Anemia of chronic disease overview

# Overview
The word "hematology," which appears to have been first used in this country in 1811, is older than might be expected, for in 1743, Thomas Schwencke (1694-1768) wrote Hamatologia, sive Sanguinis Historia, Experimentis passim superstructa etc. Hagae Comitum. Hematology, like bacteriology, has developed as the result of laboratory methods and the applications of physics and chemistry.Inflammatory cytokines induce increased amounts of hepcidin by the liver. Hepcidin blocks ferroportin from releasing iron from the body stores. Inflammatory cytokines also decrease ferroportin expression and stops erythropoiesis by increasing bone marrow erythropoietin resistance. Apart from iron sequestration, white blood cells production is promoted by inflammatory cytokines. Bone marrow stem cellsproduce both red blood cells and white blood cells cells. Therefore, the upregulation of white blood cells causes fewer stem cells to differentiate into red blood cells. This may also have a role in inhibition of erythropoiesis ,even when erythropoietin levels are normal, and aside from the effects of hepcidin. Conditions that can lead to anemia of chronic disease include autoimmune disorders, such as Crohn's disease, systemic lupus erythematosus, rheumatoid arthritis, and ulcerative colitis, Cancer including lymphoma and Hodgkin's disease, chronic kidney disease, liver cirrhosis, long-term infections, such as bacterial endocarditis, osteomyelitis (bone infection), HIV/AIDS, hepatitis B or hepatitis C, less production of erythropoietin (EPO) by kidneys, resistance of bone marrow to EPO., decreased half life of red blood cells, hospitalized for severe acute infections, trauma, or other conditions that cause inflammation and aging process may cause inflammation and anemia. The primary goal in the treatment of anemia of chronic disease it to treat the disease itself. Supplemental iron is recommended, as needed, to keep the transferrin saturation of above 20 percent and a serum ferritin level of  above100 ng/mL. Intravenous iron is more effective than oral supplementaion. Stable patients can be administered synthetically prepared erythropoiesis-stimulating agent such as erythropoietin. It is important to give oral iron supplementation to all the patients receiving erythropoietin or darbepoetin, in order to maintain a transferrin saturation more than 20 percent and a serum ferritin more than 100 ng/mL. In case of severe disease, blood transfusion  is recommended.

# Historical Perspective
The word "hematology," which appears to have been first used in this country in 1811, is older than might be expected, for in 1743, Thomas Schwencke (1694-1768) wrote Hamatologia, sive Sanguinis Historia, Experimentis passim superstructa etc. Hagae Comitum. Hematology, like bacteriology, has developed as the result of laboratory methods and the applications of physics and chemistry.

# Classification
There is no established classification of anemia of chronic disease.

# Pathophysiology
Inflammatory cytokines induce increased amounts of hepcidin by the liver. Hepcidin blocks ferroportin from releasing iron from the body stores. Inflammatory cytokines also decrease ferroportin expression and stops erythropoiesis by increasing bone marrow erythropoietin resistance. Apart from iron sequestration, white blood cells production is promoted by inflammatory cytokines. Bone marrow stem cellsproduce both red blood cells and white blood cells cells. Therefore, the upregulation of white blood cells causes fewer stem cells to differentiate into red blood cells. This may also have a role in inhibition of erythropoiesis ,even when erythropoietin levels are normal, and aside from the effects of hepcidin.

# Causes
Conditions that can lead to anemia of chronic disease include autoimmune disorders, such as Crohn's disease, systemic lupus erythematosus, rheumatoid arthritis, and ulcerative colitis, Cancer including lymphoma and Hodgkin's disease, chronic kidney disease, liver cirrhosis, long-term infections, such as bacterial endocarditis, osteomyelitis (bone infection), HIV/AIDS, hepatitis B or hepatitis C, less production of erythropoietin (EPO) by kidneys, resistance of bone marrow to EPO., decreased half life of red blood cells, hospitalized for severe acute infections, trauma, or other conditions that cause inflammation and aging process may cause inflammation and anemia.

# Differentiating from Other Diseases
The most important differential is whether the patient has ACD alone or ACD with ongoing iron deficiency anemia (ACD/IDA). The following parameters will distinguish the two: Soluble transferrin receptor levels (sTfR) and/or the sTfR-ferritin index sTfR and the sTfR-ferritin index are normal in uncomplicated ACD, while both are elevated when IDA is also. Percentage of hypochromic red cells and reticulocyte hemoglobin may help.

# Epidemiology and Demographics
30 to 60 percent of patients in rheumatoid arthritis patients have anemia. More than 30 of cancer patients have anemia. The rate reached 63 percent. In elderly patients, about one third of the cases of anemia are ACD.

# Risk Factors
Risk factors for anemia of chronic disease include autoimmune disorders, chronic infection, trauma, major surgery, malignancy, HIV infection, rheumatologic disorders, inflammatory bowel disease, castleman disease, heart failure, older adults, renal insufficiency and chronic obstructive pulmonary disease.

# Screening
There is insufficient evidence to recommend routine screening for anemia of chronic disease. Age-appropriate health screening and evaluations directed at any patient symptoms can be done to find out the underlying cause of ACD.

# Natural History, Complications, and Prognosis
Potentially life-threatening complications include congestive heart failure, Angina, arrhythmia, myocardial infarction and high-output heart failure. If left untreated, anemia of chronic disease usually manifests as congestive heart failure, angina, arrhythmia, myocardial infarction and high-output heart failure.The anemia will improve when the disease that is causing it is successfully treated.

# Diagnosis

## Diagnostic Study of Choice
There is no single diagnostic study of choice for test that will reliably make the diagnosis of ACD

## History and Symptoms
Past medical history could include Autoimmune disorders, chronic infection, Trauma, major surgery, Malignancy, HIV infection, rheumatologic disorders, Inflammatory bowel disease, Castleman disease, Heart failure, older adults, Renal insufficiency and Chronic obstructive pulmonary disease.

## Physical Examination
Symptoms would be of the underlying disease rather than the anemia itself.

## Laboratory Findings
Mild normocytic and normochromic anemia with a hemoglobin concentration of 10 to 11 g/dL. Less than 25 percent of the cases have microcytic and hypochromic anemia with a mean corpuscular volume (MCV) less than 70 fL. Normal or low mean corpuscular hemoglobin (MHC) similar to the MCV, and normal to increased red cell distribution width (RDW). No significant changes in the mean corpuscular hemoglobin concentration (MCHC). 20 percent of cases have severe anemia, with a hemoglobin concentration <8 g/dL. Absolute reticulocyte count is frequently low (<25,000/microL). There could be an elevation in cytokines (eg, IL-6, interferon-gamma) and acute phase reactants (eg, fibrinogen, erythrocyte sedimentation rate, C-reactive protein, ferritin, haptoglobin, factor VIII)

## Electrocardiogram
An ECG may show left ventricular hypertrophy (LVH) in anemia of chronic disease.

## X-ray
Chest x-rays are often used to rule out infection in anemia patients.

## Echocardiography and Ultrasound
Ultrasound can detect an enlarged spleen or may demonstrate the cause of anemia such as uterine fibroids.

## CT scan
CT provides detailed images of internal organs,and lymph nodes. It can help identify an enlarged spleen or lymph node abnormalities associated with certain types of anemia, and is useful for detecting cause of bleeding such as gastrointestinal malignancies that may be causing anemia in patients who cannot undergo colonoscopy or endoscopy

## MRI
MRI is effective at imaging bone and bone marrow disorder . It also can help assess iron concentration in various organs such as heart and liver, particularly in patients with multiple blood transfusions and concern for iron overload.

## Other Imaging Findings
There are no other imaging findings associated with anemia of chronic disease.

## Other Diagnostic Studies
There are no other imaging findings associated with anemia of chronic disease.

# Treatment

## Medical Therapy
The primary goal in the treatment of anemia of chronic disease it to treat the disease itself. Supplemental iron is recommended, as needed, to keep the transferrin saturation of above 20 percent and a serum ferritin level of  above100 ng/mL. Intravenous iron is more effective than oral supplementaion. Stable patients can be administered synthetically prepared erythropoiesis-stimulating agent such as erythropoietin. It is important to give oral iron supplementation to all the patients receiving erythropoietin or darbepoetin, in order to maintain a transferrin saturation more than 20 percent and a serum ferritin more than 100 ng/mL. In case of severe disease, blood transfusion  is recommended. If the case is underlying malignancy, chemotherapy or radiotherapy may transiently exacerbate anemia  due to mylesuppressive effects, however in the long term, it leads to improvement. If the cause is inflammatory disorder, such as rheumatoid arthritis the management of the disease with a disease-modifying antirheumatic drug (DMARD) improves the anemia significantly.

## Interventions

## Surgery
Surgical intervention is not recommended for the management of anemia of chronic disease.

## Primary Prevention
There are no established measures for the primary prevention of anemia of chronic disease.

## Secondary Prevention
There are no established measures for the secondary prevention of anemia of chronic disease.