What is Langerhans Cell Histiocytosis (LCH)? Is your little one at risk?

Have you ever heard of Langerhans Cell Histiocytosis, or what we call LCH for short? Maybe the name sounds a bit complicated and scary. But in reality, this is a very rare disease that mainly affects our young children, especially newborns and children under 15 years of age. So don't worry, let's talk about it simply, in Sinhala that you can understand very well, in detail, as if you were talking to a close friend.

What exactly is (LCH)?

Simply put, (LCH) is a condition that occurs when a child's body has too many Langerhans cells, a type of special cell in our immune system. These Langerhans cells are actually a type of white blood cell. Their main function is to fight germs that enter our body and protect us from disease.

These cells are normally found throughout our bodies, especially in the skin, lungs, lymph nodes, bone marrow, spleen, and liver. However, in the case of (LCH), these Langerhans cells accumulate in excess in one or more places. When this happens, these organs can be damaged and lesions can form.

The course of the disease can vary from person to person. Some children recover completely from the disease with appropriate treatment. Surprisingly, sometimes, especially if it only affects the skin, it can get better without any treatment. However, if the condition (LCH) affects vital organs such as the child's bone marrow, spleen or liver, more intensive treatment may be needed.

Is (LCH) cancer?

This is a question that many people have. In fact, most researchers consider LCH to be a cancerous condition, that is, a neoplasm. However, some scientists now consider it to be an inflammatory disease. However, oncologists are doctors who specialize in cancer and blood diseases. Sometimes, cancer treatments, such as chemotherapy, are also used to treat the condition.

Who is most affected by this (LCH) condition?

LCH is most common in newborns and children between the ages of 1 and 15. LCH in adults is very rare, but it is not impossible.

How common is this?

According to statistics, one or two out of every million newborns are affected by LCH each year. Also, about five out of every million children under the age of 15 are affected. So you can see that this is a very rare condition.

What are the symptoms of (LCH)?

The symptoms of LCH vary greatly from person to person. It can affect just one area of ​​the body, or it can affect many areas. So, the symptoms depend on which part of the child's body is affected.

If bones are affected:

About 80% of children with LCH develop lesions in one or more of their bones. What can cause this?

• A swelling or lump may develop in areas such as the skull, the bones around the eyes, the ear bones, the jaw bones, the limbs, the spine, the hips, or the ribs. This swelling may be painful or may go away.
• Headache.
• Neck or back pain.
• Fractures.
• Difficulty walking.
• Limping.

On the skin:

Rashes are commonly seen as symptoms of skin (LCH).

• In young babies, a rash that looks like cradle cap may appear on the scalp.
• In older children and adults, it may cause a flaky rash that looks like dandruff.
• These rashes can also appear on other parts of the body (groin, arms, armpits, stomach, back, chest). They may be painful, itchy, or hard.
• Some children may develop oozing blisters.
• Things like discoloration, hardening, or peeling of the nails may also occur.

Regarding the mouth:

Symptoms that can be seen inside the mouth include:

• Tooth loosening or loss of teeth.
• Pulled tooth.
• Swelling of the gums.
• Sores on the lips, tongue, inside of the cheeks, or on the roof of the mouth.

Liver or Spleen related:

If these organs are affected, symptoms such as:

• Abdominal swelling due to enlargement of the liver and/or spleen.
• Yellowing of the skin and whites of the eyes (jaundice).
• Itching.
• Fatigue.
• Easy bruising and/or bleeding.

If the bone marrow is affected:

The bone marrow is where blood cells are made. If it is affected:

• Anemia, pale skin, fatigue, and loss of appetite due to a decrease in red blood cells.
• Frequent infections and fever due to low white blood cells.
• Easy bruising and/or bleeding due to low platelets.

Endocrine System (Endocrine System - Hormones):

LCH can affect a child's endocrine system, which is where hormones are produced, such as the pituitary gland and thyroid gland.

• If the pituitary gland is affected: excessive thirst (polydipsia) and frequent urination (also called diabetes insipidus), growth failure, early or delayed puberty, and weight gain.
• If the thyroid gland is affected: swelling of the thyroid gland, symptoms of low thyroid hormone levels (hypothyroidism), and difficulty breathing.

Regarding the ears:

• Frequent ear infections.
• Fluid draining from the ears.
• Redness.
• Itchy rash.
• Ear pain.
• Hearing loss.

Regarding the eyes:

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

Lymph Nodes:

• Swollen and painful lymph nodes in the neck, armpits, and/or groin.

Central Nervous System:

This means that the brain and/or spinal cord are affected.

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

Lungs:

Pulmonary LCH, a condition that affects the lungs, is most common in adults. People who smoke are especially at risk.

• Chest pain.
• Dry cough.
• Difficulty breathing.
• Coughing up blood.
• Lung failure (pneumothorax).

Gastrointestinal Tract:

If the child's stomach, small intestine, and/or large intestine is affected:

• Stomach pain.
• Vomiting.
• Diarrhea.
• Blood in the stool.
• Growth failure due to malnutrition.

Important: These symptoms can be caused by any number of other conditions, not just LCH. Therefore, if your child has these symptoms, it is important to seek medical advice immediately for a proper diagnosis.

What are the causes of (LCH)?

Only about half of people with LCH have a somatic mutation in a gene called BRAF. Somatic mutations are changes that occur in certain cells after conception. They are not inherited from the parents, but occur randomly during the development of the embryo.

The (BRAF) gene produces a protein that controls cell growth and development. Normally, this protein can be turned on and off according to chemical signals. However, when there is a mutation in this gene, the protein is always stuck in the "on" state. This causes (LCH) cells to grow and divide excessively. This is what causes tissue damage and tumors to form.

Scientists have also found that mutations in several other genes may also cause the disease. For example, the genes (MAP2K1), (RAS), and (ARAF). Some researchers believe that environmental toxins and viral infections may also contribute to the disease.

What are the risk factors for (LCH)?

Some factors may increase your child's risk of developing LCH. These include:

• Having a family history of LCH.
• Having Hispanic ethnicity (although this is not as relevant to our country, it is mentioned in sources).
• Smoking (especially for adults with lung cancer (LCH)).
• Exposure to certain chemicals during pregnancy.
• Exposure to metal, granite, or wood dust at the workplace.
• Infections during the newborn period.
• Not receiving recommended vaccinations during childhood.

What are the possible complications of (LCH)?

About 50% of children with LCH develop various complications due to this condition. For example:

• Scarring.
• Growth retardation.
• Musculoskeletal disability.
• A condition like diabetes (Diabetes insipidus).
• Hormonal imbalances.
• Hearing impairment.
• Mental health problems (such as depression, anxiety).
• Bone and lung problems.
• Liver cirrhosis.
• Secondary cancers (e.g. leukemia, lymphoma, Ewing sarcoma).

How is LCH diagnosed?

Your child's doctor will first ask about your child's medical history and perform a physical exam. Then, they will order several tests depending on the symptoms your child is experiencing. Depending on the results of these tests, your child may be referred to a pediatric hematologist/oncologist, who will coordinate your child's treatment and care.

What tests are done for diagnosis?

Because LCH can affect different parts of the body, several tests are needed to accurately diagnose the disease.

• Blood tests:
• Complete blood count (CBC): This checks the child's red blood cell, white blood cell, and platelet levels.
• Blood chemistry tests: These check the levels of certain substances released by the body's organs and tissues.
• Liver function tests: These check the levels of substances released by the liver.

• Urine tests:
• Urinalysis: The child's urine is checked for the amount of red blood cells, white blood cells, protein, and sugar.
• Water deprivation test: This tests how much urine the child urinates and whether the urine becomes concentrated when not given water.

• Biopsies:
• Biopsy: A doctor takes a tissue sample, and a pathologist looks at it under a microscope to check for LCH cells.
• Bone marrow aspiration and biopsy: A hollow needle is used to remove bone marrow, blood, and a small piece of bone from the child's hip bone. This is also examined by a pathologist.

• Genetic testing:
• A blood or tissue sample is used to check for changes in the (BRAF) gene.

• Imaging tests:
• X-rays: Pictures of the bones and organs of the body are taken. Sometimes a skeletal survey of the entire body is done to look for abnormalities.
• Bone scan: A radioactive substance is injected into a vein and a scanner is used to look for abnormal deposits in the bones. This is not used much anymore.
• CT scan (Computed tomography - CT scan): The child is given a special liquid to drink or injected into a vein, and detailed pictures are taken from different angles inside the body.
• Positron emission tomography (PET scan): A small amount of radioactive sugar (glucose) is injected into a vein, and the scanner is moved around the body to take pictures of where the sugar is being used. Diseased cells appear bright on this scan.
• MRI scan (Magnetic resonance imaging - MRI scan): A substance called gadolinium is injected into a vein and a series of detailed pictures are taken using magnets, radio waves, and a computer. Diseased areas appear brighter.
• Ultrasound: Uses high-energy sound waves to create images of the inside of the body by reflecting back echoes from organs and tissues.

How is LCH treated?

Treatment for LCH depends on where the LCH cells are in the child's body and whether the disease is "low-risk" or "high-risk."

Low-risk organs are:

• Skin
• Bone
• Lungs
• Lymph nodes
• Gastrointestinal system
• Pituitary gland
• Thyroid gland
• Thymus

High-risk organs are:

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

Doctors classify the condition (LCH) as "single-system LCH" and "multi-system LCH." This means:

• Single-system (LCH): LCH cells are found in only one part of a single organ or body system. The most common type is LCH that affects only the bones.
• Multisystem (LCH): There are LCH cells in two or more organs, or throughout the body. This is slightly less common than single-system (LCH).

In some cases, especially those affecting only the skin or bones (LCH), the condition may resolve without any treatment. In such cases, doctors will monitor the disease to see if it comes back or spreads.

(LCH) Treatment Options:

• Steroid therapy: Your doctor may use steroids, such as prednisone, especially for skin LCH. These reduce the activity of white blood cells, which can also affect LCH cells.
• Surgery: LCH tumors and the surrounding tissue can be removed surgically. A procedure called curettage involves scraping the LCH cells from the bone with a sharp, spoon-like instrument (curette).
• Chemotherapy: This involves giving cancer cells drugs to stop them from growing. They either kill the cells or stop them from dividing. These drugs are taken by mouth, injected into a vein or muscle, or sometimes applied to the skin as a cream.
• Radiation therapy: High-energy X-rays or other types of radiation are used to kill cancer cells or stop them from growing and dividing.
• Immunotherapy: A method of using the child's own immune system to fight cancer. The body's natural defenses are strengthened by using substances made by the body itself or those made in a laboratory.
• Targeted therapy: Uses drugs or other substances to identify and attack specific cancer cells. For example, drugs called BRAF inhibitors can kill cancer cells by blocking proteins that are needed for cell growth. Monoclonal antibodies are immune system proteins made in the lab.
• Stem cell transplant: Transplantation of new cells to replace blood-forming cells destroyed by chemotherapy.

Can LCH be prevented?

LCH is largely preventable because it is caused by a genetic mutation. We cannot control some risk factors, such as family history and ethnicity. However, there are some things we can manage:

• No smoking.
• Avoiding certain harmful chemicals during pregnancy.
• Getting all recommended vaccinations.

What is the prognosis of (LCH)?

The outlook for LCH depends on several factors:

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

Generally, children with single-system (LCH) and multisystem (LCH) that does not affect the liver, spleen, or bone marrow fall into the "low-risk" category. With treatment, children in this category have a nearly 100% chance of survival. However, the disease can recur and/or develop other long-term complications.

Children with multisystem hematopoietic stem cell (LCH) that affects the liver, spleen, or bone marrow fall into the "high risk" category.

When should my child see the doctor?

Even after your child has completed treatment, the doctor will need to see your child regularly. This is because the risk of the disease recurring is high. Therefore, your child will need to be monitored for several years. During these follow-up tests, the same tests that were done when the child was diagnosed, such as ultrasound, MRI, CT scan, and PET scan, will need to be repeated. The doctor will tell you how often you should bring your child in.

What questions should I ask my child's doctor?

You may have many questions about your child's diagnosis. It's a good idea to write them down and bring them with you to your next doctor's appointment. Here are some questions you can ask:

• How will Langerhans cell histiocytosis affect my child?
• Does my child need treatment?
• What treatment options are available for my child?
• What are the side effects of the treatment?
• Will my child be completely cured with these treatments?
• What is the outlook for my child's illness?
• Are there any support groups you can recommend?

Finally, a Take-Home Message

Langerhans Cell Histiocytosis (LCH) is a rare condition that most often affects children. If your child is going through this, you may be feeling a lot of emotions. You may feel sad and scared for your child. You may be very scared inside, but you may be trying to be strong on the outside. All of your feelings are valid. But remember, you don't have to go through this journey alone. Your child's medical team knows what you're going through. They are there to help you every step of the way, to understand your child's condition, and to give you the strength to cope.

Remember, early diagnosis and proper treatment can give your child a better health. Don't be afraid, face this with courage.

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