How to manage anemia with elevated RDW in a patient with Behcet's disease on azathioprine (Imuran) 150 mg daily and prednisone 5 mg daily?

Management of Anemia with Elevated RDW in Behçet's Disease on Azathioprine and Prednisone

Immediate Diagnostic Workup

Check iron studies (serum ferritin and transferrin saturation) first, as iron deficiency is the most common cause of elevated RDW in patients on chronic immunosuppression. 1

• Obtain serum ferritin: levels <12 μg/dL confirm iron deficiency 1
• Measure transferrin saturation: <30% supports iron deficiency 1
• Review complete blood count for microcytosis, though this may be absent in combined deficiencies 1
• Check vitamin B12 and folate levels to identify combined deficiencies 1

Assess for Azathioprine-Induced Myelosuppression

Review recent blood counts specifically for early signs of bone marrow suppression, which can present as anemia before progressing to more severe cytopenias. 2, 1

• Monitor lymphocyte count: reduce azathioprine dose if <0.5 × 10⁹/L 1
• Check platelet count: hold azathioprine if <50 × 10⁹/L 2, 1
• Assess neutrophil count: hold azathioprine if <1.0 × 10⁹/L 2, 1
• Consider TPMT genotyping or phenotyping if not previously done, as 73% of patients who develop severe myelosuppression have normal TPMT activity, but testing identifies high-risk patients 3, 4

Management Based on Findings

If Iron Deficiency Confirmed

Initiate oral iron supplementation immediately and investigate the source of iron loss. 1

• Start oral ferrous sulfate 325 mg (65 mg elemental iron) three times daily 1
• Evaluate for gastrointestinal blood loss, particularly given the association between Behçet's disease and GI ulceration 1
• Consider upper and lower endoscopy if occult GI bleeding suspected 1
• Monitor ferritin and hemoglobin monthly until normalized 1

If Combined Deficiency Present

Replace both deficiencies concurrently with appropriate supplementation. 1

• Add vitamin B12 1000 mcg intramuscularly weekly for 4 weeks if B12 deficient, then monthly 1
• Add oral folate 1-5 mg daily if folate deficient 1

If Azathioprine-Induced Myelosuppression Diagnosed

Immediately reduce azathioprine dose or discontinue based on severity of cytopenias. 2, 1

• For mild suppression (blood indices at lower normal ranges): reduce azathioprine dose from 150 mg to 100 mg daily and monitor weekly 2
• For significant myelosuppression (blood indices below normal): immediately withdraw azathioprine 2
• Platelet count <50 × 10⁹/L or neutrophil count <1.0 × 10⁹/L requires joint management with hematology 2
• Consider alternative immunosuppression such as methotrexate or anti-TNF therapy (infliximab) for Behçet's disease control 5, 6

Monitoring Schedule Adjustment

Increase monitoring frequency to weekly complete blood counts and liver function tests until the anemia resolves and blood counts stabilize. 2, 3, 4

• Weekly CBC for first month after any intervention 3, 4
• Twice monthly for months 2-3 3
• Return to monthly monitoring once stable 3, 4
• Monitor liver function tests concurrently, as azathioprine hepatotoxicity can occur even with concurrent prednisone and may present rapidly 2, 7

Behçet's Disease-Specific Considerations

Maintain immunosuppressive control of Behçet's disease unless cytopenias mandate modification. 1

• Continue prednisone 5 mg daily as this low dose is appropriate for maintenance 1
• If azathioprine must be discontinued, transition to alternative immunosuppression within 2-4 weeks to prevent disease flare 5, 6
• For patients with ocular or neurological Behçet's involvement, consider adding anti-TNF therapy (infliximab) rather than reducing immunosuppression if disease remains active 5, 6
• Assess for active mucocutaneous lesions, ocular inflammation, vascular involvement, or neurological manifestations that would require escalation rather than reduction of therapy 8

Critical Pitfalls to Avoid

• Do not attribute anemia solely to chronic disease without checking iron studies, as iron deficiency is highly treatable and common in this population 1
• Do not continue full-dose azathioprine if significant cytopenias develop, as delayed hematologic suppression can occur and may be life-threatening 4
• Do not reduce immunosuppression for mild macrocytosis alone, as this is a common finding with azathioprine and can indicate compliance rather than toxicity 3
• Do not assume normal TPMT testing excludes risk of myelosuppression, as most patients who develop severe toxicity have normal TPMT activity 3, 4
• Monitor for signs of infection vigilantly, as patients on combined azathioprine and prednisone are at increased risk for opportunistic infections including PML 4