Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening condition of the immune system. Your immune system defends against infections and keeps you healthy. In HLH, the immune system gets confused. Sometimes, it works too much, causing excessive inflammation and tissue damage. Other times, the immune system fails to work normally, leaving patients at risk for serious infections.
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
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
Because HLH can become fatal quickly, your child’s doctor may decide to start treatment even before the genetic test results are known. Even though HLH is not cancer, chemotherapy is often needed. The goal is to calm the overactive immune system. Limiting immune system function slows the damage HLH does to the body. At the same time, it is important to prevent and treat infections with antibiotics and other medicines. Children being treated for HLH can be very sick and need help breathing. Many children will require blood transfusions.
The only cure for primary HLH is a stem cell transplant in which bone marrow from a healthy donor is transplanted into your child’s bones. For children with secondary HLH, chemotherapy and immunosuppression may be enough.
HLH is a serious condition. HLH and the procedures used to treat it can be fatal. However, follow-up with survivors indicates that most of them return to a normal or near-normal life.
For proper, successful treatment and good long-term prospects, children with HLH should be diagnosed and treated at a pediatric stem cell transplant center with experience dealing with HLH.
Key Points to Remember
Key Points to Remember
- Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening problem with the immune system.
- There are two types of HLH: primary and secondary. They have similar symptoms and require genetic testing to diagnose accurately.
- The only cure for primary HLH is stem cell transplant. For children with secondary HLH, chemotherapy and immunosuppression may be enough.
- HLH progresses very rapidly and can be fatal if untreated, so it is important to recognize the condition and start treatment quickly.
- HLH may at first seem to be a fever illness, but it lasts longer and children begin showing symptoms uncommon in typical infections, such as yellowing, pale or bruised skin.
Support Services & Resources
Support Services & Resources
Visit the source listed below to learn more about HLH.
Riley at IU Health offers a broad range of supportive services to make life better for families who choose us for their children's care.
The Histiocytosis Association helps patients and families learn to manage HLH and supports research for a cure. The organization's website shares information about the condition, current research initiatives and more.
In addition to our primary hospital location at the Academic Health Center in Indianapolis, IN, we have convenient locations to better serve our communities throughout the state.