In a 79‑year‑old man with newly diagnosed rheumatoid arthritis, mild normocytic anemia (hemoglobin 12.6 g/dL, hematocrit 38 %, mean corpuscular volume 88.8 fL) with low serum iron, low transferrin saturation, low‑normal total iron‑binding capacity, and high ferritin, plus severe vitamin D deficiency (25‑hydroxy‑vitamin D 17 ng/mL), what is the appropriate management?

Management of Anemia and Vitamin D Deficiency in Newly Diagnosed Rheumatoid Arthritis

This patient has anemia of chronic disease (ACD) with concurrent severe vitamin D deficiency; treat the rheumatoid arthritis aggressively to control inflammation, supplement vitamin D immediately to achieve levels >30 ng/mL, and avoid iron supplementation because the elevated ferritin indicates adequate iron stores despite low serum iron and transferrin saturation.

Understanding the Anemia Pattern

The laboratory pattern—low serum iron (44), low-normal TIBC (255), low transferrin saturation (17%), and markedly elevated ferritin (599)—is pathognomonic for anemia of chronic disease, not iron deficiency anemia. 1, 2

• The elevated ferritin (599 ng/mL) definitively excludes true iron deficiency, as ferritin <30 μg/L is required to diagnose iron deficiency in the absence of inflammation 1, 3
• In rheumatoid arthritis, ferritin behaves as an acute-phase reactant and rises with disease activity, making it an unreliable marker of iron stores in active inflammatory disease 4
• The normocytic anemia (MCV 88.8 fL) with mild hemoglobin reduction (12.6 g/dL) is consistent with ACD rather than iron deficiency, which typically produces microcytosis 1, 5

A critical pitfall: The low transferrin saturation does NOT indicate iron deficiency in this context—it reflects inflammatory cytokine-mediated iron sequestration in reticuloendothelial stores, not depleted body iron. 2

Primary Management Strategy

1. Aggressive Rheumatoid Arthritis Treatment

The cornerstone of managing ACD in rheumatoid arthritis is controlling the underlying inflammatory disease, as the anemia will improve when disease activity is suppressed. 6, 2

• Initiate or optimize disease-modifying antirheumatic drug (DMARD) therapy according to treat-to-target principles, aiming for remission or low disease activity 6
• Methotrexate should be escalated to 20-25 mg weekly or maximum tolerated dose, with consideration of subcutaneous administration if needed 6
• Inflammatory cytokines directly impair erythropoietin production and erythroid progenitor responsiveness; suppressing inflammation reverses these mechanisms 2

2. Vitamin D Replacement

With a 25-hydroxy-vitamin D level of 17 ng/mL, this patient has severe vitamin D deficiency requiring immediate supplementation. 6

• Prescribe high-dose vitamin D supplementation (typically 50,000 IU weekly for 8-12 weeks, then maintenance dosing of 1,000-2,000 IU daily) to achieve target levels >30 ng/mL 6
• Vitamin D deficiency is common in rheumatoid arthritis and should be corrected as part of comprehensive management 6
• Adequate vitamin D status may have beneficial effects on disease activity and inflammation 6

3. Iron Supplementation: NOT Indicated

Do not prescribe iron supplementation in this patient despite the low serum iron and transferrin saturation. 1, 2

• The ferritin of 599 ng/mL indicates adequate or even excessive iron stores; the low serum iron reflects inflammatory sequestration, not deficiency 1, 2
• Iron delivery to the bone marrow is not impaired in ACD, and erythroid iron utilization remains adequate 2
• Administering iron in ACD is ineffective and potentially harmful, as it will be rapidly sequestered in reticuloendothelial stores without improving erythropoiesis 2

The only scenario requiring iron supplementation would be if ferritin were <30-60 μg/L with low transferrin saturation, indicating true coexistent iron deficiency. 1, 7, 8

Monitoring and Follow-Up

Reassess After Disease Control

• Recheck complete blood count 3-6 months after initiating or optimizing DMARD therapy 6
• Hemoglobin should improve as disease activity decreases and inflammatory markers normalize 4, 2
• If anemia persists despite controlled disease activity (remission or low disease activity), then reconsider alternative causes including occult iron deficiency, vitamin B12 deficiency, or myelodysplastic syndrome 6, 5

Additional Workup if Anemia Persists

If hemoglobin fails to improve after 6 months of controlled disease activity, obtain: 1, 5

• Vitamin B12 and folate levels, as deficiencies occur in 29% and 21% of anemic RA patients respectively 5
• Reticulocyte count to assess bone marrow response 1
• Consider hematology referral if unexplained persistent anemia after addressing inflammation and nutritional deficiencies 3

Vitamin D Monitoring

• Recheck 25-hydroxy-vitamin D level after 3 months of supplementation to confirm adequate repletion 6
• Maintain levels >30 ng/mL with ongoing supplementation 6

Common Pitfalls to Avoid

Do not misinterpret low transferrin saturation as iron deficiency when ferritin is elevated in inflammatory disease. 1, 8, 2

• In rheumatoid arthritis, ferritin >60 μg/L generally excludes iron deficiency, though this threshold is higher than in non-inflammatory conditions 7, 8
• Multiple types of anemia frequently coexist in RA (52% iron deficiency, 29% B12 deficiency, 21% folate deficiency among anemic patients), but this patient's elevated ferritin rules out iron deficiency 5

Do not delay vitamin D supplementation—severe deficiency requires immediate correction regardless of anemia management. 6

Do not attribute all anemia to RA without excluding other causes if hemoglobin is disproportionately low or fails to improve with disease control. 6, 3

Lifestyle and Cardiovascular Risk Management

Given the new RA diagnosis in a 79-year-old, address cardiovascular risk factors comprehensively. 6

• Counsel on Mediterranean diet rich in vegetables, fruits, whole grains, olive oil, and fish while limiting processed foods and animal fats 6
• Encourage at least 150 minutes weekly of moderate aerobic activity, adapted to physical limitations 6
• Assess lipid profile and consider statin therapy, as RA patients have elevated cardiovascular risk and statins reduce major cardiovascular events by 34% in this population 6