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Marc A Judson - One of the best experts on this subject based on the ideXlab platform.
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the development of Sarcoidosis in patients receiving daclizumab a case series from multiple clinical trials
Respiratory Medicine, 2019Co-Authors: Marc A Judson, Brett M Elicker, Thomas V Colby, Sooyeon Kwon, Elizabeth De Windt, Spyros Chalkias, Claudia Prada, Karen Smirnakis, Priya SinghalAbstract:Abstract Introduction Several drugs have been associated with druginduced Sarcoidosis-like reactions (DISRs) that are clinically indistinguishable from Sarcoidosis. Daclizumab is a humanized monoclonal IgG1 antibody that binds to CD25 that has been studied for the treatment of multiple sclerosis (MS). During MS clinical trials of daclizumab, 12 subjects developed clinical conditions potentially consistent with Sarcoidosis. Therefore, an independent adjudication committee of individuals with expertise in Sarcoidosis was organized to determine the likelihood of these cases representing Sarcoidosis. Methods The adjudication committee consisted of a pulmonologist, pathologist, and radiologist with clinical experience in Sarcoidosis. The committee had access to the subjects' laboratory data, narratives of all suspect adverse reaction reports, radiographic imaging and histology from biopsies. A priori, a grading system was developed to determine criteria to establish the likelihood that the patient had developed Sarcoidosis. Results The adjudication confirmed Sarcoidosis in 11/12 subjects. The committee's decisions were unanimous in all cases. Biopsies were available in 7/11 of these. In the 4 subjects who did not have a biopsy, they all had presentations, clinical findings, and/or laboratory findings that were highly specific for Sarcoidosis. Alternative causes for these clinical findings were reasonably excluded in all cases. The lung (8/11) and skin (6/11) were the most common organs involved. The mean daclizumab dose given when signs or symptoms of Sarcoidosis occurred was 5413 ± 2704 mg and the median time from first daclizumab dose was 996 days. The incidence rate of developing Sarcoidosis in those participating in these daclizumab trials was 154/100,000 patient-years compared with incidence rates of Sarcoidosis in the United States of 3.2–17.8/100,000/year. These data suggest that these Sarcoidosis cases may have represented DISRs related to daclizumab therapy. Conclusions Given the clinical presentation and subsequent evaluation of these 11 subjects, we suspect that they had DISRs from daclizumab.
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Sarcoidosis like reactions induced by checkpoint inhibitors
Journal of Thoracic Oncology, 2018Co-Authors: Ioannis Gkiozos, Marc A Judson, Alexandra Kopitopoulou, Alexandros Kalkanis, Ioannis Vamvakaris, Konstantinos N SyrigosAbstract:Immune checkpoint inhibitors (ICIs) are a newly developed component of cancer care that expands the treatment possibilities for patients. Their use has been associated with several immune-related adverse events, including ICI-induced Sarcoidosis-like reactions. This article reviews the data concerning ICI-induced Sarcoidosis-like reactions currently available in the medical literature. These reactions have been reported in three classes of ICIs: anti-cytotoxic T-lymphocyte associated protein 4 antibodies, programmed death 1 inhibitors and programmed death ligand 1 inhibitors. These reactions are indistinguishable from Sarcoidosis with a similar histology, pattern of organ involvement, and pattern of clinical manifestations. The most common locations to observe granulomatous inflammation from these reactions is in intrathoracic locations (the lung and/or mediastinal lymph nodes) and the skin. The median time between initiation of an ICI and the development of a Sarcoidosis-like reaction averaged 14 weeks. Clinicians have opted to use corticosteroids and/or discontinue the ICI, or take no action when these reactions have developed. Regardless of whether the clinician performed an intervention or not, these reactions have uniformly improved or resolved after ICI-treatment, which provides additional temporal evidence supporting the presence of a Sarcoidosis-like reaction as opposed to Sarcoidosis. There is even evidence that the development of an ICI-induced Sarcoidosis-like reaction suggests that the ICI is effective as an anti-tumor agent and should be continued. As is the case for Sarcoidosis, Sarcoidosis-like reactions do not mandate antiSarcoidosis therapy, especially if the condition is asymptomatic. When treatment of Sarcoidosis-like reaction is required, it may be prudent to continue ICI therapy and add antiSarcoidosis therapy because standard antiSarcoidosis regimens seem to be effective. Further research into the mechanisms involved in the development of ICI-induced Sarcoidosis-like reactions may give insights into the immunopathogenesis of Sarcoidosis.
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Clinical Features of Extrapulmonary Sarcoidosis Without Lung Involvement
Chest, 2018Co-Authors: Walter Ennis James, Marc A Judson, Efstratios Koutroumpakis, Biplab Kumar Saha, Alireza Nathani, Leahruth Saavedra, Recai YucelAbstract:Background Compared with pulmonary Sarcoidosis, Sarcoidosis without lung involvement may involve other immunopathologic mechanisms and be associated with other demographic and clinical features. Methods This was a retrospective analysis of clinical data collected in real time on 1,686 patients with biopsy-proven Sarcoidosis from two large university Sarcoidosis outpatient clinics in the United States. We compared differences in demographics characteristics and clinical presentation between pulmonary and nonpulmonary Sarcoidosis (NPS). Patients were considered to have NPS only if they had normal chest imaging and no features consistent with pulmonary involvement on the basis of currently accepted criteria. Results A total of 8.3% of this Sarcoidosis cohort met criteria for NPS. NPS was significantly more common in white than black patients, and more common in women than men. The skin was the most common organ involved, and was observed in nearly one-half of patients with NPS. Isolated skin Sarcoidosis was the overwhelmingly most common pattern of organ involvement seen in the NPS group (25%), and no other pattern of involvement was found in more than 5% of patients with NPS. Conclusions Significant demographic and sex differences were observed between patients with pulmonary and nonpulmonary Sarcoidosis. These differences reflect previous data concerning differences between patients with skin and lung Sarcoidosis because the skin was the major organ involved with NPS. Although the lungs are likely the primary site of exposure in pulmonary Sarcoidosis, the high prevalence of skin involvement in NPS suggests the skin is the most conducive site of antigen capture outside of the respiratory tract.
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The Clinical Features of Sarcoidosis: A Comprehensive Review
Clinical Reviews in Allergy & Immunology, 2015Co-Authors: Marc A JudsonAbstract:Sarcoidosis has innumerable clinical manifestations, as the disease may affect every body organ. Furthermore, the severity of Sarcoidosis involvement may range from an asymptomatic state to a life-threatening condition. This manuscript reviews a wide variety of common and less common clinical characteristics of Sarcoidosis. These manifestations are presented organ by organ, although additional sections describe systemic and multiorgan presentations of Sarcoidosis. The lung is the organ most commonly involved with Sarcoidosis with at least 90 % of Sarcoidosis patients demonstrating lung involvement in most series. The skin, eye, liver, and peripheral lymph node are the next most commonly clinically involved organs in most series, with the frequency of involvement ranging from 10 to 30 %. The actual frequency of Sarcoidosis organ involvement is probably much higher as it is frequently asymptomatic and may avoid detection. This is particularly common with lung, liver, cardiac, and bone involvement. Cardiac Sarcoidosis is present in 25 % of all Sarcoidosis but only causes clinical problems in 5 % of them. Nevertheless, unlike Sarcoidosis involvement of most other organs, it may be suddenly fatal. Therefore, it is important to screen for cardiac Sarcoidosis in all Sarcoidosis patients. All Sarcoidosis patients should also be screened for eye involvement as asymptomatic patients may have eye involvement that may cause permanent vision impairment. Pulmonary fibrosis from Sarcoidosis is usually slowly progressive but may be life-threatening because of the development of respiratory failure, pulmonary hypertension, or hemoptysis related to a mycetoma or bronchiectasis. Some manifestations of Sarcoidosis are not organ-specific and probably are the result of a release of mediators from the sarcoid granuloma. Two such manifestations include small fiber neuropathy and fatigue syndromes, and they are observed in a large percentage of patients.
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the wasog Sarcoidosis organ assessment instrument an update of a previous clinical tool
Sarcoidosis Vasculitis and Diffuse Lung Diseases, 2014Co-Authors: Marc A Judson, Ulrich Costabel, Marjolein Drent, Athol U Wells, Lisa A Maier, Laura L Koth, Hidenobu Shigemitsu, Dan A Culver, Jeffrey M Gelfand, Dominique ValeyreAbstract:Introduction: A Case Control Etiology of Sarcoidosis Study (ACCESS) Sarcoidosis organ assessment instrument has been used for more than a decade to establish uniform standards for the probability of Sarcoidosis organ involvement. The ACCESS instrument has become increasingly outdated as new technologies have been developed. Furthermore, the ACCESS instrument failed to address all possible organs involved with Sarcoidosis. For these reasons, the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) developed a new Sarcoidosis organ assessment instrument. Methods: Clinical Sarcoidosis experts assessed various clinical manifestations for the probability of Sarcoidosis organ involvement. Two criteria were required to apply this assessment: 1) histologic evidence of granulomatous inflammation of unknown cause in an organ that was not being assessed; 2) the clinical manifestation being addressed required that alternative causes other than Sarcoidosis had been reasonably excluded. Clinical manifestations were assessed as either: a) highly probable: likelihood of Sarcoidosis causing this manifestation of at least 90%.; b) probable: likelihood of Sarcoidosis causing this manifestation of between 50 and 90%; c) possible: likelihood of Sarcoidosis causing this manifestation of less than 50%. The Sarcoidosis experts voted on the likelihood of Sarcoidosis causing each manifestation using Delphi study methodology where at least 70% agreement of the experts was needed for consensus. Results: Various clinical manifestations were classified as highly probable, at least probable, possible, or indeterminate when no consensus could be reached. Conclusion: An instrument was developed by expert opinion that may be useful for the clinician and researcher in establishing criteria for Sarcoidosis organ involvement.
David H Garfield - One of the best experts on this subject based on the ideXlab platform.
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determining factors in diagnosing pulmonary Sarcoidosis by endobronchial ultrasound guided transbronchial needle aspiration
The Annals of Thoracic Surgery, 2015Co-Authors: Huizhen Yang, Jiajun Teng, Jie Zhang, Heng Zhao, David H GarfieldAbstract:Background Although the role of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) in pulmonary Sarcoidosis has previously been investigated, the determining factors in diagnosing Sarcoidosis by EBUS-TBNA without rapid on-site evaluation (ROSE) are unclear. Methods Patients with clinically and radiographically suspected Sarcoidosis underwent EBUS-TBNA without ROSE in a prospective study. Presence of non-caseating epithelioid cell granulomas was pathologic evidence of Sarcoidosis. Results The EBUS-TBNA was performed in 120 patients, 111 of whom had confirmed Sarcoidosis. For the patients with Sarcoidosis (62 stage I, 49 stage II) EBUS-TBNA provided sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 93.69%, 100%, 100%, 56.25%, and 94.17%, respectively, in the diagnosis of Sarcoidosis. Diagnostic yield of EBUS-TBNA for Sarcoidosis was associated with disease stage, but not associated with serum angiotensin converting enzyme level, number of lymph node stations sampled per patient, or total number of passes performed per patient. At EBUS-TBNA, 284 mediastinal and hilar lymph nodes were aspirated in 111 patients. Multivariate logistic regression revealed that short-axis diameter and more than 1 needle pass per lymph node were independent risk factors associated with positive pathology. No major procedure-related complications were observed. Conclusions Endobronchial ultrasound-guided transbronchial needle aspiration is a safe procedure with high sensitivity for diagnosing Sarcoidosis, having a higher diagnostic yield in stage I than stage II. To obtain a higher diagnostic yield of EBUS-TBNA in pulmonary Sarcoidosis without ROSE, operators should select the largest mediastinal or hilar lymph node accessible and puncture with 3 to 5 passes.
Suzuko Moritani - One of the best experts on this subject based on the ideXlab platform.
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prospective study of endobronchial ultrasound guided transbronchial needle aspiration of lymph nodes versus transbronchial lung biopsy of lung tissue for diagnosis of Sarcoidosis
The Journal of Thoracic and Cardiovascular Surgery, 2012Co-Authors: Masahide Oki, Hideo Saka, Chiyoe Kitagawa, Yoshihito Kogure, Naohiko Murata, Shu Ichihara, Suzuko MoritaniAbstract:Objective Endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) has been reported to be an accurate and safe method to confirm a pathologic diagnosis of Sarcoidosis. However, only a few retrospective or small prospective studies have been published on EBUS-TBNA versus transbronchial lung biopsy (TBLB), which has been the standard method for making a pathologic diagnosis of Sarcoidosis so far. The aim of this study was to compare the diagnostic yield of EBUS-TBNA and TBLB through a flexible bronchoscope in patients with stage I and II Sarcoidosis. Methods A total of 62 patients with suspected stage I and II Sarcoidosis were included in this prospective study. EBUS-TBNA was performed (2 lymph nodes, 2 needle passes for each lymph node), followed by TBLB (5 biopsy specimens from multiple lung segments) in the same setting. The final diagnosis of Sarcoidosis was based on clinicoradiologic compatibility and pathologic findings. Results Of the 62 patients enrolled, 54 were given a final diagnosis of Sarcoidosis. The diagnostic yield of EBUS-TBNA and TBLB for sarcoidois by showing noncaseating epithelioid cell granuloma was 94% (stage I, 97%; stage II, 88%) and 37% (stage I, 31%; stage II, 50%), respectively. The difference was statistically significant ( P Conclusions The diagnostic yield of EBUS-TBNA for stage I and II Sarcoidosis is higher than for TBLB.
Huizhen Yang - One of the best experts on this subject based on the ideXlab platform.
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determining factors in diagnosing pulmonary Sarcoidosis by endobronchial ultrasound guided transbronchial needle aspiration
The Annals of Thoracic Surgery, 2015Co-Authors: Huizhen Yang, Jiajun Teng, Jie Zhang, Heng Zhao, David H GarfieldAbstract:Background Although the role of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) in pulmonary Sarcoidosis has previously been investigated, the determining factors in diagnosing Sarcoidosis by EBUS-TBNA without rapid on-site evaluation (ROSE) are unclear. Methods Patients with clinically and radiographically suspected Sarcoidosis underwent EBUS-TBNA without ROSE in a prospective study. Presence of non-caseating epithelioid cell granulomas was pathologic evidence of Sarcoidosis. Results The EBUS-TBNA was performed in 120 patients, 111 of whom had confirmed Sarcoidosis. For the patients with Sarcoidosis (62 stage I, 49 stage II) EBUS-TBNA provided sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 93.69%, 100%, 100%, 56.25%, and 94.17%, respectively, in the diagnosis of Sarcoidosis. Diagnostic yield of EBUS-TBNA for Sarcoidosis was associated with disease stage, but not associated with serum angiotensin converting enzyme level, number of lymph node stations sampled per patient, or total number of passes performed per patient. At EBUS-TBNA, 284 mediastinal and hilar lymph nodes were aspirated in 111 patients. Multivariate logistic regression revealed that short-axis diameter and more than 1 needle pass per lymph node were independent risk factors associated with positive pathology. No major procedure-related complications were observed. Conclusions Endobronchial ultrasound-guided transbronchial needle aspiration is a safe procedure with high sensitivity for diagnosing Sarcoidosis, having a higher diagnostic yield in stage I than stage II. To obtain a higher diagnostic yield of EBUS-TBNA in pulmonary Sarcoidosis without ROSE, operators should select the largest mediastinal or hilar lymph node accessible and puncture with 3 to 5 passes.
Masahide Oki - One of the best experts on this subject based on the ideXlab platform.
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prospective study of endobronchial ultrasound guided transbronchial needle aspiration of lymph nodes versus transbronchial lung biopsy of lung tissue for diagnosis of Sarcoidosis
The Journal of Thoracic and Cardiovascular Surgery, 2012Co-Authors: Masahide Oki, Hideo Saka, Chiyoe Kitagawa, Yoshihito Kogure, Naohiko Murata, Shu Ichihara, Suzuko MoritaniAbstract:Objective Endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) has been reported to be an accurate and safe method to confirm a pathologic diagnosis of Sarcoidosis. However, only a few retrospective or small prospective studies have been published on EBUS-TBNA versus transbronchial lung biopsy (TBLB), which has been the standard method for making a pathologic diagnosis of Sarcoidosis so far. The aim of this study was to compare the diagnostic yield of EBUS-TBNA and TBLB through a flexible bronchoscope in patients with stage I and II Sarcoidosis. Methods A total of 62 patients with suspected stage I and II Sarcoidosis were included in this prospective study. EBUS-TBNA was performed (2 lymph nodes, 2 needle passes for each lymph node), followed by TBLB (5 biopsy specimens from multiple lung segments) in the same setting. The final diagnosis of Sarcoidosis was based on clinicoradiologic compatibility and pathologic findings. Results Of the 62 patients enrolled, 54 were given a final diagnosis of Sarcoidosis. The diagnostic yield of EBUS-TBNA and TBLB for sarcoidois by showing noncaseating epithelioid cell granuloma was 94% (stage I, 97%; stage II, 88%) and 37% (stage I, 31%; stage II, 50%), respectively. The difference was statistically significant ( P Conclusions The diagnostic yield of EBUS-TBNA for stage I and II Sarcoidosis is higher than for TBLB.
