Langerhans' cell histiocytosis

What is Langerhans' cell histiocytosis?

Langerhans' cells are white blood cells in the immune system that normally play an important role in protecting the body against viruses, bacteria, and other invaders. They are normally found in the skin, lymph nodes, spleen, bone marrow, and lungs.

In Langerhans' cell histiocytosis, Langerhans' cells multiply abnormally. Instead of helping to protect the body, these cells, in massive numbers, cause tissue injury and destruction, especially in the bones, lungs, and liver. Some forms of Langerhans' cell histiocytosis are now considered cancerous while others are classified as benign. For this reason some people with the disease can be cured, while in others it may be fatal.

Langerhans' cell histiocytosis can develop in only one site or organ (especially the bone, skin, lungs, or brain), or it can involve several different sites and organs. Most Langerhans' cell histiocytosis that affects multiple body systems occurs in children younger than age 5, whereas single-site disease may occur in people of any age.

The cause of the disorder is unknown. Researchers are studying the possibility that some common substance in the environment — perhaps a viral infection — may trigger the disease by causing the immune system to overreact. However, researchers have not yet identified an infection or substance that triggers the disease. One intriguing observation is that almost all people who have the disease affecting only the lungs are current or former cigarette smokers. However, even among smokers this condition is rare.

Langerhans' cell histiocytosis is rare, affecting one in 250,000 children and one in one million adults in the United States. Although it can strike at any age, it is most common in children between the ages of 1 and 3, and about 70% of cases occur before age 17.

Langerhans' cell histiocytosis has gone by different names in the past, including histiocytosis X, diffuse reticuloendotheliosis, eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease.

Symptoms of Langerhans' cell histiocytosis

Symptoms can include:

• persistent pain and swelling on a bone, especially in an arm or leg
• a bone fracture, especially one that happens without any apparent trauma or after only a minor injury
• skin rash
• swollen glands (enlarged lymph nodes
• enlarged liver, yellowing of the skin and eyes (jaundice), or abnormal accumulation of fluid in the abdomen
• headache, double vision, problems with balance or coordination
• shortness of breath and cough
• stunted growth or inability to maintain weight
• excessive thirst or urination caused by hormone abnormalities
• fever and sweats.

Diagnosing Langerhans' cell histiocytosis

Because Langerhans' cell histiocytosis is rare and tends to cause symptoms that could be caused by more common medical problems, this disease often is difficult to diagnose, and diagnosis can take time. Because of this, your doctor may ask questions that are related to those other medical problems, rather than about Langerhans' cell histiocytosis.

Your doctor will examine you, paying special attention to the areas of your body where you are having symptoms. If you have bone pain or swelling, your doctor probably may recommend that you have a series of standard bone x-rays, and possibly a bone scan. These x-rays may show an area of bone destruction called a lytic lesion, and the bone scan may show "hot spots" where bone is injured and attempting repair.

A computed tomography (CT) scan of the spine or pelvis may be recommended if your doctor suspects bone in those areas may be involved. If you have signs of liver disease, blood and ultrasound testing are standard. A chest x-ray or a (CT) scan may be recommended if you have lung symptoms, or if your doctor suspects your lungs are involved based on the physical examination. An MRI scan of the brain may be recommended if your doctor suspects your brain may be involved. A newer imaging technique, PET scanning, may also be useful.

If your doctor suspects that you have Langerhans' cell histiocytosis a biopsy may be recommended, as this is the only way to confirm the diagnosis. In a biopsy, a small piece of tissue or bone is removed and examined in a laboratory. In most cases, this biopsy sample will be taken from a part of the body that is affected by the disease, such as a portion of bone or bone marrow, lung, lymph node, or skin. In addition, genetic testing may be performed looking for mutations linked to Langerhans' cell histiocytosis.

Expected duration of Langerhans' cell histiocytosis

How long Langerhans' cell histiocytosis will last is hard to predict. In some cases it disappears gradually without treatment. This is most likely to happen in people who have Langerhans' cell histiocytosis involving only one area of the body such as the bone or skin, or when a person whose lungs are affected stops smoking. In other cases the disease can be fatal, most commonly in people who have multiple parts of the body affected. For people who smoke, the disease rarely improves while smoking continues.

Preventing Langerhans' cell histiocytosis

Because the cause of Langerhans' cell histiocytosis is not known, there is no way to prevent it. However, since almost all cases involving the lungs develop in people who smoke cigarettes, not smoking may prevent the development of Langerhans' cell histiocytosis in the lungs.

Treating Langerhans' cell histiocytosis

In general, treatment depends on the extent of illness, the person’s age, and whether genetic mutations are present. In some cases, no treatment may be needed unless the condition worsens over time. When treatment is necessary, options vary depending on what parts of the body are affected.

• Single-system Langerhans' cell histiocytosis. Effective treatments include corticosteroids such as prednisone (sold under several brand names), with or without chemotherapy (including vinblastine/Velban), and removing the involved area of the bone with a scraping procedure called curettage. For isolated skin involvement, topical corticosteroids or oral hydroxyurea, thalidomide, lenalidomide, or methotrexate may be effective. Radiation therapy may be recommended if bone involvement (such as the upper leg or spine) causes a weakened area that is likely to fracture. Spinal fusion may be appropriate if disease involves instability of bones in the neck. This would help decrease the risk of damage to the spinal cord.
• Multisystem Langerhans' cell histiocytosis. Chemotherapy may be effective, though success rates are much lower than when only one system is affected. In children, initial therapy often includes a combination of vinblastine (Velban) and prednisone; other chemotherapies, including 6-mercaptopurine (6-MP) may be recommended. In adults, multisystem treatment may include cladribine (Leustatin), cytarabine (Cytosa,Tarabine), or other chemotherapies. If a genetic mutation is present, vemurafenib, dabrafenib, or cobimetinib may be recommended. Radiation treatment is offered when certain bone or brain involvement is present. The best therapy is not known. Transplantation of the liver, bone marrow, or lung are occasionally recommended, although there is no consensus regarding which people with Langerhans' cell histiocytosis should receive organ transplantation.

Enrollment in a clinical trial may be recommended, especially when the disease is not responding to standard treatment.

When to call a professional

Call your doctor or your child's pediatrician if you or your child develops pain or swelling on a bone, a persistent rash, or other symptoms of Langerhans' cell histiocytosis.

Prognosis

Many people with single-system Langerhans' cell histiocytosis recover completely. While many people with multisystem disease respond to chemotherapy, the condition may be fatal in severe or resistant cases.

People with Langerhans' cell histiocytosis may have a higher-than-average risk of developing cancer later in life, including lymphoma and leukemia. The reason for this increased risk is not known.

Additional info

Office of Rare Diseases
National Institutes of health
http://rarediseases.info.nih.gov/

Histiocytosis Association of America
http://www.histio.org/