HLH is a potentially life threatening condition where certain cells in your immune system become hyperactivated, leading to excess inflammation and organ damage. It can be treated with medications and potentially a stem cell transplant.

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition in which parts of the immune system become hyperactivated. This can lead to potentially life threatening inflammation and tissue damage.

There are two types of HLH: primary and secondary HLH.

Primary HLH most often impacts children and young adults, affecting 1.2 per million individuals each year in the United States. Meanwhile, secondary HLH is more common in adults, with some research identifying 16,136 adult cases over a 15-year period.

Keep reading to learn more about HLH, including symptoms, diagnosis, and treatment.

HLH occurs when white blood cells, specifically cytotoxic T cells (CTLs) and natural killer (NK) cells, become dysregulated. This can occur due to a genetic change or a triggering event.

Both CTLs and NK cells normally respond to infections and other diseases by releasing granules. These granules contain substances that kill an infected or diseased cell.

However, in HLH, CTLs and NK cells become unable to effectively release their granules. Because the infection or disease isn’t addressed, the immune response is prolonged.

This extended immune response means that more immune cells continue to be recruited. There’s also an increase in the release of inflammatory cytokines, which are chemical messengers that boost the immune response. Other immune cells, known as macrophages, also contribute to elevated cytokine levels.

Taken together, the result is excess inflammation throughout the body and hemophagocytosis, a condition in which immune cells engulf and destroy healthy blood cells. This can all lead to tissue damage, organ failure, and possibly death.

There are two types of HLH:

  • Primary HLH: This happens due to genetic changes. These are typically inherited from birth. Primary HLH is also referred to as familial HLH.
  • Secondary HLH: This is when HLH is triggered by an infection, cancer, or an autoimmune disease. HLH brought on by an autoimmune disease is called macrophage activation syndrome.

Primary HLH is caused by genetic changes that affect the release of granules by CTLs or NK cells. It’s most common in children and young adults, although adults with this type of HLH have been reported.

The genetic changes that lead to primary HLH can be inherited in different ways and may also be associated with other genetic syndromes, such as Chediak-Higashi syndrome and X-linked lymphoproliferative disorder.

Secondary HLH is brought on by a trigger like an infection, cancer, or autoimmune disease. The exact mechanism by which this happens isn’t fully understood, but it likely involves a combination of genetic and environmental factors.

Examples of potential secondary HLH triggers include:

Secondary HLH more often happens in adults, with an average onset age of 50 years old.

If you have HLH, you may experience:

HLH is a serious condition that can lead to organ damage and death if it’s left untreated. It’s important to get immediate medical attention if you experience HLH symptoms.

As with many conditions, prompt treatment of HLH can help improve your outlook.

Two classification systems have been used to aid in the diagnosis of HLH. The first of these is the HLH-94 system.

In the HLH-94 system, all five of the following criteria must be met for a diagnosis of HLH to be made:

  • fever
  • low blood cell counts in at least two types of blood cells
  • enlarged spleen
  • high triglycerides, with or without low levels of fibrinogen
  • bone marrow biopsy for proof of blood cell destruction by immune cells (hemophagocytosis)

The HLH-2004 system updated the HLH-94 system by adding an additional three criteria:

  • ferritin levels over 500 mg/mL
  • low or absent NK cell activity
  • levels of sIL2Ra, a protein made in response to immune activation, equal to or greater than 2,400 U/mL

The HLH-2004 system requires five out of eight criteria to diagnose HLH, and it’s currently the most commonly used system.

A variety of tests may be used to help make an HLH diagnosis, including:

HLH is typically treated by multiple healthcare professionals. In addition to a hematologist, other specialists on a care team may include:

Initial treatment of HLH involves reducing the excessive inflammation in the body. This is done using the following drugs:

If HLH is also causing neurological symptoms, another immunosuppressant called methotrexate, with or without the corticosteroid prednisone, may be injected directly into the cerebrospinal fluid (CSF).

If HLH is difficult to manage, emapalumab (Gamifant) can be used. Emapalumab is a monoclonal antibody against interferon-gamma, an inflammatory cytokine. It’s the first targeted therapy approved specifically for HLH.

If initial treatment effectively manages inflammation, an allogenic stem cell transplant may be recommended. This potentially curative procedure aims to replace faulty immune cells.

Find a medical specialist in your area today

Your healthcare team may comprise several people who can provide support.

Sometimes, a medical specialist will be required to help diagnose, manage, or treat a healthcare condition.

You can find the following medical specialists in your area today:

HLH in children is often fatal without treatment. However, researchers have found that the 5-year survival rate with treatment is 54%.

It’s possible for adults with HLH to go into spontaneous remission. Estimating survival in adults is also difficult, as it’s hard to tell if deaths are due to HLH itself or due to the condition that brought it on, such as an infection or cancer.

HLH is a rare and potentially life threatening condition that causes excess inflammation in the body. It occurs when CTLs and NK cells are dysregulated, leading to an increase in inflammation throughout the body. This can lead to organ damage.

Primary HLH is caused by genetic changes and mainly affects children and young adults. Secondary HLH is brought on by a trigger and typically impacts adults.

HLH is treated with several medications and, ideally, a stem cell transplant. Be sure to seek medical attention promptly if you experience any symptoms of HLH. Early diagnosis and treatment can help improve the outlook.