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Review Question - QID 213771

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QID 213771 (Type "213771" in App Search)
A 31-year-old woman presents to her primary care physician with a 4 month history of fatigue and shortness of breath. She says that she started experiencing these symptoms while exercising but assumed that was because she was starting to get older. Over time, the symptoms have gotten worse such that she now becomes fatigued even while doing activities of daily living like shopping. Her past medical history is significant for rheumatoid arthritis for which she takes methotrexate. She is vegan, drinks 2 glasses of wine per night, and lives in an old house. Family history reveals multiple relatives with anemia. Physical exam reveals a thin, disheveled woman with conjunctival pallor. Selected laboratory tests are shown below:

Hemoglobin: 9.5 g/dL
Mean corpuscular volume: 73 fl
Ferritin: 230 ng/ml

Which of the following is most likely responsible for this patient's symptoms?

Ferrochelatase inhibition

7%

10/143

Folate deficiency

12%

17/143

Increased hepcidin expression

48%

69/143

Inherited hemoglobinopathy

4%

6/143

Iron deficiency

24%

34/143

Select Answer to see Preferred Response

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This patient with rheumatoid arthritis who presents with a microcytic anemia and has increased ferritin levels most likely has anemia of chronic disease. This disease is caused by increased hepcidin expression.

Anemia of chronic disease is caused by increased expression of the acute phase reactant hepcidin in response to chronic inflammation. Hepcidin normally functions to suppress iron release from macrophages by binding to the iron transporter ferroportin. When active for short durations, this function allows the body to deny iron to infectious organisms; however, when active for long durations, hepcidin will cause anemia due to iron deficiency despite increased total body iron stores. Common underlying causes of this disease include autoimmune diseases, chronic infections, and malignancy. Treatment of the underlying condition is the most important factor for resolving anemia of chronic disease.

Incorrect Answers:
Answer 1: Ferrochelatase inhibition is seen in lead poisoning anemia, which can also present with a microcytic anemia; however, this disease will characteristically present with neurological deficits such as wrist drop in addition to anemia.

Answer 2: Folate deficiency can be associated with methotrexate treatment; however, anemia due to folate deficiency would be megaloblastic and macrocytic rather than microcytic as seen in this case. Notably, no neurological deficits are seen in folate deficiency as compared with cobalamin deficiency.

Answer 4: Inherited hemoglobinopathies such as alpha-thalassemia and beta-thalassemia will present with a normocytic anemia rather than a macrocytic anemia. Furthermore, they usually present in childhood rather than adulthood.

Answer 5: Iron deficiency anemia will present as a microcytic anemia; however, this disease would present with decreased total body iron stores and therefore have decreased serum ferritin levels.

Bullet Summary:
Anemia of chronic disease is caused by increased expression of the acute phase reactant hepcidin.

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