From the Guidelines
Hemophagocytic Lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome induced by aberrantly activated macrophages and cytotoxic T cells, which can be primary (genetic) or secondary (acquired) and is characterized by recurrent fever, cytopenia, liver dysfunction, and a sepsis-like syndrome that may rapidly progress to terminal multiple organ failure. According to the most recent and highest quality study, HLH can affect adults of all ages and is often triggered by infections, malignancies, or autoinflammatory/autoimmune disorders 1. The diagnosis of HLH can be challenging, as patients may present with a phenotype indistinguishable from sepsis or multiple organ dysfunction syndrome, and the HLH-2004 diagnostic criteria developed for children are not validated for adults 1. Key features of HLH include:
- Recurrent fever
- Cytopenia
- Liver dysfunction
- Sepsis-like syndrome
- Rapid progression to terminal multiple organ failure It is essential to recognize HLH early to prevent irreversible organ damage and subsequent death, and treatment protocols such as HLH-94 and HLH-2004 may be used, but with consideration of dose reductions and individualized tailoring of treatment duration for adults 1.
From the Research
Definition and Characteristics of Hemophagocytic Lymphohistiocytosis (HLH)
- HLH is a rare and life-threatening condition characterized by an overactive response of the immune system with excessive production of proinflammatory cytokines 2, 3, 4, 5, 6.
- It is marked by widespread inflammation due to massive immune activation and cytokine release 4.
- HLH can be primary or familial, and secondary or acquired 4.
- The condition is characterized by non-neoplastic proliferation and macrophage activation that induces cytokine-mediated bone marrow suppression and features of intense phagocytosis in the bone marrow and liver, leading to multi-organ dysfunction and ultimate failure 3.
Clinical Presentation and Diagnosis
- Initial presentation of HLH often mimics and overlaps with many diseases including infections, sepsis, and multiorgan failure syndrome, making diagnosis challenging 2.
- Patients may present with fever, central nervous system symptoms, cytopenias, or elevated liver enzymes 5.
- Diagnosis is made by fulfilling 5 of 8 criteria as determined by the Histiocyte Society 4.
- Laboratory and bone marrow biopsy findings are used to establish the diagnosis 2, 3, 6.
Treatment and Management
- Treatment includes etoposide, dexamethasone, with or without intrathecal methotrexate in the presence of neurologic involvement, as well as treating the underlying cause in secondary HLH 4, 6.
- The HLH-94 protocol is the standard treatment, consisting of dexamethasone and chemotherapy like etoposide 3.
- Early recognition and treatment initiation of HLH are crucial to prevent adverse outcomes and mortality 3.
- Treatment should be tailored based on the underlying HLH trigger, as chemotherapy-based treatment regimens may result in overtreatment and unnecessary toxicities 3.