How should a patient with rheumatoid arthritis and anemia be managed?

Management of Anemia in Rheumatoid Arthritis

This patient requires immediate investigation to determine the type of anemia, followed by treatment of the underlying RA disease activity while simultaneously addressing any iron deficiency with supplementation.

Initial Diagnostic Workup

The first priority is distinguishing between anemia of chronic disease (ACD), iron deficiency anemia (IDA), or a combination of both, as this fundamentally changes management 1.

Essential Laboratory Tests

• Complete blood count with red cell indices including MCV, MCH, MCHC, and RDW 2
• Serum ferritin - the most powerful test for iron deficiency, though levels up to 100 μg/L may still reflect iron deficiency in the presence of inflammation 3
• Transferrin saturation to help differentiate iron deficiency from ACD 2
• C-reactive protein to assess inflammatory activity 2
• Reticulocyte count 2
• Vitamin B12 and folate levels - unrecognized B12 deficiency was found in 12 of 25 patients with macrocytic anemia in RA 1

Critical Pitfall to Avoid

Do not assume this is simply anemia of chronic disease without investigation. In a large cohort study of 199 anemic RA patients, only 39% had pure ACD, while 45% had iron deficiency anemia and 13% had macrocytic anemia 1. Established malignancy was present in 10% of anemic RA patients, making thorough investigation essential 1.

Determining the Type of Anemia

Iron Deficiency Anemia (IDA)

• Low ferritin (<30 μg/L in absence of inflammation, <100 μg/L with inflammation) 3
• Low transferrin saturation 3
• Microcytic indices (though may be normocytic early or with combined deficiency) 2

Anemia of Chronic Disease (ACD)

• Normal or elevated ferritin 4
• Low transferrin saturation 4
• Typically normocytic 4
• Elevated inflammatory markers 4

Combined IDA and ACD

• Common in RA patients 1, 4
• Ferritin 30-100 μg/L with low transferrin saturation suggests combined deficiency 3

Management Algorithm

For Iron Deficiency Anemia (Pure or Combined)

Investigate the source of blood loss before assuming it's disease-related:

• In premenopausal women: Consider menstrual blood loss, but don't exclude GI investigation if clinically indicated 3, 2
• In postmenopausal women and men: GI blood loss is the most common cause and requires investigation 3
• Among 90 RA patients with IDA, 30 had identifiable bleeding sources: 25 gastrointestinal, 3 gynecological, 2 urinary 1

Screen for coeliac disease in all patients with IDA, as malabsorption is an important consideration 3

Consider medication-related causes: NSAIDs commonly cause GI bleeding and are frequently used in RA 3

Iron Supplementation Strategy

Oral iron therapy:

• Ferrous sulfate 200 mg three times daily, or ferrous gluconate/fumarate 2
• Continue for three months after correction of anemia to replenish iron stores 2
• In IBD (similar inflammatory condition), oral iron should contain no more than 100 mg elemental iron daily due to impaired absorption with inflammation 3

Intravenous iron therapy:

• Consider when oral preparations are not tolerated 3
• Preferred in inflammatory conditions as it overcomes hepcidin-induced absorption blockade 3
• Indicated for moderate to severe anemia (Hb <100 g/L) with intolerance to oral iron 3

For Anemia of Chronic Disease

The primary treatment is optimizing RA disease control 3, 5:

• Intensification of RA therapy improved ACD in 45 of 78 patients in one study 1
• Infliximab treatment significantly improved hemoglobin levels in RA patients even after adjusting for disease activity 3
• Treatment intensification with TNF inhibitors (etanercept) and corticosteroids showed average hemoglobin increases of 1.3 g/dL 5

Erythropoiesis-stimulating agents (ESAs):

• Consider only after optimizing RA treatment and if insufficient response to intravenous iron 3
• Target hemoglobin level should not exceed 12 g/dL 3
• Required in 9 of 78 ACD patients who didn't respond to RA treatment intensification 1

When to Consider Blood Transfusion

Reserve transfusions for specific situations 3:

• Hemoglobin concentration below 7 g/dL 3
• Above 7 g/dL if symptomatic or cardiovascular risk factors present 3
• Hemodynamic instability 3

Important caveat: Blood transfusions don't correct underlying pathology and have no lasting effect - they should be followed by intravenous iron supplementation 3

Monitoring and Follow-up

• Recheck hemoglobin after initiating treatment to assess response 1
• If hemoglobin cannot be restored or maintained with iron therapy despite adequate supplementation, further investigation for occult blood loss or small bowel disease is warranted 3
• Screen for Helicobacter pylori in patients with recurrent IDA and normal endoscopic findings, and eradicate if present 3

Special Considerations for This Patient

Given this 42-year-old woman's presentation with fatigue, headaches, pallor, and hemoglobin of 9.1 g/dL:

• Her symptoms (fatigue, headaches) are consistent with anemia and warrant treatment 2
• The hemoglobin of 9.1 g/dL is moderate anemia requiring investigation and treatment 3
• As a premenopausal woman, menstrual blood loss is possible, but RA-related causes must still be investigated 3, 1
• The combination of optimizing RA disease control while addressing iron deficiency (if present) will provide the best outcomes for both hemoglobin levels and quality of life 3, 5