Hemophago­c­ytic Lymphohistio­­cytosis

When your child has hemophagocytic lymphohistiocytosis, it means their immune system is overreacting. Instead of defending your child from things like bacteria, viruses and fungi, their body starts attacking itself.

Types of HLH in children

There are two types of pediatric hemophagocytic lymphohistocytosis:

• Primary (familial): This happens when a genetic mutation (change) causes a predisposition to HLH (higher chance of getting it). Symptoms usually show up in the first few years of life.
• Secondary: This happens when another medical condition, like cancer, an infection or other autoimmune condition, affects your child’s immune system.

We often find primary HLH in early childhood, usually among toddlers. Secondary HLH is more often diagnosed in older children, adolescents and young adults.

The most common symptoms of HLH are a fever that lasts for many days, a rash and an enlarged liver, spleen or lymph nodes. Your child might also be irritable, have headaches, feel weak or dizzy and have pale skin or jaundice (yellow skin).

Other health conditions they might have with HLH include:

• Anemia
• Thrombocytopenia
• Hypertriglyceridemia
• Hypofibrinogenemia (low levels of fibrinogen, a blood clotting protein)
• Ferritinemia (high levels of the protein ferritin that stores iron in their blood)
• High levels of soluble interleukin 2 / CD25 (a marker that shows increased immune system activity)
• Neutropenia
• Decreased natural killer function (low levels of white blood cells that destroy infected cells)

Life-threatening symptoms that need emergency treatment include trouble breathing, seizures, loss of consciousness or coma.

What to expect at your first visit

At your child’s first appointment, their provider will take some time getting to know them and you. They’ll ask questions like:

• What kind of symptoms is your child having?
• When did you first notice them?
• Are they getting worse?
• How are they affecting your child’s life?
• Does your child have any other health conditions?
• What health conditions do family members have?

Next, your child will have a physical exam to look for noticeable signs of hemophagocytic lymphohistiocytosis. Their provider may also order some tests to help confirm the diagnosis and look for some of the less visible signs of HLH.

Testing for HLH

Many signs of HLH will show up in your child’s blood cells. So, we’ll do tests to see what’s going on in your child’s blood. Your child may have:

• Blood tests: Include a complete blood count (CBC) and tests to look at levels of blood cells, triglycerides, ferritin, how well their blood clots and signs of infections.
• Liver function tests: Check to see how well their liver is working.
• Bone marrow biopsy: Checks for blood cell levels in their bone marrow.

We may also do genetic testing to confirm whether your child has HLH.

Second opinions for HLH

Hearing your child has a rare immune condition like hemophagocytic lymphohistiocytosis can be overwhelming. There are so many things to think about. So much to digest. Feeling confident that you’re working with a team you trust completely to give your child the best care is an important first step. That’s why we encourage second opinions.

Our skilled, experienced pediatric providers will spend time with you and your child to help you better understand HLH. They’ll also talk with you about what they feel are the best treatment options for your child. And because HLH responds best to treatment if caught early, we always try to meet with you and your child as soon as possible. Getting a second opinion can help you feel in control of your child’s care and give you peace of mind knowing they’re in the most capable hands.

Meet Our HLH Team

When your child comes to Cleveland Clinic Children’s, they’ll have an expert care team of pediatric providers from different specialties — all working together to make sure they get the most personalized care. Their team may include:

• Pediatric hematologists
• Pediatric rheumatologists
• Pediatric immunologists (immune disorder specialists)
• Pediatric pathologists
• Pediatric gastroenterologists
• Pediatric oncologists
• Pediatric genetic counselors
• Child life specialists
• Child psychologists
• Social workers

Once we’re sure your child has HLH, we’ll start building a personalized treatment plan for them. We base this plan on your child’s age, overall health, test results, symptoms and if they have primary or secondary HLH. We also consider the cause of their HLH — a genetic mutation or another underlying condition, like an autoimmune condition, cancer or Epstein-Barr virus.

If your child has secondary HLH, we’ll treat the condition causing it. For example, we may use chemotherapy to treat cancer. By treating the condition causing secondary HLH, we may be able to stop it, but it’s important to know that HLH can sometimes come back (recur).

If your child has primary HLH, they’ll need an allogenic bone marrow transplant (BMT) from a related or unrelated donor. But first, we’ll need to calm the inflammation caused by their hyper-inflamed immune system. Your child’s provider may use a combination of steroids and chemotherapy to do this. Or we may use  monoclonal antibody therapy using a drug called emapalumab (Gamifant^®).

Depending on the results of your child’s blood tests, we may treat primary or secondary HLH with a blood transfusion to increase their blood cell levels. Other treatments we offer for both primary and secondary HLH include:

Medications

Some medications can help manage or stop HLH symptoms or cell growth. Immunosuppressants can make your child’s immune system less active. Antibiotics and antivirals can treat or prevent infections.

If we use immunosuppressants or antibody therapy to treat your child’s HLH, we’ll check on them regularly to make sure their symptoms don’t come back. If they do, we may recommend an allogeneic stem cell transplant.

Allogeneic stem cell transplant

If your child hasn’t responded well to other treatments, we may recommend an allogeneic stem cell transplant. Stem cells are in your child’s bone marrow and make new blood cells. In this type of transplant, your child will get new stem cells from a donor to replace their unhealthy ones.

After a transplant, your child will take immunosuppressant medications, so their body doesn’t reject the new stem cells. While they’ll likely get better physically in a few months, it can take up to two years for their immune system to fully recover. We’ll keep a close eye on your child during this time. And we’ll show you how best to care for them after they go home.

We understand that deciding for your child to have a transplant is a big decision. We’ll walk you through the process to help you feel confident about next steps.

Life after hemophagocytic lymphohistiocytosis treatment

After treatment, your child will have regular follow-up visits and tests with their pediatric care team. Their providers will keep an eye on their test results, symptoms and general health to make sure HLH hasn’t returned. And if it does, they’ll start treatment quickly.

Coping with a serious health condition, like HLH, can be stressful and overwhelming for your child and for you. If needed, we may recommend speaking with mental health professionals like child psychologists, psychologists or social workers.

Taking the Next Step

Having a rare immune system condition like hemophagocytic lymphohistiocytosis isn’t the life you planned for your child. But with early diagnosis and treatment by specialists experienced with this condition, your child may be able to get back to living a full, active life. Cleveland Clinic Children’s pediatric team of specialists can provide the treatment and support your child and family need to understand and manage their HLH. We’re here to help your child get the best treatment results so they can get back to being a kid.