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 acts as a scavenger to remove foreign material from the blood and tissues. Research that demonstrated Langerhans cell involvement as well as histiocytes 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, which are characterized by a distinct inflammatory and proliferative process but which differ from each other regarding what parts of the body are involved. The least severe of the histiocytosis X/LCH family is eosinophilic granuloma. Approximately 60 to 80 percent of all diagnosed cases are in this classification, which usually occurs in children aged five to ten years. The bones are involved 50 to 75 percent 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 percent 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.

Demographics

Histiocytosis X is a rare disorder affecting only approximately one in 200,000 children or adults each year.

Causes and symptoms

Because histiocytosis X 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
ears: chronic discharge
liver or spleen: abdominal discomfort or swelling
pituitary gland: affected at some stage in approximately 20 percent to 30 percent of children, causing a disturbance in water balance and producing thirst and frequent urination
eyes: behind-the-eye bulging may occur (exophthalmos)
lungs: breathing problems

KEY TERMS

Anemia —A condition in which there is an abnormally low number of red blood cells in the bloodstream. It may be due to loss of blood, an increase in red blood cell destruction, or a decrease in red blood cell production. Major symptoms are paleness, shortness of breath, unusually fast or strong heart beats, and tiredness.

Biopsy —The surgical removal and microscopic examination of living tissue for diagnostic purposes or to follow the course of a disease. Most commonly the term refers to the collection and analysis of tissue from a suspected tumor to establish malignancy.

Computed tomography (CT) —An imaging technique in which cross-sectional x rays of the body are compiled to create a three-dimensional image of the body's internal structures; also called computed axial tomography.

Cytokines —Chemicals made by the cells that act on other cells to stimulate or inhibit their function. They are important controllers of immune functions.

Dendritic —Branched like a tree.

Eosinophil —A type of white blood cell containing granules that can be stained by eosin (a chemical that produces a red stain). Eosinophils increase in response to parasitic infections and allergic reactions.

Epidermal —The outermost layer of the skin.

Inflammatory —Pertaining to inflammation.

Magnetic resonance imaging (MRI) —An imaging technique that uses a large circular magnet and radio waves to generate signals from atoms in the body. These signals are used to construct detailed images of internal body structures and organs, including the brain.

Pituitary gland —The most important of the endocrine glands (glands that release hormones directly into the bloodstream), the pituitary is located at the base of the brain. Sometimes referred to as the "master gland," it regulates and controls the activities of other endocrine glands and many body processes including growth and reproductive function. Also called the hypophysis.

Prostaglandins —A group of hormone-like molecules that exert local effects on a variety of processes including fluid balance, blood flow, and gastrointestinal function. They may be responsible for the production of some types of pain and inflammation.

Serous —Pertaining to or resembling serum.

Diagnosis

The diagnosis can only be made by performing a biopsy (taking a tissue sample under anesthesia from a site in the patient thought to be involved and having it tests). Blood and urine tests, chest and other x rays , magnetic resonance imaging (MRI) and computed tomography scans (CT 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. Moreover, 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 can still be long-term complications because of the damage done while the disease was active.

Resources

BOOKS

Ladisch, Stephan. "Histiocytosis Syndromes of Childhood." In Nelson Textbook of Pediatrics. Edited by Richard E. Behrman et al. Philadelphia: Saunders, 2004.

PERIODICALS

Katz, B. Z. "Treatment for multisystem Langerhans' cell histiocytosis." Journal of Pediatrics 86 (February 2002): 280.

Seward, J. L. "Generalized eruptive histiocytosis." Journal of the American Academy Dermatology 86 (January 2004): 116–20.

ORGANIZATIONS

Histiocytosis Association of America. 302 North Broadway, Pitman, NJ 08071. Web site: http://www.histio.org.

Linda K. Bennington, CNS Rosalyn Carson-DeWitt, MD