# Erdheim-Chester disease

Source: https://onco.cc/cancers/erdheim-chester-disease/  
OnCo record `erdheim-chester-disease` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Erdheim-Chester disease is a rare histiocytosis, a cancer-like overgrowth of immune cells called histiocytes that scar the long bones, the tissue around the kidneys and heart, the brain and the skin. Most cases carry the BRAF V600E mutation or another fault in the same growth pathway, and the melanoma drugs vemurafenib and cobimetinib now control the disease in most patients.

## Summary

Erdheim-Chester disease is a clonal neoplasm of foamy CD68-positive, CD1a-negative histiocytes that infiltrate and fibrose tissues in a characteristic distribution: symmetrical sclerosis of the long bones (seen on bone scan and PET in almost every patient), a rind of tissue around the kidneys and aorta ('hairy kidney' and 'coated aorta'), infiltration of the heart and pericardium, the pituitary (diabetes insipidus), the cerebellum and brainstem, the orbits and the skin (xanthelasma-like plaques). It was reclassified in 2016 with Langerhans cell histiocytosis in the L group of histiocytoses because the two share MAPK pathway mutations and often occur together, and the WHO now lists it among myeloid neoplasms; in some patients the histiocytes derive from a clone that also produces a myeloid neoplasm such as chronic myelomonocytic leukaemia. BRAF V600E is found in more than half of patients, and most of the rest have mutations in MAP2K1, ARAF, NRAS, KRAS or PIK3CA or kinase fusions, so the disease is almost always driven by one activating lesion in the RAS-MAPK pathway.

Interferon alfa, the standard from the 1990s to the 2010s, slowed the disease but rarely reversed it. The discovery of BRAF V600E in 2012 led to treatment with vemurafenib, which in the VE-BASKET trial produced responses in most patients and in 2017 became the first drug approved for Erdheim-Chester disease, and to the MEK inhibitor cobimetinib, which produced responses in most patients with or without a BRAF mutation in a phase 2 trial (Nature Medicine 2019) and was approved in the United States in 2022 for histiocytic neoplasms including Erdheim-Chester disease, Langerhans cell histiocytosis and Rosai-Dorfman disease. Dabrafenib with trametinib is used as an alternative BRAF-directed regimen. The 2020 consensus recommendations (Blood) advise targeted therapy for all patients with symptomatic or organ-threatening disease, with interferon alfa, anakinra, cladribine or methotrexate as second-choice options, and observation for the minority with asymptomatic disease confined to bone. Kinase inhibitors are usually continued indefinitely because relapse follows withdrawal, at doses lowered to limit skin, joint and cardiac toxicity, and plasma BRAF V600E cell-free DNA is used to follow response. Survival has improved from a median of a few years to a normal life expectancy for most patients treated early.

## Fields

- Kind: Cancer
- Last checked: 2026-09-18
- Also known as: ECD; Polyostotic sclerosing histiocytosis; L-group histiocytosis (adult); BRAF-mutant histiocytosis
- Tags: subtype-page; haematologic
- Group: haematologic
- Burden: A rare disease of adults in their fifties and sixties, with a few hundred cases described before 2010 and many more since BRAF testing and PET became routine; men are affected more often than women.
- Subtypes: BRAF V600E-mutant Erdheim-Chester disease (vemurafenib, dabrafenib-trametinib, cobimetinib); BRAF wild-type Erdheim-Chester disease with MAP2K1, ARAF, RAS or PIK3CA mutations (cobimetinib); Erdheim-Chester disease with cardiac or central nervous system involvement (urgent targeted therapy); Bone-limited asymptomatic Erdheim-Chester disease (observation); Mixed Erdheim-Chester and Langerhans cell histiocytosis; Erdheim-Chester disease with an associated myeloid neoplasm
- Biomarkers: BRAF V600E in tissue and plasma cell-free DNA (diagnosis and monitoring); MAP2K1, ARAF, NRAS, KRAS, PIK3CA and kinase fusions on sequencing; CD68 and CD163 positive, CD1a and langerin negative histiocytes with Touton giant cells; FDG-PET/CT for extent and response (long bone uptake); Cardiac MRI, brain MRI and pituitary function; Blood count and myeloid mutation panel for an associated clonal myeloid neoplasm

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/erdheim-chester-disease/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/erdheim-chester-disease/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/erdheim-chester-disease/#what-it-is [6 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/erdheim-chester-disease/#finding-it [6 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/erdheim-chester-disease/#treating-it [5 settings, 5 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/erdheim-chester-disease/#evidence [5 key papers, 7 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/erdheim-chester-disease/#science [3 targets, 1 pathway]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/erdheim-chester-disease/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/erdheim-chester-disease/#living-with-it [17 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/erdheim-chester-disease/coming/ [6 medicines, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/erdheim-chester-disease/data/ [31 connected records]

## Standard of care

- Diagnosis: Biopsy of an accessible lesion with BRAF V600E testing and broader sequencing; FDG-PET/CT, cardiac and brain MRI, endocrine assessment. ([BRAF V600E mutation](https://onco.cc/terms/braf-v600-mutation/), [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [FDG PET](https://onco.cc/technologies/fdg-pet/), [MRI](https://onco.cc/technologies/mri/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/))
- BRAF V600E-mutant symptomatic disease: Vemurafenib (approved 2017) or dabrafenib with trametinib; cobimetinib as an alternative; dose reduction to limit toxicity, treatment continued long term. ([Vemurafenib](https://onco.cc/drugs/vemurafenib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Cobimetinib](https://onco.cc/drugs/cobimetinib/), [BRAF](https://onco.cc/targets/braf/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/))
- BRAF wild-type symptomatic disease: Cobimetinib (approved 2022 for histiocytic neoplasms); trametinib as an alternative MEK inhibitor. ([Cobimetinib](https://onco.cc/drugs/cobimetinib/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/))
- Second-choice or intolerant: Interferon alfa or pegylated interferon, anakinra, cladribine, methotrexate. ([Interferon alfa-2a/2b](https://onco.cc/drugs/interferon-alfa/), [Cladribine](https://onco.cc/drugs/cladribine/), [Methotrexate](https://onco.cc/drugs/methotrexate/))
- Asymptomatic bone-limited disease: Observation with periodic PET and organ screening. ([FDG PET](https://onco.cc/technologies/fdg-pet/), [Active surveillance](https://onco.cc/technologies/active-surveillance/))

## State of the art

- Targeted BRAF and MEK inhibition controls the disease in most patients and has normalised life expectancy for many.
- Erdheim-Chester disease is the first histiocytosis with an approved targeted drug.
- Plasma BRAF V600E DNA gives a blood test for disease burden.

## Open problems

- Kinase inhibitors are usually needed for life and relapse follows their withdrawal.
- Long-term cardiac, skin and secondary-cancer effects of indefinite BRAF and MEK inhibition are unknown.
- Established fibrosis and neurological damage do not reverse.
- Diagnosis is still delayed by years because the disease is unfamiliar.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Erdheim%E2%80%93Chester_disease
- ECD consensus recommendations (Blood 2020): https://doi.org/10.1182/blood.2019003507
- Cobimetinib in histiocytosis (Nature 2019): https://doi.org/10.1038/s41586-019-1012-y
- Wikipedia: https://en.wikipedia.org/wiki/Erdheim%E2%80%93Chester_disease

## Connected records

- cancers: [BRAF V600-mutant melanoma](https://onco.cc/cancers/braf-v600-melanoma/), [Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms](https://onco.cc/cancers/histiocytoses/), [Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement)](https://onco.cc/cancers/lch-multisystem/), [Rosai-Dorfman-Destombes disease](https://onco.cc/cancers/rosai-dorfman-disease/)
- technologies: [Active surveillance](https://onco.cc/technologies/active-surveillance/), [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [FDG PET](https://onco.cc/technologies/fdg-pet/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRI](https://onco.cc/technologies/mri/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ARAF](https://onco.cc/targets/araf/), [BRAF](https://onco.cc/targets/braf/), [PIK3CA / PI3K-alpha](https://onco.cc/targets/pik3ca/)
- drugs: [Cladribine](https://onco.cc/drugs/cladribine/), [Cobimetinib](https://onco.cc/drugs/cobimetinib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Interferon alfa-2a/2b](https://onco.cc/drugs/interferon-alfa/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Vemurafenib](https://onco.cc/drugs/vemurafenib/)
- terms: [BRAF V600E mutation](https://onco.cc/terms/braf-v600-mutation/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Driver mutation](https://onco.cc/terms/driver-mutation/), [Retroperitoneum](https://onco.cc/terms/retroperitoneum/)
- key papers: [Efficacy of MEK inhibition in patients with histiocytic neoplasms](https://onco.cc/key-papers/paper-diamond-nature/), [Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis and treatment in the molecular era](https://onco.cc/key-papers/paper-erdheim-chester-disease-consensus-recommendations-blood-2020/), [Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages](https://onco.cc/key-papers/paper-emile-revised-classification-of-histiocytoses-blood-2016/), [VE-BASKET: vemurafenib for BRAF V600-mutant Erdheim-Chester disease and Langerhans cell histiocytosis](https://onco.cc/key-papers/paper-ve-basket-vemurafenib-erdheim-chester-lch-jama-oncol-2018/), [WHO classification of haematolymphoid tumours, fifth edition: myeloid and histiocytic neoplasms](https://onco.cc/key-papers/paper-who-2022-myeloid-khoury-leukemia-2022/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)

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JSON: https://onco.cc/api/v1/entities/erdheim-chester-disease.json