Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis first described in 1930 with a wide range of manifestations. The number of new cases has dramatically increased over the past 10 years due to the better recognition of this condition. To date, less than 500 cases have been reported in the world literature. Diagnosis of ECD is based on a tissue biopsy sample disclosing histiocytes which are typically foamy with an immunostaining CD68+ CD1a-, whereas histiocytes of the Langerhans Cell Histiocytosis (LCH) are CD68+ CD1a+. Two signs highly evocative of ECD are the nearly constant tracer uptake by the long bones on 99Technetium bone scintigraphy and a “hairy kidney” appearance on abdominal CT scan present in approximatively 50% of cases. Based on our experience regarding a personal series of 75 patients, the sex ratio shows a strong male predominance with 73% of men and 27% of women. Mean age at diagnosis in the 2011 series published by our team is 55 yr ± 14 (range, 16–80 yr). ECD is far less described among children, as there have been only 8 pediatric cases reported.
The clinical course of ECD is largely dependent on the extent and distribution of the disease, and may range from asymptomatic bone lesions to multisystemic, life-threatening forms with poor prognosis. ECD is a systemic disease characterized by proteiform manifestations, including skeletal involvement with bone pain, exophthalmos, diabetes insipidus, xanthelasma, interstitial lung disease, bilateral adrenal enlargement, retroperitoneal fibrosis with perirenal and/or ureteral obstruction, renal impairment, testis infiltration, central nervous system (CNS), and/or cardiovascular involvements. CNS involvement is a major prognostic factor in ECD, as underlined in our 2011 survival analysis, as we found it to be an independent predictor of death (hazard ratio = 2.51; 95% confidence interval, 1.28-5.52; P=0.006).
Interferon a (and/or pegylated interferon a) (IFNa) appears to be a valuable first-line therapy for prolonged treatment of ECD and significantly improves survival: we have recently reported a survival analysis revealing that treatment with IFNa and/or PEGylated IFNa was a major independent predictor of survival among a personal series of 53 patients (HR =0.32; 95% CI, 0.14-0.70; P =.006). Nevertheless, treatments by IFNa, which should be given on a long-term basis, at high doses when patients have CNS and cardiovascular involvements, are sometimes difficult due to side-effects such as depression and fatigue. The efficacy of IFNa on the pseudo-degenerative forms of cerebellar involvements (which are similar to those observed in LCH) is much more disappointing. Alternative treatments remain to be defined.
Pathophysiology is better understood with a complex network of cytokines and chemokines and a systemic immune Th-1–oriented perturbation. We have indeed recently analyzed 23 cytokines in serum samples obtained from a large cohort of 37 ECD patients. Our data reveal an intense systemic immune activation mainly involving IFNa, IL-1/IL1-RA, IL-6, IL-12, and MCP-1. These data may provide further clues to understand the pathogenesis of ECD, as well as provide new tools for diagnosis and targeted therapy.
ECD, although a rare and orphan disease, has been overlooked and numerous new cases are currently diagnosed due to general better knowledge of this histiocytosis.
Disclosure of Interest None Declared
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