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There are two types of HLH. “Primary,” or “familial,” HLH is caused by an inherited problem of the immune system. “Secondary” HLH can occur when the immune system is disturbed (e.g., infections), but not necessarily because of an inherited condition. Both types of HLH are life-threatening. HLH can lead to liver failure, breathing problems, inflammation in the brain, and the inability to fight infection.

HLH happens more often in infants and children. But it can occur at any age, including in the teenage years and adulthood.

HLH is considered a rare disease. Statistics say it occurs in about one in 50,000 children. Because of that, many healthcare providers are unfamiliar with its symptoms, and it often goes undiagnosed for too long.

HLH can be challenging to diagnose because the initial symptoms may mimic common infections. Symptoms of HLH that you may notice in your child include:

Other issues that your child’s doctor may find include:

Because HLH is so rare, many healthcare providers don’t recognize its symptoms. HLH can “look like” certain cancers in the early stages of the illness. For these reasons, the disease often is misdiagnosed or goes undiagnosed for too long.

HLH can only be diagnosed with proper blood tests in the appropriate clinical setting. Doctors might collect some fluid from the spinal canal to look for HLH in the brain. It is important to remember certain malignancies (including leukemia and lymphoma) can mimic HLH, therefore these conditions should be appropriately investigated during the work-up of a suspected patient with HLH.

Doctors must use the following tests to diagnose HLH and develop a personalized treatment plan.

“Primary” or “familial” HLH is caused by inherited problems in genes that control how the immune system kills virus-infected or other abnormal cells in a person’s body. These genes include PRF1, MUNC13-4, STXBP2 and STX11. Primary HLH also occurs in some closely related inherited diseases. These include:

“Secondary” HLH can occur when the immune system is disturbed (e.g., infections), but not necessarily because of an inherited condition.

The T and NK cells in patients with primary HLH can’t kill virus-infected or other abnormal cells like they normally would. T cells and NK cells usually do this by secreting death signals into targeted abnormal cells. When they can’t do this they get ‘overexcited’ and this leads to severe and unusual inflammation.

The proteins made by the MUNC13-4, STXBP2, STX11, Rab27a and LYST genes work like the machinery of a conveyor belt and are responsible for the secretion of the death signals produced by T and NK cells. The PRF1 gene makes a protein called perforin. It works like a key that allows the secreted death signals to enter inside a targeted abnormal cell, where the death signals can work.

SH2D1A is responsible for a more specialized killing mechanism and controls how the T cells themselves die. It is not yet entirely clear why XIAP mutations cause HLH.

Prompt treatment is very important for patients with HLH, as the condition is often fatal. The first treatments are typically used to stop the inflammation in the body. These treatments suppress the immune system which helps decrease the damage to a patient’s body.

Treatment may include:

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