Anemia of Chronic Disease

What is Anemia of Chronic Disease?

Anemia of chronic disease (ACD), also known as anemia of inflammation, is a type of anemia that occurs in people with conditions that cause prolonged inflammation. It is the second most common form of anemia worldwide, after iron deficiency anemia. This condition develops when chronic diseases interfere with the body's ability to produce red blood cells and use iron effectively.

Unlike iron deficiency anemia where iron stores are depleted, in ACD, the body has adequate iron stores but cannot use them properly. The inflammatory process triggers the production of certain proteins that trap iron in storage sites, making it unavailable for red blood cell production. This is sometimes called "functional iron deficiency" because the iron is present but functionally inaccessible.

ACD typically develops over weeks to months and is usually mild to moderate in severity. The anemia itself is often overshadowed by symptoms of the underlying chronic condition. Understanding this type of anemia is crucial because treatment approaches differ significantly from other types of anemia, and inappropriate iron supplementation can potentially be harmful.

Common Symptoms

Causes and Risk Factors

Anemia of chronic disease results from the body's response to long-term inflammation, which disrupts normal iron metabolism and red blood cell production:

Underlying Conditions

Chronic Infections

• HIV/AIDS
• Tuberculosis
• Chronic hepatitis B or C
• Osteomyelitis (bone infection)
• Endocarditis
• Chronic fungal infections

Autoimmune and Inflammatory Diseases

• Rheumatoid arthritis
• Systemic lupus erythematosus
• Inflammatory bowel disease (Crohn's, ulcerative colitis)
• Vasculitis
• Sarcoidosis
• Temporal arteritis

Malignancies

• Lymphomas
• Multiple myeloma
• Solid tumors (lung, breast, colon)
• Leukemias
• Metastatic cancers

Other Chronic Conditions

• Chronic kidney disease
• Congestive heart failure
• Chronic liver disease
• Diabetes with complications
• Chronic obstructive pulmonary disease (COPD)

Pathophysiology

The development of ACD involves several mechanisms:

• Hepcidin production: Inflammation triggers production of hepcidin, which blocks iron release from stores
• Shortened red blood cell lifespan: Inflammatory cytokines cause premature destruction
• Impaired erythropoietin response: Reduced kidney production and bone marrow sensitivity
• Direct bone marrow suppression: Inflammatory mediators inhibit red blood cell production
• Iron sequestration: Iron trapped in macrophages becomes unavailable

Risk Factors

• Age over 65 (higher prevalence of chronic diseases)
• Hospitalized patients
• Residents of long-term care facilities
• Immunocompromised individuals
• Patients with multiple chronic conditions
• Those undergoing cancer treatment

Diagnosis

Diagnosing anemia of chronic disease requires distinguishing it from other types of anemia, particularly iron deficiency anemia:

Laboratory Tests

Complete Blood Count (CBC)

• Hemoglobin: Usually 8-11 g/dL (mild to moderate anemia)
• Hematocrit: Proportionally reduced
• Red blood cell indices:
  • Usually normocytic (normal size) and normochromic (normal color)
  • Can be microcytic (small) in 20-30% of cases
• Red cell distribution width (RDW): Usually normal

Iron Studies

• Serum iron: Low
• Total iron-binding capacity (TIBC): Low to normal
• Transferrin saturation: Low to normal
• Ferritin: Normal or elevated (key distinguishing feature)
• Soluble transferrin receptor: Normal (elevated in iron deficiency)

Additional Tests

• C-reactive protein (CRP): Often elevated
• Erythrocyte sedimentation rate (ESR): Usually elevated
• Hepcidin levels: Elevated (not routinely available)
• Reticulocyte count: Low or inappropriately normal
• Vitamin B12 and folate: To rule out other causes

Diagnostic Challenges

• Distinguishing from iron deficiency anemia when both conditions coexist
• Identifying the underlying chronic disease if not already known
• Determining when anemia is multifactorial
• Interpreting ferritin levels (acute phase reactant)

Diagnostic Criteria

ACD is typically diagnosed when:

• Anemia is present (low hemoglobin)
• Evidence of chronic disease or inflammation exists
• Ferritin is normal or elevated
• TIBC is low or normal
• Other causes of anemia are excluded

Treatment Options

Treatment of anemia of chronic disease focuses primarily on managing the underlying condition, with supportive care for the anemia when necessary:

Management Strategies

Living with anemia of chronic disease requires a comprehensive approach:

Lifestyle Modifications

• Pace activities: Plan rest periods between activities
• Prioritize tasks: Focus energy on most important activities
• Exercise regularly: Light to moderate exercise as tolerated
• Maintain good sleep hygiene: Quality sleep helps manage fatigue
• Stress management: Reduce inflammation through stress reduction

Nutritional Considerations

• Balanced diet with adequate protein
• Foods rich in B vitamins
• Anti-inflammatory diet may help
• Adequate hydration
• Avoid excessive alcohol
• Consider nutritionist consultation

Monitoring

• Regular CBC checks (frequency depends on severity)
• Monitor underlying disease activity
• Track symptom changes
• Watch for treatment side effects
• Annual comprehensive metabolic panel

Prognosis

The outlook for anemia of chronic disease depends largely on the underlying condition:

• Generally good when underlying disease is controlled
• Anemia improves as inflammation decreases
• Rarely life-threatening on its own
• Quality of life can be significantly improved with treatment
• May persist if chronic disease remains active
• Complete resolution possible if underlying cause is cured

Factors Affecting Prognosis

• Type and severity of underlying disease
• Response to treatment of primary condition
• Presence of other types of anemia
• Overall health status
• Age and comorbidities
• Access to appropriate medical care

When to See a Doctor

Seek medical attention if you experience:

• Persistent fatigue affecting daily activities
• Shortness of breath with minimal exertion
• Dizziness or fainting episodes
• Rapid or irregular heartbeat
• Chest pain or pressure
• Worsening of underlying chronic disease symptoms
• Signs of infection (fever, chills)

Prevention

While ACD cannot always be prevented, these strategies may help:

• Manage chronic conditions: Keep underlying diseases well-controlled
• Regular medical care: Monitor chronic conditions closely
• Infection prevention: Practice good hygiene, stay up-to-date with vaccinations
• Healthy lifestyle: Diet, exercise, and stress management
• Medication compliance: Take prescribed medications as directed
• Early detection: Regular check-ups can identify problems early
• Avoid inflammation triggers: When possible, minimize exposure

Special Considerations

Elderly Patients

• Higher prevalence due to multiple chronic conditions
• Symptoms may be attributed incorrectly to aging
• Increased risk of complications
• May require adjusted treatment approaches
• Drug interactions more common

Cancer Patients

• Anemia may be from cancer, chemotherapy, or both
• ESAs use requires careful consideration
• Quality of life is primary concern
• Frequent monitoring needed
• Multidisciplinary approach beneficial

Chronic Kidney Disease

• Reduced erythropoietin production compounds problem
• ESAs are standard treatment
• Iron management is complex
• Dialysis patients need special consideration
• Target hemoglobin levels are specific

Related Conditions

Conditions that may occur with or be confused with anemia of chronic disease:

• Iron Deficiency Anemia: Can coexist with ACD
• Anemia of Chronic Kidney Disease: Specific subtype of ACD
• Vitamin B12 Deficiency: May complicate the picture
• Folate Deficiency: Can occur in inflammatory bowel disease
• Myelodysplastic Syndromes: In elderly patients
• Thalassemia Trait: May cause diagnostic confusion
• Sideroblastic Anemia: Rare but important differential