A 54-year-old woman comes to the office due to 3 months of progressive pain and prolonged morning stiffness in her hand joints. She has tried over-the-counter naproxen without significant relief. Review of systems is positive for fatigue. The patient has no other chronic medical conditions and takes no other medications regularly. Vital signs are normal. Swelling and tenderness of the proximal interphalangeal joints and metacarpophalangeal joints are present in both hands. Laboratory studies reveal a hemoglobin of 9.8 g/dL and MCV of 86. The patient is prescribed methotrexate therapy. Laboratory results 6 months later reveal that hemoglobin has increased to 12 g/dL. If measured, which of the following changes were most likely present in this patient before the start of methotrexate therapy?

Question

Quizplus · Accepted Answer

This patient's polyarticular hand joint pain, swelling, and prolonged morning stiffness are suggestive of rheumatoid arthritis (RA). Patients with chronic rheumatologic diseases such as RA have high circulating levels of inflammatory cytokines, which can trigger anemia of chronic disease (ACD) due to maladaptive changes in iron utilization. ACD is primarily mediated by 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, leading to reduced iron absorption in the gut and reduced iron recycling by the reticuloendothelial system (the site of senescent erythrocyte destruction and the source of >95% of daily iron for new RBC production). These changes significantly reduce circulating iron levels, which impairs the generation of heme for new erythrocytes. Although patients with suspected ACD do not generally require bone marrow biopsy for diagnosis, it would show increased sequestration of iron within macrophages and reduced quantities of erythrocyte precursor cells (eg, normoblasts, reticulocytes). Patients with ACD typically develop a normocytic (or slightly microcytic) anemia with low reticulocyte count. Treatment of the underlying inflammatory condition (eg, methotrexate for RA) reduces serum inflammatory cytokine levels and generally improves the anemia. (Choice B) In contrast to ACD, patients with iron deficiency anemia have reduced serum iron levels and reduced bone marrow iron levels due to low total body iron stores. Educational objective: Anemia of chronic disease is caused by elevated inflammatory cytokine levels (eg, hepcidin), which increase sequestration of iron within the reticuloendothelial system and reduce circulating iron levels. Many patients have improvement in anemia with treatment of the underlying condition that caused the inflammation.

A 54-Year-Old Woman Comes to the Office Due to 3