Erdheim-Chester disease: A systematic review

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans-cell histiocytosis, associated in more than 50% of cases to BRAF(V600E) mutations in early multipotent myelomonocytic precursors or in tissue-resident histiocytes. It encompasses a spectrum of disorders ranging from asymptomatic bone lesions to multisystemic, life-threatening variants. We reviewed all published reports of histologically-confirmed ECD and explored clinical, radiological, prognostic and therapeutic characteristics in a population of 448 patients, including a unique patient from our Department. To find a clinically relevant signature defining differentiated prognostic profiles, the patients' disease features were compared in relation to their CNS involvement that occurred in 56% of the entire population. Diabetes insipidus, visual disturbances, pyramidal and extra-pyramidal syndromes were the most recurrent neurological signs, whereas concomitant pituitary involvement, retro-orbital masses and axial lesions in the presence of symmetric bilateral osteosclerosis of long bones depicted the typical ECD clinical picture. Patients with CNS infiltration showed a lower occurrence of heart involvement and a higher incidence of bone, skin, retro-peritoneal, lung, aortic and renal infiltration. No difference in the therapeutic algorithm was found after stratification for CNS involvement. A better understanding of the disease pathogenesis, including BRAF deregulation, in keeping with improved prognostic criteria, will provide novel suggestions for the management of ECD. (C) 2015 Elsevier Ireland Ltd. All rights reserved.