scholarly journals Classification and Prognosis of Central Nervous System Involvement in Erdheim-Chester Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4272-4272
Author(s):  
Fleur Cohen-Aubart ◽  
Ahmed Idbaih ◽  
Damien Galanaud ◽  
Bruno Law-Ye ◽  
Jean-François Emile ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Targeted Therapy ◽  
Mapk Pathway ◽  
Central Nervous System Involvement ◽  
Cns Involvement ◽  
Mek Inhibitors ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

Background: Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytosis, characterized by the infiltration of tissues by foamy CD68+CD1a- histiocytes, with 1500 known-cases since 90 years. Mutations activating the MAPK pathway are found in more than 80% of ECD patients, mainly the BRAFV600E in 57 to 70%. Central nervous system (CNS) involvement during ECD lead to significant morbidity and mortality. We assessed CNS manifestations in a French cohort of 253 ECD patients. Since 2012, close to 200 patients worldwide with multi-systemic and refractory ECD (e.g. heart and/or CNS involvements) have benefited from BRAF and MEK inhibitors, which have proven highly beneficial. Methods: CNS manifestations were determined by clinical examination and brain and/or spine magnetic resonance imaging (MRI). Targeted therapy efficacy was assessed using physician and radiologist global assessment. Results: Ninety-seven (38%) among the 253 of the whole cohort of ECD patients had CNS involvement. CNS involvement was significantly associated with a younger age at diagnosis (mean 55.5 years) and at symptoms onset (mean 50.5 years), and also with the presence of the BRAFV600E mutation (in 77% of cases), xanthelasma (34%), and diabetes insipidus (36%). Median survival among patients with CNS involvement was significantly lower than in ECD patients without CNS involvement (124 months versus 146 months, p=0.03). Seventy-four CNS MRI were centrally reviewed, corresponding to 3 patterns: tumoral in 66%, degenerative in 50%, and vascular in 18%. Targeted therapy (BRAF and/or MEK inhibitors) was associated with improvement of symptoms in 43% of patients, and MRI improvement in 45%. Conclusions: CNS manifestations are typically associated with a poor prognosis in ECD. Three distinct patterns may be recognized: tumoral, degenerative, and vascular. Targeted therapy leads to clinical and/or imaging improvement in almost 50% of patients. OffLabel Disclosure: Targeted therapies such as BRAF inhibitor (vemurafenib) and MEK inhibitor (cobimetinib) are used in severe histiocytosis in EU but are off label

Central nervous system involvement in Erdheim-Chester disease

Neurology ◽  
2020 ◽  
Vol 95 (20) ◽  
pp. e2746-e2754 ◽  
Author(s):  
Fleur Cohen Aubart ◽  
Ahmed Idbaih ◽  
Damien Galanaud ◽  
Bruno Law-Ye ◽  
Jean-François Emile ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Central Nervous System Involvement ◽  
Class Iii ◽  
Cns Involvement ◽  
Erdheim Chester Disease ◽  
Younger Age ◽  
Spine Mri ◽  
Erdheim Chester ◽  
Chester Disease

ObjectiveCNS involvement in Erdheim-Chester disease (ECD) leads to substantial morbidity and mortality. To assess CNS manifestations in a French cohort of 253 patients with ECD, we determined clinical characteristics and outcomes, including those under targeted therapies.MethodsThis was a retrospective longitudinal study. CNS manifestations were determined by clinical examination and brain or spine MRI. Targeted therapy efficacy was assessed using global assessment from a physician and a radiologist. The study was approved by the ethics committee Comité de Protection des Personnes Ile de France III.ResultsNinety-seven of 253 patients (38%) with ECD had CNS involvement. CNS involvement was significantly associated with a younger age at diagnosis (mean 55.5 years) and at symptom onset (mean 50.5 years), as well as with the presence of the BRAFV600E mutation (in 77% of cases), xanthelasma (34%), and diabetes insipidus (36%). Median survival among patients with CNS involvement was significantly lower than that of patients with ECD without CNS involvement (124 months vs 146 months, p = 0.03). Seventy-four CNS MRIs were centrally reviewed, which showed 3 patterns: tumoral in 66%, pseudo-degenerative in 50%, and vascular in 18%. Targeted therapy (BRAF or MEK inhibitors) was associated with improved symptoms in 43% of patients and MRI improvement in 45%.ConclusionsCNS manifestations are typically associated with poor prognosis in patients with ECD. Three distinct patterns can be recognized: tumoral, pseudodegenerative, and vascular.Classification of evidenceThis study provides Class III evidence that targeted therapy leads to clinical or imaging improvement in almost 50% of patients.

scholarly journals Intracranial mass lesions and skin discoloration in the armpits as unusual clues to Erdheim-Chester disease: a case report

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pedro Gustavo Barros Rodrigues ◽  
Isabelle de Sousa Pereira ◽  
Valter Barbalho Lima Filho ◽  
Daniel Aguiar Dias ◽  
Paulo Ribeiro Nóbrega ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Involvement ◽  
Skin Lesions ◽  
Neurological Signs ◽  
Intracranial Mass ◽  
Erdheim Chester Disease ◽  
Mass Lesions ◽  
Erdheim Chester ◽  
Chester Disease

Abstract Background Erdheim–Chester disease (ECD) is a non-Langerhans histiocytosis that results in multi-organ disease involving the skin, bones, lungs and kidneys. Central nervous system (CNS) involvement occurs in about 50 % of patients, and diabetes insipidus, visual disturbances, and cerebellar ataxia are the most frequent neurological signs. We report a case of Erdheim-Chester disease with central nervous system involvement in the form of enhancing intracranial mass lesions with massive edema. Case presentation The patient presented with vertigo, ataxia, encephalopathy and pyramidal signs. Diagnosis was suggested by xanthomatous skin lesions and a biopsy was compatible with Erdheim-Chester disease demonstrating xanthogranulomas CD68 positive (clone KP1) and CD1a and S100 negative. Testing for BRAF mutation was negative, which precluded treatment with Vemurafenib. Treatment with steroids and interferon resulted in improvement of neurological signs and regression of edema on MRI. Conclusions The diagnosis of Erdheim-Chester disease should be considered in intracranial mass lesions. Xanthomatous skin lesions are a clue to the diagnosis.

scholarly journals A case of Erdheim Chester disease with central nervous system involvement

2015 ◽  
Vol 18 (3) ◽  
pp. 338 ◽  
Author(s):  
Mathew Alexander ◽  
Nanda Kachare ◽  
Sunithi Mani ◽  
Sudhakar Sniya ◽  
Sanjith Aaron ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Involvement ◽  
System Involvement ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

scholarly journals Successful treatment with cladribine of Erdheim-Chester disease with orbital and central nervous system involvement developing after treatment of langerhans cell histiocytosis

2016 ◽  
Vol 73 (1) ◽  
pp. 83-87 ◽  
Author(s):  
Predrag Peric ◽  
Branislav Antic ◽  
Slavica Knezevic-Usaj ◽  
Olga Radic-Tasic ◽  
Sanja Radovinovic-Tasic ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Langerhans Cell Histiocytosis ◽  
Braf V600e Mutation ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Cns Involvement ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

Introduction. Erdheim-Chester disease (ECD) is a rare, systemic form of non-Langerhans cell histiocytosis of the juvenile xantho-granuloma family with characteristic bilateral symmetrical long bone osteosclerosis, associated with xanthogranulomatous extras-keletal organ involvement. In ECD, central nervous system (CNS) and orbital lesions are frequent, and more than half of ECD patients carry the V600E mutation of the proto-oncogene BRAF. The synchronous or metachronous development of ECD and Langerhans cell histiocytosis (LCH) in the same patients is rare, and the possible connection between them is still obscure. Cladribine is a purine substrate analogue that is toxic to lymphocytes and monocytes with good hematoencephalic penetration. Case report. We presented a 23-year-old man successfully treated with cladribine due to BRAF V600E-mutation-negative ECD with bilateral orbital and CNS involvement. ECD developed metachronously, 6 years after chemotherapy for multisystem LCH with complete disease remission and remaining central diabetes insipidus. During ECD treatment, the patient received 5 single-agent chemotherapy courses of cladribine (5 mg/m2 for 5 consecutive days every 4 weeks), with a reduction in dose to 4 mg/m2 in a fifth course, delayed due to severe neutropenia and thoracic dermatomal herpes zoster infection following the fourth course. Radiologic signs of systemic and CNS disease started to resolve 3 months after the end of chemotherapy, and CNS lesions completely resolved within 2 years after the treatment. After 12-year follow-up, there was no recurrence or appearance of new systemic or CNS xanthogranu-lomatous lesions or second malignancies. Conclusion. In accordance with our findings and recommendations provided by other authors, cladribine can be considered an effective alternative treatment for ECD, especially with CNS involvement and BRAF V600E-mutation-negative status, when interferon-? as the first-line therapy fails.

Case 78: Erdheim-Chester Disease with Central Nervous System Involvement

Radiology ◽  
2005 ◽  
Vol 234 (1) ◽  
pp. 111-115 ◽  
Author(s):  
Carmen Adem ◽  
Olivier Hélie ◽  
Christophe Lévêque ◽  
Hervé Taillia ◽  
Yves-Sébastien Cordoliani
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Involvement ◽  
System Involvement ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

Central Nervous System Complications of Erdheim-Chester Disease

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Nuh Filizoglu ◽  
Salih Ozguven ◽  
Tunc Ones ◽  
Halil Turgut Turoglu ◽  
Tanju Yusuf Erdil
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

scholarly journals Erdheim-Chester Disease of the Central Nervous System: New Manifestations of a Rare Disease

2011 ◽  
Vol 32 (11) ◽  
pp. 2126-2131 ◽  
Author(s):  
P. Sedrak ◽  
L. Ketonen ◽  
P. Hou ◽  
N. Guha-Thakurta ◽  
M.D. Williams ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Rare Disease ◽  
Erdheim Chester Disease ◽  
The Central Nervous System ◽  
Erdheim Chester ◽  
Chester Disease

scholarly journals BRAF V600E mutation in Juvenile Xanthogranuloma family neoplasms of the central nervous system (CNS-JXG): a revised diagnostic algorithm to include pediatric Erdheim-Chester disease

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
J. Picarsic ◽  
T. Pysher ◽  
H. Zhou ◽  
M. Fluchel ◽  
T. Pettit ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Diagnostic Algorithm ◽  
Braf V600e ◽  
Juvenile Xanthogranuloma ◽  
Female Ratio ◽  
Integrated Diagnosis ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

Abstract The family of juvenile xanthogranuloma family neoplasms (JXG) with ERK-pathway mutations are now classified within the “L” (Langerhans) group, which includes Langerhans cell histiocytosis (LCH) and Erdheim Chester disease (ECD). Although the BRAF V600E mutation constitutes the majority of molecular alterations in ECD and LCH, only three reported JXG neoplasms, all in male pediatric patients with localized central nervous system (CNS) involvement, are known to harbor the BRAF mutation. This retrospective case series seeks to redefine the clinicopathologic spectrum of pediatric CNS-JXG family neoplasms in the post-BRAF era, with a revised diagnostic algorithm to include pediatric ECD. Twenty-two CNS-JXG family lesions were retrieved from consult files with 64% (n = 14) having informative BRAF V600E mutational testing (molecular and/or VE1 immunohistochemistry). Of these, 71% (n = 10) were pediatric cases (≤18 years) and half (n = 5) harbored the BRAF V600E mutation. As compared to the BRAF wild-type cohort (WT), the BRAF V600E cohort had a similar mean age at diagnosis [BRAF V600E: 7 years (3–12 y), vs. WT: 7.6 years (1–18 y)] but demonstrated a stronger male/female ratio (BRAF V600E: 4 vs WT: 0.67), and had both more multifocal CNS disease ( BRAFV600E: 80% vs WT: 20%) and systemic disease (BRAF V600E: 40% vs WT: none). Radiographic features of CNS-JXG varied but typically included enhancing CNS mass lesion(s) with associated white matter changes in a subset of BRAF V600E neoplasms. After clinical-radiographic correlation, pediatric ECD was diagnosed in the BRAF V600E cohort. Treatment options varied, including surgical resection, chemotherapy, and targeted therapy with BRAF-inhibitor dabrafenib in one mutated case. BRAF V600E CNS-JXG neoplasms appear associated with male gender and aggressive disease presentation including pediatric ECD. We propose a revised diagnostic algorithm for CNS-JXG that includes an initial morphologic diagnosis with a final integrated diagnosis after clinical-radiographic and molecular correlation, in order to identify cases of pediatric ECD. Future studies with long-term follow-up are required to determine if pediatric BRAF V600E positive CNS-JXG neoplasms are a distinct entity in the L-group histiocytosis category or represent an expanded pediatric spectrum of ECD.

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