Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytic disorder most commonly characterized by multifocal osteosclerotic lesions of the long bones demonstrating sheets of foamy histiocytes on biopsy with or without histiocytic infiltration of extraskeletal tissues. ECD was first described by Erdheim and Chester in 1930 . Only several hundred cases have been reported in the medical literature since that time.
Histocytic disorders are thought to be derived from mononuclear phagocytic cells (macrophages and dendritic cells) or histiocytes. This group has generally been divided into Langerhans cell histiocytosis and non-Langerhans histiocytosis. Langerhans cell histiocytosis is so named for its presumed derivation from the Langerhans cells, which are specialized dendritic cells found in the skin and mucosa. In contrast, non-Langerhans histiocytoses are thought to be derived from the monocyte-macrophage lineage.
The epidemiology, clinical manifestations, pathologic features, diagnosis, and management of ECD will be presented here. The diagnosis and management of Langerhans cell histiocytosis is presented separately. (See "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis" and "Pulmonary Langerhans cell histiocytosis" and "Langerhans cell histiocytosis (eosinophilic granuloma) of bone in children".)
Erdheim-Chester disease (ECD) is a rare histiocytic disorder and the incidence is unknown. Fewer than 500 cases have been reported in the published literature . ECD has been diagnosed in all age groups, but is most common in adults. The mean age at diagnosis is 53 years . There is a slight male predominance. Although there is speculation that ECD and other histiocyte disorders may represent an aberrant response to infection, no infectious etiology has been identified. There is no evidence that ECD is an inheritable genetic disorder.
The pathogenesis of Erdheim-Chester disease (ECD) is poorly understood. Attempts to establish clonality have produced varied results, and although occasional clonal cytogenetic aberrations have been identified, none are characteristic or diagnostic [3-5]. A study of tissue from a single patient demonstrated inducible production of tumor necrosis factor-α (TNF-α) as well as spontaneous secretion of interleukin (IL)-6 and CXC chemokine ligand 8/IL-8 (CXCL8/IL-8), which is known to attract monocytes and polymorphonuclear cells [6,7]. Data from a larger series of patients demonstrated that the cellular infiltrate of ECD contains a significant number of T cell helper 1 (Th-1) lymphocytes, and the infiltrating histiocytes express the interferon-gamma induced chemokine CXCL10/IP-10 as well as IL-1 . Subsequent studies demonstrated a significant increase in the serum levels of IFN-α but not interferon-gamma in untreated ECD patients compared with controls.