From the Guidelines
Anemia of chronic disease (ACD) is primarily caused by the body's inflammatory response during chronic conditions, such as chronic infections, autoimmune disorders, and chronic diseases, which disrupt normal iron metabolism and erythropoiesis. The main causes of ACD include chronic infections (like tuberculosis, HIV, or endocarditis), autoimmune disorders (such as rheumatoid arthritis, lupus, or inflammatory bowel disease), and chronic diseases (including cancer, chronic kidney disease, and congestive heart failure) 1. These conditions trigger inflammation that disrupts normal iron metabolism through several mechanisms, including the increase of hepcidin production, which blocks iron absorption from the gut and iron release from storage sites 2.
Key Mechanisms
- Inflammatory cytokines like IL-6 increase hepcidin production, which blocks iron absorption from the gut and iron release from storage sites 1
- Inflammation shortens red blood cell lifespan, impairs the bone marrow's response to erythropoietin, and reduces erythropoietin production 3
- The body also sequesters iron in macrophages and the liver, making it unavailable for red blood cell production
Diagnosis and Treatment
- ACD typically presents as a mild to moderate normocytic, normochromic anemia, though it can become microcytic in long-standing cases 1
- Treatment focuses primarily on addressing the underlying chronic condition rather than iron supplementation, which is generally ineffective unless concurrent iron deficiency exists 2
- The distinction between iron deficiency anaemia and ACD is important, since both conditions typically overlap, and the choice of the appropriate treatment is based on this distinction 3
Important Considerations
- In the presence of biochemical or clinical evidence of inflammation, the lower limit of serum ferritin consistent with normal iron stores should be increased to 100 μg/L 2
- A combination of parameters, including serum ferritin, transferrin saturation, and CRP, should be assessed to determine the exact type of anaemia in any specific clinical scenario 2
From the Research
Causes of Anemia of Chronic Disease (ACD)
The causes of ACD are complex and multifactorial, involving various pathways and mechanisms. Some of the key causes include:
- Chronic inflammatory disorders, such as chronic infections, cancer, or autoimmune diseases 4, 5, 6, 7
- Activation of the immune system, leading to the production of pro-inflammatory cytokines and hepcidin, which regulate iron homeostasis 4, 5, 6, 7
- Diversion of iron traffic, resulting in iron-restricted erythropoiesis 4, 7
- Diminished erythropoiesis, due to reduced erythropoietin production or activity 4, 6
- Shortened erythrocyte half-life, suppressed erythropoietin response to anemia, and inhibition of erythroid cell differentiation by inflammatory mediators 7
- Chronic kidney disease, congestive heart failure, chronic pulmonary diseases, and obesity, which can also contribute to the development of ACD 7
Underlying Diseases
ACD often coexists with various underlying diseases, including:
- Cancer 4, 5, 7
- Chronic infections 4, 5, 6, 7
- Autoimmune diseases, such as rheumatoid arthritis 6
- Kidney failure 5
- Chronic inflammatory disorders 4, 5, 6, 7
Pathophysiology
The pathophysiology of ACD involves a complex interplay between inflammation, iron metabolism, and erythropoiesis. Key factors include:
- Hepcidin, which regulates iron homeostasis and blocks intestinal iron absorption 5, 7
- Pro-inflammatory cytokines, such as IL-6, IL-1, TNF alpha, and TGF beta, which contribute to the development of ACD 6
- Iron metabolism, including iron deficiency and iron overload, which can influence the proliferation of B and T lymphocytes and differentially affect T helper (TH)-1 and TH-2 lymphocytes 6