Erdheim-Chester disease is an extremely rare multisystem neoplasm characterised by excessive production and accumulation of histiocytes within organs and tissues.

It was discovered in 1930 by Jacob Erdheim and William Chester. The term was coined by Jaffe in 1972 to describe this rare disorder characterised by the infiltration of bone marrow with histiocytes, macrophages, lymphocytes and multi-nucleated giant cells. In nearly half of patients, there is mutation of the BRAF gene (V600E). Immunohistochemistry revealed that ECD histiocytes are positive for CD68, CD163, and factor XIIIa, and negative for CD1a, S100 protein and langerin (CD207). ECD is a clonal disorder with recurrent BRAFV600E mutations in more than half of the patients in whom chronic uncontrolled inflammation is an important mediator of disease pathogenesis, due to frequent hyperactivation of mitogen-activated protein kinase signalling.
Nearly 550 cases have been described in the literature to date. It is usually a disease presenting in adulthood, between the 4th and 7th decade of life (40–70 years of age), with slight male preponderance. It can also, rarely, present in childhood. The major sites of involvement include the long bones (with epiphyseal sparing), cardiovascular system, lungs, orbit, brain, retroperitoneum and the skin. The commonest presenting complaint is bone pain.
Non-osseous involvement includes fibrotic infiltration of the cerebral, retroperitoneal, retro- orbital, pericardial and pulmonary tissues. Other general symptoms include fever, polyuria, polydipsia, weight loss, weakness, night sweats and fatigue. Children may present with failure to thrive, though it is rare in the paediatric population. The characteristic radiographic feature of ECD is bilateral and symmetrical osteosclerosis in the di-metaphyseal region, with sparing of epiphyses and the axial skeleton, although this is not universally present. 99mTc bone scintigraphy typically demonstrates symmetric and abnormally strong 99mTc labelling of the distal ends of the long bones. A similar finding can be observed in a positron emission tomography scan. Central nervous system involvement occurs in nearly half of all patients and can manifest as diabetes insipidus, exophthalmos, cerebellar ataxia, panhypopituitarism and papilloedema. A macrophage activation syndrome (MAS) is a dreaded complication which can be triggered in patients of severe ECD due to various stressors like infection and surgery.