The Role of Immune Mechanisms, Inflammatory Pathways, and Macrophage Activation Syndrome in the Pathogenesis of Hemophagocytic Lymphohistiocytosis

Abstract

This review article describes the pathophysiology of hemophagocytic lymphohistiocytosis (HLH). The condition is characterized by excessive stimulation of inflammatory cytokines, lymphocytes, and macrophages, leading to hyperinflammatory disorder with immune dysfunction. The main clinical and diagnostic features include fever ≥38.5°C, splenomegaly, hyperferritinemia, cytopenia, hypofibrinogenemia, hemophagocytosis on the bone marrow, low or absent of natural killer (NK) cell activity, and elevated soluble CD25. Various immunological and inflammatory mechanisms are involved in the pathogenesis of HLH. Moreover, the condition can result in multisystem organ failure, contributing to the high mortality rate in hospital settings. A thorough literature search was conducted by collecting data from multiple articles published on PubMed, Medline, and Google Scholar. The article discusses the cellular and molecular pathways that lead to HLH. Due to the high rate of morbidity and mortality, early diagnosis needs to be established. More research pertaining to molecular biology, immunology, and the genetics of HLH is needed to explore the effective management and treatment of this rare disorder.