What is Erdheim-Chester disease?
Erdheim-Chester disease (ECD) is an ultra-rare disorder in which immune cells called histiocytes multiply abnormally and build up in tissues throughout the body. These cells carry fat-laden (foamy) material and cause thickening and scarring of the organs they infiltrate.
ECD is now classified as a histiocytic neoplasm (a slow-growing blood-cell disorder) because most patients have an acquired gene change in the MAPK signalling pathway. The commonest is the BRAF V600E mutation, found in over half of patients. This discovery has transformed treatment.
ECD usually appears in middle age and is slightly more common in men. Because it affects many organs, care is coordinated between pulmonology, haematology and oncology, cardiology, nephrology, endocrinology and neurology.
Symptoms of Erdheim-Chester disease
Symptoms depend on which organs are involved and often develop slowly over years.
- Bones: aching pain in the legs, particularly around the knees and ankles, is the commonest feature
- Lungs: dry cough and gradually increasing breathlessness, and some patients develop fluid around the lungs
- Kidneys: tissue around the kidneys and ureters can cause back discomfort or obstruct urine flow
- Heart and blood vessels: fluid around the heart, a mass in the right atrium, or thickening around the aorta
- Pituitary gland: excessive thirst and passing large volumes of urine (diabetes insipidus)
- Eyes and skin: bulging eyes, and yellowish fatty deposits on the eyelids
- Brain: unsteadiness, slurred speech or changes in behaviour
- General symptoms such as fever, tiredness and weight loss
Lung involvement is found in a substantial proportion of patients on CT, even when breathing symptoms are mild.
Causes
ECD arises from acquired (not inherited) mutations in histiocyte precursor cells, most often in BRAF and less often in MAP2K1, KRAS, NRAS or other genes in the same pathway. These mutations switch on growth signals and trigger chronic inflammation. ECD is not infectious and is not passed from parents to children. Some patients also have Langerhans cell histiocytosis at the same time.
How Erdheim-Chester disease is diagnosed
Diagnosis combines typical imaging with a tissue biopsy. Because ECD is rare and its features are scattered across many organs, it is often recognised late.
| Test | What it shows |
|---|---|
| Biopsy of an affected site | Foamy histiocytes that stain for CD68 and CD163 but not CD1a, confirming the diagnosis |
| BRAF and MAPK pathway mutation testing | The driver mutation, which determines targeted treatment |
| High-resolution CT chest | Thickened interlobular septa, small nodules, ground-glass change and pleural thickening |
| PET-CT and bone imaging | Symmetrical changes in the long bones of the legs and the overall extent of disease |
| Cardiac MRI and echocardiography | Heart, pericardial and aortic involvement |
| Brain and pituitary MRI | Nervous system and pituitary involvement |
| Lung function tests | Restriction and reduced gas transfer when the lungs are affected |
When lung tissue is needed, bronchoscopy with lavage and biopsy, or surgical lung biopsy, may be used, although a biopsy from bone or the tissue around the kidneys is often easier. The lung changes can look like other forms of interstitial lung disease or heart failure.
Treatment
Most patients with ECD need treatment, because untreated disease tends to progress and can damage the heart, brain and kidneys. Treatment is planned with haematology and oncology colleagues.
Targeted therapy
For patients with a BRAF V600E mutation, BRAF inhibitors such as vemurafenib or dabrafenib produce responses in most patients. For patients with other MAPK pathway mutations, or without a detectable mutation, MEK inhibitors such as cobimetinib are effective. These drugs control the disease rather than cure it, and treatment is usually long term.
Other treatments
Interferon-alpha has long been used as first-line treatment where targeted drugs are unsuitable or unavailable. Other options include cladribine, anakinra and methotrexate in selected patients.
Supportive care
Hormone replacement for diabetes insipidus, drainage of pleural or pericardial fluid, relief of kidney obstruction, and pain control for bone disease are added as needed. Lung disease is monitored with symptoms, lung function and CT.
Outlook and follow-up
Before targeted therapies, ECD carried a serious outlook, mostly because of heart and brain involvement. Survival has improved considerably with BRAF and MEK inhibitors. Regular follow-up with PET-CT, heart imaging and blood tests tracks response and monitors drug side effects, which include skin rashes, joint pain and heart rhythm changes.
When to seek urgent care
Seek urgent medical attention for breathlessness at rest or when lying flat, chest pain, fainting or palpitations, a sharp drop in urine output, sudden severe thirst with confusion, new weakness, unsteadiness or slurred speech, or high fever while on treatment.
Frequently asked questions
Is Erdheim-Chester disease a cancer?
It is classified as a histiocytic neoplasm, meaning the abnormal cells carry acquired gene changes and grow in an uncontrolled way. It usually behaves as a slowly progressive inflammatory disease rather than a typical cancer, and it is treated by haematology and oncology teams.
How common is lung involvement?
Lung changes are seen on CT in a substantial proportion of patients, although many have few or no breathing symptoms. Serious lung disease is less common than bone, kidney or heart involvement.
Why does BRAF testing matter?
Patients with the BRAF V600E mutation usually respond well to BRAF inhibitor tablets. Those without it may respond to MEK inhibitors. The mutation result therefore guides the choice of treatment.
Will I need treatment for life?
Targeted drugs control the disease but rarely cure it, and disease often returns if they are stopped. The duration of treatment is decided individually with the haematology and oncology team.
Is Erdheim-Chester disease inherited?
No. The gene changes are acquired during life in the abnormal cells and are not passed on to children.
Why did it take so long to diagnose?
ECD is ultra-rare and its symptoms appear in different organs at different times, so it often resembles more common conditions. Diagnosis usually needs specialist imaging and a biopsy reviewed by an experienced pathologist.
Related conditions and procedures
Consult Dr. Gogineni Ratnakara Rao
Apollo Hospitals, Financial District: Monday to Saturday, 8:30 AM to 5:00 PM. Anything in Lung Clinic, Chanda Nagar: Monday to Saturday (Thursday closed), 6:00 PM to 9:00 PM.