What is the management plan for a 15-year-old boy with prolonged leukopenia (low white blood cell count), specifically neutropenia (low neutrophil count) and lymphocytopenia (low lymphocyte count), two months after recovering from non-hemorrhagic dengue (dengue fever)?

Management of Prolonged Leukopenia Following Dengue Fever

Direct Recommendation

This 15-year-old boy requires immediate evaluation for secondary hemophagocytic lymphohistiocytosis (HLH) and bone marrow assessment, as prolonged neutropenia and lymphocytopenia two months post-dengue is highly abnormal and suggests a serious underlying complication rather than typical post-viral recovery. 1, 2

Clinical Context and Urgency

Dengue-associated cytopenias typically resolve within 7-10 days after fever resolution. Persistent neutropenia and lymphocytopenia at 2 months post-infection is pathological and demands investigation. 2, 3

Key Distinguishing Features to Assess Immediately:

• Fever pattern: Any recurrent or persistent fever spikes suggest HLH, which occurs as a rare but life-threatening dengue complication 1
• Hepatosplenomegaly: New or persistent organomegaly is a red flag for HLH 1
• Constitutional symptoms: Ongoing fatigue, weight loss, or malaise beyond expected recovery 1
• Bleeding manifestations: Persistent or new-onset bleeding despite platelet recovery 1

Diagnostic Workup Required

Immediate Laboratory Evaluation:

• Complete blood count with differential: Document absolute neutrophil count (ANC) and absolute lymphocyte count precisely 4, 5
• Serum ferritin: Level >3000 ng/mL strongly suggests HLH 1
• Triglycerides: Elevation >314 mg/dL supports HLH diagnosis 1
• Liver function tests: Assess for persistent hepatitis 1
• Fibrinogen level: Hypofibrinogenemia occurs in HLH 1

Bone Marrow Evaluation:

Bone marrow biopsy is indicated for persistent, unexplained neutropenia of this duration to assess for hemophagocytosis, primary bone marrow disorders, or marrow suppression. 6, 1 This is not optional—prolonged neutropenia in this context requires morphologic assessment. 6

HLH-2004 Diagnostic Criteria Assessment:

The patient should be evaluated against HLH-2004 criteria, which include: fever, splenomegaly, cytopenias (affecting ≥2 cell lines), hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis in bone marrow, elevated ferritin, and elevated soluble IL-2 receptor. 1

Management Algorithm

If HLH is Diagnosed:

Initiate intravenous dexamethasone 10 mg/m²/day for the first 2 weeks, followed by a tapering regimen over 8 weeks. 1 This immunosuppressive therapy is life-saving and should not be delayed once HLH is confirmed. 1

If HLH is Excluded:

• **For severe neutropenia (ANC <500/mm³)**: Consider G-CSF (filgrastim) 5 mcg/kg/day subcutaneously until ANC >1000/mm³ 4
• For moderate neutropenia (ANC 500-1000/mm³): Weekly CBC monitoring and infection precautions 4
• Fluoroquinolone prophylaxis: Consider if ANC <100/mm³ expected for >7 days 4

Infection Monitoring Protocol:

• Any fever (≥38.0°C) requires immediate evaluation: Obtain blood and urine cultures, start broad-spectrum antibiotics empirically, and perform chest X-ray if respiratory symptoms present 4
• Do not delay antibiotic therapy while awaiting culture results in neutropenic patients 4

Critical Pitfalls to Avoid

Common Errors in Post-Dengue Cytopenias:

• Assuming "normal recovery": Dengue-associated neutropenia lasting beyond 2-3 weeks is never normal and requires investigation 2, 3
• Missing HLH diagnosis: Delayed recognition of HLH significantly worsens mortality; persistent fever and cytopenias after dengue should trigger HLH evaluation 1
• Inadequate monitoring: Weekly CBC monitoring is mandatory until complete normalization 4
• Failing to provide infection precautions: Patients with ANC <500/mm³ require protective measures and education about fever management 4

Specific Dengue-Related Considerations:

Severe neutropenia (<500/mm³) has been reported in dengue but is rare and typically transient. 2 When neutropenia persists beyond the acute phase, alternative diagnoses must be pursued aggressively. 2 In pediatric patients with underlying conditions, dengue can cause atypical presentations with prolonged cytopenias. 3

Follow-Up Strategy

• Weekly CBC with differential until complete normalization of all cell lines 4
• Repeat ferritin and triglycerides if HLH suspected but initial values borderline 1
• Hematology referral is mandatory for persistent unexplained neutropenia beyond 4 weeks 4
• Bone marrow biopsy should not be delayed beyond 2-4 weeks if no clear etiology identified 6