{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T16:24:02Z","timestamp":1789057442366,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reports"],"abstract":"<jats:p>Background: Visceral Leishmaniasis (VL), a severe systemic parasitic disease caused by Leishmania 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. Case Presentation: We present two cases of adult males (60 and 72 years old) from Greece, an endemic area for L. infantum, who presented with prolonged fever, pancytopenia, hepatosplenomegaly, and impaired liver function. Both patients exhibited extremely elevated ferritin (all &gt; 2000 ng\/mL and one &gt; 20,000 ng\/mL) and hypertriglyceridemia, fulfilling key laboratory criteria for HLH. Diagnosis was confirmed by the visualization of Leishmania 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 \u201cspectacular improvement\u201d solely after receiving liposomal Amphotericin B, did not require HLH-specific immunosuppression. Conclusions: 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.<\/jats:p>","DOI":"10.3390\/reports9010029","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T08:36:33Z","timestamp":1768898193000},"page":"29","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Case Reports of Visceral Leishmaniasis-Associated Hemophagocytic Lymphohistiocytosis in Adults: A Complex Immune Phenomenon"],"prefix":"10.3390","volume":"9","author":[{"given":"Touba","family":"Bougiouklou","sequence":"first","affiliation":[{"name":"2nd University Department of Internal Medicine, University General Hospital Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios","family":"Petrakis","sequence":"additional","affiliation":[{"name":"2nd University Department of Internal Medicine, University General Hospital Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioulia","family":"Dragoumani","sequence":"additional","affiliation":[{"name":"2nd University Department of Internal Medicine, University General Hospital Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evanthia","family":"Gouveri","sequence":"additional","affiliation":[{"name":"2nd University Department of Internal Medicine, University General Hospital Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4846-2178","authenticated-orcid":false,"given":"Dimitrios","family":"Papazoglou","sequence":"additional","affiliation":[{"name":"2nd University Department of Internal Medicine, University General Hospital Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"543","DOI":"10.4269\/ajtmh.2011.10-0321","article-title":"Who is a typical patient with visceral leishmaniasis? 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