histiocytosis X


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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 5-10 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. One recent case study involved swelling of the eyes caused by histiocytosis in a three-year-old girl. 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. The International Histiocyte Society formed a registry in 2000 that has registered a total of 274 adults from 13 countries as of 2003. Because histiocytic disorders are so rare, little research has been done to determine their cause. Over time, histiocytosis 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; of the 274 adults in the international registry, only one came from a family with a history of the disease.
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 be made only 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 diagnosed with it 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.

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.
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.

Resources

Books

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Histiocytic Syndromes." Section 11, Chapter 137 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.
Behrman, Richard E., Robert Kliegman, and Hal B. Jenson, editors. Nelson Textbook of Pediatrics. Philadelphia: W. B. Saunders, 2000.

Periodicals

Arico, M., M. Girschikofsky, T. Genereau, et al. "Langerhans Cell Histiocytosis in Adults. Report from the International Registry of the Histiocyte Society." European Journal of Cancer 39 (November 2003): 2341-2348.
Eckhardt, A., and A. Schulze. "Maxillofacial Manifestations of Langerhans Cell Histiocytosis: A Clinical and Therapeutic Analysis of 10 Patients." Oral Oncology 39 (October 2003): 687-694.
Kobyahsi, M., O. Yamamoto, Y. Suenaga, and M. Asahi. "Electron Microscopic Study of Langerhans Cell Histiocytosis." Journal of Dermatology July 27, 2000: 453-7.
Levy, J., T. Monos, J.Kapelushnik, et al. "Langerhans Cell Histiocytosis with Periorbital Cellulitis." American Journal of Ophthalmology 136 (November 2003): 939-942.

Organizations

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

Other

"Immunity Disorders." NurseMinerva. June 26, 2001. 〈http://nurseminerva.co.uk/immunity.htm〉.

histiocytosis

 [his″te-o-si-to´sis]
a condition marked by the abnormal appearance of histiocytes in the blood.
Langerhans cell histiocytosis a generic term that encompasses a group of disorders characterized by proliferation of Langerhans cells, which are specialized cells found in the epidermis that function as part of the immune system. These disorders are believed to arise from disturbances in regulation of the immune system. Children are more often affected than adults, and the bone marrow, endocrine system, and lungs may be involved (the lungs are affected more commonly in adults than in children). Langerhans cell histiocytosis is divided into unifocal and multifocal variants; there is also an acute, disseminated form (letterer-siwe disease). This group of disorders was formerly called histiocytosis X and was classified in three forms: Letterer-Siwe disease, Hand-Schüller-Christian disease, and eosinophilic granuloma. Called also eosinophilic granuloma, eosinophilic granulomatosis, and Langerhans cell granulomatosis.
Langerhans cell histiocytosis, acute disseminated Letterer-Siwe disease.
Langerhans cell histiocytosis, multifocal Langerhans cell histiocytosis occurring as erosive accumulations of proliferating Langerhans cells. It occurs most commonly in the marrow cavities of bones, but may also affect the skin, gingiva, lungs, and stomach. When the triad of involvement of the bones of the skull, exophthalmos, and diabetes insipidus is present, it is referred to as Hand-Schüller-Christian disease.
Langerhans cell histiocytosis, unifocal Langerhans cell histiocytosis occurring as a single osteolytic lesion, usually in a long or flat bone; it may be asymptomatic or may produce bone pain, tenderness, and swelling and, sometimes, pathologic fracture.
histiocytosis X former name for Langerhans cell histiocytosis.

Lang·er·hans cell histiocytosis

(lahng'ĕr-hahnz), [MIM*604856]
a set of closely related disorders unified by a common proliferating element, the Langerhans cell. Three overlapping clinical syndromes are recognized: a single site disease (eosinophilic granuloma), a multifocal unisystem process (Hand-Schuller-Christian syndrome), and a multifocal, multisystem histiocytosis (Letter-Siwe syndrome.) Formerly this process was known as histiocytosis X.
Synonym(s): histiocytosis X

histiocytosis X

[his′tē·ōsītō′sis]
Usage notes: obsolete,
a cluster of conditions encompassing benign eosinophilic granuloma and several malignant lymphomatous diseases.

Langerhans’ cell histiocytosis

A group of conditions characterised by proliferation of Langerhans cells, which are lymphoreticular cells. Langerhans cell aggregates are nodular, especially in the lungs, and are variably accompanied by eosinophils, foamy cells, neutrophils, and fibrosis.

Prognosis
Good if limited to a single system. Multi-system involvement carries a 10–20% mortality rate due to organ failure; 50–60% have chronic disease; 30–40% have long-term clinical remission.

Langerhans cell histiocytosis types 
Pulmonary LCH
A lesion virtually exclusive to cigarette smokers, which is a form of smoking-related interstitial lung disease. Smoking cessation may lead to reversal of changes or evolution to pulmonary fibrosis and pulmonary hypertension.
 
Unifocal LCH
Eosinophilic granuloma, solitary bone involvement
A lesion affecting younger patients; may affect any bone, most commonly the cranial vault, jaw, humerus, rib and femur (often spares the hands and feet).

Imaging
Mimics Ewing sarcoma.
 
Treatment
Curettage.
 
Prognosis
Excellent.
 
Multifocal unisystem
LCH Hand-Schüller-Christian disease, multiple bone involvement.

Polyostotic eosinophilic granuloma 
A lesion that may affect the skin, accompanied by proptosis, diabetes insipidus, or chronic otitis media or combination thereof, marked by a chronic course with waxing and waning symptoms.

Prognosis
Relatively good.
 
Multifocal multisystem LCH
Letterer-Siwe disease, multiple organ involvement
A lesion that affects bone, lung and skin; while histologically indistinct, it is more aggressive than the other forms.

Prognosis
Poor if < 18 months at time of diagnosis; haemorrhagic skin lesions; hepatomegaly, anemia; thrombocytopenia; bone marrow involvement.

histiocytosis X

Langerhans' cell histiocytosis, see there.

his·ti·o·cy·to·sis X

(his'tē-ō-sī-tō'sis)
Proliferation of Langerhans cells of undetermined clinical type, possibly Hand-Schüller-Christian disease, Letterer-Siwe disease, and eosinophilic granuloma.
References in periodicals archive ?
1) Up to 80% of histiocytosis X lesions in children are of solitary EG type and up to 90% occur in children.
Relative efficacy of radiographic and radionuclide bone surveys in the detection of skeletal lesions of histiocytosis X.
Histiocytosis X (LC histiocytosis) Prognostic role of histopathology.
Histiocytosis X of the head and neck in a pediatric population.
Prognostic criteria, treatment and survival in disseminated histiocytosis X.
The Langerhans cell histiocytosis X files revealed.
DISCUSSION: Histiocytosis X has been defined as a non neoplastic, proliferative disorder of histiocytes of unknown etiology, which is pathogenetically similar to an inflammatory reaction with multiple clinical manifestations mirroring the widespread distribution of the histiocytic system of the body (3).
Histiocytosis X mimicking recurrent malignant disease: a report of two cases.