How do you interpret ferritin levels in Rheumatoid Arthritis (RA) patients to guide iron supplementation needs?

Interpreting Ferritin in Rheumatoid Arthritis to Guide Iron Supplementation

In RA patients without active inflammation, use ferritin <30 μg/L to diagnose iron deficiency; however, in the presence of active disease or inflammation, ferritin up to 100 μg/L may still indicate iron deficiency requiring supplementation. 1

Key Principle: Inflammation Status Determines Ferritin Thresholds

The critical factor in interpreting ferritin in RA is whether inflammation is present, as ferritin acts as an acute-phase reactant and becomes falsely elevated during active disease. 1

In Clinically Inactive RA (No Inflammation):

• Ferritin <30 μg/L = Iron deficiency 1, 2
• This threshold has 88.2% sensitivity and 84.5% specificity for detecting depleted bone marrow iron stores in RA patients 3
• Use this cutoff when there is no clinical, endoscopic, or biochemical evidence of active disease 1

In Active RA (Inflammation Present):

• Ferritin up to 100 μg/L may still represent iron deficiency 1, 2
• Ferritin becomes unreliable as it rises independently of iron stores during inflammation 4
• Even "normal" ferritin values (30-100 μg/L) can mask true iron deficiency 5

Diagnostic Algorithm for Iron Status in RA

Step 1: Assess Inflammation Status

Measure C-reactive protein (CRP) and assess clinical disease activity to determine which ferritin threshold to apply. 1

Step 2: Interpret Ferritin Based on Inflammation

Without inflammation:

• Ferritin <30 μg/L → Iron deficiency confirmed 1
• Ferritin ≥30 μg/L → Iron deficiency unlikely 1

With inflammation present:

• Ferritin <30 μg/L → Iron deficiency confirmed 1
• Ferritin 30-100 μg/L → Likely mixed picture: both iron deficiency AND anemia of chronic disease 1
• Ferritin >100 μg/L with transferrin saturation <20% → Anemia of chronic disease predominates 1

Step 3: Use Adjunctive Tests When Ferritin is Equivocal (30-100 μg/L with inflammation)

When ferritin falls in the 30-100 μg/L range during active inflammation, add:

• Transferrin saturation <20% suggests functional iron deficiency even with higher ferritin 1
• Serum transferrin receptor (sTfR) and sTfR-log ferritin index can distinguish true iron deficiency from anemia of chronic disease with high accuracy 6
• Low MCV, raised red cell distribution width, and transferrin saturation <16% support iron deficiency 1

Treatment Decisions Based on Ferritin Interpretation

Oral Iron Supplementation:

Use as first-line when: 1, 2

• Disease is clinically inactive
• Mild anemia (hemoglobin >100 g/L)
• No previous intolerance to oral iron
• Ferritin confirms iron deficiency by above criteria

Intravenous Iron Supplementation:

Use as first-line when: 1, 2

• Clinically active RA (inflammation present)
• Previous intolerance to oral iron
• Hemoglobin <100 g/L
• Need for erythropoiesis-stimulating agents

Monitoring Strategy

Active disease: Check complete blood count, ferritin, and CRP every 3 months 1

Remission or mild disease: Check every 6-12 months 1

After successful treatment: Re-initiate iron when ferritin drops below 100 μg/L or hemoglobin falls below 120 g/L (women) or 130 g/L (men) 1, 2

Critical Pitfalls to Avoid

Do not rely on ferritin alone during active RA. A ferritin of 50-80 μg/L may appear "normal" but actually represents iron deficiency masked by inflammation. 5, 4 In one study, RA patients with active disease and iron deficiency showed normal ferritin values that failed to reflect true iron stores. 5

Do not use conventional iron markers (serum iron, TIBC, MCHC) as primary indicators in RA. These correlate poorly with bone marrow iron stores in RA patients. 3 Ferritin remains superior despite its limitations.

Ferritin >60 μg/L has poor predictive value (only 50%) for excluding iron deficiency in anemic RA patients. 7 This reinforces why the 100 μg/L threshold is appropriate during inflammation.

Target ferritin levels of 50-100 μg/L during maintenance to avoid both deficiency and overload. 2