scholarly journals A scale for patient-reported symptom assessment for patients with Erdheim-Chester disease

2019 ◽  
Vol 3 (7) ◽  
pp. 934-938 ◽  
Author(s):  
Eli L. Diamond ◽  
Anne S. Reiner ◽  
Justin J. Buthorn ◽  
Elyse Shuk ◽  
Allison J. Applebaum ◽  
...  
Keyword(s):  
Psychological Symptoms ◽  
Mapk Pathway ◽  
Clinical Care ◽  
Symptom Assessment ◽  
Symptom Scale ◽  
Symptom Inventory ◽  
Erdheim Chester Disease ◽  
Patient Reported ◽  
Erdheim Chester ◽  
Chester Disease

Abstract Erdheim-Chester disease (ECD) is an ultra-rare hematologic neoplasm characterized by somatic mutations of the MAPK pathway and by accumulation of lesional histiocytes within tissues. Clinical phenotypes and sites of disease involvement are heterogenous in ECD, and no tool exists for systematic and comprehensive assessment of ECD symptomatology. We describe a collaborative effort among ECD specialists, patient-reported outcome (PRO) methodologists, and ECD patients to develop the Erdheim-Chester Disease Symptom Scale (ECD-SS): a symptom inventory for clinical ECD care and evaluation of ECD therapies. Methodologically rigorous focus groups led to the identification of 63 ECD symptoms in 6 categories, incorporated into the ECD-SS with respect to both severity and frequency. Among 50 ECD patients participating in a prospective registry study completing the ECD-SS, 46 (92%) reported neurological/psychological symptoms, 29 (58%) reported pain, and at least one-half reported mood symptoms, memory problems, or fatigue. Symptoms were highly frequent or almost constant regardless of their severity. The ECD-SS is a rigorously developed, patient-centered tool that demonstrates the wide and previously unappreciated burden of symptomatology experienced by ECD patients. Further studies will refine the symptom inventory and define its psychometric properties and role in clinical care and investigation in the context of ECD.

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

Erdheim-Chester disease

Blood ◽  
2020 ◽  
Vol 135 (16) ◽  
pp. 1311-1318 ◽  
Author(s):  
Julien Haroche ◽  
Fleur Cohen-Aubart ◽  
Zahir Amoura
Keyword(s):  
Mapk Pathway ◽  
Myeloproliferative Neoplasms ◽  
Acquired Resistance ◽  
Central Nervous System Involvement ◽  
Long Bone ◽  
Interferon Α ◽  
Braf Mutations ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

Abstract Erdheim-Chester disease (ECD) is characterized by the infiltration of tissues by foamy CD68+CD1a− histiocytes, with 1500 known cases since 1930. Mutations activating the MAPK pathway are found in more than 80% of patients with ECD, mainly the BRAFV600E activating mutation in 57% to 70% of cases, followed by MAP2K1 in close to 20%. The discovery of BRAF mutations and of other MAP kinase pathway alterations, as well as the co-occurrence of ECD with LCH in 15% of patients with ECD, led to the 2016 revision of the classification of histiocytoses in which LCH and ECD belong to the “L” group. Both conditions are considered inflammatory myeloid neoplasms. Ten percent of ECD cases are associated with myeloproliferative neoplasms and/or myelodysplastic syndromes. Some of the most striking signs of ECD are the long bone involvement (80%-95%), as well as the hairy kidney appearance on computed tomography scan (63%), the coated aorta (40%), and the right atrium pseudo-tumoral infiltration (36%). Central nervous system involvement is a strong prognostic factor and independent predictor of death. Interferon-α seems to be the best initial treatment of ECD. Since 2012, more than 200 patients worldwide with multisystem or refractory ECD have benefitted from highly effective therapy with BRAF and MEK inhibitors. Targeted therapies have an overall, robust, and reproducible efficacy in ECD, with no acquired resistance to date, but their use may be best reserved for the most severe manifestations of the disease, as they may be associated with serious adverse effects and as-yet-unknown long-term consequences.

scholarly journals Histiocytic disorders: insights into novel biology and implications for therapy of Langerhans cell histiocytosis and Erdheim-Chester disease

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 395-399
Author(s):  
Kenneth McClain
Keyword(s):  
Dendritic Cells ◽  
Langerhans Cell Histiocytosis ◽  
Mapk Pathway ◽  
Langerhans Cell ◽  
Renal Diseases ◽  
Myeloid Dendritic Cells ◽  
Mek Inhibitors ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

Abstract Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are caused by mutations of the MAPK pathway, most often BRAFV600E, in myeloid dendritic cells that lead to some overlapping and other unique presentations of the two diseases. LCH occurs in both children and adults, but ECD is primarily found in the latter. The challenges in diagnosing these conditions relates to the rarity of the conditions and that they mimic diseases that are more widely understood, such as certain rashes; bone, lung, and renal diseases; and other malignancies. The histopathology of LCH is definitive, but not so for ECD. Treatment with BRAF and MEK inhibitors has become one of the important advances in the care of these patients.

scholarly journals Efficacy and improved tolerability of combination therapy with interleukin-1 blockade and MAPK pathway inhibitors for the treatment of Erdheim-Chester disease

2019 ◽  
pp. annrheumdis-2019-216610 ◽  
Author(s):  
Corrado Campochiaro ◽  
Giulio Cavalli ◽  
Nicola Farina ◽  
Alessandro Tomelleri ◽  
Giacomo De Luca ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Mapk Pathway ◽  
Interleukin 1 ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

scholarly journals AB0038 IMMUNE PHENOTYPING OF ERDHEIM-CHESTER DISEASE THROUGH MASS CYTOMETRY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1321.2-1322
Author(s):  
M. Papo ◽  
A. Corneau ◽  
F. Cohen ◽  
B. Robin ◽  
J. F. Emile ◽  
...  
Keyword(s):  
Th17 Cells ◽  
Mapk Pathway ◽  
Specific Treatment ◽  
Th2 Cells ◽  
Mass Cytometry ◽  
Erdheim Chester Disease ◽  
Inflammatory Phenotype ◽  
Classical Monocytes ◽  
Erdheim Chester ◽  
Chester Disease

Background:The understanding of Erdheim-Chester Disease (ECD) pathogenesis has been greatly improved these past few years with the discovery of activating MAPK pathway mutations in most of ECD patients. However, the inflammatory phenotype of ECD remains widely unknown.Objectives:We aimed to explore the inflammatory phenotype of Erdheim-Chester disease (ECD) using mass cytometry.Methods:We analyzed peripheral blood mononuclear cells from 13 ECD patients and 11 healthy donors (HD) using mass cytometry with 29 metal-conjugated antibodies.Results:Compared to HD, untreated ECD patients had increased proportion of classical monocytes (90.8 [87.1-96.5] vs 81.6 [76.2-87.5] %, p=0.02) and decreased proportion of non-classical monocytes (4.7 [3.4-9.7] vs 11.8 [6.6-17.2] %, p=0.047). Untreated ECD patients had more circulating Th17 cells compared to HD (3.3 [3-5.3] vs 1.3 [0.4-2.3] %, p=0.015) and ECD patients treated with BRAF or MEK inhibitors (3.3 (3-5.3] vs 1.9 [0.6-2.4] %, p=0.005). Moreover Treg cells were lower in ECD patients than HD, with an increased Th17/Treg ratio (1.37 [0.74-1.9] vs 0.34 [0.19-0.43], p=0.0004). There was no difference regarding Th1 cells, Th2 cells, B cells, NK cells and circulating dendritic cells.Conclusion:ECD monocyte profile seems similar to what have been described in CMML. Inflammation observed in ECD may be driven through Th17 cells, and might be targeted with specific treatment.Disclosure of Interests:None declared

scholarly journals Erdheim-Chester Disease and Small Lymphocytic Lymphoma Collision Tumour Presenting as a Perirenal Mass

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Antonio Maietta ◽  
Maryam Razmpoosh
Keyword(s):  
Mapk Pathway ◽  
Small Lymphocytic Lymphoma ◽  
Disease Manifestation ◽  
Fibrous Stroma ◽  
Collision Tumour ◽  
Myeloid Neoplasms ◽  
Erdheim Chester Disease ◽  
The Central Nervous System ◽  
Erdheim Chester ◽  
Chester Disease

Background. Erdheim-Chester disease is a rare histiocytic neoplasm associated with MAPK pathway mutations. Disease manifestation is variable often involving many different organs, mainly bone, retroperitoneum, the heart, and the central nervous system. Histological findings include foamy histiocytes in a fibrous stroma with scattered inflammatory infiltrate. Histiocytes are CD68 positive and S100 negative. Case Report. We report a case of Erdheim-Chester disease associated with small lymphocytic lymphoma presenting as a perirenal mass with a review of the recent literature. Conclusions. Erdheim-Chester disease rarely can be associated with other cancers, namely myeloid neoplasms. We report a case of Erdheim-Chester disease presenting with small lymphocytic lymphoma as a perirenal mass. The association of Erdheim-Chester disease with lymphoproliferative disorders needs to be elucidated.

Case report of Erdheim-Chester disease in a female cardiac surgery patient

2011 ◽  
Vol 59 (S 01) ◽  
Author(s):  
HR Mahoozi ◽  
A Zittermann ◽  
K Hakim-Meibodi ◽  
J Gummert ◽  
N Mirow
Keyword(s):  
Cardiac Surgery ◽  
Case Report ◽  
Cardiac Surgery Patient ◽  
Erdheim Chester Disease ◽  
Surgery Patient ◽  
Erdheim Chester ◽  
Chester Disease

Erdheim-Chester Disease Presenting with Histiocytic Colitis and Cytokine Storm

2017 ◽  
Vol 26 (2) ◽  
pp. 183-187
Author(s):  
George P. Christophi ◽  
Yeshika Sharma ◽  
Quader Farhan ◽  
Umang Jain ◽  
Ted Walker ◽  
...  
Keyword(s):  
Periodic Acid ◽  
Poor Response ◽  
Rare Type ◽  
Periodic Acid Schiff ◽  
Hematopoietic Stem ◽  
Hemodynamic Compromise ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease ◽  
Segmental Colitis

Background: Non-Langerhans histiocytosis is a group of inflammatory lymphoproliferative disorders originating from non-clonal expansion of hematopoietic stem cells into cytokine-secreting dendritic cells or macrophages. Erdheim-Chester Disease (ECD) is a rare type of non-Langerhans cell histiocytosis characterized by tissue inflammation and injury caused by macrophage infiltration and histologic findings of foamy histiocytes. Often ECD involves the skeleton, retroperitoneum and the orbits. This is the first report documenting ECD manifesting as segmental colitis and causing cytokine-release syndrome.Case presentation: A 68-year old woman presented with persistent fever without infectious etiology and hematochezia. Endoscopy showed segmental colitis and pathology revealed infiltration of large foamy histiocytes CD3-/CD20-/CD68+/CD163+/S100- consistent with ECD. The patient was empirically treated with steroids but continued to have fever and developed progressive distributive shock.Conclusion: This case report describes the differential diagnosis of infectious and immune-mediated inflammatory and rheumatologic segmental colitis. Non-Langerhans histiocytosis and ECD are rare causes of gastrointestinal inflammation. Prompt diagnosis is imperative for the appropriate treatment to prevent hemodynamic compromise due to distributive shock or gastrointestinal bleeding. Importantly, gastrointestinal ECD might exhibit poor response to steroid treatment and other potential treatments including chemotherapy, and biologic treatments targeting IL-1 and TNF-alpha signaling should be considered.Abbreviations: AFB: acid-fast bacilli; ECD: Erdheim-Chester Disease; IBD: inflammatory bowel disease; PASD: periodic acid-Schiff with diastase; TB: tuberculosis

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