Question:
A patient diagnosed with dengue initially improved but later returned with high-grade fever, severe thrombocytopenia (platelet count 15,000), and leukopenia. What is the next best investigation to evaluate the cause?
A patient diagnosed with dengue initially improved but later returned with high-grade fever, severe thrombocytopenia (platelet count 15,000), and leukopenia. What is the next best investigation to evaluate the cause?
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Any patient with severe viral illness or autoimmune flare who develops sudden massive organomegaly, profound new-onset cytopenias, and a ridiculously high Ferritin level ($>$10,000) has secondary HLH/MAS until proven otherwise. Treat aggressively with steroids, etoposide, or cyclosporine.
Updated On: Sep 3, 2026
- Peripheral blood flow cytometry
- S. Ferritin, Triglycerides, Fibrinogen, NK Cells, bone marrow biopsy
- LDH
- Procalcitonin
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The Correct Option is B
Solution and Explanation
Concept:
The clinical scenario of a viral infection (Dengue) that initially improves but is followed by a secondary surge of high unremitting fever, profound cytopenias (thrombocytopenia and leukopenia), and systemic collapse should raise immediate suspicion for secondary Hemophagocytic Lymphohistiocytosis (HLH), also known as Macrophage Activation Syndrome (MAS).
Explanation:
• Hemophagocytic Lymphohistiocytosis (HLH) is a severe, life-threatening hyperinflammatory syndrome caused by the uncontrolled activation of macrophages and T-cells, leading to a massive cytokine storm.
• Secondary HLH is most commonly triggered by viral infections (classically EBV, but increasingly recognized in Dengue, CMV, and HIV), autoimmune diseases, and malignancies.
• To formally diagnose HLH, the HLH-2004 criteria are utilized. Diagnosis requires a molecular diagnosis OR at least 5 of the following 8 criteria:
1. Fever $\geq$ 38.5°C
2. Splenomegaly
3. Cytopenias affecting $\geq$ 2 lineages (Hb $<$ 9, Platelets $<$ 100k, Neutrophils $<$ 1000)
4. Hypertriglyceridemia (fasting $>$ 265 mg/dL) and/or Hypofibrinogenemia ($\leq$ 1.5 g/L)
5. Hemophagocytosis in bone marrow, spleen, or lymph nodes
6. Low or absent NK-cell activity
7. Hyperferritinemia (often $>$ 500 $\mu$g/L, frequently $>$ 10,000)
8. High soluble CD25 (sIL-2R).
• Option (B) lists the exact diagnostic workup required to fulfill the HLH-2004 criteria (Ferritin, Triglycerides, Fibrinogen, NK cell activity, and bone marrow biopsy for hemophagocytosis).
• Options (A), (C), and (D) are non-specific and do not provide the targeted diagnostic panel required for HLH.
Final answer:
To diagnose post-Dengue Hemophagocytic Lymphohistiocytosis, the criteria-specific workup listed in Option (B) must be performed immediately.
The clinical scenario of a viral infection (Dengue) that initially improves but is followed by a secondary surge of high unremitting fever, profound cytopenias (thrombocytopenia and leukopenia), and systemic collapse should raise immediate suspicion for secondary Hemophagocytic Lymphohistiocytosis (HLH), also known as Macrophage Activation Syndrome (MAS).
Explanation:
• Hemophagocytic Lymphohistiocytosis (HLH) is a severe, life-threatening hyperinflammatory syndrome caused by the uncontrolled activation of macrophages and T-cells, leading to a massive cytokine storm.
• Secondary HLH is most commonly triggered by viral infections (classically EBV, but increasingly recognized in Dengue, CMV, and HIV), autoimmune diseases, and malignancies.
• To formally diagnose HLH, the HLH-2004 criteria are utilized. Diagnosis requires a molecular diagnosis OR at least 5 of the following 8 criteria:
1. Fever $\geq$ 38.5°C
2. Splenomegaly
3. Cytopenias affecting $\geq$ 2 lineages (Hb $<$ 9, Platelets $<$ 100k, Neutrophils $<$ 1000)
4. Hypertriglyceridemia (fasting $>$ 265 mg/dL) and/or Hypofibrinogenemia ($\leq$ 1.5 g/L)
5. Hemophagocytosis in bone marrow, spleen, or lymph nodes
6. Low or absent NK-cell activity
7. Hyperferritinemia (often $>$ 500 $\mu$g/L, frequently $>$ 10,000)
8. High soluble CD25 (sIL-2R).
• Option (B) lists the exact diagnostic workup required to fulfill the HLH-2004 criteria (Ferritin, Triglycerides, Fibrinogen, NK cell activity, and bone marrow biopsy for hemophagocytosis).
• Options (A), (C), and (D) are non-specific and do not provide the targeted diagnostic panel required for HLH.
Final answer:
To diagnose post-Dengue Hemophagocytic Lymphohistiocytosis, the criteria-specific workup listed in Option (B) must be performed immediately.
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