Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune disorder characterized by excessive immune activation and inflammation, leading to organ damage.
Understanding Hemophagocytic Lymphohistiocytosis (HLH)
HLH, affects both children and adults, and is not a single disease but rather a syndrome resulting from different underlying causes. The key feature is an overactive and dysregulated immune system. Usually, the immune system works to fight off infections and diseases. However, in HLH, immune cells such as T cells and macrophages become hyperactivated. This hyperactivation leads to an uncontrolled release of inflammatory molecules (cytokines), which damage organs and tissues.
Key Characteristics
- Hyperinflammation: The excessive immune response causes widespread inflammation throughout the body.
- Cytokine Storm: Overproduction of cytokines, leading to systemic symptoms and organ damage.
- Hemophagocytosis: Macrophages, a type of immune cell, start engulfing (phagocytosing) other blood cells, such as red blood cells, white blood cells, and platelets, in the bone marrow, spleen, and liver. This contributes to anemia, low white blood cell count, and low platelet count.
- Organ Damage: The uncontrolled inflammation can lead to multi-organ failure, affecting the liver, spleen, brain, and bone marrow.
Types of HLH
HLH can be broadly classified into two main categories:
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Primary HLH (Familial HLH): This is a genetic disorder caused by mutations in genes involved in immune regulation. These mutations impair the function of cytotoxic T cells and natural killer (NK) cells, which are crucial for controlling the immune response.
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Secondary HLH (Acquired HLH): This form is triggered by underlying conditions, such as:
- Infections (viral, bacterial, fungal, parasitic)
- Autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis)
- Cancers (e.g., lymphoma, leukemia)
- Immunodeficiency syndromes
Symptoms
The symptoms of HLH can vary depending on the severity of the disease and the organs involved. Common symptoms include:
- Fever
- Enlarged spleen (splenomegaly)
- Enlarged liver (hepatomegaly)
- Low blood cell counts (anemia, thrombocytopenia, neutropenia)
- Neurological symptoms (seizures, irritability, ataxia)
- Skin rash
- Jaundice
Diagnosis
Diagnosing HLH can be challenging because its symptoms can mimic other conditions. Diagnostic criteria typically include:
- Clinical findings: Persistent fever, splenomegaly, cytopenias, liver dysfunction, neurological abnormalities.
- Laboratory findings: Elevated ferritin levels, elevated triglycerides, low fibrinogen, elevated sCD25 (soluble IL-2 receptor), absent or reduced NK cell activity.
- Bone marrow biopsy: Evidence of hemophagocytosis.
Treatment
HLH is a medical emergency and requires prompt treatment. Treatment strategies aim to control the hyperinflammation and address the underlying cause. Common treatment options include:
- Immunosuppressive therapy: Medications like corticosteroids, etoposide, and cyclosporine are used to suppress the immune system.
- Chemotherapy: Used in some cases to deplete hyperactivated immune cells.
- Hematopoietic stem cell transplantation (HSCT): Considered a curative option for primary HLH and some cases of secondary HLH.
- Treatment of underlying trigger: If HLH is triggered by an infection or other underlying condition, treating the trigger is crucial.
In summary, HLH is a complex and life-threatening inflammatory syndrome characterized by immune dysregulation and organ damage, requiring immediate medical attention.
