Langerhans' Cell Histiocytosis (Histiocytosis X)
What Is It?
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 found in the skin, lymph nodes, spleen, bone marrow and lungs.
In Langerhans' cell histiocytosis (formerly known as histiocytosis X), 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. Although this overgrowth of cells may be like cancer, most researchers do not consider Langerhans' cell histiocytosis to be a form of cancer. In fact, the cells appear to be normal. There are just too many of them. Instead, it seems to be disease of the immune system, in which immune cells multiply abnormally and promote inflammation and damage of surrounding tissues.
Langerhans' cell histiocytosis can develop in only one site or organ, or it can involve several different sites and organs. In most cases, Langerhans' cell histiocytosis that affects many body systems typically occurs in children younger than 2, whereas single-site disease may occur in people of any age.
The cause of the disorder is unknown. However, 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 with the disease whose lungs are involved are current or former cigarette smokers. However, even among smokers, this condition is rare, and smoking seems to play no role in the disease when it affects parts of the body outside the lungs. Other theories suggest that the primary cause of Langerhans' cell histiocytosis is an abnormal immune system.
Langerhans' cell histiocytosis is rare, affecting one in 250,000 children and one in 1 million adults in the United States. Although it can strike at any age, it is most common in children and young adults, with about 70% of cases occurring before age 17. During childhood, Langerhans' cell histiocytosis peaks between ages 1 and 3.
Langerhans' cell histiocytosis includes disorders previously considered separate diseases: diffuse reticuloendotheliosis, eosinophilic granuloma, Hand-Schüller-Christian disease and Letterer-Siwe disease.
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
Loose teeth, if Langerhans' cell histiocytosis affects the jaw bones
Ear infection or a discharge from the ear, if Langerhans' cell histiocytosis affects skull bones near the ear
Skin rash, usually on the buttocks or scalp
Swollen glands (enlarged lymph nodes)
Enlarged liver, with or without signs of liver malfunction, such as yellowing of the skin and eyes (jaundice) and abnormal accumulation of fluid in the abdomen (ascites)
Bulging eyes, caused by Langerhans' cell histiocytosis behind the eyes
Shortness of breath and cough, if the lungs are involved
Stunted growth and excessive urination caused by hormone abnormalities
Less common symptoms include fever, weight loss, irritability and inability to maintain weight and fitness ("failure to thrive").
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 will want you to have a series of standard bone X-rays and 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, your doctor will order blood tests to help determine how well your liver is functioning. 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. A CT scan of the head 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, lung, lymph node or skin. Blood tests will determine whether the bone marrow is involved.
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.
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.
Treatment depends on the extent of illness:
Single-system Langerhans' cell histiocytosis — Highly effective treatments include corticosteroids, such as prednisone (sold under several brand names), with or without chemotherapy, and removing the involved area of the bone with a scraping procedure called curettage. For isolated skin involvement, a form of chemotherapy (nitrogen mustard) applied directly to the skin may eliminate the disease. Thalidomide or methotrexate may be effective for skin involvement. 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. While a number of drugs have been tried, including vinblastine (Velban), etoposide (VePesid, Etopophos, Toposar), 6-mercaptopurine (6-MP), cladribine (Leustatin), cytosine arabinoside and methotrexate (several brand names), 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.
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.
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.
Office of Rare Diseases
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