Anemia of chronic disease: Difference between revisions
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==[[Anemia of chronic disease classification|Classification]]== | ==[[Anemia of chronic disease classification|Classification]]== | ||
There is no established classification of anemia of chronic disease. | |||
==[[Anemia of chronic disease pathophysiology|Pathophysiology]]== | ==[[Anemia of chronic disease pathophysiology|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 cells]]<nowiki/>produce both [[red blood cells]] and [[white blood cells]] [[Stem 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]]. | |||
==[[Anemia of chronic disease causes|Causes]]== | ==[[Anemia of chronic disease causes|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]], c[[Chronic kidney disease|hronic 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 a[[Aging|ging]] process may cause [[inflammation]] and [[anemia]]. | |||
==[[Anemia of chronic disease differential diagnosis|Differentiating Anemia of chronic disease from other Diseases]]== | ==[[Anemia of chronic disease differential diagnosis|Differentiating Anemia of chronic disease from other Diseases]]== | ||
==[[Anemia of chronic disease epidemiology and demographics|Epidemiology and Demographics]]== | ==[[Anemia of chronic disease epidemiology and demographics|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. | |||
==[[Anemia of chronic disease risk factors|Risk Factors]]== | ==[[Anemia of chronic disease risk factors|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]]. | |||
==[[Anemia of chronic disease screening|Screening]]== | ==[[Anemia of chronic disease screening|Screening]]== | ||
There is insufficient evidence to recommend routine screening for anemia of chronic disease. | |||
==[[Anemia of chronic disease natural history, complications and prognosis|Natural History, Complications and Prognosis]]== | ==[[Anemia of chronic disease natural history, complications and prognosis|Natural History, Complications and Prognosis]]== | ||
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==Diagnosis== | ==Diagnosis== | ||
[[Anemia of chronic disease diagnostic study of choice|Diagnostic study of choice]] | [[Anemia of chronic disease history and symptoms|History and Symptoms]] | [[Anemia of chronic disease physical examination|Physical Examination]] | [[Anemia of chronic disease laboratory findings|Laboratory Findings]] | [[Anemia of chronic disease x ray|X Ray]] | [[Anemia of chronic disease echocardiography and ultrasound|Echocardiography and Ultrasound]] | [[Anemia of chronic disease CT scan|CT scan]] | [[Anemia of chronic disease MRI|MRI]] | [[Anemia of chronic disease other imaging findings|Other Imaging Findings]] | [[Anemia of chronic disease other diagnostic studies|Other Diagnostic Studies]] | [[Anemia of chronic disease diagnostic study of choice|Diagnostic study of choice]] | [[Anemia of chronic disease history and symptoms|History and Symptoms]] | [[Anemia of chronic disease physical examination|Physical Examination]] | [[Anemia of chronic disease laboratory findings|Laboratory Findings]] | [[Anemia of chronic disease x ray|X Ray]] | [[Anemia of chronic disease echocardiography and ultrasound|Echocardiography and Ultrasound]] | [[Anemia of chronic disease CT scan|CT scan]] | [[Anemia of chronic disease MRI|MRI]] | [[Anemia of chronic disease other imaging findings|Other Imaging Findings]] | [[Anemia of chronic disease other diagnostic studies|Other Diagnostic Studies]] | ||
==Treatment== | ==Treatment== | ||
Revision as of 15:52, 2 October 2018
| Anemia of chronic disease | |
| MedlinePlus | 000565 |
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Anemia of chronic disease Microchapters | |
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Differentiating Anemia of chronic disease from other Diseases | |
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Diagnosis | |
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Treatment | |
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Case Studies | |
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Anemia of chronic disease On the Web | |
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American Roentgen Ray Society Images of Anemia of chronic disease | |
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Risk calculators and risk factors for Anemia of chronic disease | |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Omer Kamal, M.D.[2] Badria Munir M.B.B.S.[3]
For patient information, click here
Synonyms and keywords: Anemia of inflammation.
Overview
Historical Perspective
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 Anemia of chronic disease from other Diseases
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.
Natural History, Complications and Prognosis
Diagnosis
Diagnostic study of choice | History and Symptoms | Physical Examination | Laboratory Findings | X Ray | Echocardiography and Ultrasound | CT scan | MRI | Other Imaging Findings | Other Diagnostic Studies
Treatment
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Initial approach — The preferred initial therapy for ACD is correction of the underlying disorder. (See 'Underlying disorder' below.)
Other complicating factors (eg, blood loss, deficiencies of iron, folate, and/or vitamin B12) should be treated, if present, and may obviate the need for blood transfusions or an erythropoiesis-stimulating agent (eg, erythropoietin, darbepoetin). (See "Approach to the adult with anemia".)
Red blood cell transfusions or use of an erythropoiesis-stimulating agent may be necessary for those with severe, symptomatic anemia. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult".)
●Most patients with ACD have mild anemia that produces no symptoms, being compatible with the patient's often limited lifestyle. It has been suggested that ACD is a biologically adaptive response in which, for example, low serum iron levels serve to inhibit the growth of iron-requiring microorganisms [95].
●Some patients have more severe anemia, leading to impaired function and an impaired quality of life [12,96]. Since ACD can complicate the course of aging-related disorders, its presence has considerable importance, since anemia negatively influences the outcome of several associated disorders [97,98]. (See "Anemia in the older adult" and "Evaluation of health-related quality of life (HRQL) in patients with a serious life-threatening illness".)
Underlying disorder — Typically, the underlying disorder(s) responsible for ACD will be known to the patient and the clinician. Therapy for the underlying disorder should be pursued, with the specific interventions depending on the clinical status of the patient and the available therapeutic options.
The degree to which ACD responds to treatment of the underlying disorder may depend on several factors, including whether the inflammatory component is controlled and the presence of other contributing factors. As an example, in patients with diabetes, improved glucose control may not lead to resolution of ACD, because it may not correct concomitant renal insufficiency or inflammatory changes.
In other cases, treatment of the underlying disorder may be more effective in improving the anemia. As examples:
●If the anemia is due to underlying malignancy, successful treatment with surgery, chemotherapy, and/or radiation therapy may, in the long term, lead to improvement in the anemia. However, anemia may be transiently or permanently exacerbated by the myelosuppressive effects of chemotherapy and radiation. Treatment of cancer-associated anemia is discussed in depth separately. (See "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer".)
●If the anemia is due to an underlying disorder with a major inflammatory component (eg, rheumatoid arthritis, Castleman disease), treatment of the inflammatory disorder with a disease-modifying antirheumatic drug (DMARD) may lead to improvement in the anemia. (See "Initial treatment of rheumatoid arthritis in adults", section on 'DMARD therapy' and "HHV-8-negative/idiopathic multicentric Castleman disease", section on 'IL-6 inhibitors'.)
In the rare case in which an underlying disorder is not obvious in a patient with ACD, a search for inflammatory disorders such as inflammatory bowel disease and possibly malignancy should be pursued. It is best to start with age-appropriate health screening and evaluations directed at any patient symptoms. The aggressiveness of the search should be determined by the clinicians familiar with the patient’s symptoms, severity of the anemia, and other relevant information.
Erythropoietin — Measurement of the plasma erythropoietin (EPO) concentration may be helpful in patients with ACD who have symptomatic anemia and/or who have not responded to treatment of their underlying disorder and continue to have symptomatic anemia requiring treatment.
●Patients with cancer, rheumatoid arthritis, or AIDS who have EPO levels <500 mU/mL (although some authors suggest a cutoff of 100 mU/mL) may respond to the administration of an erythropoiesis-stimulating agent (ESA) [99-103]. (See 'Pathogenesis' above and "Hematologic manifestations of rheumatoid arthritis", section on 'Anemia'.)
●Advice for the use of EPO or darbepoetin in patients with malignancy is presented separately. (See "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer", section on 'ESAs: efficacy, side effects, and clinical use'.)
EPO can be given once per week, while darbepoetin has an effectiveness equal to that of EPO when given once every two or three weeks. Supplemental iron should be given in all patients receiving EPO or darbepoetin in order to maintain a transferrin saturation ≥20 percent and a serum ferritin ≥100 ng/mL. Such use of erythropoiesis-stimulating agents is considered "unlabeled or investigational" in the United States and may not be reimbursed.
Because our aim is to obtain a short-range response to the anemia while an investigation is underway to determine the underlying cause of the ACD, we prefer the use of EPO rather than darbepoetin.
Dosage — Although one of the hallmarks of ACD is a reduced erythropoietic response to both endogenous as well as exogenous EPO, high doses of EPO may overcome this hyporesponsiveness. (See 'Pathogenesis' above and "Hematologic manifestations of rheumatoid arthritis", section on 'Anemia'.)
Two treatment options are available.
●Standard dosing of EPO is a starting dose of 100 to 150 units/kg subcutaneously three times weekly along with supplemental iron. Responders may show a rise in the hemoglobin concentration of at least 0.5 g/dL by two to four weeks [102,104]. If there is no elevation in the hemoglobin concentration by six to eight weeks, the regimen can be intensified to daily therapy or 300 units/kg three times weekly. It is not worthwhile to continue EPO in patients who do not have a clinically meaningful response by 12 weeks [102].
●An alternative treatment schedule is to employ 30,000 to 40,000 units of EPO given SQ once per week, a single dose that is numerically equivalent to a dose of 140 to 190 units/kg three times per week for a 70 kg person [105]. This dose can be increased to 60,000 units if there is no response (ie, hemoglobin rise <1 g/dL) at four weeks.
For ease of use and to minimize inconvenience to the patient, we prefer the latter of these two schedules.
●This simplified, well-tolerated dosing regimen has also been recommended for treatment of the anemia associated with HIV infection. (See "Hematologic manifestations of HIV infection: Anemia", section on 'Recombinant human erythropoietin'.)
●There is conflicting evidence regarding the benefits versus risks of using EPO in critically ill patients. This subject is discussed separately. (See "Use of blood products in the critically ill", section on 'RBC alternatives'.)
Adverse side effects of EPO treatment in patients with ACD have not been rigorously studied, although there is considerable information available on adverse side effects of EPO in patients with cancer-related anemia. Accordingly, potential adverse side effects are minimized by initiating treatment when the patient’s hemoglobin is <10 g/dL and stopping treatment with EPO when hemoglobin levels reach 12 g/dL. (See "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer", section on 'ESAs: efficacy, side effects, and clinical use'.)
Darbepoetin — Although darbepoetin has had limited use in the treatment of ACD in humans, it is capable of reversing anemia due to chronic inflammatory disease in experimental animals [106]. A dose of darbepoetin equivalent to the above-noted dose of erythropoietin is in the range of 60 to 100 mcg/week, or 300 mcg every three weeks. However, since we are looking for a rapid, short-term response of the anemia, darbepoetin, with its prolonged half-life, may result in excessive and prolonged stimulation. Accordingly, we prefer EPO for this purpose.
Supplemental iron — To achieve and maintain target hemoglobin levels noted above with either erythropoietin or darbepoetin, sufficient body iron stores are required. Supplemental iron should be administered, as needed, to maintain a transferrin saturation of ≥20 percent and a serum ferritin level of ≥100 ng/mL [107]. Intravenous iron is more effective than oral iron. Two factors associated with increased hepcidin production in ACD limit the availability of oral iron preparations to achieve these levels (see 'Hepcidin' above). These are:
●Suboptimal intestinal absorption of oral iron preparations is expected when hepcidin levels are increased.
●Subjects with ACD have functional iron deficiency due to hepcidin-mediated inhibition of the transfer of iron from macrophages to the developing erythron [65]. Such functional iron deficiency cannot be overcome with oral preparations but does respond to the use of parenteral iron preparations.
Accordingly, if the patient has not responded to treatment with oral iron preparations, with or without EPO, intravenous iron should be administered before considering the patient to be a nonresponder. (See "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer", section on 'Iron monitoring and supplementation'.)
Transfusion — Transfusion of packed red cells is appropriate when the patient with ACD develops symptomatic anemia and the clinician believes that there is insufficient time for the patient to respond either to treatment of the underlying condition or to respond to treatment with an erythropoiesis-stimulating agent. The use of transfusion in such settings as well as the trigger hemoglobin level for such treatment are discussed separately. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult", section on 'Overview of our approach'.)
Investigational agents — Studies are underway using agents capable of altering/inhibiting the function of hepcidin (eg, hepcidin antagonists) and the hepcidin receptor (ferroportin) in order to alleviate the various disorders of iron metabolism associated with increased levels of hepcidin, including ACD [108-113]. (See 'Hepcidin' above.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anemia in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)