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Difficulty: MediumHematology and Oncology

A 58-year-old woman comes to the clinic for follow-up of fatigue and joint pain. She has a 6-year history of rheumatoid arthritis, currently treated with methotrexate and low-dose prednisone. She reports that her fatigue has progressively worsened over the past three months, limiting her daily activities. Over the same period, she has experienced increased morning stiffness lasting up to 2 hours and worsening swelling in her hands and wrists. She has no history of gastrointestinal bleeding or melena. Vital signs are normal. Physical examination reveals active synovitis with swelling and tenderness in the bilateral metacarpophalangeal and proximal interphalangeal joints.

Laboratory studies show:

Laboratory ParameterResultReference Range
Hemoglobin9.2 g/dL9.2 \text{ g/dL}12.0−16.0 g/dL12.0-16.0 \text{ g/dL}
Mean corpuscular volume86 \mum386 \text{ \mu m}^380−100 \mum380-100 \text{ \mu m}^3
Leukocyte count8,400/mm38,400/\text{mm}^34,500−11,000/mm34,500-11,000/\text{mm}^3
Platelet count410,000/mm3410,000/\text{mm}^3150,000−400,000/mm3150,000-400,000/\text{mm}^3
Serum iron30 \mug/dL30 \text{ \mu g/dL}50−170 \mug/dL50-170 \text{ \mu g/dL}
Total iron-binding capacity (TIBC)220 \mug/dL220 \text{ \mu g/dL}250−450 \mug/dL250-450 \text{ \mu g/dL}
Ferritin480 ng/mL480 \text{ ng/mL}10−150 ng/mL10-150 \text{ ng/mL}
Erythrocyte sedimentation rate85 mm/h85 \text{ mm/h}0−20 mm/h0-20 \text{ mm/h}
Serum creatinine0.9 mg/dL0.9 \text{ mg/dL}0.6−1.2 mg/dL0.6-1.2 \text{ mg/dL}

Which of the following is the most appropriate next step in the management of this patient's anemia?

  1. Escalation of disease-modifying antirheumatic therapyAnswer
  2. B
    Initiation of oral ferrous sulfate therapy
  3. C
    Administration of an erythropoiesis-stimulating agent
  4. D
    Referral for bone marrow aspiration and biopsy
  5. E
    Transfusion of packed red blood cells

Answer

The most appropriate next step is escalation of disease-modifying antirheumatic therapy.
The correct answer is the escalation of disease-modifying antirheumatic therapy. This patient presents with a normocytic anemia characterized by a low serum iron, low total iron-binding capacity (TIBC), and an elevated ferritin level. This profile is the classic presentation of anemia of chronic disease (also known as anemia of inflammation). The underlying pathogenesis involves inflammation-induced hepatic production of hepcidin. Hepcidin binds to ferroportin (the iron export channel) on macrophages and enterocytes, leading to its degradation. This prevents the release of iron into the serum, resulting in iron sequestration (high ferritin) and reduced available serum iron for erythropoiesis. The most effective and appropriate management for anemia of chronic disease is to treat the underlying inflammatory disorder. In this case, the patient has active rheumatoid arthritis that is inadequately controlled on her current regimen. Escalating her immunosuppressive therapy will reduce inflammation, decrease hepcidin levels, and subsequently improve her hemoglobin.

Step-by-Step Solution

1
Analyze the patient's clinical presentation and complete blood count.
The patient has a normocytic anemia (hemoglobin 9.2 g/dL9.2 \text{ g/dL}, MCV 86 \mum386 \text{ \mu m}^3) in the setting of poorly controlled rheumatoid arthritis (indicated by active synovitis and an elevated ESR of 85 mm/h85 \text{ mm/h}).
Establishing the presence of active inflammation is crucial for contextualizing the anemia.
2
Interpret the iron studies.
Serum iron is low, TIBC is low, and ferritin is elevated.
These findings definitively differentiate anemia of chronic disease (where iron is sequestered in macrophages) from true iron deficiency anemia (which would present with high TIBC and low ferritin).
3
Determine the appropriate management based on the diagnosis.
The primary treatment for anemia of chronic disease is to address the underlying inflammatory condition.
Treating the rheumatoid arthritis will reduce hepatic hepcidin production, restoring normal iron mobilization and enabling proper erythropoiesis.

Key Concept

The definitive treatment for anemia of chronic disease (anemia of inflammation) is optimization of the underlying inflammatory condition, which reduces hepcidin levels and resolves iron sequestration.
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Topics

Hematology and Oncology

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