From the Guidelines
Definition and Characteristics of Hemophagocytic Lymphohistiocytosis (HLH)
Hemophagocytic Lymphohistiocytosis (HLH) is a severe and life-threatening immune disorder characterized by excessive activation and proliferation of immune cells, leading to tissue damage and organ dysfunction 1. The condition is often triggered by infections, autoimmune disorders, or malignancies, and is diagnosed based on clinical and laboratory criteria, including fever, splenomegaly, and elevated levels of ferritin and soluble CD25 1.
Diagnostic Criteria
The diagnosis of HLH can be established if a molecular diagnosis consistent with HLH is made or if 5 of the 8 diagnostic criteria are fulfilled, which include:
- Fever
- Splenomegaly
- Cytopenias (affecting ≥2 of 3 lineages in the peripheral blood)
- Hemophagocytosis in bone marrow or spleen or lymph nodes
- Hypertriglyceridemia and/or hypofibrinogenemia
- Low or no NK cell activity
- Ferritin ≥ 500 mg/L
- sCD25 (ie, soluble IL-2 receptor) ≥ 2400 U/mL 1
Treatment
Treatment typically involves immunosuppressive therapy with medications such as etoposide and dexamethasone, with the goal of reducing immune cell activation and preventing organ damage 1. The treatment protocols HLH-94 and HLH-2004 have been established for diagnosis, classification, and treatment of HLH in patients younger than 18 years, but may need to be modified for adult patients due to differences in triggers, organ reserve, fitness, and clinical presentation 1.
Key Considerations
It is essential to recognize HLH early to prevent irreversible organ damage and subsequent death 1. The condition can present with a phenotype indistinguishable from sepsis or multiple organ dysfunction syndrome, making diagnosis challenging 1. A high index of suspicion and awareness of the diagnostic criteria are crucial for timely diagnosis and treatment.
From the Research
Definition and Characteristics of Hemophagocytic Lymphohistiocytosis (HLH)
- HLH is a rare and life-threatening condition characterized by excessive activation of the immune system, leading to a proinflammatory state and multiorgan failure 2, 3, 4, 5, 6.
- It can be primary, caused by mutations in immune-regulatory genes, or secondary, resulting from an aberrant immune response to triggers such as viral or bacterial infections, malignancies, or autoimmune diseases 2, 4, 5, 6.
Clinical Presentation and Diagnosis
- HLH often presents as a multisystem febrile illness, requiring an extensive differential diagnosis 2.
- Diagnosis is based on a combination of clinical and laboratory findings, including fever, splenomegaly, hypertriglyceridemia, hypofibrinogenemia, low natural killer cell function, high ferritin, and soluble interleukin 2 receptor levels 4, 5.
- Bone marrow biopsy and peripheral blood smear may show hemophagocytosis or atypical lymphocytes consistent with underlying conditions such as T-cell lymphoma 4, 5.
Treatment and Prognosis
- The basic mechanism of therapy involves interrupting the aberrant immune response through destruction and suppression of T-lymphocyte function, typically achieved with corticosteroids and etoposide 2, 3, 4.
- Early diagnosis and initiation of therapy are crucial for increasing the chance of recovery, but the prognosis remains poor, especially in adults 2, 5.
- In some cases, additional treatments such as intravenous immunoglobulin (IVIG) and reduction of immunosuppressants may be necessary, particularly in patients with underlying autoimmune diseases or post-transplantation 6.