Erdheim-Chester disease

Erdheim-Chester disease (ECD), also known as Erdheim-Chester histiocytosis or polyostotic sclerosing histiocytosis, is a rare non-Langerhans cell histiocytosis characterized by the abnormal accumulation and infiltration of lipid-laden histiocytes (a type of immune cell called macrophages) into various tissues and organs. It was first described in 1930 and is now classified as a histiocytic neoplasm. The disease most commonly affects the long bones, but it is a multisystemic disorder that can involve nearly any organ system, including the cardiovascular system (coating of the aorta and heart), the central nervous system (brain lesions, diabetes insipidus), the retroperitoneum (encasement of the kidneys, known as 'hairy kidney'), the lungs, the skin, and the orbits (causing bulging eyes or exophthalmos). The hallmark finding of ECD is bilateral symmetric osteosclerosis (abnormal hardening) of the long bones, particularly the femur and tibia, which can be detected on bone X-rays or bone scintigraphy. Patients frequently present with bone pain, diabetes insipidus due to pituitary involvement, exophthalmos, and cardiovascular complications. Neurological involvement can include cerebellar dysfunction, and retroperitoneal fibrosis may lead to kidney obstruction. The severity of the disease varies widely, ranging from asymptomatic bone lesions to life-threatening multisystem involvement. A major breakthrough in understanding ECD came with the discovery that approximately 50-60% of patients harbor the BRAF V600E mutation, and additional mutations in the MAPK/ERK signaling pathway (such as MAP2K1, NRAS, KRAS, and PIK3CA) have been identified in many remaining cases. This has transformed the treatment landscape. The BRAF inhibitor vemurafenib was approved by the FDA in 2017 specifically for ECD patients with the BRAF V600E mutation, representing the first targeted therapy for this condition. Other treatments include MEK inhibitors (such as cobimetinib) for patients with or without BRAF mutations, interferon-alpha (previously a first-line therapy), and in some cases, cladribine or anakinra. Prognosis depends heavily on the extent of organ involvement, particularly cardiovascular and central nervous system disease.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Erdheim-Chester disease