ReviewErdheim-Chester Disease: Characteristics and Management
Section snippets
Differential diagnosis: Langerhans cell histiocytosis vs non-Langerhans cell histiocytosis
ECD is a non-Langerhans cell histiocytosis; however, it may coexist with Langerhans histiocytosis.2 As an example, Haroche et al12 reported overlapping histiocytosis in 12 of the 75 (16%) patients who have been followed at their institution. Mononuclear phagocytic cells are divided into macrophages and dendritic cells. The latter are thought to be the abnormal cells that trigger Langerhans cell histiocytosis.13 In contrast, non-Langerhans cell histiocytosis is believed to stem from an abnormal
Prognosis
Poorer prognosis is dictated by the degree of organ involvement, particularly the CNS.1 Sequelae range from asymptomatic bone sclerosis to life-threatening visceral infiltration. Although ECD is not curable, we have seen prolonged responses in our clinic after various agents. Survival in recent larger series1 is better than previously described in other older smaller series.24 Indeed, Arnaud et al1 reported 1- and 5-year survival rates of 96% and 68%, respectively, which is compatible with our
Pathophysiology
The underlying pathophysiology of ECD is largely unknown, although it seems to be associated with cytokine disturbances.3, 28, 29, 30, 31 Serum samples from 37 patients with ECD were assessed for 23 cytokines. It was found that IL-6 and IFN-α levels (TH-1–induced pro-inflammatory chemokines) were elevated in untreated patients; IL-1 and IFN-γ levels were high in patients treated with IFN-α.3 Earlier attempts to elucidate the etiology of ECD did not focus on the balance among cytokines, an
Therapy
Systemic treatment is deemed not to have curative potential, though, on the basis of retrospective analysis, it can improve symptoms as well as outcomes.1 There is no standard of care (approved therapies), and no randomized trials have been performed for ECD. Until recently, treatment included diverse approaches such as steroids, cladribine-based chemotherapy,6 and cytokine-based agents. The recent reports of BRAF mutations in patients with ECD support testing BRAF inhibitors in the clinic.5
The
Future Directions
Erdheim-Chester disease is an uncommon non-Langerhans histiocytosis that may coexist with Langerhans histiocytosis.80 It involves diverse organs, and it is often difficult to diagnose. Common features include bone sclerosis, orbital infiltration with proptosis, CNS involvement with diabetes insipidus, cardiac involvement, and pulmonary infiltration. Deregulation of cytokine pathways has been implicated in the pathogenesis of ECD. Responses have been seen with steroids, cytotoxic chemotherapy,
Conclusion
ECD is an uncommon multisystem non-Langerhans histiocytosis. Rare diseases are uniquely challenging from a therapeutic point of view, though increasingly many cancers may be stratified into small molecular subsets.83, 84, 85 The present review details our approach to the management of ECD.
Acknowledgments
Drs Munoz and Janku share first authorship because they contributed equally to this work.
References (85)
- et al.
CNS involvement and treatment with interferon-alpha are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients
Blood
(2011) - et al.
Associated Langerhans cell histiocytosis and Erdheim-Chester disease [in French]
Ann Dermatol Venereol
(2011) - et al.
Systemic perturbation of cytokine and chemokine networks in Erdheim-Chester disease: a single-center series of 37 patients
Blood
(2011) - et al.
High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses
Blood
(2012) - et al.
Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation
Blood
(2013) - et al.
Interferon therapy for orbital infiltration secondary to Erdheim-Chester disease
Am J Ophthalmol
(2001) - et al.
Successful treatment of Erdheim-Chester disease, a non-Langerhans-cell histiocytosis, with interferon-alpha
Blood
(2005) - et al.
Rationale and efficacy of interleukin-1 targeting in Erdheim-Chester disease
Blood
(2010) The histiocytoses: the fall of the Tower of Babel
Eur J Cancer
(1999)Advances in the management of histiocytic disorders
Paediatr Child Health
(2008)
Erdheim-Chester disease: evidence for a disease entity different from Langerhans cell histiocytosis? Three cases with detailed radiological and immunohistochemical analysis
Hum Pathol
Erdheim-Chester disease [French]
La Presse Médicale
Erdheim-Chester disease: a rare multisystem histiocytic disorder associated with interstitial lung disease
Am J Med Sci
Recurrent BRAF mutations in Langerhans cell histiocytosis
Blood
Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial
Lancet
Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial
Lancet Oncol
Treatment of Langerhans cell histiocytosis with alpha-interferon
Lancet
Imatinib mesylate for platelet-derived growth factor receptor-beta-positive Erdheim-Chester histiocytosis
Blood
Erdheim-Chester disease: multisystem involvement and management with interferon-alpha
Leuk Res
Treatment of Erdheim-Chester disease with long-term high-dose interferon-alpha
Semin Arthritis Rheum
How I treat Philadelphia chromosome-positive acute lymphoblastic leukemia
Blood
How I treat chronic myeloid leukemia in the imatinib era
Blood
Erdheim-Chester disease
Rheum Dis Clin North Am
BRAFV600E mutant protein is expressed in cells of variable maturation in Langerhans cell histiocytosis
Blood
Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification
Blood
Novel therapeutic targets in non-small cell lung cancer
J Thorac Oncol
Successful treatment of Erdheim-Chester disease by 2-chlorodeoxyadenosine-based chemotherapy. Two case studies and a literature review [in Czeck]
Vnitr Lek
Response of histiocytoses to imatinib mesylate: fire to ashes
J Clin Oncol
Treatment of pediatric Erdheim-Chester disease with interleukin-1-targeting drugs
Arthritis Rheum
Erdheim-Chester disease
Curr Opin Rheumatol
Paul Langerhans
J Clin Pathol
Pulmonary Langerhans'-cell histiocytosis
N Engl J Med
Orbital Erdheim-Chester disease
J Francais D'Ophtalmologie
Erdheim-Chester disease: typical radiological bone features for a rare xanthogranulomatosis
Ann Rheum Dis
Erdheim-Chester disease: clinical, radiologic, and histopathologic findings in five patients with interstitial lung disease
Am J Surg Pathol
Cardiovascular involvement, an overlooked feature of Erdheim-Chester disease: report of 6 new cases and a literature review
Medicine (Baltimore)
Erdheim-Chester disease of the central nervous system: new manifestations of a rare disease
AJNR. Am J Neuroradiol
Pulmonary involvement in Erdheim-Chester disease: a single-center study of thirty-four patients and a review of the literature
Arthritis Rheum
Bone involvement in Erdheim-Chester disease: imaging findings including periostitis and partial epiphyseal involvement
Radiology
Images in cardiovascular medicine. Cardiac involvement in Erdheim-Chester disease: magnetic resonance and computed tomographic scan imaging in a monocentric series of 37 patients
Circulation
Evans syndrome in a patient with Langerhans cell histiocytosis: possible pathogenesis of autoimmunity in LCH
Int J Hematol
Tumor necrosis factor α as a master regulator of inflammation in Erdheim-Chester disease: rationale for the treatment of patients with infliximab
J Clin Oncol
Cited by (63)
Erdheim-Chester disease: Typical radiologic findings of a multisystemic disease
2022, Radiology Case ReportsErdheim–Chester disease presenting with bilateral orbital involvement: Report of three cases
2020, Journal Francais d'OphtalmologieErdheim-Chester disease presenting with cough, abdominal pain, and headache
2020, Radiology Case ReportsCitation Excerpt :Bone pain is the most incident presenting symptom [3,4]. Other extraskeletal sites of involvement include orbits, CNS, heart, retroperitoneal region, lungs, and skin [5–9]. The rarity and the heterogeneous presentation could lead to a diagnostic delay.
Choroidal mass as the first presentation of Erdheim-Chester disease
2019, American Journal of Ophthalmology Case ReportsErdheim-Chester disease in a psoriatic arthritis patient
2024, Archives of Rheumatology
Grant Support: R.K. has received research grant support from Genentech and Hoffmann-LaRoche.