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Phagocyte Biology & its Disorders
Prognostic factors of Erdheim–Chester disease: a nationwide survey in Japan
Takashi Toya,1* Mizuki Ogura,1* Kazuhiro Toyama,2 Akihide Yoshimi,1
Aya Shinozaki-Ushiku,3 Akira Honda,1 Kenjiro Honda,4 Noriko Hosoya,5 Yukako Murakami,6 Hiroyuki Kawashima,7 Yasuhito Nannya,1 Shunya Arai,1 Fumihiko Nakamura,1 Yusuke Shinoda,8 Masaomi Nangaku,4
Kiyoshi Miyagawa,5 Masashi Fukayama,3 Akiko Moriya-Saito,9
Ichiro Katayama,6 Takashi Ogura10 and Mineo Kurokawa1,2
*TT and MO contributed equally to this work
ABSTRACT
Erdheim–Chester disease is a rare histiocytosis with insufficient clin- ical data. To clarify the clinical features and prognostic factors of Erdheim–Chester disease, we conducted a nationwide survey to collect the detailed data of 44 patients with Erdheim–Chester disease in Japan. The median age of onset of the participants was 51 (range: 23–76) years, and the median number of involved organs per patient was 4 (range: 1–11). The existence of central nervous system disease was corre- lated with older age (P=0.033), the presence of cardiovascular lesions (P=0.015), and an increased number of involved organs (P=0.0042). The median survival from the onset was 10.4 years, and >3.0 mg/dL C-reac- tive protein level at onset was associated with worse outcome (median survival, 14.6 vs. 7.4 years; P=0.0016). In a multivariate analysis, age >60 years (hazard ratio, 25.9; 95% confidence interval, 2.82–237; P=0.0040) and the presence of digestive organ involvement (hazard ratio, 4.74; 95% confidence interval, 1.05–21.4; P=0.043) were correlated with worse sur- vival. Fourteen patients had available histological samples of Erdheim– Chester disease lesions. BRAFV600E mutation was detected in 11 patients (78%) by Sanger sequencing. A correlation between BRAF mutation sta- tus and clinical factors was not observed. Our study revealed that age and digestive organ involvement influence the outcome of Erdheim–Chester disease patients, and an inflammatory marker, such as C-reactive protein, might reflect the activity of this inflammatory myeloid neoplasm.
Introduction
Erdheim–Chester disease (ECD) is a rare non-Langerhans histiocytosis that was first reported by Jakob Erdheim and William Chester in 1930.1 The number of reports has drastically increased recently, perhaps due to the increased recognition of the disease, and approximately 650–1000 cases have been reported.2-4 ECD typ- ically develops among middle-aged males, and bilateral cortical osteosclerosis occurs in more than 95% of ECD patients.5 Furthermore, some patients experience involvements of the central nervous system (CNS), cardiovascular system, and var- ious other organs.6,7
Ferrata Storti Foundation
1Department of Hematology & Oncology, Graduate School of Medicine, The University of Tokyo; 2Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital; 3Department of Pathology, Graduate School of Medicine, The University of Tokyo; 4Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine; 5Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo; 6Department of Dermatology, Osaka University Graduate School of Medicine; 7Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences; 8Department of Rehabilitation Medicine Graduate School of Medicine, The University of Tokyo; 9Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi and 10Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan
Haematologica 2018 Volume 103(11):1815-1824
Correspondence:
kurokawa-tky@umin.ac.jp
Received: February 8, 2018. Accepted: July 4, 2018. Pre-published: July 5, 2018.
doi:10.3324/haematol.2018.190728
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/11/1815
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