Histiocytosis X

Definition

Histiocytosis X is a generic term that refers to an increase in the number of histiocytes, a type of white blood cell, that act as scavengers to remove foreign material from the blood and tissues. Since recent research demonstrated Langerhan cell involvement as well as histiocytes, this led to a proposal that the term Langerhans Cell Histiocytosis (LCH) be used in place of histiocytosis X. Either term refers to three separate illnesses (listed in order of increasing severity): eosinophilic granuloma, Hand-Schuller-Christian disease and Letterer-Siwe disease.

Description

Epidermal (skin) Langerhans cells (a form of dendritic cell) accumulate with other immune cells in various parts of the body and cause damage by the release of chemicals. Normally, Langerhans cells recognize foreign material, including bacteria, and stimulate the immune system to react to them. Langerhans cells are usually found in skin, lymph nodes, lungs, and the gastrointestinal tract. Under abnormal conditions these cells affect skin, bone, and the pituitary gland as well as the lungs, intestines, liver, spleen, bone marrow, and brain. Therefore, the disease is not confined to areas where Langerhans cells are normally found. The disease is more common in children than adults and tends to be most severe in very young children.

Histiocytosis X or LCH is a family of related conditions characterized by a distinct inflammatory and proliferative process but differs from each other in which parts of the body are involved. The least severe of the histiocytosis X/LCH family is eosinophilic granuloma. Approximately 60-80% of all diagnosed cases are in this classification, which usually occurs in children aged five to 10 years. The bones are involved 50-75% of the time, which includes the skull, or mandible, and the long bones. If the bone marrow is involved, anemia can result. With skull involvement, growths can occur behind the eyes, bulging them forward. The lungs are involved less than 10% of the time, and this involvement signals the worst prognosis.

Next in severity is Hand-Schuller-Christian disease, a chronic, scattered form of histiocytosis. It occurs most commonly from the age of one to three years and is a slowly progressive disease that affects the softened areas of the skull, other flat bones, the eyes, and skin. Letterer-Siwe disease is the acute form of this series of diseases. It is generally found from the time of birth to one year of age. It causes an enlarged liver, bruising and skin lesions, anemia, enlarged lymph glands, other organ involvement, and extensive skull lesions.

Causes and symptoms

This is a rare disorder affecting approximately 1 in 200,000 children or adults each year. Because it is so rare, little research has been done to determine the cause. Over time, it may lessen in its assault on the body but there are still problems from damage to the tissues. There are no apparent inheritance patterns in these diseases with the exception of a form involving the lymphatic system.

The symptoms of histiocytosis are caused by substances called cytokines and prostaglandins, which are normally produced by histiocytes and act as messengers between cells. When these chemicals are produced in excess amounts and in the wrong places, they cause tissue swelling and abnormal growth. Thus, symptoms may include painful lumps in the skull and limbs as well as rashes on the skin. General symptoms may include: poor appetite, failure to gain weight, recurrent fever, and irritability. Symptoms from other possible sites of involvement include:

• gums: swelling, usually without significant discomfort

• ear: chronic discharge

• liver or spleen: abdominal discomfort or swelling

• pituitary: This gland at the base of the brain is affected at some stage in approximately 20%-30% of children causing a disturbance in water balance to produce thirst and frequent urination.

• eyes: Due to the bony disease, behind-the-eye bulging may occur (exophthalmos)

• lungs: breathing problems

Diagnosis

The diagnosis can only be made by performing a biopsy, that is, taking a tissue sample under anesthesia from a site in the patient thought to be involved. Blood and urine tests, chest and other x rays, magnetic resonance imaging (MRI) and computed tomography scans (CAT scans) (to check the extent of involvement), and possibly bone marrow or breathing tests may be required to confirm the diagnosis.

Treatment

Although this disease is not cancer, most patients are treated in cancer clinics. There are two reasons for this:

• Historically, cancer specialists treated it before the cause was known.

• The treatment requires the use of drugs typically required to treat cancer.

Any cancer drugs utilized are usually given in smaller doses, which diminishes the severity of their side effects. Radiation therapy is rarely used, and special drugs may be prescribed for skin symptoms. If there is only one organ affected, steroids may be injected locally, or a drug called indomethacin may be used. Indomethacin is an anti-inflammatory medication that may achieve a similar response with less severe side effects.

Prognosis

The disease fluctuates markedly. If only one system is involved, the disease often resolves by itself. Multisystem disease usually needs treatment although it may disappear spontaneously. The disease is not normally fatal unless organs vital to life are damaged. In general, the younger the child at diagnosis and the more organs involved, the poorer the outlook. If the condition resolves, there could still be long-term complications because of the damage done while the disease was active.

Key Terms

Anemia

Abnormally low level of red blood cells in the blood.

Biopsy

Surgical removal of tissue for examination.

CT or CAT

Computed tomography, a radiologic imaging that uses computer processing to generate an image of tissue density in slices through the patient's body.

Cytokines

The term used to include all protein messengers that regulate immune responses.

Dendritic

Branched like a tree.

Eosinophils

A leukocyte with coarse, round granules present.

Epidermal

The outermost layer of the skin.

Inflammatory

A localized protective response of the body caused by injury or destruction of tissues.

MRI

Magnetic resonance imaging, a noninvasive nuclear procedure that uses electromagnetic energy to create images of structures inside the body.

Pituitary gland

The master gland located in the middle of the head that controls the endocrine glands and affects most bodily functions.

Prostaglandins

A group of nine naturally occurring chemicals in the body that affect smooth muscles.

Serous

Thin and watery, like serum.

For Your Information

Books

• Behrman, Richard E., Robert Kliegman, and Hal B. Jenson, eds. Nelson Textbook of Pediatrics, Philadelphia: W. B. Saunders, 2000.

• Kobyahsi, M., O. Yamamoto, Y. Suenaga, and M. Asahi. "Electron Microscopic Study of Langerhans Cell Histiocytosis." Journal of Dermatology (July 27, 2000): 453-7.

• Kusumakumary, P., F. V. James, V. G. Chellam, K. Ratheesan, and M. K. Nair. "Disseminated Langerhans Cell Histiocytosis in Children: Treatment Outcome." American Journal of Clinical Oncology, (April 2, 1999): 180-83.

• Histiocytosis Association of America, 302 North Broadway, Pitman, NJ 08071. 800-548-2758 (USA and Canada). http://www.histio.org.

• "Immunity Disorders." Nurse Minerva. 26 June 2001. http://nurseminerva.co.uk/immunity.htm.

Source: Gale Encyclopedia of Medicine, Published December, 2002 by the Gale Group

The Essay Author is Linda K. Bennington CNS.

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