Langerhans cell histiocytosis starts when the body makes too many immune cells that help fight infections. It’s the most common type of histiocytosis.

Most often, LCH is a mild illness that affects the skin or only a few bones. In some people, it makes tumors grow in many organs.

What are the symptoms of LCH?

The symptoms of Langerhans cell histiocytosis look like many other skin conditions. That’s why experts think LCH is more common, but often it’s not diagnosed.

There are many symptoms. People with LCH most often get:

• Skin rashes, which can sometimes be very painful. About half of the people with LCH have skin lesions.
• Pain and swelling in the skull, jaw, hips, or other areas when LCH affects the bones. Nearly 4 out of 5 people with LCH have lesions in the bones, often the skull.
• Balance, speech, and coordination problems when LCH affects the brain. This is a rare but serious condition.

Who gets LCH?

LCH is most common in children from newborn babies up through age 4. It affects Hispanic people more often. LCH is more common in children than adults, but anyone can get it.

What causes LCH?

Most cases of LCH are caused by genetic changes (mutations or variants). These mutations happen in genes that control how some immune cells work. Common genetic mutations for Langerhans cell histiocytosis include changes in these genes:

• BRAF
• MAP2K1
• RAS
• ARAF

MSK is researching new therapies that target these genes. If you have a family history of histiocytosis, you can talk with our Clinical Genetics Service. They can assess your risk and offer genetic testing.

We do not know what causes LCH in some people. Researchers have not found any risk factors, behaviors, or environmental exposures that cause LCH.

Langerhans cell histiocytosis treatment

LCH that affects the skin, bones, or lymph nodes often gets better with little treatment. People with mild symptoms may not need any treatment. But they should be monitored (watched) over time.

When LCH is in the liver, spleen, brain, and bone marrow, it’s harder to treat with success.

• Children under age 1 year may have LCH only in the skin. It can be confused with cradle cap when it’s only on the head. This form of LCH often goes away on its own.
• LCH that affects only 1 part of the body is called unifocal LCH. It sometimes can be treated with surgery and skin treatments. You may have a biopsy, a procedure to get a tissue sample. Tests on the sample may show you do not need treatment.
• People with LCH lesions in several parts of the body often need chemotherapy, radiation therapy, or targeted drugs. An example of a targeted drug is cobimetinib (Cotellic®), which blocks a protein called MEK. We rarely use radiation therapy to treat children with LCH.

Rosai-Dorfman disease (RDD) is a rare form of histiocytosis. RDD can affect lymph nodes and make them swell.

RDD outside of the lymph nodes is called extranodal RDD. It can affect the skin and bones, and many other body parts. RDD in the skin is called cutaneous RDD. Orbital RDD affects the eye and eyelids.

In the past, RDD was called sinus histiocytosis with massive lymphadenopathy (SHML). It’s also called Rosai-Dorfman-Destombes disease.

What are the symptoms of RDD?

Common symptoms of Rosai-Dorfman disease are:

• Swollen lymph nodes in the neck. There also can be lymph node swelling in the chest, groin, or armpits.
• Skin lumps that can be itchy and painful.
• Fever, night sweats, and a general feeling of being sick.
• Lesions in the bones, sinuses, organs of the chest and abdomen, eyes, and brain. Lesions are less common and are a rare side effect of RDD.

How is RDD diagnosed?

RDD is diagnosed with a biopsy to get a tissue sample from areas that are affected. Blood tests and imaging exams can also confirm the diagnosis. These tests help doctors learn what parts of the body are involved and whether you also have other conditions.

Who gets RDD?

RDD is most common in children, but adults can also get it. RDD can affect people with autoimmune diseases. This is a condition where your immune system attacks your own body. RDD also affects people with blood cancers.

What causes RDD?

We do not know the exact cause of Rosai-Dorfman. The causes may not be the same for everyone. Like other histiocytosis diseases, genetic changes (mutations or variants) have been found in RDD. This includes changes in the KRAS and MAP2K1 genes. Doctors do not know why some people get RDD along with autoimmune diseases.

Rosai-Dorfman disease treatments

Some forms of RDD do not need treatment and get better on their own.

For RDD that does not get better, treatments include:

• Chemotherapy drugs, such as cladribine, cytarabine, vinblastine, hydroxyurea, and methotrexate.
• Cobimetinib, approved for adults with RDD.
• Drugs that affect the immune system, such as prednisone and lenalidomide (Revlimid®).
• Targeted medicinces, such as sirolimus (Rapamune®).

Surgery and radiation therapy are rarely used as RDD treatments.

Juvenile xanthogranuloma (zan-thow-gra-nyuh-LOW-muh) is a rare type of histiocytosis in children. It’s mild and often goes away on its own. Rarely, it can cause bad health problems. There are many types of JXG, based on the body parts it affects and the pattern of illness.

What are the symptoms of JXG?

JXG can start as a single skin lesion. Children under 6 months of age can have several lesions. Rarely, JXG can also affect the bones, eyes, and brain. JXG symptoms are similar to those of LCH. You will need a biopsy procedure before your care team can make the right diagnosis.

Who gets JXG?

JXG happens in children, mostly infants and toddlers. Children get it at an average age of 2. Boys get it more often than girls.

What causes JXG?

We do not know what causes JXG. Gene changes (mutations or variants) have been found in some tumors. This suggests the disease behaves like a blood cancer, just like other histiocytoses.

How is JXG treated?

In infants, JXG often goes away by itself when it only affects the skin.

• Children with JXG eye lesions may need steroids, low-dose radiation therapy, or both to prevent loss of vision.
• Surgery may be a treatment option if JXG affects how well an organ works.
• A few children may need chemotherapy if JXG causes symptoms or harms organs.
• Radiation therapy is rarely used for JXG.

Langerhans cell histiocytosis starts when the body makes too many immune cells that help fight infections. It’s the most common type of histiocytosis.

Most often, LCH is a mild illness that affects the skin or only a few bones. In some people, it makes tumors grow in many organs.

What are the symptoms of LCH?

The symptoms of Langerhans cell histiocytosis look like many other skin conditions. That’s why experts think LCH is more common, but often it’s not diagnosed.

There are many symptoms. People with LCH most often get:

• Skin rashes, which can sometimes be very painful. About half of the people with LCH have skin lesions.
• Pain and swelling in the skull, jaw, hips, or other areas when LCH affects the bones. Nearly 4 out of 5 people with LCH have lesions in the bones, often the skull.
• Balance, speech, and coordination problems when LCH affects the brain. This is a rare but serious condition.

Who gets LCH?

LCH is more common in children than adults, but anyone can get it. It affects Hispanic people more often.

What causes LCH?

Most cases of LCH are caused by genetic changes (mutations or variants). These mutations happen in genes that control how some immune cells work. Common genetic mutations for Langerhans cell histiocytosis include changes in these genes:

• BRAF
• MAP2K1
• RAS
• RAF

MSK is researching new therapies that target these genes. If you have a family history of histiocytosis, you can talk with our Clinical Genetics Service. They can assess your risk and offer genetic testing.

We do not know what causes LCH in some people. Researchers have not found any risk factors, behaviors, or environmental exposures that cause LCH.

LCH treatment

LCH that affects the skin, bones, or lymph nodes often gets better with little treatment. People with mild symptoms may not need any treatment. But they should be monitored (watched) over time.

When LCH is in the liver, spleen, brain, and bone marrow, it’s harder to treat with success.

• LCH that affects only 1 part of the body is called unifocal LCH. It sometimes can be treated with surgery and skin treatments. You may have a biopsy, a procedure to get a tissue sample. Tests on the sample may show you do not need treatment.
• People with LCH lesions in several parts of the body often need chemotherapy, radiation therapy, or targeted drugs. An example of a targeted drug is cobimetinib (Cotellic®), which blocks a protein called MEK.

Erdheim-Chester disease is a rare type of histiocytosis that can affect the whole body. It most often affects the leg bones, kidney area, skin, area behind the eyes, and sometimes the brain. Nearly everyone with ECD has tumors in their leg bones.

What are the symptoms of ECD?

Symptoms of Erdheim-Chester disease can be hard to diagnose because it can affect any part of the body. It also can cause many different symptoms.

To diagnose ECD, you may have a biopsy, a procedure to get a tissue sample. The biopsy results, however, do not always give a clear answer.

The most common symptoms include:

• Pain in the bones or joints. Nearly everyone with ECD has pain. The areas with pain may not match where their tumors are.
• Weakness and fatigue (feeling very tired).
• Fevers, night sweats, and a general feeling of illness.
• Kidney or blood vessel problems, if ECD affects these parts.
• Problems with coordination (movement), balance, speech, mood, thinking, and memory if ECD affects the brain.
• Shortness of breath, fatigue, and swelling in the legs and feet, if ECD is in the heart or lungs.
• Eye pain, redness, bulging eyes, double vision, or blurry vision if ECD affects the eyes.

Who gets ECD?

Mostly adults get this kind of histiocytosis. The average age they learn they have ECD is about age 50. Teens and children rarely get ECD.

What causes ECD?

We do not know the exact cause of ECD. We think genetic changes (mutations or variants) in blood cells play a role.

• About half of ECD tumor samples show BRAF V600E gene mutations.
• Other tumors have mutations in the genes MAP2K1 and KRAS, among others.

Erdheim-Chester disease treatments

Some people with ECD feel just a little ill or have only a few symptoms. They can be watched without treatment.

Other people have very bad symptoms and trouble doing their normal daily activities. They need treatment right away.

Therapies for ECD include:

• Targeted medicine aimed at the genes that fuel ECD growth. Examples include vemurafenib (Zelboraf®) and other BRAF inhibitors, such as dabrafenib (Tafinlar®) and encorafenib (Braftovi®). We may also use Cobimetinib and other MEK inhibitors, such as trametinib (Mekinist®) and binimetinib (Mektovi®).
• Chemotherapy drugs, such as cladribine and methotrexate.
• Medicine to help with inflammation, such as anakinra (Kineret®).

We rarely use surgery and radiation therapy to remove or shrink ECD tumors.

Rosai-Dorfman disease (RDD) is a rare form of histiocytosis. RDD can affect lymph nodes and make them swell.

RDD outside of the lymph nodes is called extranodal RDD. It can affect the skin and bones, and many other body parts. RDD in the skin is called cutaneous RDD. Orbital RDD affects the eye and eyelids.

In the past, RDD was called sinus histiocytosis with massive lymphadenopathy (SHML). It’s also called Rosai-Dorfman-Destombes disease.

What are the symptoms of RDD?

Common symptoms of Rosai-Dorfman disease are:

• Swollen lymph nodes in the neck. There also can be lymph node swelling in the chest, groin, or armpits.
• Skin lumps that can be itchy and painful.
• Fever, night sweats, and a general feeling of being sick.
• Lesions in the bones, sinuses, organs of the chest and abdomen, eyes, and brain. Lesions are less common and are a rare side effect of RDD

How is RDD diagnosed?

RDD is diagnosed with a biopsy to get a tissue sample from areas that are affected. Blood tests and imaging exams can also confirm the diagnosis. These tests help doctors learn what parts of the body are involved and whether you also have other conditions.

Who gets RDD?

RDD is most common in children, but adults can also get it. RDD can affect people with autoimmune diseases. This is a condition where your immune system attacks your own body. RDD also affects people with blood cancers.

What causes RDD?

We do not know the exact cause of Rosai-Dorfman. The causes may not be the same for everyone. Like other histiocytosis diseases, genetic changes (mutations or variants) have been found in RDD. This includes changes in the KRAS and MAP2K1 genes. Doctors do not know why some people get RDD along with autoimmune diseases.

Rosai-Dorfman disease treatments

Some forms of RDD do not need treatment and get better on their own. For RDD that does not get better, treatments include:

• Chemotherapy drugs, such as cladribine, cytarabine, vinblastine, hydroxyurea, and methotrexate.
• Cobimetinib, approved for adults with RDD.
• Drugs that affect the immune system, such as prednisone and lenalidomide (Revlimid®).
• Targeted medicinces, such as sirolimus (Rapamune®).

Surgery and radiation therapy are rarely used as RDD treatments.

Xanthogranuloma (zan-thow-gra-nyuh-LOW-muh) is a rare type of histiocytosis in adults. It’s mild and often goes away on its own. Rarely, it can cause bad health problems. There are many types of AXG, based on the body parts it affects and the pattern of illness.

What are the symptoms of AXG?

AXG can start as a single skin lesion. Rarely, AXG can also affect the bones, eyes, and brain. AXG symptoms are similar to those of LCH. You will need a biopsy procedure before your care team can make the right diagnosis.

Who gets AXG?

AXG starts in older people.

What causes AXG?

We do not know what causes AXG. Gene changes (mutations or variants) have been found in some tumors. This suggests the disease behaves like a blood cancer, just like other histiocytoses.

How is AXG treated?

• Surgery may be a treatment option if AXG affects how well an organ works.
• A few people may need chemotherapy if AXG causes symptoms or harms organs.
• Radiation therapy is rarely used for AXG.

Malignant histiocytic disorders (histiocytic sarcoma)

Malignant histiocytoses are very rare types of cancer. They often grow fast. They include histiocytic sarcoma, Langerhans cell sarcoma, and other tumors. They can affect the skin, lymph nodes, brain, and other organs.