Acquired Hypolipoproteinemia and Hemophagocytic Lymphohistiocytosis: A Case Series and Review.

Abstract

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome characterized by uncontrolled macrophage activation. Secondary HLH is more common in adults and may be triggered by infection, malignancy, or autoimmune disease. Dyslipidemia, particularly hypolipoproteinemia, has been described but remains underexplored.

Methods: We retrospectively reviewed 18 adult HLH cases diagnosed between 2012 and 2020 at two institutions where complete lipid profiles were obtained at or near diagnosis. HLH was defined according to HLH-2004 criteria.

Results: Among 18 patients, 17 (94%) had secondary HLH, most commonly idiopathic (n = 5, 28%) or Epstein-Barr virus-associated (n = 3, 17%). Hypolipidemia was nearly universal: all (18/18) had HDL-C < 30 mg/dL, 15/18 (83%) had HDL-C < 20 mg/dL, and 12/18 (67%) had HDL-C < 10 mg/dL. LDL-C was <100 mg/dL in 12/18 (67%), with 6/18 (33%) undetectable. Triglycerides were variably elevated (median 279 mg/dL, range 96-1658 mg/dL). Three representative cases with profound hypolipoproteinemia demonstrated lipid normalization after HLH-directed therapy.

Conclusions: Severe reductions in HDL-C and LDL-C appear to accompany HLH and may contribute to its pathophysiology by impairing antioxidant defenses, destabilizing membranes, and potentiating macrophage activation. This case series highlights a consistent association between hypolipoproteinemia and HLH, suggesting potential diagnostic value. However, the observational design and small cohort limit generalizability. Larger prospective studies are needed to clarify mechanisms and evaluate whether full lipid profiling should be incorporated into diagnostic algorithms.