title: Clinical considerations and key issues in the management of patients with Erdheim-Chester Disease: a seven case series.
abstract: BACKGROUND
  Erdheim-Chester Disease (ECD), a non Langerhans' cell histiocytosis of orphan nature and propensity for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and complication management.
  
  
  OBJECTIVE
  The objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex patients.
  
  
  METHODS
  Patients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a coherent timeline of all the substantial clinical events in the evolution of their patients' illness.
  
  
  RESULTS
  Seven patients (five men, two women) were recruited to the study. The median age at presentation was 53 years (range: 39 to 62 years). The median follow-up time was 36 months (range: 1 to 72 months). Notable ECD involvement sites included the skeleton (seven), pituitary gland (seven), retroperitoneum (five), central nervous system (four), skin (four), lungs and pleura (four), orbits (three), heart and great vessels (three) and retinae (one). Prominent signs and symptoms were fever (seven), polyuria and polydipsia (six), ataxia and dysarthria (four), bone pain (four), exophthalmos (three), renovascular hypertension (one) and dyspnea (one). The V600E BRAF mutation was verified in three of six patients tested. Interferon-α treatment was beneficial in three of six patients treated. Vemurafenib yielded dramatic neurological improvement in a BRAF mutated patient. Infliximab facilitated pericardial effusion volume reduction. Cladribine improved cerebral blood flow originally compromised by perivenous lesions.
  
  
  CONCLUSIONS
  ECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements and strongly dependent on impaired RAS/RAF/MEK/ERK signaling.
authors.forename: Roei D
authors.initials: RD
authors.lastname: Mazor
authors.forename: Mirra
authors.initials: M
authors.lastname: Manevich-Mazor
authors.forename: Anat
authors.initials: A
authors.lastname: Kesler
authors.forename: Orna
authors.initials: O
authors.lastname: Aizenstein
authors.forename: Iris
authors.initials: I
authors.lastname: Eshed
authors.forename: Ronald
authors.initials: R
authors.lastname: Jaffe
authors.forename: Yakov
authors.initials: Y
authors.lastname: Pessach
authors.forename: Ilan
authors.initials: I
authors.lastname: Goldberg
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
authors.forename: Iris
authors.initials: I
authors.lastname: Yaish
authors.forename: Alexander
authors.initials: A
authors.lastname: Gural
authors.forename: Chezi
authors.initials: C
authors.lastname: Ganzel
authors.affiliation: The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel. shoenfel@post.tau.ac.il.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001706:Biopsy; D017338:Cladribine / Q000627:therapeutic use; D031249:Erdheim-Chester Disease / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D000069285:Infliximab; D007372:Interferons / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013449:Sulfonamides / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; D017338:Cladribine; D007372:Interferons; D000069285:Infliximab; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf