A Fatal Case of Erdheim-Chester Disease with Hepatic Involvement.
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ABSTRACT:
SUBMITTER: Balasubramanian G
PROVIDER: S-EPMC5541758 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:Erdheim-Chester disease is a type of non-Langerhans cell histiocytosis. It is a rare, multisystem disorder with unknown etiology. Heterogeneity of the clinical symptoms makes the diagnosis challenging. On the other hand, knowing the signs and radiological findings of the disease helps to establish a correct diagnosis. In this article, we present a 51-year-old male patient with skeletal and urinary system manifestations who finally underwent right nephrectomy due to renal insufficiency. The diagnosis was suspected by the retroperitoneal infiltrative process and radiological findings of the tubular bones. Erdheim-Chester disease diagnosis was confirmed with CD68(+) CD1a(-) histiocytes detected by immunohistochemical analysis of the nephrectomy specimen.
| S-EPMC6190995 | biostudies-other
Project description:Erdheim-Chester disease is a rare multisystemic non-Langerhans histiocytosis characterized by histiocytes that stain positive for CD68 and negative for CD1a. Skeletal involvement is reported to be present in up to 96% cases and BRAF mutation in about half of the cases. Here, we report a patient with an unusual longstanding BRAF-negative Erdheim-Chester disease without bone lesions who developed pleuropulmonary and cardiac involvement.
| S-EPMC8688944 | biostudies-literature
Project description:Erdheim-Chester disease (ECD) is a rare histiocytosis of the "L" (Langerhans) group with multisystem involvement that can affect the large and medium-sized arteries mimicking vasculitis. Aortic involvement is common but the frequency and outcome of aortic branch vessel abnormalities are less well described.Patients with ECD were retrospectively identified. Images containing information of arterial involvement within 6 months of diagnosis were considered baseline and compared to last follow-up studies. Two physicians independently reviewed the studies to evaluate for presence of abnormalities attributable to ECD. Age and sex-adjusted logistic regression models were used to examine associations between patient characteristics and vessel involvement at baseline.Among a cohort of 64 patients with ECD, 63 had baseline imaging of vascular structures. ECD involvement of at least 1 segment of the aorta was observed in 56%. Abnormalities were also observed in aortic arch branches (26%), visceral branch arteries (40%), iliofemoral arteries (31%), coronary (5%), and pulmonary (3%) arteries. Perinephric fibrosis was strongly associated with the identification of abnormalities in the thoracic aorta (OR 4.92 [1.54, 15.75]; P?=?.007), abdominal aorta (OR 7.57 [2.28, 25.07]; P?=?.001) and visceral branch arteries (OR 6.05 [1.52, 24.03]; P?=?.01) but not pelvic/lower extremity arteries. Complete normalization of arterial abnormalities at follow-up was only observed in 9% or less of arterial segments involved at baseline.Aortic and aortic branch vessel abnormalities are frequently observed in patients with ECD and are often asymptomatic. Partial and/or complete resolution of arterial findings is uncommon.
| S-EPMC6310516 | biostudies-literature
Project description:Erdheim-Chester disease (ECD) is rare non-Langerhans histiocytosis with distinctive radiologic and pathologic entities. We report a rare case of which ECD was involving the breast with only eight similar cases reported in the English literature. Our patient was a 52-year-old female patient with ECD involving the breast, mesentery, left kidney, retroperitoneum and the skeleton. The diagnosis was based on distinctive imaging and histopathological findings. The patient received a new novel treatment as part of a clinical trial in the United States and showed clinical and radiological improvement.
| S-EPMC6148982 | biostudies-literature
Project description:Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by infiltration of organs by CD68+ and CD1a- lipid-laden histiocytes, including the central nervous system in more than a third of patients. Molecular analysis of ECD samples has demonstrated the prevalence of BRAF V600E mutations as high as 54%. Recently, vemurafenib became the only Food and Drug Administration-approved treatment for patients with ECD who carry the BRAF V600E mutation. However, dabrafenib has been suggested to have greater brain distribution. We describe a 44-year-old female patient treated from August of 2015 through November 2017. She presented with a 2-year history of light-headedness, fatigue, and vertigo. She was moderately dysmetric, diffusely hyperreflexic, and dysarthric in the bilateral upper and lower extremities. Her gait was wide-based. She had dysarthria and nystagmus on horizontal gaze bilaterally. Magnetic resonance imaging showed an extensive area of increased T2/fluid-attenuated inversion recovery signal in the brain stem, enhancement in the pons and midbrain, and thickening of the pituitary stalk. Positron emission tomography/computed tomography (PET/CT) and whole-body technetium Tc99m bone scintigraphy showed intense symmetrical radiotracer uptake in the distal femur and tibia bilaterally, which was biopsied. Immunohistochemistry was negative for BRAF V600E, but genomic sequencing revealed the mutation. The patient received combination therapy with dabrafenib and trametinib. Her nystagmus, dysarthria, dysmetria, and gait improved remarkably. Subsequent PET/CT and magnetic resonance imaging showed complete resolution of all radiographic evidence of disease. In this case report, we demonstrate the success of a combination therapy with dabrafenib and trametinib.
| S-EPMC6132217 | biostudies-literature
Project description:OBJECTIVE:To characterize the spectrum of neurologic involvement in Erdheim-Chester Disease (ECD), a treatable inflammatory neoplasm of histiocytes. METHODS:Sixty-two patients with ECD were prospectively enrolled in a natural history study that facilitated collection of clinical, imaging, laboratory, neurophysiologic, and pathologic data. RESULTS:Ninety-four percent of the patients had neurologic abnormalities on examination or imaging, and 22% had neurologic symptoms as the initial presentation of ECD. The most common neurologic findings were cognitive impairment, peripheral neuropathy, pyramidal tract signs, cranial nerve involvement, and cerebellar ataxia. Imaging revealed atrophy and demyelination along with focal lesions that were located throughout the nervous system, dura, and extra-axial structures. The BRAF V600E variant correlated with cerebral atrophy. Brain pathology revealed lipid-laden, phagocytic macrophages (histiocytes) accompanied by demyelination and axonal degeneration. INTERPRETATION:In patients with ECD, neurologic morbidity is common and contributes significantly to disability. Since neurologic symptoms can be the presenting feature of ECD and, given the mean delay in ECD diagnosis is 4.2 years, it is critical that neurologists consider of ECD and other histiocytosis in patients with inflammatory, infectious, or neoplastic-appearing white matter. Furthermore, given the broad spectrum of neurologic involvement, neurologists have an important role in a team of specialists treating ECD patients.
| S-EPMC7187721 | biostudies-literature
Project description:With approximately 750 cases reported, Erdheim-Chester disease is an exceedingly rare histiocyte cell disorder. Affected sites typically include long bones, large vessels and central nervous system. However, cutaneous and pulmonary involvement can also occur. The diagnosis is ascertained by identification of foamy histiocytes positive for CD68, CD163, and factor XIIIa on immunoperoxidase staining. Recently published literature have described an association between Erdheim-Chester disease and BRAF V600E mutation. This finding prompted the investigation of therapeutic possibilities with BRAF inhibitors, successful agents against other BRAF mutation-positive diseases. Vemurafenib, a BRAF kinase inhibitor, has been shown to be effective in BRAF V600E mutation-positive malignancies, such as NSCLC and melanoma, as well as in several case reports of Erdheim-Chester disease. We report a case of Erdheim-Chester disease diagnosed at our institution, treated with vemurafenib.
| S-EPMC5153444 | biostudies-literature
Project description:Treatment of Erdheim-Chester disease (ECD), a rare non-Langerhans histiocytosis, relies on interferon-?, chemotherapeutic agents such as purine analogs, cytokine-blocking agents and BRAF inhibitors. Since interleukin (IL)-6 levels are elevated in serum and lesions of ECD patients, we evaluated the therapeutic efficacy and safety of IL-6 blockade with tocilizumab. We conducted an open-label, single-arm, phase II, prospective study of tocilizumab in three patients with multisystem ECD and poor tolerance/contraindications to IFN-?. Modifications of symptoms attributed to ECD represented the criteria for evaluation of clinical response. Changes at positron emission tomography scan, computed tomography scan, and magnetic resonance imaging at month 6 represented the main criteria for the evaluation of radiological response. Sustained complete clinical response and partial radiological improvement were observed in two patients, paralleled by modulation of systemic pro-inflammatory mediators. In spite of disease stabilization or improvement at extra-neurological sites, a third patient experienced a radiologic and clinical progression of central nervous system involvement, mirrored by a dramatic increase of circulating IL-6 and related cytokines. These findings indicate that IL-6 inhibition can be effective in ECD, but caution is advisable in patients with neurologic involvement. IL-6 emerges as a central mediator in ECD pathogenesis.
| S-EPMC5486186 | biostudies-literature
Project description:Erdheim-Chester disease (ECD) is a clonal hematopoietic disorder characterized by the accumulation of foamy histiocytes within organs (in particular, frequent retroperitoneal involvement) and a high frequency of BRAFV600E mutations. Although ECD is not commonly recognized to have overt peripheral blood (PB) or bone marrow (BM) disease, we recently identified that ECD patients have a high frequency of a concomitant myeloid malignancy. We thus conducted a systematic clinical and molecular analysis of the BM from 120 ECD patients. Surprisingly, 42.5% of ECD patients (51 of 120) had clonal hematopoiesis whereas 15.8% of patients (19 of 120) developed an overt hematologic malignancy (nearly all of which were a myeloid neoplasm). The most frequently mutated genes in BM were TET2, ASXL1, DNMT3A, and NRAS. ECD patients with clonal hematopoiesis were more likely to be older (P < .0001), have retroperitoneal involvement (P = .02), and harbor a BRAFV600E mutation (P = .049) than those without clonal hematopoiesis. The presence of the TET2 mutation was associated with a BRAFV600E mutation in tissue ECD lesions (P = .0006) and TET2-mutant ECD patients were more likely to have vascular involvement than TET2 wild-type ECD patients. Clonal hematopoiesis mutations in ECD were detected in cells derived from CD34+CD38- BM progenitors and PB monocytes but less frequently present in PB B and T lymphocytes. These data identify a heretofore unrecognized high frequency of clonal hematopoiesis in ECD patients, reaffirm the development of additional high risk of myeloid neoplasms in ECD, and provide evidence of a BM-based precursor cell of origin for many patients with ECD.
| S-EPMC8555377 | biostudies-literature
Project description:ImportanceErdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis affecting multiple organs and commonly caused by somatic pathogenic variants in BRAF V600E and mitogen-activated protein kinase genes. Clinical features of ECD result from histiocytic involvement of various tissues; while endocrine involvement in ECD occurs frequently, the prevalence of central or primary hypothyroidism has not been thoroughly investigated.ObjectiveTo assess hypothalamus-pituitary-thyroid (HPT) dysfunction in patients with ECD.Design, setting, and participantsThis cross-sectional study included 61 patients with ECD who were enrolled in a natural history study at a tertiary care center between January 2011 and December 2018. ECD was diagnosed on the basis of clinical, genetic, and histopathological features. Data were analyzed in March 2020.ExposureDiagnosis of ECD.Main outcomes and measuresMain outcome was the prevalence of thyroid dysfunction in adults with ECD compared with community estimates. Patients underwent baseline evaluation with a thyroid function test, including thyrotropin, free thyroxine (fT4), and total thyroxine (T4), and sellar imaging with magnetic resonance imaging or computed tomography scan. The association of HPT dysfunction was assessed for differences in age, sex, body mass index, BRAF V600E status, high sensitivity C-reactive protein level, sellar imaging, and pituitary hormonal dysfunction.ResultsA total of 61 patients with ECD (46 [75%] men; mean [SD] age, 54.3 [10.9] years) were evaluated. Seventeen patients (28%) had hypothyroidism requiring levothyroxine therapy. The prevalence of both central and primary hypothyroidism were higher than community estimates (central hypothyroidism: 9.8% vs 0.1%; odds ratio, 109.0; 95% CI, 37.4-260.6; P < .001; primary hypothyroidism: 18.0% vs 4.7%; OR, 4.4; 95% CI, 2.1-8.7; P < .001). Patients with hypothyroidism (both primary and central), compared with patients with euthyroidism, had higher body mass index (median [interquartile range] 31.4 [28.3-38.3] vs 26.7 [24.4-31.9]; P = .004) and a higher prevalence of panhypopituitarism (7 [47%] vs 3 [7%]; P < .001). Among patients with hypothyroidism, those with central hypothyroidism, compared with patients with primary hypothyroidism, had a lower mean (SD) body mass index (28.3 [2.6] vs 36.3 [5.9]; P = .007) and higher frequencies of abnormal sellar imaging (5 [83%] vs 3 [27%]; P = .050) and panhypopituitarism (5 [83%] vs 3 [27%]; P = .050).Conclusions and relevanceIn this cohort study, a higher prevalence of central and primary hypothyroidism was identified in patients with ECD compared with the community. There should be a low threshold for testing for hypothyroidism in patients with ECD, and treatment should follow standard guidelines.
| S-EPMC7596581 | biostudies-literature