Langerhans Cell Histiocytosis (LCH)

LCH is a condition that occurs when the body produces too many Langerhans cells in the skin, lungs, and bone, in particular. In Langerhans cell histiocytosis, immature Langerhans cells may clump together and begin to form tumors called granulomas.  

LCH is described as single-system disease or multi-system disease.

  • Single-system LCH affects one organ or body system.
  • Multi-system LCH occurs in two or more organs or body systems.

LCH may affect low-risk organs or high-risk organs.

LCH Risk Factors

This condition affects only 1 to 2 in 100,000 individuals in the United States. About 50 percent of all cases are diagnosed in childhood, commonly between ages 2 and 3.

Most adults with LCH have a history of smoking, and roughly two-third of these patients have a form of this disease that only lodges in the lung.

Other risk factors for LCH include the following:

  • A parent who was exposed to certain chemicals such as benzene.
  • A history of infections as a newborn.
  • A family history of thyroid disease.
  • Mutations in the BRAF gene

LCH-related BRAF mutations are acquired over the course of a lifetime, not inherited, and are only present in the abnormal cells. The BRAF gene provides instructions for making a protein related to control cell growth and development.  When this protein becomes overactive, it may cause the Langerhans cells to grow and divide uncontrollably.  Viral infections, environmental toxins, and changes in other genes, may also play a role in the development of this complex disorder.

LCH Symptoms

As Langerhans cells accumulate in the bone marrow, they crowd out healthy blood-forming cells, resulting in low blood counts.

As the number of oxygen-carrying red blood cells decline, patients may develop anemia, appearing pale, tired or short of breath.  A decline in platelets that normally help the blood clot may lead to easy bruising or bleeding. A decline in white blood cells puts patients at increased risk for infections that can sometimes be life threatening.

LCH patients may experience a wide range of symptoms, depending on which organs and tissues have built-up deposits of Langerhans cells.  These symptoms may include

  • Swollen lymph nodes
  • Abdominal pain
  • Yellowing of the skin and whites of the eyes (jaundice)
  • Delayed puberty
  • Protruding eyes
  • Dizziness
  • Irritability
  • Seizures
  • Enlargement of the spleen
  • Cysts in the lungs, in more advanced stages

Roughly 1 in 50 patients with this condition suffer from impaired neurological function (neurodegeneration).

About 8 percent of patients develop one or more granulomas (small areas of inflammation) in the skull or the long bones of the arms and legs. These result in pain and swelling, and sometimes fractures.

Granulomas of the skin may cause blisters, reddish bumps, or rashes.

If the pituitary gland that produces hormones is affected, children with this condition may experience delayed onset of puberty, while older patients may experience infertility.

Pituitary damage can also lead to the production of excessive urine (diabetes insipidus) and to thyroid problems, producing changes in the patient’s metabolism, body temperature, skin and hair texture, and behavior.

Between 15 to 20 percent of patients with LCH have some form of damage to the liver or lung, as well as to the blood-forming (hematopoeitic) system.

Lung damage may involve swelling of the small airways (bronchioles) and blood vessels in the lungs, resulting in breathing problems, and increased risk of respiratory infection. Some patients develop cysts in the lung, which can sometimes cause the lungs to collapse.

LCH Diagnosis

When LCH is suspected, the patient will have laboratory blood tests, including a white blood count, liver function, and coagulation studies. 

To check for diabetes insipidus (a condition where the kidneys are unable to conserve water), a urine test may be ordered after overnight fluid deprivation.

Other diagnostic tests depend on the organs involved, and may include

  • Skin biopsy A skin lesion is removed by a physician, usually under local anesthesia, then sent to a pathologist who looks for abnormal cells.
  • X-rays of the bones (skeletal survey) This is a painless, noninvasive test that creates images of the bones in the patient’s body.
  • An audiogram or hearing test measuring the range of sound that a patient can hear, 
  • Chest X-ray or CT scan of the chest This is a painless, noninvasive test that creates images of the structures inside the patient’s chest, such as the heart, lungs, and blood vessels
  • Ultrasound of Liver/Spleen This diagnostic technique uses sound waves to evaluate parts of the body. A small instrument called a transducer emits sound waves and picks up the echoes as they bounce off the organs. A computer converts these sound wave echoes into an image that is displayed on monitor.
  • Lavage or Lung biopsy Langerhans cells can be detected, and the extent of lung involvement can often determined by bronchoalveolar lavage (BAL).  In this non-surgical procedure, a scope is passed through the patient’s mouth or nose into the lungs and fluid is squirted into a small part of the lung and then collected for examination. In some cases, a surgical biopsy of the lung might be needed.
  • Bowel Biopsy Unexplained chronic diarrhea may require a biopsy of the small bowel.
  • Magnetic Resonance Imaging (MRI) of the Central Nervous System  The MRI uses magnetic fields and radio waves to create a detailed image of the brain, the hypothalamus and pituitary organs.

LCH Treatment

The severity of LCH varies widely. For many patients, the disorder eventually resolves with appropriate treatment.  When only the skin is affected, this condition may disappear on its own.  However, some complications may be long lasting, resulting in tissue and organ damage. 

Adults currently receive the treatments proven effective for children, though it is not currently known whether they respond as well.

Isolated skin conditions may be treated by drugs and chemotherapy, including

  • Topical steroids (although these creams are effective for a small number of patients)
  • Chemotherapy agents including oral methotrexate, mercaptopurine  and intravenous chemotherapies including vinblastine or cladribine.
  • Topical application of nitrogen mustard for cutaneous LCH that is resistant to oral therapies (not used for disease involving large areas of skin).
  • Psoralen and long-wave ultraviolet radiation (PUVA).

Other forms of LCH may be treated by a combination of surgery, radiation therapy and chemotherapy

Surgery

  • Curettage (the removal of tissue) LCH bone lesions may not need complete excision, as this only increases healing time and the risk of long-term complications
  • Bracing or spinal fusion may be needed for unstable cervical vertebrae.

Radiation Therapy

  • May be used for bone lesions of the vertebrae or femoral neck, if they are at risk of collapse or fracture.

Chemotherapy

  • Vinblastine, a chemotherapy drug, may be combined with prednisone
  • Methotrexate, a chemotherapy drug
  • Mercaptopurine, a chemotherapy drug
  • Cladribine, a chemotherapy drug
  • Zoledronate, a drug that strengthens bones

Vemurafemib (Zelboraf) is a medicine that targets BRAF and has worked in some patients.