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Erdheim-Chester disease
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Erdheim-Chester disease

Erdheim-Chester disease is a rare, slow-growing blood cancer that causes an overproduction of histiocytes, leading to inflammation, tissue scarring, and potential organ damage throughout the body.

Overview & Symptoms

Erdheim-Chester disease is a rare type of slow-growing blood cancer called a histiocytic neoplasm, which results in overproduction of cells called histiocytes. Histiocytes normally function to destroy foreign substances and protect the body from infection. In Erdheim-Chester disease, the excess production of histiocytes (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.

Frequency

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.

Causes & Genetic Factors

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.

Associated Genes

  • BRAF

Inheritance

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

Other Names for This Condition

  • Lipid granulomatosis
  • Polyostotic sclerosing histiocytosis

Frequently Asked Questions

More than 50 percent of Erdheim-Chester cases harbor a BRAF V600E somatic mutation. Detecting this mutation allows the use of targeted BRAF inhibitors, such as vemurafenib or dabrafenib, which have transformed ECD treatment by rapidly reducing tumor burden and organ inflammation. If the patient tests negative for BRAF V600E, next-generation sequencing is performed to look for other MAPK pathway alterations that can be treated with MEK inhibitors like cobimetinib.
Patients receiving targeted BRAF or MEK inhibitors require continuous surveillance, including PET/CT scans every 3 to 6 months initially to assess treatment response, regular echocardiograms and electrocardiograms to monitor cardiac function and QT interval changes, and frequent dermatologic exams to identify secondary cutaneous skin lesions or squamous cell carcinomas triggered by kinase inhibitor therapy.
Central diabetes insipidus occurs when histiocytes infiltrate the pituitary stalk or hypothalamus, impairing the production of antidiuretic hormone. It is managed with synthetic desmopressin (DDAVP), administered orally, sublingually, or intranasally. While targeted cancer therapies (such as BRAF or MEK inhibitors) address the underlying disease, desmopressin is typically required indefinitely because structural pituitary damage is often irreversible.
full diagnostic workup requires multimodal imaging. Technetium-99m bone scintigraphy or 18F-FDG PET/CT is critical because nearly 95 percent of patients display symmetric cortical osteosclerosis in the lower extremities (long bones). Abdominal CT or MRI is used to detect retroperitoneal infiltration, often described as a hairy kidney or coated aorta appearance. In addition, brain MRI and cardiac MRI are essential to check for brainstem, pituitary, or pericardial histiocytic involvement.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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