Miscellaneous
Treatment of Erdheim-Chester Disease with Long-Term High-Dose Interferon-α

https://doi.org/10.1016/j.semarthrit.2011.11.004Get rights and content

Objectives

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterized by a foamy CD68+, CD1a− histiocyte tissue infiltration. Efficacy of standard doses of interferon-α-2a (IFNα) has been suggested in a small series but with variation, depending on the organs involved. Our aim was to report our single-center experience about the use of high-dose IFNα in ECD.

Methods

Twenty-four ECD patients have received high-dose IFNα (IFNα ≥18 mIU/wk or pegylated-IFNα ≥180 μg/wk). IFNα efficacy was evaluated clinically and morphologically using a standardized protocol (median follow-up 19 months).

Results

Indication for treatment was central nervous system and/or heart involvement (n = 20), exophthalmos (n = 1), and standard-dose IFNα inefficacy (n = 3). High-dose IFNα was effective in 16 patients (67%) with improvement (n = 11, 46%) and stabilization (n = 5, 21%). Late and gradual improvement was observed during prolonged follow-up in most patients. The efficacy of high-dose IFNα was dependent on the organs involved: central nervous system and heart improvement or stabilization occurred in 7/11 (64%) and 11/14 (79%) patients, respectively. Six patients (25%) worsened. High doses of IFNα were well-tolerated: 13 (54.2%) patients had side effects but treatment interruption was infrequent (n = 3, 12.5%).

Conclusions

High-dose IFNα may be effective in severe ECD. Improvement may be slow, and high-dose IFNα treatment should be prolonged.

Section snippets

Patients

This study was based on the prospective follow-up of all ECD patients (n = 27) who received high doses of IFNα, ie, either ≥18 mIU/wk (3 injections weekly) or PEG-IFNα ≥180 μg/wk (1 injection weekly), at La Pitié-Salpêtrière Hospital (Paris, France), a tertiary care center, from April 1995 to January 2011. In all cases, ECD diagnosis was based on typical histologic features: infiltration with foamy histiocytes nested among polymorphic granuloma and fibrosis with CD68-positive and CD1a-negative

Patients

Twenty-four patients (17 men and 7 women) were included in this prospective study. The median age at diagnosis was 59 years (range, 26-77 years). Patient characteristics are summarized in Table 1. These patients were treated with IFNα 18 mIU/wk (n = 3), IFNα 27 mIU/wk (n = 11), or PEG-IFNα 180 μg/wk (n = 10).

High doses of IFNα were used as first-line (n = 9) or second-line treatment (n = 15). Of the 15 patients who received IFNα as a second-line treatment, 12 had previously received

Discussion

ECD is a slowly evolving histiocytosis and improvement under treatment usually leads only to partial remission, rather than complete recovery (7, 10, 11, 13, 15). Thus, evaluation of ECD may be challenging and requires large cohorts with a long-term follow-up. We have previously reported variable efficacy of standard-dose IFNα in a larger series of severe ECD patients (11). However, at standard IFNα doses, partial remissions depended on the sites of ECD involvement (11). We therefore conducted

References (38)

  • S.W. Schalm et al.

    Interferon-ribavirin for chronic hepatitis C with and without cirrhosis: analysis of individual patient data of six controlled trialsEurohep Study Group for Viral Hepatitis

    Gastroenterology

    (1999)
  • W. Chester

    Uber lipoidgranulomatose

    Wirchows Arch Pathol Anat

    (2010)
  • A. Stoppacciaro et al.

    Immunohistochemical evidence of a cytokine and chemokine network in three patients with Erdheim-Chester disease: implications for pathogenesis

    Arthritis Rheum

    (2006)
  • E. Dion et al.

    Bone involvement in Erdheim-Chester disease: imaging findings including periostitis and partial epiphyseal involvement

    Radiology

    (2006)
  • J. Haroche et al.

    Cardiovascular involvement, an overlooked feature of Erdheim-Chester disease: report of 6 new cases and a literature review

    Medicine (Baltimore)

    (2004)
  • F. Lachenal et al.

    Neurological manifestations and neuroradiological presentation of Erdheim-Chester disease: report of 6 cases and systematic review of the literature

    J Neurol

    (2006)
  • N. Boissel et al.

    Treatment of refractory Erdheim-Chester disease with double autologous hematopoietic stem-cell transplantation

    Ann Intern Med

    (2001)
  • S.C. Bourke et al.

    Erdheim-Chester disease: pulmonary infiltration responding to cyclophosphamide and prednisolone

    Thorax

    (2003)
  • J. Haroche et al.

    Variability in the efficacy of interferon-alpha in Erdheim-Chester disease by patient and site of involvement: results in eight patients

    Arthritis Rheum

    (2006)
  • Cited by (85)

    • Histiocytosis

      2023, Medicina Clinica
    • Erdheim-Chester disease: a comprehensive review from the ophthalmologic perspective

      2022, Survey of Ophthalmology
      Citation Excerpt :

      Pegylated IFNα in doses of 135- 180 μg once a week has also been used. Interferon administration, although generally well tolerated, in some cases is associated with severe side-effects, including weakness, myalgias, pruritus, thrombopenia, and depression, requiring cessation of therapy.163 The efficacy of IFN-α varies among patients and is related to the severity and localization of the disease.

    • Erdheim-Chester disease with intracranial involvement causing hydrocephalus: Case report

      2020, Interdisciplinary Neurosurgery: Advanced Techniques and Case Management
      Citation Excerpt :

      The mutation in the BRAF V600E gene demonstrates the most frequent correspondence, being present in 57% to 75% of the patients. These findings have allowed for the emergence of a new potential for targeted therapy [8,9,10]. In the anatomopathological and immunohistochemical study, performed in the biopsy of lesions in multiple organs, there was the accumulation of numerous macrophages of xanthomatous cytoplasm and small nuclei, giant cells, few lymphocytes and eosinophil.

    • Erdheim–Chester disease

      2020, Best Practice and Research: Clinical Rheumatology
    View all citing articles on Scopus

    The authors have no conflicts of interest to disclose.

    View full text