What Is Hemophagocytic Lymphohistiocytosis (HLH)?

Hemophagocytic lymphohistiocytosis (HLH) is a disease of the immune system, often inherited through genes. It's known as a "primary immunodeficiency." Primary immunodeficiency is a condition that makes the immune system not work as it should.

The body's immune system fights off infections and anything else it sees as foreign invaders to the body. In HLH, the body makes too many immune cells. These immune cells see the body's internal organs as invaders.

The cells attack organs, including the:

  • Liver.
  • Brain.
  • Bone marrow.

How Common is HLH?

HLH is a rare disease that affects about one in 50,000 births.

What Causes HLH?

There are two main types of HLH:

  • Primary: This means kids have inherited the disease from their parents. Changes to different genes can also cause subtypes of HLH. There are at least four genes that can cause HLH.
  • Secondary: This is when HLH happens because of another underlying condition. This type isn't inherited, but the effect on the body is the same.

With primary HLH, people can carry a gene for HLH without the disease. If both parents have a defective gene, there is a:

  • 25% chance their child will develop HLH.
  • 50% chance their child will carry the gene and not have the disease.
  • 25% chance their child will be neither a carrier nor develop HLH.

There is no difference in risk between males and females.

Secondary or acquired, HLH happens as a result of other conditions, including:

  • Epstein-Barr virus.
  • Bacterial, fungal, or viral infections.
  • Weakened immune system.
  • Juvenile arthritis.
  • Non-Hodgkin lymphoma or other cancer.

Hemophagocytic Lymphohistiocytosis Symptoms

HLH symptoms often appear within the first few months or years of birth. Symptoms of HLH are much the same as those of other childhood illnesses, making it hard to diagnose.

Some symptoms are:

  • Enlarged lymph nodes.
  • Skin rashes.
  • Fever.
  • Jaundice (yellowing of the skin and eyes).
  • Enlarged spleen.
  • Breathing problems.
  • Easy bruising.

Complications of HLH disease

HLH causes the overactive immune system to attack the body, causing organ damage. Kids with this disease can have nervous system problems, spleen enlargement, and liver and lung damage.

If HLH is causing nervous system problems in your child, you may notice symptoms such as:

  • Irritability.
  • Tiredness or fatigue.
  • Abnormal muscle tone.
  • Seizures.

Diagnosing HLH Disease

After talking to you about your child's medical history and symptoms, your doctor will use a blood test to help diagnose HLH.

If results are positive for HLH, your child might need further blood tests, including genetic testing. Genetic blood tests help doctors learn which genetic mutation is causing the disease or if there's no genetic cause.

HLH Treatment

The goal of treating HLH is to stop the immune system from attacking the body's organs. The doctor needs to identify and treat this disease quickly because of how fast it progresses.

Treatment may include medicines that suppress the immune system to control the damage it's doing to the body.

Treatments for HLH may include:

  • Chemotherapy.
  • Steroids.
  • Antibody therapy.

Some cases of HLH — mostly the type that's not genetic — go away after treatment and won't need further care.

If medicine doesn't resolve your child's genetic HLH, your doctor will offer other treatment options. A bone marrow or cord blood transplant may cure your child's disease.

Bone marrow transplant to treat HLH

Before a bone marrow transplant, your child receives chemo to destroy the immune system. Surgeons then transplant healthy bone marrow into your child.

If your child also has severe lung damage, surgeons might perform a lung transplant simultaneously. The lung tissue may potentially even be from the same donor. The Hillman Center for Pediatric Transplant has the only program in the world that offers tandem lung and bone marrow transplantation.

We also pioneered a reduced-intensity bone marrow transplant program. The program helps reduce the negative effects a bone marrow or stem cell transplant has on the body's organs.

Because transplants are high-risk treatments, your child may need to take medicine for their entire life.

Paul Szabolcs, MD

Chief, Blood and Marrow Transplantation and Cellular Therapies

Dr. Szabolcs cares for kids with rare immune disorders using "reduced-intensity" chemotherapy and pediatric transplants. He pioneered transplanting the lung and bone marrow from the same donor to treat these rare immune diseases. Dr. Szabolcs's approach can help kids with severe HLH.

Your Child's HLH Consult and Care: What to Expect

If a doctor diagnosed your child with hemophagocytic lymphohistiocytosis, we want you to know you're not alone. The Center for Rare Disease Therapy is here to help.

To make an appointment for your child or refer a kid for HLH care, contact us:

Phone: 412-692-7273

Email: rarecare@chp.edu

Here's what you can expect when you come to us for your child's HLH consult and care.

How soon can I get an appointment for my child's hemophagocytic lymphohistiocytosis?

In most cases, we can schedule a first visit within one to two weeks. We'll ask the referring doctor to send your child's medical records so we can review them before your visit.

What should I expect at my child's first visit?

You can expect your first visit to take from four to six hours. Your child will have a complete assessment. The doctor will make or confirm a hemophagocytic lymphohistiocytosis diagnosis and find out how much the disease has progressed.

Because we work as a team here at the center, other experts might see your child during your visit. These may include specialists in:

  • Immune system diseases.
  • Blood diseases.
  • Bone marrow or liver transplantation.
  • Genetic counseling.
  • Child development.

What happens after my child visits the Center for Rare Disease Therapy?

Members of your child's HLH care team will talk with you about your next steps, such as:

  • Options for treating hemophagocytic lymphohistiocytosis.
  • Ways to improve your child's quality of life at home.

If surgery might be a treatment option for your child's HLH, we'll discuss all the details. We'll let you know how you and your child can prepare.

By the end of your visit, you'll have a care plan tailored to your child's HLH disease and health needs. We'll also schedule a follow-up visit in three months.

You'll meet our nurse practitioner. You can contact them by phone or video conference if you have any questions or concerns before your next appointment.

Before you leave, please ask us about your child's HLH diagnosis, treatment, or anything else on your mind.

How long will I wait for my child's HLH test results?

We will call within two weeks to discuss the test results and the next steps for your child's HLH care.

You can also find your child's test results if you signed up for MyCHP — Children's patient portal.

MyCHP lets you manage your child's health online. It's free to everyone treated at UPMC Children's Hospital of Pittsburgh and their loved ones.

Partners in Your Child's HLH Care

When a child has a rare disease like hemophagocytic lymphohistiocytosis, it affects the whole family. At the Center for Rare Disease Therapy, we see each family member as our partner. The best care approach happens when we merge our HLH expertise with your knowledge of what's best for your child.

Contact us to learn more about HLH or make an appointment for your child:

Phone: 412-692-7273

Email: rarecare@chp.edu

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Contact Us

At the Center for Rare Disease Therapy, every child diagnosed with a rare disease receives an individualized treatment plan and family-centered care.

For an appointment, consultation, or patient referral with an expert at UPMC Children’s Hospital of Pittsburgh for a child diagnosed with HLH, please contact:

Phone: 412-692-7273

Email: rarecare@chp.edu

Clinical Studies

*Immunodeficiency and End-Stage Lung Disease Treatment with BOLT+BMT Procedure

Bilateral Orthotopic Lung Transplant (BOLT) in Tandem With CD3+ and CD19+ Cell Depleted Bone Marrow Transplant (BMT) From Partially HLA-Matched Cadaveric Donors

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*Non-Malignant Marrow Disorder Treatment using Reduced Intensity Conditioning – Phase II

Study of Reduced-Intensity Conditioning In Patients With Non-Malignant Disorders Undergoing Umbilical Cord, Bone Marrow, or Peripheral Blood Stem Cell Transplantation

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*Original research initiated by investigators at UPMC Children’s Hospital of Pittsburgh.