Learn About HLH
Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disease process resulting from uncontrolled activation of the immune system. Although HLH predominantly affects infants and children, a first episode of this syndrome can develop at any age. Symptoms of HLH may include the following: persistent fever (often high), fatigue, enlarged lymph nodes, extremely low red and white blood cell counts, excessive bleeding, liver and/or spleen enlargement, neurological symptoms such as seizures, coordination difficulty, or confusion, and increased susceptibility to infections. If left untreated, HLH can rapidly progress, leading to dysfunction and failure of multiple organs.
The symptoms of HLH result from an overactive and excessive immune response involving T-lymphocytes and macrophages, two types of white blood cells, which normally circulate in the body. This hyperactive and misdirected immune response leads to persistently high levels of circulating cytokines (molecules which, in normal quantities, up- and down-regulate immune function and inflammation). This so-called "hypercytokinemia" is potentially damaging to all the major vital organs. The hallmark of hypercytokinemia is hemophagocytosis, the process for which HLH is named. Hemophagocytosis describes the abnormal consumption of blood cells by cytokine-activated macrophages, thereby causing low blood counts.
HLH is often referred to as either “primary,” which is hereditary or congenital, or “secondary,” which is typically diagnosed in older children or adults without a family history of the disease. Secondary HLH is triggered by an underlying condition or illness – classically viral infections such as Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), or Herpes viruses, cancers such as leukemia or lymphoma, autoimmune disorders, or exposure to vaccinations. Epstein-Barr Virus (EBV) has been recognized as the leading infectious cause of secondary HLH and is associated with a poor outcome.
As clinical and laboratory features of HLH overlap with many different clinical conditions, including cancer, bone marrow dysfunction, and overwhelming septic shock, the diagnosis of HLH, especially in adults, can be incredibly challenging. Failure to recognize HLH expediently can result in delayed treatment of the disease (and underlying triggering process if secondary HLH), often leading to multi-system organ failure.
Although there are two different forms of HLH, the current treatment regimens are similar – a combination of chemotherapy, immunotherapy and steroids. Antibiotics and antiviral drugs may also be utilized to treat underlying bacterial and viral infections, respectively. In patients with persistent or recurrent HLH, despite treatment, bone marrow or stem cell transplant is often necessary to achieve a cure.