Erdheim-Chester disease
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.
Overview
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.
State of the art
- Erdheim-Chester disease is the first histiocytosis with an approved targeted drug.
- Plasma BRAF V600E DNA gives a blood test for disease burden.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Targeted BRAF and MEK inhibition controls the disease in most patients and has normalised life expectancy for many.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Check before combiningFood and drink: Dabrafenib + trametinib
Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
- Check before combiningFood and drink: Vemurafenib
Severe photosensitivity: sun protection.
- Check before combiningHeart rhythm (QT): Vemurafenib
Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
- Check before combiningKidneys: Methotrexate
High-dose methotrexate requires normal renal function, hydration, urine alkalinisation and leucovorin rescue with level monitoring.
See all on the product pages:CladribineCobimetinibDabrafenib + trametinibMethotrexateVemurafenib·Printable cards in the navigator
Anatomy and lymph node drainage
- Bone marrow (leukaemia, MDS, MPN, myeloma)
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- Nodes: cervical
- Nodes: axillary
- Nodes: mediastinal
- Nodes: para-aortic and mesenteric
- Nodes: inguinal
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
- Bone marrow (leukaemia, MDS, MPN, myeloma)Mixed Erdheim-Chester and Langerhans cell histiocytosis · Erdheim-Chester disease with an associated myeloid neoplasm
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- cervical
- axillary
- mediastinal
- para-aortic and mesenteric
- inguinal
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), Early-stage classical Hodgkin lymphoma (stage I to II), Advanced-stage classical Hodgkin lymphoma (stage III to IV), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
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.
- Liquid biopsy (ctDNA)Standard of care
- MRIStandard of care
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Biopsy of an accessible lesion with BRAF V600E testing and broader sequencing; FDG-PET/CT, cardiac and brain MRI, endocrine assessment.
Vemurafenib (approved 2017) or dabrafenib with trametinib; cobimetinib as an alternative; dose reduction to limit toxicity, treatment continued long term.
Cobimetinib (approved 2022 for histiocytic neoplasms); trametinib as an alternative MEK inhibitor.
Interferon alfa or pegylated interferon, anakinra, cladribine, methotrexate.
Observation with periodic PET and organ screening.
Subtypes & biomarkers
top- 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
- 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
How often this target appears
- 1930Jakob Erdheim and William Chester describe lipoid granulomatosis
- 2005Interferon alfa shown to prolong survival in a retrospective series
- 2012BRAF V600E found in more than half of patients
- 2016Revised histiocytosis classification places Erdheim-Chester and Langerhans cell histiocytosis together in the L group
- 2017Vemurafenib approved for BRAF V600E-mutant Erdheim-Chester disease (VE-BASKET)
- 2019Cobimetinib phase 2 shows responses in most patients regardless of mutation
- 2022Cobimetinib approved for histiocytic neoplasms in the United States
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 14 changes by month →- 2026-09-18This recordErdheim-Chester diseaseFacts on this page last checked
When this page itself was last checked or edited.
- 2022MilestoneCobimetinibCobimetinib approved for histiocytic neoplasms in the United States
A milestone in how this cancer is treated.
- 2020GuidelineErdheim-Chester diseaseGuideline Consensus recommendations for Erdheim-Chester disease (Blood 2020): Asymptomatic bone-limited disease
Observation with periodic PET and organ screening.
- 2020GuidelineErdheim-Chester diseaseGuideline Consensus recommendations for Erdheim-Chester disease (Blood 2020): 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.
- 2020GuidelineErdheim-Chester diseaseGuideline Consensus recommendations for Erdheim-Chester disease (Blood 2020): BRAF wild-type symptomatic disease
Cobimetinib (approved 2022 for histiocytic neoplasms); trametinib as an alternative MEK inhibitor.
- 2020GuidelineErdheim-Chester diseaseGuideline Consensus recommendations for Erdheim-Chester disease (Blood 2020): Diagnosis
Biopsy of an accessible lesion with BRAF V600E testing and broader sequencing; FDG-PET/CT, cardiac and brain MRI, endocrine assessment.
What is in development for Erdheim-Chester disease, drawn from the whole corpus: 0 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Nothing recorded in development for this cancer yet.
Open problems and what is being done
Kinase inhibitors are usually needed for life and relapse follows their withdrawal.
and how the field plans to fix it →What is being done about thisRecurrence and residual diseaseAvailable now- Liquid biopsy (ctDNA)Standard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Background: Circulating tumour DNA (ctDNA). Also on OnCo: Treatment journeys · Survivorship planner.
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.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Expert centres
topExpert centres
New York · cancer center | United States | 0 | 5,100 | 94,456 | #1 | ||
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Boston · hospital | United States | 0 | 3,582 | 54,857 | #16 | ||
Shanghai · hospital | China | none recorded | 0 | 2,872 | 31,534 | - | |
London · hospital | United Kingdom | none recorded | 0 | 2,376 | 28,940 | - | |
Barcelona · hospital | Spain | none recorded | 0 | 1,265 | 15,631 | - | |
Lyon · cancer center | France | none recorded | 0 | 1,071 | 14,301 | - | |
Naples · cancer center | Italy | none recorded | 0 | 961 | 15,028 | - | |
Oslo · cancer center | Norway | none recorded | 0 | 936 | 11,600 | - | |
Changsha · cancer center | China | none recorded | 0 | 930 | 14,477 | - | |
Taipei · hospital | Taiwan | none recorded | 0 | 746 | 8,966 | - | |
Marseille · cancer center | France | none recorded | 0 | 738 | 7,479 | - | |
Guangzhou · hospital | China | none recorded | 0 | 704 | 7,832 | - | |
Nagoya · cancer center | Japan | none recorded | 0 | 657 | 8,832 | - | |
Shanghai · hospital | China | none recorded | 0 | 539 | 6,491 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Erdheim-Chester disease but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Erdheim-Chester disease
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example BRAF V600E in tissue and plasma cell-free DNA, 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, Cardiac MRI, brain MRI and pituitary function), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include BRAF V600E-mutant Erdheim-Chester disease, BRAF wild-type Erdheim-Chester disease with MAP2K1, ARAF, RAS or PIK3CA mutations, Erdheim-Chester disease with cardiac or central nervous system involvement.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Diagnosis
- For my situation (diagnosis), which of the standard options do you recommend and why?Why: Guideline options include: Biopsy of an accessible lesion with BRAF V600E testing and broader sequencing; FDG-PET/CT, cardiac and brain MRI, endocrine assessment.
BRAF V600E-mutant symptomatic disease
- For my situation (braf v600e-mutant symptomatic disease), which of the standard options do you recommend and why?Why: Guideline options include: Vemurafenib (approved 2017) or dabrafenib with trametinib; cobimetinib as an alternative; dose reduction to limit toxicity, treatment continued long term.
- Am I a candidate for Vemurafenib, Dabrafenib + trametinib, Cobimetinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
BRAF wild-type symptomatic disease
- For my situation (braf wild-type symptomatic disease), which of the standard options do you recommend and why?Why: Guideline options include: Cobimetinib (approved 2022 for histiocytic neoplasms); trametinib as an alternative MEK inhibitor.
- Am I a candidate for Cobimetinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Second-choice or intolerant
- For my situation (second-choice or intolerant), which of the standard options do you recommend and why?Why: Guideline options include: Interferon alfa or pegylated interferon, anakinra, cladribine, methotrexate.
- Am I a candidate for Interferon alfa-2a/2b, Cladribine, Methotrexate, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Asymptomatic bone-limited disease
- For my situation (asymptomatic bone-limited disease), which of the standard options do you recommend and why?Why: Guideline options include: Observation with periodic PET and organ screening.
Any stage
- Are there clinical trials I could join, for example of Cobimetinib, Vemurafenib, Dabrafenib + trametinib?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Kinase inhibitors are usually needed for life and relapse follows their withdrawal”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Long-term cardiac, skin and secondary-cancer effects of indefinite BRAF and MEK inhibition are unknown”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Erdheim-Chester disease, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
8targets
2drugs
6companies
4pathways
1terms
4key papers
4The names and definitions on a marrow report (for example MDS with biallelic TP53 inactivation, or AML myelodysplasia-related) come from this document or from the parallel International Consensus Classification.
The diagnostic and treatment rows on the Erdheim-Chester page follow these recommendations.
Erdheim-Chester disease with a BRAF V600E mutation is treated first with a BRAF inhibitor; the first targeted approval in any histiocytosis.
The way OnCo groups the histiocytoses, and the recognition that LCH and ECD are cancers rather than inflammatory conditions, come from this classification.
Latest papers
topQuery for this cancer: (TITLE:"Erdheim-Chester disease" OR ABSTRACT:"Erdheim-Chester disease" OR TITLE:"ECD" OR ABSTRACT:"ECD" OR TITLE:"Polyostotic sclerosing histiocytosis" OR ABSTRACT:"Polyostotic sclerosing histiocytosis" OR TITLE:"L-group histiocytosis adult" OR ABSTRACT:"L-group histiocytosis adult" OR TITLE:"BRAF-mutant histiocytosis" OR ABSTRACT:"BRAF-mutant histiocytosis") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Erdheim-Chester disease, not a curated reading list.
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