Hemophagocytic lymphohistiocytosis in critically ill patients: A guide for clinicians

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a critical syndrome of immune dysregulation, marked by a hyperinflammatory cytokine storm and multiorgan failure. While primary forms are genetic, secondary HLH in adults is more prevalent and frequently precipitated by infections (notably viral), malignancies, or autoimmune diseases. Distinguishing secondary HLH from sepsis and multiorgan failure presents a significant clinical challenge due to overlapping clinical features, such as persistent fever and cytopenias. Diagnosis relies on clinical judgment and predictive frameworks like the HLH-2004 criteria or the HScore. Although elevated ferritin levels are a hallmark biomarker, isolated values lack sufficient specificity, necessitating a multifaceted diagnostic approach. Treatment strategies focus on controlling hyperinflammation while addressing the underlying trigger. Initial therapies often include corticosteroids, intravenous immunoglobulin, or the interleukin-1 receptor antagonist anakinra, with etoposide reserved for severe or refractory cases. Despite advances in management, mortality rates in the intensive care unit remain high, particularly when invasive organ support is required. Early recognition and multidisciplinary collaboration are essential to improve outcomes in this heterogeneous patient population. Further research is necessary to refine diagnostic cutoffs and identify personalized, phenotype-specific therapeutic interventions.

Keywords: Hemophagocytic lymphohistiocytosis; Macrophage-activation syndrome; Sepsis with hepatobiliary dysfunction and disseminated intravascular coagulation; Immune response; Multiorgan failure

Core Tip: Secondary hemophagocytic lymphohistiocytosis is a severe hyperinflammatory condition that frequently resembles or complicates sepsis in patients who are critically ill. A high level of clinical suspicion is necessary when patients present with ongoing fever, unexplained reductions in blood cell counts, and extremely high levels of ferritin. Employing the HScore or hemophagocytic lymphohistiocytosis-2004 criteria aids in making an earlier diagnosis. Swift, multidisciplinary management that emphasizes identifying triggers and applying customized immunosuppression is crucial to lowering the high mortality rates linked to multiorgan failure.