Fibroinflammatory Diseases of Aorta: The Inside Look.

ObjectiveIn this article we present a simplified algorithm-based approach to the thickening of the small and large bowel wall detected on routine computed tomography (CT) of the abdomen.BackgroundThickening of the small or large bowel wall may be caused by neoplastic, inflammatory, infectious, or ischaemic conditions. First, distinction should be made between focal and segmental or diffuse wall thickening. In cases of focal thickening further analysis of the wall symmetry and perienteric anomalies allows distinguishing between neoplasms and inflammatory conditions. In cases of segmental or diffuse thickening, the pattern of attenuation in light of clinical findings helps narrowing the differential diagnosis.ConclusionFocal bowel wall thickening may be caused by tumours or inflammatory conditions. Bowel tumours may appear as either regular and symmetric or irregular or asymmetric thickening. When fat stranding is disproportionately more severe than the degree of wall thickening, inflammatory conditions are more likely. With the exception of lymphoma, segmental or diffuse wall thickening is usually caused by benign conditions, such as ischaemic, infectious and inflammatory diseases.Key points• Thickening of the bowel wall may be focal (<5 cm) and segmental or diffuse (6-40 cm or >40 cm) in extension.• Focal, irregular and asymmetrical thickening of the bowel wall suggests a malignancy.• Perienteric fat stranding disproportionally more severe than the degree of wall thickening suggests an inflammatory condition.• Regular, symmetric and homogeneous wall thickening is more frequently due to benign conditions, but can also be caused by neoplasms such as well-differentiated adenocarcinoma and lymphoma.• Segmental or diffuse bowel wall thickening is usually caused by ischaemic, inflammatory or infectious conditions and the attenuation pattern is helpful in narrowing the differential diagnosis.

The main issue of our case report is that Erdheim-Chester disease (ECD) clinically presents most commonly with bone and joint pain. We would again like to stress that technetium-99 bone scintigraphy has an important role to identify ECD in an early phase of the disease. Most diagnoses of ECD are made serendipitously. In their reply, Aouba et al compare stand-alone [F] fluorodeoxyglucose ([F]FDG) positron emission tomography (PET) results with computed tomography (CT) scan results. This may be a somewhat obsolete discussion; a hybrid PET/CT delivers the advantage of the synergy of the anatomic and metabolic information. As in any disease, in ECD metabolic changes precede the anatomic changes, creating a higher sensitivity in early stages of the disease. The PET component of a hybrid PET/CT camera is very useful in identifying subtle lesions on CT images that would otherwise be missed. In the wide clinical range that a patient with ECD may present, our patient has the indolent and isolated bone involvement, and not a more systemic and potentially life-threatening form. The irregular mildly increased uptake in the basal field of the right lung and in the lingual of the left lung was, together with the CT findings, indicative of transient infiltrative changes caused by a banal lung infection (Fig 1A). A control CT of the thorax 1 month later showed normalized images. A repeated [F]FDG PET/CT 1 year after diagnosis revealed no lung abnormalities or any other pathology suggestive of extraskeletal involvement of ECD (Fig 1B). The characteristic symmetric pathologic uptake in both distal femurs and both proximal tibiae did not show progression. We would like to thank Aouba et al for their suggestion to use anakinra for the treatment of extra-skeletal involvement of ECD. Because our patient has no extraskeletal involvement, neither anakinra, imatinib mesylate, nor any other systemic therapy is indicated.

Efficacy of biological agents in the treatment of Erdheim-Chester disease.

Erdheim - Chester disease (ECD) is a rare, slowly progressive non-Langerhans cell histiocytosis that affects bones and multiple viscera. In 2016 the World Health Organization classified ECD as a distinct entity within the histiocytic neoplasm family. Fewer than 1500 cases have been documented in the international literature and the ECD Global Alliance registry. We report a 49-years-old man with biopsy-proven Erdheim - Chester disease (ECD) who developed acute suppurative appendicitis. After systematic evaluation he underwent laparoscopic appendectomy under general anesthesia and, because of multi-organ ECD involvement, was transferred to the intensive care unit (ICU). A multidisciplinary regimen of lung-protective ventilation, continuous renal-replacement therapy, broad-spectrum antibiotics, granulocyte colony-stimulating factor and glucocorticoids was instituted, leading to stable respiratory and renal function; he was discharged to the hematology ward on post-operative day 10. ECD patients are prone to peri-operative deterioration due to pulmonary infiltration, refractory hypoxemia, acute kidney injury and immune paralysis; successful outcome depends on coordinated multidisciplinary care, precise hemodynamic and volume management, early continuous renal replacement therapy (CRRT) and immunomodulation.

ABSTRACTErdheim–Chester disease (ECD) is an extremely rare disorder that can affect many different organs of the body. This is an unusual form of non-Langerhans-cell histiocytosis. This is characterized by excessive production and accumulation of histiocytes. The normal function of the histiocytes is to fight infections. Histiocytes accumulate in the loose connective tissue of various organ systems of the body and cause thickening of tissues and may become dense and fibrotic. In the absence of successful treatment, the disease is debilitating and can result in multi-system organ failure. Erdheim–Chester disease is often described in the medical literature as an extremely rare1 entity. Erdheim–Chester disease usually presents in adults aged between 40 and 60 years. Here we present a case report of ECD in a 26-year-old young male patient with progressive course over a period of 4 years with symptoms suggestive of multi-organ involvement.How to cite this articlePatil M, Jaiswal D. Erdheim–Chester Disease. J Med Sci 2015;1(3):55-57.

Limited information is available regarding interstitial lung disease (ILD) in Erdheim–Chester disease (ECD), a rare multisystemic non-Langerhans cell histiocytosis. Sixty-two biopsy-confirmed ECD patients were divided into those with no ILD (19.5%), minimal ILD (32%), mild ILD (29%), and moderate/severe ILD (19.5%), based on computed tomography (CT) findings. Dyspnea affected at least half of the patients with mild or moderate/severe ILD. Diffusion capacity was significantly reduced in ECD patients with minimal ILD. Disease severity was inversely correlated with pulmonary function measurements; no correlation with BRAF V600E mutation status was seen. Reticulations and ground-glass opacities were the predominant findings on CT images. Automated CT scores were significantly higher in patients with moderate/severe ILD, compared to those in other groups. Immunostaining of lung biopsies was consistent with ECD. Histopathology findings included subpleural and septal fibrosis, with areas of interspersed normal lung, diffuse interstitial fibrosis, histiocytes with foamy cytoplasm embedded in fibrosis, lymphoid aggregates, and focal type II alveolar cell hyperplasia. In conclusion, ILD of varying severity may affect a high proportion of ECD patients. Histopathology features of ILD in ECD can mimic interstitial fibrosis patterns observed in idiopathic ILD.

Erdheim-Chester disease (ECD) is a rare disease that is characterized by multi-organ involvement of foamy histiocytes. It causes systemic inflammation, and also demonstrates various clinical manifestations and has a poor prognosis. We encountered a case of ECD in a patient that had been treated for underlying polycythemia vera. As far as we know, this is the first reported case worldwide where ECD developed in association with polycythemia vera. A 59-year-old man visited our hospital due to pleuric pain at the right side of the chest. Pleural tissue that was obtained following a thoracoscopic biopsy showed non-Langerhan's cell histiocytosis, suggesting the presence of ECD. The histiocytes stained positively for CD68, but were negative for S-100 and CD1a. The patient also complained of pain at both hips and the right shoulder area. An X-ray and magnetic resonance image demonstrated that the lesion showed sclerosis and osteolysis in both the proximal femur and right humerus. Treatment was started with predinisolone, and subsequently cyclophosphamide was added. ECD is a very rare multi-systemic disease, and its cause and therapeutic options have not yet been defined. ECD has a poor prognosis. Therefore, we believe that additional case studies are needed prior to the determination of a novel therapy for ECD.

Clinical Spectrum and Outcome of Kidney Involvement in Non-Langerhans Histiocytosis

Erdheim-Chester disease is a rare, multisystem hematologic disease. Cardiovascular involvement is seen in patients with Erdheim-Chester disease and can lead to increased morbidity and mortality. In this series, we report various cardiovascular manifestations of patients with Erdheim-Chester disease. This study includes patients with Erdheim-Chester disease who were referred to our institution from 12/3/2009 through 12/13/2017. All patients had biopsy-proven Erdheim-Chester disease. Clinical data, multimodality imaging, and cardiac tests were reviewed. Cardiovascular findings in 24 patients with Erdheim-Chester disease were included in the study. We reviewed available transthoracic echocardiograms, whole body PET/CT scans, and CMR studies. Most patients were male and mean age at the time of diagnosis was 58years. Pericardial involvement (13%), myocardial infiltration (25%), endocardial involvement (4%), valvular disease (17%), aortic/vascular disease (17%), conduction system infiltration (8%), and coronary artery disease (25%) were present. At a median follow-up of 5.5years, mortality was 17%. Erdheim-Chester disease can involve various cardiovascular structures and is frequently diagnosed on an imaging modality. Some patients had asymptomatic involvement, but others presented with ischemic heart disease, heart failure, valvular disease, and conduction system abnormalities. Early recognition of cardiovascular involvement of Erdheim-Chester disease is needed because of high morbidity and mortality.

Objective: Erdheim- Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by multisystem tissue infiltration of foamy histiocytes. Very few studies have investigated the prevalence of endocrine abnormalities in patients with ECD. Based on limited data, it is known that endocrine manifestations are not uncommon. The objective of this study was to characterize the extent of endocrine gland involvement and hormonal function abnormalities in the largest reported endocrine cohort of patients with ECD. Design: Retrospective chart review study of patients with ECD evaluated at the Mayo Clinic from January 1990 to June 2018. A tissue biopsy confirming the diagnosis of ECD was necessary for inclusion in this study. In all cases, the diagnosis of ECD was confirmed using clinical criteria in conjunction with histopathologic findings. Clinical, laboratory, and imaging data were collected. Results: Eighty-three patients with confirmed ECD were included in our study (71.1% women, 83.1% Caucasian, median age at time of diagnosis 55.2[46.3-66.1]). Symptom onset preceded the diagnosis by a median time of 2.7[1.0-6.9] years. Forty-eight patients (57.8%) had at least one hormonal deficiency. Central diabetes insipidus (25.3%) was the most common endocrine manifestation at initial presentation. Fifty percent of patients with central diabetes insipidus had at least one co-existent anterior pituitary deficiency at presentation, most commonly hypogonadism (40%). Among patients that had further endocrine evaluation, 16/64 (25.0%) had primary hypothyroidism and 7/64 (10.9%) had central hypothyroidism. 7/34 (20.3%) had central secondary adrenal insufficiency and 2/34 (5.8%) had primary adrenal insufficiency. Central hypogonadism was found in 18/31 (58.1%) of patients, whereas 6/31 (19.4%) had primary hypogonadism. Growth hormone deficiency was found in 7/59 (29.7%) patients and 4/27 (14.8%) patients had hyperprolactinemia. Imaging revealed involvement of the pituitary/hypothalamus in 18 (21.7%) patients, adrenal glands in 18 (21.7%) patients and testicles in 5 (6.0%) patients. Thirty-five patients (42.2%) had at least one gland involved seen on imaging, Visible gland infiltration did not correlate with hormonal deficiencies. New hormonal deficits appeared during follow-up. Conclusions: This is the largest case series of endocrine manifestations in patients with ECD. Endocrine involvement is frequent in these patients, 57.8% have at least one hormonal deficiency. Because endocrine abnormalities can evolve throughout the course of the disease, patients should have endocrine evaluation periodically.

Background: Erdheim- Chester Disease (ECD) is a rare hematopoietic neoplasm characterized by multi-organ infiltration with CD-68 -positive, CD1a-/S100-negative foamy histiocytes causing xantho-granulomatous inflammation. ECD most commonly involves the skeleton. CNS, pulmonary and CV involvement are also reported. Clinical Case: A 47-year-old male with a prior history of central Diabetes Insipidus (DI) presented with bone pain and ataxia. He was initially referred in 1993 for evaluation of DI. It was concluded that he had lymphocytic infundibulitis (LI), based on the finding of a thickened pituitary stalk on MRI while CSF revealed no evidence of infection or neoplasm. His DI was controlled with DDAVP. He had no other anterior pituitary hormone deficiencies. Although subsequent MRI showed resolution of the pituitary stalk thickening, his DI persisted. In 2012, he developed progressive gait instability, slurred speech and impaired motor coordination. On exam, he exhibited horizontal nystagmus, dysarthria, and truncal ataxia greater than limb ataxia. A brain MRI revealed absence of the posterior pituitary bright spot, enhancement along the proximal 7th and 8th nerve complex, disproportionate cerebellar atrophy and enhancement along the bilateral cerebellar folia. He complained of progressive, chronic leg pain since 2005. In 2018, he underwent tibial bone biopsy for an osteosclerotic lesion with diagnosis of Paget’s disease (PD). His Ca, Phos, 25OH- D, PTH, and Alk Phos were normal. Subsequent X-rays noted lesions of the pedicle of the left shoulder and pelvis, medullary sclerosis in the humeral diaphysis, and symmetrical lesions in the distal femur and tibia, bilaterally. Bone scan and FDG-Pet scan showed increased activity in the lesions. A repeat tibial biopsy revealed the marrow was infiltrated with histiocytes, fibrosis and sclerosis of trabecular bone. The histiocytes were highlighted by CD163, CD68, CD14, factor XIIIa and fascin A few scattered histiocytes were BRAF V600E immuno-stain positive, consistent with a diagnosis of ECD. His symptoms improved on Vemurafenib. Conclusion: We report a male with ECD who initially presented with isolated DI and a clinical course that mimicked LI. DI is a feature that occurs early in the disease process in 25% of patients. More than 10 years later, he developed ataxia and multifocal osteosclerotic bone lesions. His bone lesions were misdiagnosed as PD, but a repeat bone biopsy led to the correct diagnosis. In contrast to PD, the bone lesions in ECD are bilateral and symmetric and affect the diaphysis of long bones, specifically. As in our case, some patients with ECD can be asymptomatic for decades. For symptomatic patients who are BRAFV600E +, the B-Raf enzyme inhibitor, Vemurafenib, is recommended. His diagnosis was challenging, because ECD is rare (500 cases) and has features that overlap with other more common medical conditions.

To describe the urological manifestations of Erdheim-Chester disease (ECD) and their computed tomography (CT) findings. We retrospectively reviewed 48 patients diagnosed with ECD at Peking Union Medical College Hospital from January 2014 to January 2020. Twenty-four patients exhibited urological manifestations. Their CT findings, including appearances of the involved area (e.g., perirenal space, renal sinus, ureters, renal arteries, and adrenal glands), occurrence rate of ECD involvement in each area, signal enhancement pattern after CT contrast agent administration, disease progression, and causes of hydronephrosis were discussed. In 24 patients with evidence of ECD urological involvement, the most common manifestation was perirenal infiltration, appearing as "hairy kidney" on unenhanced CT scans and moderate signal enhancement on enhanced CT scans (17/24, 70.8%). Other manifestations included renal sinus infiltration (16/24, 66.7%), proximal ureter involvement (14, 58.3%), renal artery sheath (10, 41.7%), hydronephrosis (14, 58.3%), and adrenal glands involvement (8, 33.3%). The histiocytic infiltrate was mostly bilateral, starting from the perirenal space and spreading to the renal sinus and ureters. Hydronephrosis was usually associated with infiltration of ureters. Kidneys are the most common visceral organs affected by ECD. CT scanning is not only advantageous in early diagnosis, but also critical for designing the treatment regime for patients with ECD.

Erdheim-Chester disease (ECD) is a rare, systemic, non-Langerhans cell histiocytosis neoplasm, which is characterized by the infiltration of CD63+ CD1a- histiocytes in multiple tissues. The BRAFV600E mutation is frequently present in individuals with ECD and has been detected in hematopoietic stem cells and immune cells from the myeloid and systemic compartments. Immune cells and pro-inflammatory cytokines are present in lesions, suggesting that ECD involves immune cell recruitment. Although a systemic cytokine T-helper-1-oriented signature has been reported in ECD, the immune cell network orchestrating the immune response in ECD has yet to be described. To address this issue, the phenotypes of circulating leukocytes were investigated in a large, single-center cohort of 78 patients with ECD and compared with those of a group of 21 control individuals. Major perturbations in the abundance of systemic immune cells were detected in patients with ECD, with decreases in circulating plasmacytoid, myeloid 1, and myeloid 2 dendritic cells, mostly in BRAFV600E carriers, in comparison with individuals in the control group. Similarly, marked decreases in blood T-helper, cytotoxic, and B-lymphocyte numbers were observed in patients with ECD, relative to the control group. Measurement of circulating immunoglobulin concentrations revealed an immunoglobulin G switch, from IgG1 to IgG4 subclasses, which are more frequently associated with the BRAF mutation. First-line therapies, including pegylated interferon-a and vemurafenib, were able to correct most of these alterations. This study reveals a profound disturbance in the systemic immune phenotype in patients with ECD, providing important new information, helping to understand the physiopathological mechanisms involved in this rare disease and improving the therapeutic management of patients.

Evaluating Treatment-Related Outcomes in the Era of Targeted Therapy for Rosai Dorman and Erdheim Chester Disease

Erdheim–Chester disease (ECD) is a rare and frequently neglected disease, usually with a poor prognosis. The first two cases of ECD were reported by Austrian pathologist: Jakob Erdheim and his apprentice student William Chester in 1930. The etiology and disease incidence are unknown. One of the main components of this disorder is a chronic uncontrollable inflammation. Clinical manifestations of the disease can be very different. ECD affects predominantly adults, usually male population. There is no effective treatment developed yet. In 2016 ECD was classified as histiocytic neoplasm by the World Health Organization and was categorized as “tumors of histiocytes and dendritic cells”. More than half of patients testing positive for the BRAF mutation. There is a Erdheim–Chester Disease Global Alliance (ECDGA), which try to unite and provide with information about diagnostics and treatment of this rare disease both patients and doctors. Today, there are 571 registered patients and only one from Russia. The final diagnosis is made on the basis of histological finding such as infiltration with foamy histiocytes, signs of inflammation and Touton giant cells. Immunohistological analysis is usually CD68 and XIIIa positive. There are radiological finding indicating a possible association with the disease. There is this specific, almost pathognomonic scintigraphic picture of the skeleton, “coated” aorta, “hairy kidney” patterns on computer tomography. We demonstrate a clinical case of a patient with a newly diagnosed ECD with bone and connective tissue involvement, with manifestation of this disease more than 10 years ago. It took four months to make the final diagnosis. There were three biopsies and a wide range of other diagnostic procedures.