial system dramatically reduces serum iron concentration. This limits the amount of iron available for the generation of new erythrocytes and typically results in a normocytic (or slightly microcytic) anemia with a low reticulocyte response. In ACD, total iron-binding capacity is generally normal or slightly reduced due to cytokine-mediated suppression of transferrin. (Choices A and E) Patients with SLE can develop immune-mediated hemolysis due to the generation of autoantibodies against the erythrocyte membrane; however, this typically results in extravascular hemolysis, which increases the intracellular enzyme lactate dehydrogenase. The presence of normal lactate dehydrogenase in this case makes hemolysis less likely. Patients with SLE also sometimes develop gastrointestinal bleeding from serositis (or chronic NSAID use), which can lead to iron deficiency anemia. However, iron deficiency anemia is typically associated with microcytic anemia and a high total iron-binding capacity (because transferrin levels are markedly increased). (Choices B and C) Conditions associated with rapid cell turnover can result in folate deficiency due to increased folate use during the generation of new cells. Intrinsic factor antibodies are a common cause of vitamin B₁₂ deficiency. However, folate and vitamin B₁₂ deficiency are generally marked by macrocytic anemia with a normal or high serum iron level. Educational objective: Anemia of chronic disease is a consequence of chronically elevated inflammatory cytokines, most importantly hepcidin. This peptide inactivates iron channels on enterocytes and reticuloendothelial macrophages, leading to reduced iron absorption and reduced iron release from the reticuloendothelial system. The net result is normocytic or slightly microcytic anemia with low reticulocyte response, low serum iron level, and normal or low total iron-binding capacity.

A 35-Year-Old Woman Comes to the Office for Evaluation of Fatigue