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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Usually normocytic but may become mildly microcytic
- Inflammation increases hepcidin, trapping iron in macrophages and reducing intestinal absorption
- Iron studies show low serum iron, low or normal TIBC, and normal or high ferritin
- Treat the underlying disease; ESAs are reserved for selected CKD, chemotherapy-associated anemia, or marrow failure contexts
- Step 2 CK pearl: low TIBC distinguishes anemia of chronic disease from iron deficiency anemia
Overview
Anemia of chronic disease, or anemia of inflammation, is a hypoproliferative anemia caused by chronic immune activation. Interleukin-6 stimulates hepcidin production, which degrades ferroportin and prevents iron export from enterocytes and macrophages. Iron is present in storage sites but unavailable for erythropoiesis. The anemia is usually mild to moderate and occurs in chronic infection, autoimmune disease, malignancy, chronic kidney disease, obesity-related inflammation, and hospitalized inflammatory states.
Epidemiology
It is one of the most common anemias in hospitalized adults and older patients. Common settings include rheumatoid arthritis, inflammatory bowel disease, chronic osteomyelitis, HIV, tuberculosis, malignancy, CKD, and chronic heart failure. CKD adds relative erythropoietin deficiency to inflammatory iron restriction.
Clinical Features
Symptoms
Fatigue, weakness, reduced exercise tolerance
Symptoms are often dominated by the underlying inflammatory, infectious, renal, or malignant disorder
Dyspnea on exertion in moderate anemia
Unintentional weight loss, night sweats, fever, or bone pain suggesting malignancy or chronic infection
Signs
Pallor and tachycardia may be present
Signs of chronic inflammation: synovitis, ulcers, lymphadenopathy, hepatosplenomegaly, or renal disease
Usually no koilonychia or pica, which point more toward iron deficiency
Jaundice or splenomegaly suggests hemolysis or malignancy rather than simple inflammatory anemia
Investigations
First-line
CBC with indicesNormocytic anemia most common; MCV may be mildly low. Reticulocyte count is low or inappropriately normal
Iron studiesLow serum iron, low/normal TIBC, low transferrin saturation, normal/high ferritin
Inflammatory and renal assessmentCRP/ESR when useful; BMP/eGFR to assess CKD contribution
Second-line
Ferritin interpretation with inflammationFerritin may be high from inflammation even when concurrent iron deficiency exists
B12, folate, TSH when indicatedEvaluate mixed anemia or unexplained macrocytosis/normocytosis
Peripheral smearUsually nonspecific; rouleaux suggests plasma cell dyscrasia
Specialist
Bone marrow biopsyReserved for unexplained cytopenias, suspected MDS, leukemia, myeloma, or marrow infiltration
Soluble transferrin receptorMay help differentiate iron deficiency from inflammation when ferritin is equivocal
1
Treat the underlying cause
- Control inflammatory disease, infection, malignancy, or renal disorder
- Review medications and nutritional factors that may contribute to anemia
- Do not reflexively prescribe iron unless iron deficiency or functional iron deficiency is present
2
Assess for concurrent iron deficiency
- Consider combined iron deficiency when ferritin is not clearly high or when bleeding risk is present
- Transferrin saturation is often low in both conditions; TIBC pattern is key
- Evaluate for gastrointestinal blood loss if true iron deficiency is confirmed
3
Supportive treatment
- RBC transfusion for severe symptomatic anemia or Hb generally <7 g/dL in stable hospitalized adults
- ESAs for selected CKD patients, chemotherapy-associated anemia, or marrow failure under specialist care
- IV iron may be used in CKD or functional iron deficiency when TSAT/ferritin thresholds support it
Complications
- Reduced quality of life: Fatigue, poor exercise tolerance, cognitive effects
- Cardiac stress: Worsening ischemia or heart failure in patients with limited reserve
- Diagnostic delay: Occult cancer, chronic infection, CKD, or autoimmune disease may be missed
USMLE Step 2 CK Exam Tips
- 1Anemia of chronic disease: low iron, low TIBC, normal/high ferritin
- 2Iron deficiency anemia: low iron, high TIBC, low ferritin
- 3Hepcidin is the mechanism: blocks iron release from macrophages and gut absorption
- 4Normocytic anemia in CKD is due to low erythropoietin plus inflammation
- 5Rouleaux on smear with anemia and bone pain points toward multiple myeloma
- 6Do not give erythropoietin casually; use in selected CKD/oncology settings after iron status is addressed
practicetest your knowledge on anemia of chronic diseaseApply what you've learnt with USMLE Step 2 CK-style questions from the iatroX Q-Bank — hematology & oncology and beyond.
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