02 August 2026
: Case report 
Histoplasmosis-Associated Hemophagocytic Lymphohistiocytosis Presenting as Pyrexia of Unknown Origin With Splenic Masses
Unusual clinical course, Challenging differential diagnosis, Unusual setting of medical care, Unexpected drug reaction, Rare disease, Educational Purpose (only if useful for a systematic review or synthesis)
Nidhi Gupta ABCDEF 1*, Kriti Yadav CDF 1, Mythri Chittilla DF 1, Charly Almonte EF 1, Rahul Sampath ABCDG 1DOI: 10.12659/AJCR.952791
Am J Case Rep 2026; 27:e952791
Table 1 HLH-2004 Diagnostic Criteria [4].
| Diagnosis requires either a confirmed genetic mutation associated with HLH or fulfillment of at least 5 of the following 8 criteria | |
|---|---|
| Criterion | Definition |
| Fever | Temperature ≥38.5°C |
| Splenomegaly | Clinically or radiographically identified enlargement |
| Cytopenias | At least 2 of 3 cell lineages affected: |
| Hypertriglyceridemia/hypofibrinogenemia | Triglycerides ≥265 mg/dL and/or fibrinogen ≤1.5 g/L |
| Hemophagocytosis | Identified in bone marrow, spleen, or lymph nodes |
| Reduced or absent NK-cell activity | Documented via functional assay |
| Hyperferritinemia | Ferritin ≥500 μg/L |
| Elevated soluble CD25 | Soluble IL-2 receptor (sCD25) ≥2400 U/mL |