{"entity":{"id":"erdheim-chester-disease","kind":"cancer","name":"Erdheim-Chester disease","aka":["ECD","Polyostotic sclerosing histiocytosis","L-group histiocytosis (adult)","BRAF-mutant histiocytosis"],"tldr":"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.\n\nInterferon 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.","asOf":"2026-09-18","wikipedia":"https://en.wikipedia.org/wiki/Erdheim%E2%80%93Chester_disease","links":[{"label":"ECD consensus recommendations (Blood 2020)","url":"https://doi.org/10.1182/blood.2019003507"},{"label":"Cobimetinib in histiocytosis (Nature 2019)","url":"https://doi.org/10.1038/s41586-019-1012-y"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Erdheim%E2%80%93Chester_disease"}],"tags":["subtype-page","haematologic"],"related":["rosai-dorfman-disease","histiocytoses","lch-multisystem","braf-v600-melanoma"],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","fdg-pet","liquid-biopsy","cgp","mri","active-surveillance"],"targets":["braf","pik3ca"],"drugs":["vemurafenib","cobimetinib","dabrafenib-trametinib","interferon-alfa","cladribine","methotrexate"],"companies":[],"institutions":[],"pathways":[],"terms":["braf-v600-mutation","driver-mutation","ctdna","retroperitoneum"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-who-2022-myeloid-khoury-leukemia-2022","paper-ve-basket-vemurafenib-erdheim-chester-lch-jama-oncol-2018","paper-erdheim-chester-disease-consensus-recommendations-blood-2020","paper-emile-revised-classification-of-histiocytoses-blood-2016"],"journals":[],"dependsOn":[],"notes":[],"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"],"standardOfCare":[{"setting":"Diagnosis","approach":"Biopsy of an accessible lesion with BRAF V600E testing and broader sequencing; FDG-PET/CT, cardiac and brain MRI, endocrine assessment.","refs":["braf-v600-mutation","cgp","fdg-pet","mri","liquid-biopsy"],"guideline":{"version":"Consensus recommendations for Erdheim-Chester disease (Blood 2020)","url":"https://doi.org/10.1182/blood.2019003507"}},{"setting":"BRAF V600E-mutant symptomatic disease","approach":"Vemurafenib (approved 2017) or dabrafenib with trametinib; cobimetinib as an alternative; dose reduction to limit toxicity, treatment continued long term.","refs":["vemurafenib","dabrafenib-trametinib","cobimetinib","braf","kinase-inhibitors"],"guideline":{"version":"Consensus recommendations for Erdheim-Chester disease (Blood 2020)","url":"https://doi.org/10.1182/blood.2019003507"}},{"setting":"BRAF wild-type symptomatic disease","approach":"Cobimetinib (approved 2022 for histiocytic neoplasms); trametinib as an alternative MEK inhibitor.","refs":["cobimetinib","ras-mapk","kinase-inhibitors"],"guideline":{"version":"Consensus recommendations for Erdheim-Chester disease (Blood 2020)","url":"https://doi.org/10.1182/blood.2019003507"}},{"setting":"Second-choice or intolerant","approach":"Interferon alfa or pegylated interferon, anakinra, cladribine, methotrexate.","refs":["interferon-alfa","cladribine","methotrexate"],"guideline":{"version":"Consensus recommendations for Erdheim-Chester disease (Blood 2020)","url":"https://doi.org/10.1182/blood.2019003507"}},{"setting":"Asymptomatic bone-limited disease","approach":"Observation with periodic PET and organ screening.","refs":["fdg-pet","active-surveillance"],"guideline":{"version":"Consensus recommendations for Erdheim-Chester disease (Blood 2020)","url":"https://doi.org/10.1182/blood.2019003507"}}],"stateOfArt":["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."],"history":[{"year":1930,"title":"Jakob Erdheim and William Chester describe lipoid granulomatosis","refs":[]},{"year":2005,"title":"Interferon alfa shown to prolong survival in a retrospective series","refs":["interferon-alfa"]},{"year":2012,"title":"BRAF V600E found in more than half of patients","refs":["braf","braf-v600-mutation"]},{"year":2016,"title":"Revised histiocytosis classification places Erdheim-Chester and Langerhans cell histiocytosis together in the L group","refs":[]},{"year":2017,"title":"Vemurafenib approved for BRAF V600E-mutant Erdheim-Chester disease (VE-BASKET)","refs":["vemurafenib"]},{"year":2019,"title":"Cobimetinib phase 2 shows responses in most patients regardless of mutation","refs":["cobimetinib"]},{"year":2022,"title":"Cobimetinib approved for histiocytic neoplasms in the United States","refs":["cobimetinib"]}],"pipeline":["cobimetinib","vemurafenib","dabrafenib-trametinib"],"openProblems":["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."],"parent":"histiocytoses"},"route":"/cancers/erdheim-chester-disease/","neighbours":{"cancer":[{"id":"braf-v600-melanoma","kind":"cancer","name":"BRAF V600-mutant melanoma","route":"/cancers/braf-v600-melanoma/"},{"id":"histiocytoses","kind":"cancer","name":"Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms","route":"/cancers/histiocytoses/"},{"id":"lch-multisystem","kind":"cancer","name":"Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement)","route":"/cancers/lch-multisystem/"},{"id":"rosai-dorfman-disease","kind":"cancer","name":"Rosai-Dorfman-Destombes disease","route":"/cancers/rosai-dorfman-disease/"}],"technology":[{"id":"active-surveillance","kind":"technology","name":"Active surveillance","route":"/technologies/active-surveillance/"},{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"}],"drug":[{"id":"cladribine","kind":"drug","name":"Cladribine","route":"/drugs/cladribine/"},{"id":"cobimetinib","kind":"drug","name":"Cobimetinib","route":"/drugs/cobimetinib/"},{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","route":"/drugs/dabrafenib-trametinib/"},{"id":"interferon-alfa","kind":"drug","name":"Interferon alfa-2a/2b","route":"/drugs/interferon-alfa/"},{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"},{"id":"vemurafenib","kind":"drug","name":"Vemurafenib","route":"/drugs/vemurafenib/"}],"term":[{"id":"braf-v600-mutation","kind":"term","name":"BRAF V600E mutation","route":"/terms/braf-v600-mutation/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"retroperitoneum","kind":"term","name":"Retroperitoneum","route":"/terms/retroperitoneum/"}],"paper":[{"id":"paper-erdheim-chester-disease-consensus-recommendations-blood-2020","kind":"paper","name":"Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis and treatment in the molecular era","route":"/key-papers/paper-erdheim-chester-disease-consensus-recommendations-blood-2020/"},{"id":"paper-emile-revised-classification-of-histiocytoses-blood-2016","kind":"paper","name":"Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages","route":"/key-papers/paper-emile-revised-classification-of-histiocytoses-blood-2016/"},{"id":"paper-ve-basket-vemurafenib-erdheim-chester-lch-jama-oncol-2018","kind":"paper","name":"VE-BASKET: vemurafenib for BRAF V600-mutant Erdheim-Chester disease and Langerhans cell histiocytosis","route":"/key-papers/paper-ve-basket-vemurafenib-erdheim-chester-lch-jama-oncol-2018/"},{"id":"paper-who-2022-myeloid-khoury-leukemia-2022","kind":"paper","name":"WHO classification of haematolymphoid tumours, fifth edition: myeloid and histiocytic neoplasms","route":"/key-papers/paper-who-2022-myeloid-khoury-leukemia-2022/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}]}}