Langerhans Cell Histiocytosis

What is Langerhans cell histiocytosis?

Langerhans cell histiocytosis (LCH) is a rare disorder that primarily affects babies and children. The disorder occurs when immune system cells called Langerhans cells build up in your child’s body. Langerhans cells are a type of white blood cell that helps your child’s immune system fight infection.

Your child has Langerhans cells throughout their body, especially in their skin, lungs, lymph nodes, bone marrow, spleen and liver. When there’s a buildup of these cells, it can damage your child’s tissues and cause lesions to form in one or more places in their body.

The outlook (prognosis) of Langerhans cell histiocytosis is wide-ranging, but in general, is good. For many children with LCH, the disease goes away with appropriate treatment. In fact, it may go away on its own, especially if it only occurs in your child’s skin. But when LCH affects your child’s bone marrow, spleen or liver, the disease may require intensive therapy.

Is Langerhans cell histiocytosis cancer?

Many researchers consider Langerhans cell histiocytosis a type of neoplasm. But some have begun to consider it an inflammatory disease. Healthcare providers who treat cancer and blood disorders (oncologists) also treat Langerhans cell histiocytosis. Sometimes, oncologists use cancer therapies like chemotherapy to treat the condition.

Who does Langerhans cell histiocytosis affect?

Most cases of LCH affect newborns and children between the ages of 1 and 15 years old. Langerhans cell histiocytosis in adults is rare, but it can occur.

How common is this condition?

Langerhans cell histiocytosis occurs in 1 to 2 out of every 1 million newborns every year. It affects about 5 out of every 1 million children ages 15 and younger each year.

What are the symptoms of Langerhans cell histiocytosis?

Langerhans cell histiocytosis varies greatly from person to person. It may involve only one part of your child’s body or many different sites. So, Langerhans cell histiocytosis symptoms will vary depending on which part of your child’s body is affected.

Bones

In about 80% of children with LCH, one or more lesions develop in their bones. This can cause swelling or a lump over a bone like your child’s skull, eye socket, ear bone, jaw bone, arms, legs, spine, hips or ribs. The swelling may or may not be painful. Additional symptoms affecting bones may include:

• Headaches.
• Neck pain or back pain.
• Fractures.
• Difficulty walking.
• Limping.

Skin

Langerhans cell histiocytosis skin symptoms typically include a rash. In infants, it may be a scalp rash that looks like cradle cap. In children and adults, a flaky rash may look like dandruff. Rashes may appear on other parts of your child’s body and be tender, painful or itching. Your child may have oozing blisters. Other areas of their body that may be affected include:

• Groin.
• Arms.
• Armpits.
• Abdomen.
• Back.
• Chest.

In addition, you may notice discoloration or hardening of your child’s nails or their nails may fall out.

Mouth

Symptoms of Langerhans cell histiocytosis that may affect your child’s mouth include:

• Loose teeth or teeth that fall out.
• Uneven teeth.
• Swollen gums.
• Sores on their lips, tongue, inside their cheeks or on the roof of their mouth.

Liver or spleen

Symptoms of LCH that may affect your child’s liver and/or spleen include:

• Swelling of their belly (abdomen) due to an enlarged liver and/or spleen.
• Yellowing of their skin and whites of their eyes (jaundice).
• Itchiness.
• Fatigue.
• Easy bruising and/or bleeding.

Bone marrow

Signs of LCH that may affect your child’s bone marrow include:

• Anemia, pale skin, fatigue and decreased appetite due to low red blood cells.
• Frequent infections and fevers due to low white blood cells.
• Easy bruising and/or bleeding due to low platelets (clotting cells).

Endocrine system (hormones)

Langerhans cell histiocytosis may affect your child’s endocrine system, including their pituitary gland and their thyroid gland. Symptoms that may affect these glands include:

• Pituitary gland: Excessive thirst (polydipsia) and frequent urination due to diabetes insipidus, slow growth, early or late puberty and weight gain.
• Thyroid gland: Swollen thyroid, signs of hypothyroidism and difficulty breathing.

Ears

Symptoms of LCH that may affect your child’s ears include:

• Chronic infections.
• Discharge from their ear canal.
• Redness.
• Itchy rash.
• Ear pain.
• Hearing loss.

Eyes

Signs of Langerhans cell histiocytosis that may affect your child’s eyes include:

• Bulging eyes.
• Swelling above their eyes.
• Vision problems.

Lymph nodes

Signs of LCH that may affect your child’s lymph nodes include:

• Swollen, tender lymph nodes in their neck, armpits and/or groin.

Central nervous system

Symptoms of LCH that may affect your child’s brain and/or spinal cord (central nervous system) include:

• Headaches.
• Dizziness.
• Vomiting.
• Excessive thirst.
• Frequent urination.
• Difficulty walking.
• Loss of balance.
• Uncoordinated body movements (ataxia).
• Difficulty speaking or seeing.
• Seizures.
• Changes in behavior and/or memory.

Lungs

Lung (pulmonary) Langerhans cell histiocytosis is more prevalent in adults. People who smoke are at a higher risk of developing pulmonary LCH. Signs of LCH in your lungs include:

• Chest pain.
• Dry cough.
• Difficulty breathing.
• Coughing up blood.
• Collapsed lung (pneumothorax).

Gastrointestinal tract

Symptoms of Langerhans cell histiocytosis that may affect your child’s stomach, intestines and/or colon may include:

• Abdominal pain.
• Vomiting.
• Diarrhea.
• Bloody poop (stools).
• Growth delay due to low nutrition.

Because the cause of these symptoms could be another condition not related to Langerhans cell histiocytosis, it’s important to seek proper medical attention to receive an accurate diagnosis.

What causes Langerhans cell histiocytosis?

In about half of the people with LCH, a somatic mutation in the BRAF gene causes the condition. A somatic mutation is a change that occurs in certain cells after conception. (You don’t inherit these mutations — they happen randomly to a developing fetus.)

The BRAF gene is responsible for making a protein that controls cell growth and development. Normally, this protein can be switched on and off in response to chemical signals. A mutation in this gene causes the protein to be stuck in the “on” position, which causes too many LCH cells to grow and divide. This can cause tissue damage and the formation of tumors.

Scientists have discovered mutations in other genes that can lead to the disease as well. These include the MAP2K1, RAS and ARAF genes. Some researchers believe other factors, like environmental toxins and viral infections, may also lead to the development of the disorder.

What are the risk factors for Langerhans cell histiocytosis?

Certain factors put your child at a higher risk of developing Langerhans cell histiocytosis. These include:

• Family history of LCH.
• Being Hispanic.
• Smoking.
• Exposure to certain chemicals during pregnancy.
• Exposure to metal, granite or wood dust in the workplace.
• Having infections as a newborn.
• Not receiving vaccinations as a child.

What are the complications of Langerhans cell histiocytosis?

Almost 50% of children with Langerhans cell histiocytosis will experience complications due to the condition, including:

• Scarring.
• Growth delay.
• Musculoskeletal disability.
• Diabetes insipidus.
• Hormonal imbalances.
• Hearing loss.
• Mental health conditions like depression and anxiety.
• Bone and lung issues.
• Liver cirrhosis.
• Secondary cancers, like leukemia, lymphoma and Ewing sarcoma.

How is Langerhans cell histiocytosis diagnosed?

Your child's healthcare provider will ask about your child’s medical history and perform a physical exam. They’ll request several tests, depending on where your child has symptoms. Based on their findings, your child’s provider may refer you to a pediatric hematologist/oncologist, who’ll coordinate the care and treatment of your child.

What tests will be done to diagnose this condition?

Langerhans cell histiocytosis can affect many different parts of your child’s body. Therefore, your child may need several tests to diagnose the condition.

Blood tests

• Complete blood count (CBC): A CBC is a blood test that checks your child’s levels of red blood cells, white blood cells and platelets.
• Blood chemistry tests: A blood chemistry study is a blood sample that looks at the amount of certain substances released into your child’s body by their organs and tissues.
• Liver function tests: A liver function test is a blood test that checks your child’s levels of substances released by their liver.

Urine tests

• Urinalysis: A urinalysis is a test that checks the amount of red blood cells, white blood cells, proteins and sugar in your child’s pee (urine).
• Water deprivation test: A water deprivation test checks how much urine your child makes and whether it becomes concentrated when water is withheld.

Biopsies

• Biopsy: During a biopsy, a healthcare provider will remove a sample of tissue. A pathologist will look at the sample under a microscope to check for LCH cells.
• Bone marrow aspiration and biopsy: A healthcare provider will insert a hollow needle into your child’s hipbone to remove a sample of bone marrow, blood and a small piece of bone. A pathologist will look at the sample under a microscope.

Genetic testing

• Genetic testing: Genetic testing uses a blood or tissue sample to look for changes in the BRAF gene.

Imaging tests

• X-rays: X-rays are images of the bones and organs inside your child’s body. A healthcare provider may sometimes take X-rays of all the bones in your child’s body (skeletal survey) to look for abnormalities.
• Bone scan: During a bone scan, a provider will inject a small amount of radioactive material into your child’s vein. This material collects in any abnormal parts of bone and shows up on the scanner. This imaging test is rare.
• Computed tomography (CT) scan: For this procedure, your child may swallow a dye or a provider may inject the dye into a vein. The scan takes detailed pictures of areas inside your child’s body at different angles.
• Positron emission tomography (PET) scan: A provider will inject a small amount of radioactive sugar (glucose) into your child’s vein. The scanner will rotate around your child’s body and take pictures of where glucose is being used. The glucose makes any diseased cells show up brighter on the scanner.
• Magnetic resonance imaging (MRI) scan: A healthcare provider will inject a substance called gadolinium into a vein, and diseased areas will show up brighter on the scan. An MRI uses magnets, radio waves and a computer to make a series of detailed pictures.
• Ultrasound: An ultrasound scan uses high-energy sound waves that bounce off your child’s organs and tissues and make echoes. This forms internal pictures of your child’s body.

How is Langerhans cell histiocytosis treated?

Treatment for Langerhans cell histiocytosis depends on where LCH cells are located in your child’s body and whether the condition is considered low-risk or high-risk.

Low-risk organs include:

• Skin.
• Bone.
• Lungs.
• Lymph nodes.
• Gastrointestinal tract.
• Pituitary gland.
• Thyroid gland.
• Thymus.

High-risk organs include:

• Liver.
• Spleen.
• Bone marrow.
• Central nervous system (CNS).

Healthcare providers classify LCH as single-system disease or multi-system disease. They classify the disease based on how many of your child’s body systems are affected:

• Single-system LCH: One part of an organ or body system contains LCH cells. The most common type of single-system LCH is bone LCH.
• Multi-system LCH: Two or more organs or body systems contain LCH cells or LCH cells are throughout your child’s body. Multi-system LCH is less common than single-system LCH.

In certain cases, LCH may improve on its own without treatment. This typically occurs in single-system LCH cases involving the skin or bone. In these cases, treatment involves observation to ensure the disease doesn’t return or spread.

Langerhans cell histiocytosis treatment

Treatment options for LCH may include:

• Steroid therapy: Your child’s healthcare provider may use a steroid like prednisone, particularly for skin LCH. Prednisone hinders the functioning of white blood cells, which could affect the LCH cells.
• Surgery: Your child’s provider may use surgery to remove LCH tumors and surrounding tissue. They use a procedure called curettage. Curettage is a type of surgery that uses a sharp, spoon-shaped tool called a curette to scrape LCH cells from bone.
• Chemotherapy: Chemotherapy uses drugs to stop the growth of neoplastic cells, either by killing them or by preventing them from dividing. Your child may take chemotherapy by mouth or a provider may inject it into a vein or muscle. You may apply a chemotherapy cream or lotion directly onto the skin as well.
• Radiation therapy: Radiation therapy uses high-energy X-rays and other types of radiation to kill cancer cells or prevent them from growing and dividing.
• Immunotherapy: Immunotherapy uses your child’s immune system to fight cancer. A provider will use substances made by your child’s body or made in a laboratory to boost, direct or restore their body’s natural defenses.
• Targeted therapy: Targeted therapy uses drugs or other substances to identify and attack specific cancer cells. Types of targeted therapy include BRAF inhibitors, which block proteins needed for cell growth and may kill cancer cells, and monoclonal antibodies, which are immune system proteins made in a laboratory to treat diseases such as cancer.
• Stem cell transplant: A stem cell transplant replaces your child’s blood-forming cells that are killed during chemotherapy treatment.

Can Langerhans cell histiocytosis be prevented?

You can’t prevent Langerhans cell histiocytosis because a genetic mutation causes it. Some risk factors for LCH are things you can’t control like your biological family history and ethnicity. But there are some factors you can manage, like:

• Not smoking.
• Avoiding certain chemicals while pregnant.
• Getting all of your recommended vaccinations.

What is the outlook (prognosis) for Langerhans cell histiocytosis?

The prognosis for LCH depends on various factors, including:

• How many body systems or organs are affected.
• Which body systems or organs are affected.
• How well the disease responds to treatment.

Typically, providers consider children with single-system LCH and multi-system LCH that doesn’t involve the liver, spleen or bone marrow low risk. With treatment, the overall survival rate for children in this category is 100%. However, disease recurrence and/or other long-term complications are common.

Providers consider children with multi-system LCH that involves the liver, spleen or bone marrow high risk.

When should my child see their healthcare provider?

Even after your child completes treatment, their healthcare provider will want to see them regularly. They’ll want to monitor your child for many years because the disease has a high risk of coming back (recurring). At their follow-up appointments, your child will repeat many of the same tests they had when they received their diagnosis. These may include ultrasounds, MRIs, CT scans and PET scans. Your child’s provider will let you know how often you need to come back for follow-up.

What questions should I ask my child’s provider?

You may have many questions about your child’s diagnosis. It may help to write them down to take with you to your child’s next appointment. A few questions you may want to ask include:

• How does Langerhans cell histiocytosis affect my child?
• Does my child need treatment?
• What are my child’s treatment options?
• What are the side effects of treatment?
• Will these treatments cure my child?
• What is my child’s prognosis?
• Can you recommend any support groups?