Hemophagocytic Lymphohistiocytosis (HLH)

The abnormal cells in HLH are called histiocytes. Normal histiocytes are a type of white blood cell found in the blood and in organs such as the lymph nodes, spleen and liver. Normal histiocytes help control infections and remove dead cells from the body.

With HLH, histiocytes become overactive and begin to attack the body’s own tissues as if they are invading organisms. The result can be damage to organs such as the brain, liver and bone marrow. HLH causes histiocytes to release chemicals into the blood and ingest other cells, mistaking them for an infection. These confused histiocytes tend to accumulate in areas where they should not. This buildup and cell destruction can lead to organ damage and multi-organ failure.

HLH is primarily a condition that affects infants and small children. About 70 percent of cases occur before the age of 1. If untreated, HLH can become fatal very quickly. It is important to recognize and begin treatment as soon as possible since the condition can progress very rapidly.

There are two types of HLH: primary and secondary. They can be difficult to tell apart because symptoms can be similar. Doctors at Riley at IU Health do special genetic testing to make the correct diagnosis. The two types of HLH are:

• Primary hemophagocytic lymphohistiocytosis. Primary HLH is caused by an inherited (passed down from parents to children) gene mutation. It is also called familial HLH. In primary HLH, one or both parents carry an abnormal gene that puts a child at risk for HLH. Several different genes have been identified for primary HLH. Often, children with these genes are diagnosed at very young ages. If a parent has or had HLH, or a parent knows that HLH occurs in his or her family, it is a good idea to visit a genetic counselor before having a baby.
• Secondary hemophagocytic lymphohistiocytosis. Secondary HLH is acquired HLH. It occurs more often in older children and adults. Secondary HLH is often triggered by viral infections such as Epstein-Barr, cytomegalovirus or herpes. Cancer and some autoimmune disorders (the immune system attacks body tissues and organs) may also trigger secondary HLH. This disorder can sometimes be seen in children with arthritis.

Initially, HLH appears to be a routine febrile (fever) illness, but it lasts longer and children begin showing symptoms uncommon in typical infections, such as yellowing, pale or bruised skin. Symptoms depend on where the histiocytes (abnormal cells) accumulate.

Symptoms of hemophagocytic lymphohistiocytosis include:

• Fevers that last for more than a week
• Enlarged lymph nodes
• Yellowing of the skin (due to liver irritation)
• Pale skin
• Bruised skin
• Enlarged liver
• Enlarged spleen
• Rashes on the skin
• Neurological changes
• Seizures

Diagnosis of Hemophagocytic Lymphohistiocytosis

In addition to taking your child’s medical history and obtaining a thorough family history, your child’s doctor will examine him or her carefully. A doctor who suspects HLH will probably request many tests, which may include:

• Complete blood count (CBC)
• Bone marrow biopsy (removal of a sample of bone marrow)
• Blood work to look at the liver and kidney function
• Blood tests to evaluate the immune system
• Genetic testing for the genes associated with HLH
• Computed tomography (CT) scan
• Magnetic resonance imaging (MRI)
• Sample of spinal fluid to test for HLH effects in the brain
• Testing for infections associated with HLH