Erdheim-Chester disease
Formal Definition
Erdheim-Chester disease (ECD) — a rare non-Langerhans cell histiocytosis characterized by infiltration of multiple organs by lipid-laden CD68+, CD1a- foamy histiocytes with admixed Touton giant cells, fibrosis, and chronic inflammation; classified as a myeloid neoplasm with clonal hematopoiesis (BRAF V600E mutation in ~50% of cases, other MAPK pathway mutations including NRAS, KRAS, MAP2K1 in additional subsets); commonly involves long bones (symmetric distal femoral/proximal tibial osteosclerosis on bone scan), CNS (diabetes insipidus, exophthalmos), cardiovascular (pericardial, periaortic "coated aorta" fibrosis), retroperitoneal (hairy kidney on CT), pulmonary, and skin sites.
How It's Used on the Ward
"ECD" — a rare histiocytic disorder diagnosed usually in middle-aged adults by the pathognomonic "coated aorta" on CT and "bilateral hairy kidney" sign, plus characteristic bone pain and symmetric long-bone involvement; non-Langerhans (vs the pediatric Langerhans cell histiocytosis); treatment has shifted from steroids/interferon to targeted BRAF/MEK inhibitors.
Example
""58-year-old man with months of bilateral symmetric bone pain in his shins, ankles, knees; progressive bilateral exophthalmos; new diabetes insipidus; leg claudication with ambulation. Bone scan: symmetric Tc-99m uptake in distal femurs/proximal tibias. CT chest/abdomen/pelvis: periaortic fibrosis encasing thoracic and abdominal aorta ("coated aorta"), perirenal soft tissue encasing kidneys without obstruction ("hairy kidney"). Perirenal biopsy: foamy CD68+ CD1a- histiocytes with Touton giant cells, BRAF V600E mutation positive. Diagnosis: Erdheim-Chester disease. Started vemurafenib (BRAF inhibitor) with dramatic symptom improvement.""
Clinical Context
Distinguishing from Langerhans cell histiocytosis (LCH): ECD has CD68+, CD1a- cells (vs CD1a+, Langerin+ in LCH), Touton giant cells, different epidemiology (adults vs children), different distribution (long bone symmetric in ECD, lytic lesions in LCH). Diagnostic triad of ECD: (1) bilateral symmetric long bone involvement (mandatory), (2) characteristic histology (foamy CD68+ CD1a- histiocytes), (3) at least 2 other organ systems with characteristic involvement. Workup: bone scan, PET for systemic involvement, brain MRI for CNS/exophthalmos/DI, cardiac MRI for pericardial/aortic involvement, kidney/wraparound appearance on CT. Treatment revolution: BRAF V600E mutation → vemurafenib targeted therapy (dramatic response). For BRAF wild-type: MEK inhibitors (cobimetinib, trametinib). Pre-targeted era: interferon-alpha, pegylated interferon, anakinra (IL-1R antagonist), cladribine. ECD natural history was historically poor but targeted therapy has significantly improved outcomes. Multidisciplinary care with hematology/oncology, cardiology (pericardial/aortic involvement), nephrology, endocrinology (DI), ophthalmology.