Erdheim-Chester disease

Erdheim-Chester disease (ECD) is rare form of non-Langerhans cells histiocytosis with multiorgan involvement. Individuals are more frequently affected in their fifth decade and there is a slight male prevalence. Recent studies have demonstrated that ECD patients bare mutations in the proto-oncogene BRAF (and more rarely in other genes involved in the MAPK activation pathway), suggesting a critical role of this pathway in the pathogenesis and a possible clonal origin of the disease. Clinical manifestations are extremely protean and virtually every organ system can be affected. The most common clinical features include skeletal involvement with typical bilateral osteosclerotic lesions of long bones of the lower limbs, diabetes insipidus, cardiovascular involvement with circumferential thickening of the aorta (“coated aorta”), and retroperitoneal fibrosis (“hairy kidney”). Cardiovascular and central nervous system (CNS) involvement are associated with the worst prognosis. Biopsy is necessary to establish a definite diagnosis with the identification of CD68+/CD1a−/S100− foamy histiocytes. Currently, interferon-α is the first-line treatment in ECD, as it has been clearly demonstrated to increase overall survival. Anakinra and infliximab have also led to encouraging results and should be taken into consideration when treatment with interferon-α fails. More recently, the BRAF-inhibitor vemurafenib has been used in small groups of ECD patients with optimal efficacy in all treated cases. Nevertheless, its adverse effects and the scanty data on its long-term efficacy and safety still discourage its use as a first-line option. Further studies are still warranted to better understand and treat this neglected and overlooked disease.