Erdheim-Chester disease

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What is Erdheim-Chester disease?

Erdheim-Chester disease is a rare disorder characterized by histiocytosis, a condition in which the immune system produces excess quantities of cells called histiocytes. Histiocytes normally function to destroy foreign substances and protect the body from infection. Erdheim-Chester disease is classified as a form of non-Langerhans cell histiocytosis to distinguish it from Langerhans cell histiocytosis, which involves accumulation of a specific type of histiocyte called Langerhans cells. In Erdheim-Chester disease, histiocytosis leads to inflammation that can damage organs and tissues throughout the body, causing them to become thickened, dense, and scarred (fibrotic); this tissue damage may lead to organ failure.

People with Erdheim-Chester disease often have bone pain, especially in the lower legs and upper arms, due to an abnormal increase in bone density (osteosclerosis). Damage to the pituitary gland (a structure at the base of the brain that produces several hormones, including a hormone that controls the amount of water released in the urine) may result in hormonal problems such as a condition called diabetes insipidus that leads to excessive urination. Abnormally high pressure of the cerebrospinal fluid within the skull (intracranial hypertension) caused by accumulation of histiocytes in the brain may result in headaches, seizures, cognitive impairment, or problems with movement or sensation. People with this condition can also have shortness of breath, heart or kidney disease, protruding eyes (exophthalmos), skin growths, or inability to conceive a child (infertility). Affected individuals may also experience fever, night sweats, fatigue, weakness, and weight loss.

The signs and symptoms of Erdheim-Chester disease usually appear between the ages of 40 and 60, although the disorder can occur at any age. The severity of the condition varies widely; some affected individuals have few or no associated health problems, while others have severe complications that can be life-threatening.

How common is Erdheim-Chester disease?

Erdheim-Chester disease is a rare disorder; its exact prevalence is unknown. More than 500 affected individuals worldwide have been described in the medical literature. For unknown reasons, men are slightly more likely to develop the disease, accounting for about 60 percent of cases.

What genes are related to Erdheim-Chester disease?

More than half of people with Erdheim-Chester disease have a specific mutation in the BRAF gene. Mutations in other genes are also thought to be involved in this disorder.

The BRAF gene provides instructions for making a protein that helps transmit chemical signals from outside the cell to the cell's nucleus. This protein is part of a signaling pathway known as the RAS/MAPK pathway, which controls several important cell functions. Specifically, the RAS/MAPK pathway regulates the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (migration), and the self-destruction of cells (apoptosis).

The BRAF gene mutation that causes Erdheim-Chester disease is somatic, which means that it occurs during a person's lifetime and is present only in certain cells. The mutation occurs in histiocytes or in immature precursor cells that will develop into histiocytes. This mutation leads to production of a BRAF protein that is abnormally active, which disrupts regulation of cell growth and division. The unregulated overproduction of histiocytes results in their accumulation in the body's tissues and organs, leading to the signs and symptoms of Erdheim-Chester disease.

The BRAF gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. Researchers disagree on whether Erdheim-Chester disease should be considered a form of cancer because of the unregulated accumulation of histiocytes.

How do people inherit Erdheim-Chester disease?

This condition is not inherited. It arises from a somatic mutation in histiocytes or their precursor cells during an individual's lifetime.

Where can I find information about diagnosis or management of Erdheim-Chester disease?

These resources address the diagnosis or management of Erdheim-Chester disease and may include treatment providers.

Histiocytosis Association: Erdheim-Chester Disease Diagnosis and Treatment

You might also find information on the diagnosis or management of Erdheim-Chester disease inEducational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about Erdheim-Chester disease?

You may find the following resources about Erdheim-Chester disease helpful. These materials are written for the general public.

MedlinePlus - Health information (6 links)
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases
Educational resources - Information pages (2 links)
Patient support - For patients and families (3 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature

What other names do people use for Erdheim-Chester disease?

lipid granulomatosis
polyostotic sclerosing histiocytosis

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about Erdheim-Chester disease?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding Erdheim-Chester disease?

apoptosis ; bone density ; cancer ; cell ; class ; diabetes ; differentiation ; exophthalmos ; fever ; gene ;hormone ; hypertension ; immune system ; infection ; infertility ; inflammation ; inherited ; kidney ;lipid ; mutation ; nucleus ; pituitary gland ; precursor ; prevalence ; proliferation ; protein ; RAS ;somatic mutation ; tissue

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (7 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook