Case Reports of Visceral Leishmaniasis-Associated Hemophagocytic Lymphohistiocytosis in Adults: A Complex Immune Phenomenon

<b>Background</b>: Visceral Leishmaniasis (VL), a severe systemic parasitic disease caused by <i>Leishmania</i> species, can be complicated by secondary Hemophagocytic Lymphohistiocytosis (HLH). HLH is a life-threatening hyperinflammatory syndrome characterized by excessive immune activation that results in multiorgan dysfunction. The co-occurrence of VL and HLH in adults is a rare but critical diagnostic and therapeutic challenge, often leading to fatal outcomes if treatment is delayed. <b>Case Presentation</b>: We present two cases of adult males (60 and 72 years old) from Greece, an endemic area for <i>L. infantum</i>, who presented with prolonged fever, pancytopenia, hepatosplenomegaly, and impaired liver function. Both patients exhibited extremely elevated ferritin (all > 2000 ng/mL and one > 20,000 ng/mL) and hypertriglyceridemia, fulfilling key laboratory criteria for HLH. Diagnosis was confirmed by the visualization of <i>Leishmania</i> amastigotes in bone marrow aspirates, which also demonstrated features of hemophagocytosis. Case 1, critically ill with acute kidney injury and coagulopathy, required combined treatment with liposomal Amphotericin B and immunoglobulin therapy for HLH. Case 2, who showed rapid and "spectacular improvement" solely after receiving liposomal Amphotericin B, did not require HLH-specific immunosuppression. <b>Conclusions</b>: VL-associated HLH should be considered in adult patients presenting with complex systemic inflammation, fever, and cytopenias, particularly in endemic settings. Our cases illustrate that the prompt initiation of anti-leishmanial therapy with liposomal Amphotericin B can be sufficient to reverse the HLH syndrome by eliminating the infectious trigger. However, intensive immunomodulation may be necessary in patients presenting with critical multi-organ failure.