What is the management approach for a patient with Bechets disease on Imuran (azathioprine) and low-dose prednisone presenting with elevated Red Cell Distribution Width (RDW)?

Management of Elevated RDW in Behçet's Disease Patient on Azathioprine and Low-Dose Prednisone

The elevated RDW in this patient most likely indicates iron deficiency anemia (IDA) or a combined nutritional deficiency, and you should immediately check a complete blood count with differential, serum ferritin, iron studies, and vitamin B12/folate levels to distinguish between iron deficiency, azathioprine-induced myelosuppression, or combined deficiencies. 1

Initial Diagnostic Approach

Check for iron deficiency first, as this is the most common cause of elevated RDW in patients on chronic immunosuppression:

• Obtain serum ferritin: A level <12 μg/dL is diagnostic of iron deficiency, though ferritin may be falsely elevated above 12-15 μg/dL in the presence of chronic inflammation (common in Behçet's disease), but if >100 μg/dL, iron deficiency is almost certainly absent 1
• Measure transferrin saturation: <30% supports iron deficiency diagnosis 1
• Review complete blood count: Look specifically for microcytosis (low MCV), though this may be absent in combined deficiencies (e.g., concurrent folate or B12 deficiency), which is why RDW becomes elevated—it reflects the mixed population of red blood cells 1

Azathioprine-Related Considerations

Monitor for azathioprine-induced myelosuppression, which is a critical differential:

• Review recent blood counts: Azathioprine causes cytopenias during maintenance therapy, with isolated lymphopenia being common and not necessarily requiring intervention unless <0.5 × 10⁹/L 1
• Check for early myelosuppression: The earliest feature is leucopenia followed by thrombocytopenia; a downward trend even within normal ranges warrants increased vigilance 1
• Dose reduction is recommended if: Lymphocyte count falls below 0.5 × 10⁹/L, platelet count below 50 × 10⁹/L, or neutrophil count below 1.0 × 10⁹/L 1
• Consider TPMT status: If not previously checked, measure thiopurine methyltransferase (TPMT) activity, as deficiency increases risk of myelosuppressive toxicity 1

Monitoring Schedule During Investigation

Increase monitoring frequency immediately:

• Weekly complete blood counts and liver function tests until the cause of elevated RDW is identified and stabilized 1, 2
• Continue azathioprine at current dose unless frank cytopenias develop (neutrophils <1.0 × 10⁹/L or platelets <50 × 10⁹/L), in which case immediate withdrawal is required and joint management with hematology is necessary 1

Management Based on Findings

If Iron Deficiency is Confirmed:

• Investigate the source: In patients on chronic corticosteroids and azathioprine, gastrointestinal blood loss from NSAID use (if applicable), peptic ulcer disease, or occult bleeding should be considered 1
• Initiate oral iron supplementation: Start therapeutic iron replacement and reassess response after 3 weeks 1
• Consider gastrointestinal evaluation: If no obvious source and patient has risk factors for occult bleeding 1

If Combined Deficiency (Iron + B12/Folate):

• This explains the elevated RDW: Mixed cell populations (microcytic from iron deficiency and macrocytic from B12/folate deficiency) create high RDW even with normal MCV 1
• Replace both deficiencies concurrently with appropriate supplementation

If Azathioprine-Induced Myelosuppression:

• Reduce azathioprine dose or discontinue: Depending on severity of cytopenias 1
• For Behçet's disease specifically: If azathioprine must be reduced or stopped, consider transitioning to alternative immunosuppression such as mycophenolate mofetil or biologic agents (infliximab is first-line for severe/refractory Behçet's) 3, 4, 5
• Maintain low-dose prednisone: Continue current corticosteroid dose during transition to prevent disease flare 6

Critical Pitfalls to Avoid

• Do not assume elevated RDW is solely from azathioprine toxicity: Iron deficiency is more common and must be excluded first, as missing this diagnosis delays appropriate treatment 1
• Do not stop azathioprine prematurely: Unless frank cytopenias are present (neutrophils <1.0 × 10⁹/L, platelets <50 × 10⁹/L), continue therapy while investigating 1
• Do not overlook combined deficiencies: Elevated RDW with normal MCV strongly suggests mixed nutritional deficiencies requiring comprehensive evaluation 1
• Do not forget that ferritin is an acute phase reactant: In active Behçet's disease, ferritin may be falsely normal despite true iron deficiency; use transferrin saturation and consider therapeutic trial of iron if ferritin is 12-100 μg/dL 1

Ongoing Management for Behçet's Disease

Maintain current immunosuppressive regimen unless cytopenias require modification:

• Azathioprine at 2-3 mg/kg/day is standard maintenance for Behçet's disease with ocular or systemic involvement 3, 7
• Low-dose prednisone (typically 5-10 mg/day) is appropriate for maintenance after achieving disease control 6
• Monitor every 3 months minimum once stable: Complete blood count, liver function tests, and disease activity assessment 1, 2