Involvement In Systemic Sarcoidosis Research Articles

Inflammation and Myocardial Blood Flow in Cardiac Sarcoidosis.

Cardiac involvement in systemic sarcoidosis or isolated cardiac sarcoidosis plays a pivotal role in the clinical manifestation and prognostication. Active-inflammatory cardiac sarcoidosis is associated with a regional impairment of coronary microvascular function that may confer further detrimental effects on myocardial function needing further characterization. Clinical investigations with cardiac positron emission tomography/computed tomography in conjunction with 18F-fluorodeoxyglucose to determine myocardial inflammation and 13N-ammonia to quantify myocardial blood flow (MBF) in patients with known or suspected cardiac sarcoidosis outlined that sarcoidosis-induced myocardial inflammation was associated with adverse effects on corresponding regional coronary microvascular function. Notably, immune-suppressive treatment caused reductions in myocardial inflammation were paralleled by improvements of coronary microvascular dysfunction outlining direct adverse effect of inflammation on coronary arteriolar function. This review summarizes contributions of cardiac PET imaging in the identification and characterization of active-inflammatory cardiac sarcoidosis, its effect on coronary microvascular function, treatment responses, and prognostic implications.

Radiological predictive remission factors of pulmonary involvement in systemic sarcoidosis: a computed tomography scan study.

As little is known about the prognostic value of CT scan findings at onset in patients presenting with sarcoidosis, we aimed to identify factors independently associated with radiological remission of pulmonary involvement in systemic sarcoidosis on CT scan findings. We conducted a retrospective descriptive and analytic study of patients with a biopsy proven systemic sarcoidosis. We compared patients on radiological remission (group 1) to those on stabilization or progression (group 2). Multivariate analysis of variables significantly associated with radiological remission in univariate analysis was performed using binary logistic regression. Out of 65 records of systemic sarcoidosis, 43 were analyzed. 18.6% where male and 81.6% female with a sex-ratio of 0.22 and a mean age at diagnosis of 47.2 ±13.6 years. We found atypical lesions in CT scan findings in 16 patients (37.2%). Comparative pulmonary CT scan findings at admission and at 12 months follow-up revealed 13 patients (30.2%) in remission (group1) and 30 patients in radiological stabilization or progression (group 2). On multivariate analysis, lymphopenia, calcifications, and typical CT scan findings at presentation were predictive factors of remission of pulmonary involvement in systemic sarcoidosis (aOR=27.57; 95%IC=2.67-284.63; p=0.005) (aOR= 37.2; 95%IC= 2.08-663.89; p= 0.014) (aOR=47.1; 95%IC= 1.79-1238.7; p=0.021) respectively. In patients with systemic sarcoidosis with no lymphopenia at onset or calcifications or typical CT scan findings at presentation, we suggest a close follow-up as well as an intensive treatment.

Real-Life Utilization of Criteria Guidelines for Diagnosis of Cardiac Sarcoidosis (CS).

Despite the increasing recognition of cardiac involvement in systemic sarcoidosis, the diagnosis of cardiac sarcoidosis (CS) remains challenging. Our aim is to present a comprehensive, retrospective case series of CS patients, focusing on the current diagnostic guidelines and management of this life-threatening condition. In our case series, patient data were collected retrospectively, including hospital admission records and rheumatology and cardiology clinic visit notes, detailing demographic, clinical, laboratory, pathology, and imaging studies, as well as cardiac devices and prescribed medications. Cases were divided into definite and probable CS based on the 2014 Heart Rhythm Society guidelines as well as presumed CS based on imaging criteria and clinical findings. Overall, 19 CS patients were included, 17 of whom were diagnosed with probable or presumed CS based on cardiac magnetic resonance imaging (CMR) and/or cardiac positron emission tomography using 18F-Fluorodeoxyglucose (PET-FDG) without supporting endomyocardial biopsy (EMB). The majority of CS patients were male (53%), with a mean age of 52.9 ± 11.8, with CS being the initial manifestation of sarcoidosis in 63% of cases. Most patients presented with high-grade AVB (63%), followed by heart failure (42%) and ventricular tachyarrhythmia (VT) (26%). This case series highlights the significance of utilizing updated diagnostic criteria relying on CMR and PET-FDG given that cardiac involvement can be the initial manifestation of systemic sarcoidosis, requiring prompt diagnosis and treatment to prevent morbidity and mortality.

Lacrimal Gland involvement in systemic Sarcoidosis

Lacrimal gland lesions generallypresent as palpable masses in thesuperolateral aspects of the orbits. Approximately 50% of lacrimalgland masses are inflammatory lesions, 25% are lymphoid lesions or lymphoma, and the other 25% are salivary gland type tumors. Although there are overlaps and exceptions, features such as laterality, portion of gland involvement, presence or absence of bony findings, enhancement pattern, andclinical presentation are valuable in differentiating among lacrimal gland lesions. The 3D ultrasound has been used to define lacrimal gland shape, size, density, structural features the pattern of blood supply, as well as the anatomic and topographic position in the orbit. The study was conducted in the B- and 3D-modes of ultrasonography with color and energy Doppler mapping on both sides.

The challenging management of cardiac involvement in systemic sarcoidosis

A 34 year-old young man came to our attention after an occasional finding of complete AV block. We made the diagnosis of systemic sarcoidosis with cardiac involvement through an FDG-PET even with a normal CMR. We started corticosteroid therapy and we decided to follow-up the patient through an implantable loop recorder (ILR). Beyond an initial regression of the AV block, after 8 months the ILR revealed AV block and pauses more than 3 s during the day; a new FDG-PET evidenced FDG uptake in new areas of left ventricle. Hence we started infliximab and implanted a dual chamber ICD.

Ultrasonography of Lacrimal Gland involvement in systemic Sarcoidosis

Lacrimal gland lesions generally present as palpable masses in the superolateral aspects of the orbits. Approximately 50% of lacrimal gland masses are inflammatory lesions, 25% are lymphoid lesions or lymphoma, and the other 25% are salivary gland type tumors. Although there are overlaps and exceptions, features such as laterality, portion of gland involvement, presence or absence of bony findings, enhancement pattern, and clinical presentation are valuable in differentiating among lacrimal gland lesions. The 3D ultrasound has been used to define lacrimal gland shape, size, density, structural features the pattern of blood supply, as well as the anatomic and topographic position in the orbit. The study was conducted in the B- and 3D-modes of ultrasonography with color and energy Doppler mapping on both sides.

Unilateral Retinal Arteritis and Macroaneurysm in Sarcoidosis

ABSTRACT Background Sarcoidosis, an idiopathic systemic disorder characterized by noncaseating granulomas, is often associated with granulomatous uveitis. Anterior segment involvement can present with mutton-fat keratic precipitates, anterior chamber cell, and iris nodules. Sarcoid associated posterior uveitis may present with vitritis, retinal vasculitis, and choroidal lesions. Case summary Sarcoid-associated retinal vasculitis is classically thought of as predominantly involving veins, but in this case report we describe a 76-year-old Caucasian woman presenting with bilateral posterior uveitis, unilateral optic nerve head granuloma, and retinal arteritis as the first manifestation of ocular involvement in systemic sarcoidosis. Conclusion This case describes the uncommon first manifestation of ocular involvement in systemic sarcoidosis presenting with unilateral retinal arteritis, macroaneurysms and optic nerve head granuloma.

Novel PET Tracers in the Management of Cardiac Sarcoidosis.

Sarcoidosis is a systemic inflammatory disease of unknown etiology, pathologically characterized by non-caseating granulomas involving several organs and tissues. This pathological process can eventually affect the heart during his course leading to fibrosis associated with systolic dysfunction, conduction disturbance, and even sudden cardiac death. Due to this prognostic impact, diagnosis is crucial to optimize clinical management. The low sensitivity of endomyocardial biopsy and its invasive nature prevents its application as a first-line diagnostic approach. Thus, several efforts have been dedicated to the identification of advanced imaging tools for the diagnosis and monitoring of cardiac involvement in systemic sarcoidosis, including Positron Emission Tomography (PET). Starting from strengths and disadvantages of 18F-Fluorodeoxyglucose (18F-FDG) PET imaging, the present narrative review will summarize state of the art and future perspectives about radiotracers other than 18F-FDG of potential interest in the field of CS, including somatostatin receptor- ligands, proliferation markers and hypoxia displaying agents.

Deterioration of biventricular strain is an early marker of cardiac involvement in confirmed sarcoidosis.

Risk assessment of developing cardiac involvement in systemic sarcoidosis can be challenging because of limited data. Recently, attention has been given to left ventricular and right ventricular (LV and RV) involvement in cardiac sarcoidosis (CS) and its prevalence, relevance, and prognostic value. The aim of this study was to assess the role of biventricular strain to predict prognosis in confirmed sarcoidosis patients. LV and RV longitudinal strains (LSs) were evaluated by 2D speckle tracking in 139 consecutive confirmed sarcoidosis patients without other pre-existing structural heart diseases, and 52 age- and gender-matched control subjects. The primary endpoint was CS-related events (cardiac death or development of cardiac involvement). Sarcoidosis without cardiac involvement had significantly lower LV and RV free wall LS compared with control subjects. Basal LS had a higher area under the curve for differentiation of sarcoidosis in patients without cardiac involvement compared to control (cut-off value: -18% with 89% sensitivity and 69% specificity). During a median period of 50 months, the occurrence of CS-related events was observed in 20 patients. In a multivariate analysis, basal LV LS and RV free wall LS were associated with the events [hazard ratio (HR) 0.72, P < 0.001 and HR: 0.83, P = 0.006, respectively]. Patients with impaired biventricular function had significantly shorter event-free survival than those with preserved biventricular function (P < 0.001). Deterioration of biventricular strain was associated with CS-related events. This information might be useful for clinical evaluation and follow-up in sarcoidosis.

Updates on the Role of Imaging in Cardiac Sarcoidosis.

The non-specific symptom profile and subclinical nature of disease along with variable region of cardiac involvement in systemic sarcoidosis make the diagnosis particularly challenging. The yield of endomyocardial biopsy, a gold standard for diagnosis, is not high unless coupled with additional imaging modalities to detect regional involvement. This review is focused on highlighting the major recent advances in imaging modalities and diagnosis of cardiac sarcoidosis. There has been much interest and increasing research focused on developing newer and improved imaging modalities to establish diagnosis. CMR and 18F- FDG-PET are now considered imaging modalities of choice in most centers worldwide, but the data comparing both methodologies head-to-head is limited. Nevertheless, novel radiotracers (i.e. 68Ga-DOTANOC, 18F-Flurpiridaz, 13N-Ammonia) and hybrid combination PET/CMR imaging are coming to spotlight with improved sensitivity and specificity for earlier detection of myocardial sarcoid. As CMR and PET are showing increased utilization in cardiac sarcoidosis, 201Th-SPECT, 99mTc MDP SPECT, 67Ga Scintigraphy, and 82Rb PET are falling out of favor. Newer imaging modalities, radionuclide tracers, and hybrid PET/CMR combinations have been promising in better detecting cardiac sarcoidosis and are currently being evaluated in larger trials.

Bilaterally Diffuse Lacrimal Gland Involvement: Initial Presentation of Systemic Sarcoidosis.

Orbital involvement in systemic sarcoidosis is a rare condition. We report a case of orbital sarcoidosis with bilaterally huge lacrimal gland involvement as the initial manifestation of systemic sarcoidosis. A 20-year-old woman admitted the ophthalmology department with progressive bilateral upper eyelid swelling for 6 months. The only pathologic finding was the presence of bilateral, symmetrical, solid, lobular masses at the lateral upper eyelids at the location of lacrimal glands. On systemic examination, bilateral parotid and submandibular glands appeared swollen. Magnetic resonance imaging of the orbit revealed bilateral symmetrical diffuse enlargement of the lacrimal glands with maximum and minimum thickness of 11 mm and 7 mm, respectively. The biopsy findings were compatible with sarcoidosis. Although lacrimal gland involvement has been reported in different studies, we for the first time report an unusual case with bilateral diffuse huge lacrimal gland involvement. Normal lacrimal gland thickness is approximately 4-5 mm in magnetic resonance imaging, while our case had bilateral diffuse enlargement of lacrimal glands, which showed maximum and minimum thickness of 11 mm and 7 mm, respectively. Although orbital involvement is uncommon in sarcoidosis, it should be remembered in the differential diagnosis of orbital masses.

T1 and T2 Mapping in Recognition of Early Cardiac Involvement in Systemic Sarcoidosis.

Purpose To determine whether quantitative tissue characterization with T1 and T2 mapping supports recognition of myocardial involvement in patients with systemic sarcoidosis. Materials and Methods Fifty-three consecutive patients with a biopsy-proven extracardiac diagnosis of systemic sarcoidosis (21 men; median age, 45 years; interquartile range, 22 years) and 36 normotensive previously healthy control subjects (14 men; median age, 43 years; interquartile range, 18 years) underwent cardiovascular magnetic resonance imaging, which was performed to assess cardiac function and late gadolinium enhancement, and T1 and T2 mapping. A follow-up substudy was performed in 40 patients (mean follow-up interval, 144 days ± 35 [standard deviation]); of these 40 patients, 18 underwent anti-inflammatory treatment for systemic symptoms. Binary logistic regression and receiver operating characteristic curve analyses were used to assess discrimination between health and disease; Wilcoxon signed rank test was used to assess the effect of treatment. Results When compared with control subjects, patients had higher ventricular volume, higher myocardial native T1 and T2, and lower longitudinal strain and ejection fraction (P < .05 for all). Myocardial native T1 and T2 had higher discriminatory accuracy (area under the receiver operating characteristic curve [AUC]: 0.96 and 0.89, respectively) for separation between control subjects and patients when compared with the standard diagnostic criteria (AUC < 0.67). Native T1 was the independent discriminator between health and disease (specificity, 90%; sensitivity, 96%; accuracy, 94%). There was a significant reduction of native T1 and T2 in the patients who underwent treatment (z score: -3.72 and -2.88; P < .01) but not in the patients who did not (z score, -1.42 and -1.38; P > .15). Conclusion Quantitative myocardial tissue characterization with T1 and T2 mapping may enable noninvasive recognition of cardiac involvement and activity of myocardial inflammation in patients with systemic sarcoidosis. Future studies will be performed to confirm their role in risk stratification and guidance of clinical management. © RSNA, 2017 Online supplemental material is available for this article.

Young Investigator Award session – Clinical Science442Left bundle branch block and coronary artery disease in coronary ct angiography443Focal myocardial fibrosis and abnormal left ventricular strain in patients with sarcoidosis without clinical evidence of cardiac disease444Arhgap24, a first gene for fibro elastic deficiency mitral valve prolapse? A phenotypic study445Advantage of using ASE/EACVI criteria for detection of subclinical cardiotoxicity in breast cancer

Young Investigator Award session – Clinical Science442Left bundle branch block and coronary artery disease in coronary ct angiography443Focal myocardial fibrosis and abnormal left ventricular strain in patients with sarcoidosis without clinical evidence of cardiac disease444Arhgap24, a first gene for fibro elastic deficiency mitral valve prolapse? A phenotypic study445Advantage of using ASE/EACVI criteria for detection of subclinical cardiotoxicity in breast cancer

Advances in radionuclide imaging of cardiac sarcoidosis.

Radionuclide imaging for the diagnosis and monitoring of cardiac involvement in sarcoidosis has advanced significantly in recent years. This article is based on published clinical guidelines, literature review and our collective clinical experience. Gallium-67 scintigraphy is among the diagnostic criteria for cardiac involvement in systemic sarcoidosis, and it is strongly associated with response to treatment. However, fluorine-18, 2-fluoro-deoxyglucose (FDG) positron emission tomography (PET) is now preferred both for diagnosis and for assessing prognosis. Most data are from small observational studies that are potentially biased. Quantitative imaging to assess changes in disease activity in response to treatment may lead to FDG-PET having an important routine role in managing cardiac sarcoidosis. Larger prospective studies are required, particularly to assess the effectiveness of radionuclide imaging in improving clinical management and outcome.

Vertigo as a Predominant Manifestation of Neurosarcoidosis

Sarcoidosis is a granulomatous disease of unknown etiology that affects multiple organ systems. Neurological manifestations of sarcoidosis are less common and can include cranial neuropathies and intracranial lesions. We report the case of a 21-year-old man who presented with vertigo and uveitis. Extensive workup including brain imaging revealed enhancing focal lesions. A lacrimal gland biopsy confirmed the diagnosis of sarcoidosis. The patient was initially treated with prednisone, which did not adequately control his symptoms, and then was switched to methotrexate with moderate symptomatic improvement. Our patient had an atypical presentation with vertigo as the predominant manifestation of sarcoidosis. Patients with neurosarcoidosis typically present with systemic involvement of sarcoidosis followed by neurologic involvement. Vertigo is rarely reported as an initial manifestation. This case highlights the importance of consideration of neurosarcoidosis as an entity even in patients that may not have a typical presentation or systemic involvement of disease.

Sarcoidosis and the heart: A review of the literature.

Sarcoidosis is a chronic multisystem disorder without any defined etiology. Cardiac sarcoidosis (CS) is detected in 2-7% of patients with sarcoidosis and more than 20% of the cases of sarcoidosis are clinically silent. Cardiac involvement in systemic sarcoidosis (SS) and isolated cardiac sarcoidosis (iCS) are associated with arrhythmia and severe heart failure (HF) and have a poor prognosis. Early diagnosis of CS and prompt initiation of corticosteroid therapy with or without other immunosuppressants is crucial. Electrocardiography, Holter monitoring, and Doppler echocardiography with speckle tracking imaging can serve as the initial steps to diagnosis of CS. Cardiac magnetic resonance (CMR) imaging and positron emission tomography (PET) are promising techniques for both diagnosis and follow-up of CS. This review discusses the main aspects of cardiac involvement in sarcoidosis.

Correlation of late gadolinium enhancement MRI and quantitative T2 measurement in cardiac sarcoidosis

To investigate the potentially improved detection and quantification of cardiac involvement using novel late-gadolinium-enhancement (LGE) cardiac magnetic resonance imaging (MRI) and quantitative T2 measurement to achieve better myocardial tissue characterization in systemic sarcoidosis. Twenty-eight patients with systemic sarcoidosis underwent a cardiac magnetic resonance imaging (CMR) study on a 1.5T system. Precontrast CMR included left ventricular (LV) and right ventricular (RV) function and quantitative T2 measurement. Postcontrast LGE-MRI included inversion-recovery fast-gradient-echo (IR-FGRE) and multicontrast late-enhancement imaging (MCLE). LV functional parameters were normal in all patients (LVEF=61.2±8.5%) including with cardiac involvement (LVEF=59.4±12.1%) and without (LVEF=61.7±7.5%) while the average RV function was comparatively decreased (RVEF=48.0±6.6%, P<0.0001). 21.4% of patients had cardiac involvement showing patchy or multiple focal hyperenhancement patterns in LV free wall, papillary muscles (PM), or interventricular septum. In two cases with PM involvement, the PM abnormal LGE foci were only observed on MCLE. For precontrast T2 measurements, a significantly decreased T2 measurement was observed in regions demonstrating LGE, compared to the LGE-negative group (focal LGE-positive regions vs. negative: 40.0±2.4 msec vs. 53.0±2.6 msec, P<0.0001). LGE-MRI can identify cardiac involvement in systemic sarcoidosis. MCLE might be more sensitive at detecting subtle myocardial lesion. The decreased T2 observed in cardiac sarcoid may reflect its inactive phase, thus might provide a noninvasive method for monitoring disease activity or therapy.

134 MRI Detection and Quantitative T2 Measurement of Cardiac Involvement in Systemic Sarcoidosis: Initial Results

Cardiac involvement (CI) in patients with systemic sarcoidosis is a major risk factor for sudden cardiac death. The incidence of CI on autopsy can be up to 40% although it is only observed in 5-10% patients diagnosed clinically with systemic sarcoidosis. Early detection of CI may therefore potentially alter prognosis and treatment options. In this study, we investigated the prevalence of CI in a cohort of biopsy proven sarcoid patients using quantitative cardiac MRI techniques of late-gadolinium-enhancement (LGE) and T2 mapping. 28 patients with systemic sarcoidosis, but without overt cardiac involvement [17 males (60%), ages of 50±10 years] had undergone an MRI study on a 1.5T magnet system. Pre-contrast MRI included left ventricular (LV) and right ventricular (RV) function and quantitative T2 measurements using T2 maps derived from a Multi-echo fast-spin-echo sequence (MEFSE) or T2 preparation spiral scan. Post-contrast LGE-MRI included inversion recovery fast-gradient-echo (IR-FGRE) and multi-contrast late-enhancement (MCLE) imaging. CMR42 was used for ventricular function measurement, LGE determination and quantitative T2 calculation. LV functional parameters in 28 patients were normal while the RV function was decreased (mean LVEF: 61.2±8.5%; mean RVEF 48.0±6.6%). 21.4% of subjects (6/28) had CI showing patchy or multiple focal hyper-enhancement patterns in LV free wall, papillary muscles (PM) or inter-ventricular septum. In two cases with PM involvement, the PM abnormal LGE foci were only observed on MCLE. The LV systolic function was preserved in patients with CI (n=6, LVEF=59.4±12.1%). For pre-contrast T2 measurements at the mid-LV level, there was no significant difference in T2 averaged over the myocardium between LGE negative (n=22) and positive group (n=6) (LGE negative vs. positive: 53.0±2.6 ms vs.53.4±2.4 ms, p=0.76). However, a significant decrease in T2 was observed in LGE-positive regions, compared to the LGE negative group (focal LGE-positive regions vs. negative: 40.0±2.4 ms vs. 53.0±2.6 ms, p<0.0001). Extra-cardiac MRI findings were documented in 63.4% of patients, primarily hilar and mediastinal lymph node enlargement. In three LGE-positive patients, follow-up MRI at 15-26 months demonstrated LGE foci were stable in 2 subjects whilst one subject demonstrated new transmural LGE. LGE-MRI especially MCLE method can detect cardiac involvement in sarcoidosis. In focal areas of LGE, there is a decrease in T2. This may be secondary to asteroid bodies containing calcified proteins - suggesting chronic stable disease. Changes in T2 might therefore reflect different phases of cardiac sarcoid, thus providing a non-invasive method for monitoring disease and therapy.

Cardiac magnetic resonance imaging in the evaluation of cardiac sarcoidosis: an Australian single‐centre experience

Cardiac involvement in systemic sarcoidosis is common; however, current diagnostic tools are imprecise. Recognition of cardiac sarcoidosis (CS) is important as it has a relatively poor prognosis. Gadolinium-enhanced cardiac magnetic resonance imaging (Gad-CMR) is emerging as an excellent technique in determining the presence of and extent to which cardiac muscle is affected by sarcoidosis. A retrospective analysis was performed on all patients with biopsy-proven systemic sarcoidosis referred for Gad-CMR scanning to evaluate potential cardiac involvement. All patients also underwent an electrocardiogram, Holter monitor and echocardiography. Gallium-67 radionuclide investigation, positron emission tomography and cardiac biopsy were ordered at the discretion of the treating physician. Eleven of the 20 patients had Gad-CMR images supportive of the diagnosis of CS. Eight of these 11 patients met the Japanese Ministry of Health and Welfare (JMHW) criteria for the diagnosis of CS; three abnormal Gad-CME scans consistent with diagnosis of CS were seen in patients who did not meet JMHW criteria. No patients with normal Gad-CMR scan met JMHW criteria for CS. These findings suggest that Gad-CMR is potentially superior to the JMHW criteria in the diagnosis of cardiac sarcoidosis.

Extrapulmonary sarcoidosis of liver and pancreas: A case report and review of literature

Sarcoidosis is a chronic multisystemic granulomatous disease of unknown origin, which can involve nearly all organs. In the case of an infrequent gastrointestinal tract involvement in systemic sarcoidosis, granulomas of the liver are most commonly described while isolated pancreatic sarcoid lesions are rarely seen. We report a case of systemic sarcoidosis with exclusive extrapulmonal involvement of the liver and the pancreas in a 71-year-old white man. The diagnosis of liver involvement was confirmed by biopsy. Pancreatic surgery was needed because preoperative evaluation could not exclude pancreatic cancer and for biliary decompression. An extensive literature review of systemic sarcoidosis, focusing on reported cases with unusual presentation of sarcoidosis in the liver and the pancreas, its diagnosis, treatment, and prognosis was made.