Anaemia is a condition characterised by a deficiency of red blood cells or haemoglobin, resulting in reduced oxygen delivery to tissues. Anaemia of chronic disease (ACD) is a prevalent type of anaemia that occurs in chronically ill and hospitalised patients. It is caused by an immune response to chronic infection, malignancy, autoimmune disease, or chronic kidney disease. This blog will discuss the pathogenesis, differential diagnosis, and management of ACD.
Pathogenesis
The pathogenic pathways involved in ACD reflect an effective and adaptive immune system response. Systemic immune activation results in the deprivation of iron to invading cells. Inflammatory cytokines, hepcidin, and iron-binding peptides inhibit iron release from bone marrow macrophages and alter iron absorption, suppressing erythropoietic activity. This results in increased iron storage and decreased availability of iron. ACD is typically found in conditions of acute and chronic infection as well as autoimmune disease, malignancy, and chronic kidney disease.
Differential Diagnosis
The signs and symptoms of ACD mimic iron deficiency anaemia (IDA) and include fatigue, weakness, poor memory and concentration, exercise intolerance, and impaired cardiovascular performance. ACD is considered a diagnosis of elimination and is based on underlying alterations in iron homeostasis along with clinical evidence of inflammation. Iron studies reveal reduced serum iron concentrations and transferrin saturation, with normal or elevated serum ferritin levels. Ferritin is an acute-phase protein that is induced in the presence of inflammation and is the most useful differentiating parameter in ACD. However, between 20 and 85% of patients with ACD also suffer from true iron deficiency, further complicating diagnosis and treatment.
Management
The management of ACD involves identifying and treating underlying conditions causing chronic inflammation. Several nutritional therapies are being considered in the management of ACD. These strategies aim to inhibit the action of hepcidin and downregulate inflammatory cytokines. Vitamin D, curcumin, and omega-3 fatty acids have been shown to regulate hepcidin expression and correct anaemia in several population groups. It appears that modulation of immune-inflammatory pathways is critical in managing ACD. The management of other underlying drivers, such as GIT dysfunction, dysbiosis, autoimmune pathways, or dietary contributors, is also warranted.
Conclusion
Iron therapy may or may not be appropriate, given that ACD represents a relative rather than an absolute deficiency in iron availability. Identifying patients who present with concurrent ACD and IDA is essential, as iron therapy may be required, particularly in cases of cardiovascular complications and/or a necessity to maintain tissue oxygen supply.
