Langerhans cell histiocytosis (LCH)

What is Langerhans cell histiocytosis?

Langerhans cell histiocytosis, or LCH, is a rare disorder in which too many Langerhans cells (a type of white blood cell) build up in the body. These excess Langerhans cells often form masses called granulomas.

In about 80% of children with LCH, one or more granulomas form in bones. Granulomas can also grow in many other parts of the body, including the skin, lungs, liver, spleen and bone marrow.

Although there's debate over whether LCH is a type of cancer, it behaves like cancer in its most serious form and is treated by cancer specialists. Treatments include oral and topical medications, chemotherapy and sometimes radiation therapy.

LCH affects children more often than adults, frequently between 1 and 3 years of age. In young kids, LCH may affect many parts of the body simultaneously. In children over 5, LCH frequently is limited to the bones. When only one organ is involved, the child needs less intense treatment.

LCH was previously known by several other names, including histiocytosis X, eosinophilic granuloma, Hand-Schüller-Christian disease and Letterer-Siwe disease.

Causes of Langerhans cell histiocytosis (LCH)

In about half of all people with LCH, the Langerhans cells have mutations in a gene called the BRAF gene. These mutations happen randomly – they aren't inherited. Because the BRAF gene plays a role in cell development, the mutation may allow Langerhans cells to grow and divide uncontrollably. Scientists also have identified changes in other genes in some patients with LCH.

Other factors, such as viral infections and exposure to toxins, may play a role in LCH as well.

Symptoms of Langerhans cell histiocytosis (LCH)

LCH symptoms depend on which body parts are affected.

Bones

LCH can involve any bone, but among kids, it typically affects the skull, thigh bones, ribs, vertebrae or upper arm bones. The child may experience pain and swelling at the site. The affected bone is prone to breaking.

Skin

Signs of LCH in the skin include:

• Flaky scalp (may be mistaken for cradle cap or dandruff)
• Flaky skin in body creases, such as the inner elbow
• Raised rashes
• Ulcers on the scalp, behind the ears or in the groin area

Lymph nodes or thymus

If LCH involves the lymph nodes (bean-shaped organs that make and store infection-fighting cells) or thymus (a gland in the neck that's also part of the lymphatic system), symptoms may include:

• Swollen lymph nodes
• Cough
• Fast or labored breathing
• Swelling of the face, neck and upper arms

Pituitary gland

The pituitary is a hormone-producing gland at the base of the brain. When LCH affects the pituitary, symptoms include:

• Delayed puberty
• Frequent urination and intense thirst (due to a condition called diabetes insipidus)
• Slow growth
• Obesity

Liver or spleen

Signs of LCH in the liver or spleen include:

• Swollen abdomen
• Yellowing of the skin and whites of the eyes (jaundice)
• Itching
• Fatigue
• Bruising or bleeding easily
• Diarrhea or bloody stools (poop)

Mouth

Signs of LCH in the mouth include:

• Sores inside the mouth
• Swollen, tender gums
• Teeth loosening or falling out
• In babies, early eruption of teeth

Lungs

Lung involvement is more common among adult LCH patients than in children. Signs include:

• Trouble breathing
• Chest pain
• Dry cough

Central nervous system

When LCH involves the central nervous system (brain and spinal cord), it may cause:

• Problems with balance and coordination
• Trouble walking
• Trouble speaking
• Memory problems

Bone marrow

When Langerhans cells crowd out blood-forming cells in the bone marrow, patients may experience:

• Fatigue – due to low numbers of red blood cells (anemia)
• Frequent infections – due to low numbers of white blood cells
• Easy bruising and bleeding – due to low numbers of platelets

Symptoms seen in LCH can be caused by other conditions. For an accurate diagnosis, your child should be evaluated by a doctor.

Diagnosis of Langerhans cell histiocytosis (LCH)

If LCH is suspected, your child's doctor may order one or more of the following tests:

• Bone X-ray or skeletal series. An X-ray of a particular bone or an X-ray series of the entire skeleton can help the doctor determine the degree of bone involvement.
• Complete blood count (CBC). This lab test uses a blood sample to check for problems with fluid volume, such as blood loss, and for abnormalities in the production, lifespan and destruction of blood cells. Certain results may indicate an infection or clotting problems.
• Skin biopsy. A skin sample may be taken and microscopically examined for the presence of Langerhans cells.
• Genetic testing. A tissue or blood sample may be taken to look for mutations in the BRAF gene.
• Magnetic resonance imaging (MRI) scan. During this imaging test, your child may be injected with a substance that collects around LCH cells and makes them look brighter in the images.
• Positron emission tomography (PET) scan. This imaging test is used to locate tumors in the body.
• Bone marrow aspiration. Bone marrow (the spongy tissue inside bones) has both liquid and solid components. For a bone marrow aspiration, a needle is used to remove a sample from the liquid part so that the cells can be checked for evidence of histiocytosis (abnormal numbers of certain types of white blood cells ). This procedure may be done periodically throughout your child's treatment.
• Bone marrow biopsy. Immediately after a bone marrow aspiration, your child also may undergo a bone marrow biopsy, which removes a small sample of solid bone marrow. This procedure is necessary because liquid bone marrow may not contain enough cells to confirm the presence of histiocytosis.

A bone marrow aspiration and biopsy procedure usually takes 15 to 20 minutes. Understanding that kids and parents often find these tests frightening, we offer the option of performing them under general anesthesia (with the patient completely asleep) whenever possible. To control pain, we inject a fast-acting local anesthetic deep under the skin, numbing the puncture site.

We usually use the same site for both aspiration and biopsy. Although the biopsy needle may look scary, we remove only a very small sample of the spongy marrow. The technique is similar to bone marrow aspiration except that a side-to-side motion of the needle is needed to collect the sample. This is the most painful part of the procedure.

Treatment of Langerhans cell histiocytosis (LCH)

Treatment for LCH depends on the extent of the disease and which organs or tissues are involved. LCH in the liver, spleen or bone marrow is considered higher risk than LCH in the bones, skin, lymph nodes or pituitary gland.

In some cases, LCH goes away on its own. Your child may only need regular appointments to monitor the status of the disease.

If treatment is needed, options include:

• Steroid therapy. Many patients with Langerhans cell histiocytosis are treated with steroid medications, such as prednisone.
• Chemotherapy. Anticancer drugs can be effective for LCH. They may be injected intravenously (into a vein), taken orally or applied to the skin.
• Surgery. LCH cells may be removed with a sharp, spoon-shaped tool called a curette. This procedure is known as curettage.
• Radiation therapy. Low-dose radiation therapy may be used in certain cases.
• Targeted therapies. As their name suggests, these treatments target specific molecules that cancer cells need to grow and spread. Targeted therapies, such as BRAF inhibitors, may be used to treat LCH.
• Clinical trials. Our specialists are active in research to improve LCH care. Your child may be able to receive a promising experimental treatment by participating in a clinical trial.

LCH sometimes comes back after treatment. Your child will need regular follow-up visits to check for signs of recurrence or complications from the disease or treatment.