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1.
Eur Respir Rev ; 29(155)2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32198217

RESUMO

A variety of phenotypic categorisations have been developed for sarcoidosis. Phenotyping has been used for genetics studies and to guide treatment selection. The authors participated in a Delphi expert consensus panel to develop a proposed phenotype categorisation and treatment recommendations for pulmonary sarcoidosis patients. Panellists reached consensus that asymptomatic patients with normal pulmonary function and adenopathy alone or normal chest imaging do not require therapy, while symptomatic patients with impaired pulmonary function or infiltrates should be treated. The panel did not reach consensus on asymptomatic patients with abnormal chest imaging or reduced pulmonary function, or symptomatic patients with normal chest imaging and pulmonary function. The proposed phenotype categories and associated treatment recommendations are asymptomatic (no therapy), acute (disease duration <1-2 years, apparently self-limited, corticosteroids), chronic (antimetabolites and other second-line therapies) and advanced (biologics). Some clinical settings, such as dyspnoea/hypoxaemia at rest, severely impaired or rapidly decreasing pulmonary function tests, and severe cardiac, neurologic, ocular or renal involvement warrant immediate therapy.

2.
Eur Respir Rev ; 29(155)2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32198218

RESUMO

Pulmonary sarcoidosis presents substantial management challenges, with limited evidence on effective therapies and phenotypes. In the absence of definitive evidence, expert consensus can supply clinically useful guidance in medicine. An international panel of 26 experts participated in a Delphi process to identify consensus on pharmacological management in sarcoidosis with the development of preliminary recommendations.The modified Delphi process used three rounds. The first round focused on qualitative data collection with open-ended questions to ensure comprehensive inclusion of expert concepts. Rounds 2 and 3 applied quantitative assessments using an 11-point Likert scale to identify consensus.Key consensus points included glucocorticoids as initial therapy for most patients, with non-biologics (immunomodulators), usually methotrexate, considered in severe or extrapulmonary disease requiring prolonged treatment, or as a steroid-sparing intervention in cases with high risk of steroid toxicity. Biologic therapies might be considered as additive therapy if non-biologics are insufficiently effective or are not tolerated with initial biologic therapy, usually with a tumour necrosis factor-α inhibitor, typically infliximab.The Delphi methodology provided a platform to gain potentially valuable insight and interim guidance while awaiting evidenced-based contributions.

3.
Eur Respir Rev ; 29(155)2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32198219

RESUMO

In patients treated with repository corticotrophin injection (RCI) for pulmonary sarcoidosis, effective management of adverse events may improve adherence. However, management of adverse events may be challenging due to limitations in real-world clinical experience with RCI and available published guidelines.We surveyed 12 physicians with a modified Delphi process using three questionnaires. Questionnaire 1 consisted of open-ended questions. Panellists' answers were developed into a series of statements for Questionnaires 2 and 3. In these, physicians rated their agreement with the statements using a Likert scale.Key consensus recommendations included a starting dose of 40 units twice a week for patients with less severe disease, continued at a maintenance dose for patients who responded, particularly those with chronic refractory sarcoidosis. Panellists reached consensus that concomitant steroids should be quickly tapered in patients receiving RCI, but that concomitant use of immunosuppressive medications should be continued. Panellists developed consensus recommendations for adverse event management, and reached consensus that RCI should be down-titrated or discontinued if other interventions for the adverse effects fail or if the adverse effect is severe.In the absence of clinical evidence, our Delphi consensus opinions may provide practical guidance to physicians on the management of RCI to treat pulmonary sarcoidosis.

4.
Eur Respir J ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32139456

RESUMO

INTRODUCTION: Sarcoidosis associated pulmonary hypertension (SAPH) is associated with reduced survival in single center studies. An international registry for SAPH (ReSAPH) with long-term follow-up was established to enrich our knowledge of this complication of sarcoidosis. This analysis aims to elucidate factors associated with reduced transplant-free survival in SAPH patients. METHODS: ReSAPH contains prospectively collected outcomes of SAPH patients since the time of registry enrollment. Information analyzed includes right heart catheterization data, pulmonary function testing, chest x-ray Scadding stage, six minute walk distance (6MWD) among others. Cox regression models were used to identify independent predictors of transplant-free survival. RESULTS: Data from a total of 215 patients followed for a mean of 2.5±1.9 years were available for analysis. In the 159 pre-capillary patients, the KM adjusted 1, 3 and 5 year transplant free survival was 89.2%, 71.7% and 62.0%, respectively. In the incident and prevalent groups, KM adjusted 1, 3 and 5 year transplant free survival was 83.5%, 70.3% and 58.3% and 94.7%, 72.2%, and 66.3% respectively. Patients with reduced DLCO (<35% predicted) and 6MWD <300 m in the pre-capillary cohort had significantly worse transplant-free survival. Reduced 6MWD and preserved FEV1/FVC ratio were identified as independent risk factors for reduced transplant-free survival in the pre-capillary cohort. CONCLUSION: Reduced diffusion capacity (<35% of predicted) and 6MWD <300 m at the time of registry enrollment were associated with reduced transplant-free survival in the overall precapillary cohort. Preserved FEV1/FVC ratio was also identified as an independent risk factor for worsened outcomes.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31825646

RESUMO

RATIONALE: Socioeconomic factors are associated with worse disease severity at presentation in sarcoidosis, but the relative importance of socioeconomic variables on morbidity and disease burden has not been fully elucidated. OBJECTIVES: To determine the association between income and sarcoidosis outcomes after controlling for socioeconomic and disease-related factors. METHODS: Using the Sarcoidosis Advanced Registry for Cures (SARC) database, we analyzed data from 2318 United States sarcoidosis patients to determine the effect of income and other variables on outcomes. We divided comorbidities arising after diagnosis into those likely related to steroid use and those likely related to sarcoidosis. We assessed the development of health-related, functional and socioeconomic outcomes following the diagnosis of sarcoidosis. MEASUREMENTS AND MAIN RESULTS: In multivariate analysis, low income patients had significantly higher rates of new sarcoidosis related comorbidities [<$35,000 OR 2.4 (1.7-3.3), $35,000-$85,000 OR 1.4 (1.1-1.9), >$85,000 (REF)], new steroid related comorbidities [<$35,000 OR 1.3 (0.9-2.0), $35,000-$85,000 OR 1.5 (1.1-2.1), >$85,000 (REF)], had lower health-related quality of life as assessed by the Sarcoidosis Health Questionnaire (p<0.001) and experienced more impact on family finances [<$35,000 OR 7.9 (4.9-12.7), $35,000-$85,000 OR 2.7 (1.9-3.9), >$85,000 (REF)]. The use of supplemental oxygen, need for assistive devices, and job loss were more common in lower income patients. Development of comorbidities after diagnosis of sarcoidosis occurred in 63% of patients and were strong independent predictors of poor outcomes. In random forest modeling, income was consistently a leading predictor of outcome. CONCLUSIONS: These results suggest the burden from sarcoidosis preferentially impacts the economically disadvantaged.

6.
Clin Exp Rheumatol ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31820728

RESUMO

OBJECTIVES: Patients with advanced sarcoidosis often require third-line therapies including infliximab, adalimumab, rituximab, and repository corticotropin injection (RCI). Over time, some patients discontinue therapy. METHODS: In a retrospective review of patients at the University of Cincinnati Sarcoidosis Clinic, we identified patients who received one or more third-line treatments. Age, race, gender, organ involvement, and initial date of therapy were collected. For patients in whom a drug was discontinued, the last date of treatment, reason for drug discontinuation, and outcome of drug withdrawal were noted. RESULTS: Of the 2109 patients identified, 317 (15%) had received one or more third-line therapies (infliximab: 258 patients; adalimumab: 52 patients; rituximab: 34 patients; RCI: 101 patients). Patients with neurologic, cutaneous, or ocular sarcoidosis involvement were more likely to have received third-line therapy. Overall, 225 (50.6%) of treatment regimens were discontinued. Rate of discontinuation was higher for infliximab (55%), adalimumab (58%), or RCI (43%) than for rituximab (29%, Chi square=11.959, p=0.0075). Compared to RCI, the hazard ratio (HR) for discontinuing therapy due to infection was increased for infliximab (HR=12.14, p=0.0134) and adalimumab (HR=9.71, p=0.0356). The hazard ratio was higher for drug discontinuation due to allergic reactions to infliximab (HR=9.40, p=0.0017) or adalimumab (HR=5.83, p=0.0273). For patients receiving at least two years of therapy, drug survival was significantly shorter for infliximab compared to other therapies (Chi square=5.4054, p=0.0201). CONCLUSIONS: While third-line therapies are often initially effective, a significant number of patients discontinued individual treatments and initiated an alternative third-line therapy.

7.
ERJ Open Res ; 5(4)2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31687368

RESUMO

Our study presents findings on a previously developed standard set of clinical outcome data for pulmonary sarcoidosis patients. We aimed to assess whether changes in outcome varied between the different centres and to evaluate the feasibility of collecting the standard set retrospectively. This retrospective observational comparative benchmark study included six interstitial lung disease expert centres based in the Netherlands, Belgium, the UK and the USA. The standard set of outcome measures included 1) mortality, 2) changes in pulmonary function (forced vital capacity (FVC), forced expiratory volume in 1 s, diffusing capacity of the lung for carbon monoxide), 3) soluble interleukin-2 receptor (sIL-2R) change, 4) weight changes, 5) quality-of-life (QoL) measures, 6) osteoporosis and 7) clinical outcome status (COS). Data collection was considered feasible if the data were collected in ≥80% of all patients. 509 patients were included in the retrospective cohort. In total six patients died, with a mean survival of 38±23.4 months after the diagnosis. Centres varied in mean baseline FVC, ranging from 110 (95% CI 92-124)% predicted to 99 (95% CI 97-123)% pred. Mean baseline body mass index (BMI) of patients in the different centres varied between 27 (95% CI 23.6-29.4) kg·m-2 and 31.8 (95% CI 28.1-35.6) kg·m-2. 310 (60.9%) patients were still on systemic therapy 2 years after the diagnosis. It was feasible to measure mortality, changes in pulmonary function, weight changes and COS. It is not (yet) feasible to retrospectively collect sIL-2R, osteoporosis and QoL data internationally. This study shows that data collection for the standard set of outcome measures for pulmonary sarcoidosis was feasible for four out of seven outcome measures. Trends in pulmonary function and BMI were similar for different hospitals when comparing different practices.

8.
Medicine (Baltimore) ; 98(47): e18037, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764823

RESUMO

Dyspnea and exercise intolerance are usually attributed to pulmonary disease in sarcoidosis patients. However, cardiac involvement may also be responsible for these symptoms. Data regarding the impact of heart involvement on lung function in cardiac sarcoidosis (CS) is limited.The aim of study was to compare the results of pulmonary function tests (PFTs) in patients with and without heart involvement. We performed a retrospective analysis of PFTs in a group of sarcoidosis patients both with and without heart involvement evaluated by cardiovascular magnetic resonance (CMR) study. The study was performed in the period between May 2008 and April 2016.We included data of sarcoidosis patients who underwent testing for possible CS (including CMR study) at a national tertiary referral center for patients with interstitial lung diseases. All patients had histopathologicaly confirmed sarcoidosis and underwent standard evaluation with PFTs measurements including spirometry, plethysmography, lung transfer factor (TL,CO), and 6-minute walking test (6MWT) assessed using the most recent predicted values.We identified 255 sarcoidosis patients (93 women, age 42 ±â€Š10.7 y): 103 with CS and 152 without CS (controls). CS patients had significantly lower left ventricular ejection fraction (LVEF; 56.9 ±â€Š7.0 vs 60.4 ±â€Š5.4, P < .001). Any type of lung dysfunction was seen in 63% of CS patients compared with 31% in the controls (P = .005). Ventilatory disturbances (obstructive or restrictive pattern) and low TL,CO were more frequent in CS group (52% vs 23%, P < .001 and 38% vs 18% P < .01 respectively). CS (OR = 2.13, 95% CI: 1.11-4.07, P = .02), stage of the disease (OR = 3.13, 95% CI: 1.4-7.0, P = .006) and LVEF (coefficient = -0.068 ±â€Š0.027, P = .011) were independent factors associated with low FEV1 but not low TL,CO. There was a significant correlation between LVEF and FEV1 in CS group (r = 0.31, n = 89, P = .003). No significant difference in 6MWD between CS patients and controls was observed.Lung function impairment was more frequent in CS. Lower LVEF was associated with decreased values of FEV1. Relatively poor lung function may be an indication of cardiac sarcoidosis.


Assuntos
Cardiomiopatias/fisiopatologia , Sarcoidose/fisiopatologia , Volume Sistólico , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Testes de Função Respiratória , Estudos Retrospectivos , Índice de Gravidade de Doença
9.
Clin Exp Rheumatol ; 37(6): 1052-1064, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31498063

RESUMO

In sarcoidosis, a rare multiorgan disease of unknown aetiology characterised by non-caseating epitheloid cell granulomas, three geoepidemiological factors are major aetiopathogenic factors: geolocation, ethnicity, and personal environment. Geographically, sarcoidosis is mainly reported in the Northern Hemisphere, with the highest incidence rates uniformly reported in countries located at the highest latitudes. The main geoepidemiological-driven differences across the world are of greater female involvement in Southern Europe, the Southern US and Japan, a differentiated radiological pattern (predominance of stage I in Southern Europe and Middle East/Asia and of stage II in Northern Europe, China and India, with the US and Japan having the highest frequencies of stages III/IV) and the extrathoracic phenotype: the most frequent extrathoracic organs involved are the skin in Southern Europe and Middle East/Asia, the eyes in Northern Europe, Northeast US and Japan, the liver in India and the lymph nodes in China. In addition, there are large ethnicity-driven variations in the frequency, epidemiology, clinical expression and outcome of sarcoidosis. The highest incidence rates are uniformly reported in Black/African-American people, independently of the geographical location, with rates between 2- and 10-fold higher than those reported in White people living in the same geographical area. Furthermore, ethnicity heavily influences the clinical phenotype by modifying the age at diagnosis and the rates of thoracic and extrathoracic involvements. Geoepidemiological studies enhanced by big data may yield important clues to understanding the role of these factors in the frequency and clinical phenotypes of sarcoidosis.


Assuntos
Grupos Étnicos , Sarcoidose , Distribuição por Idade , Ásia , Big Data , China , Grupos Étnicos/estatística & dados numéricos , Europa (Continente) , Feminino , Humanos , Índia , Japão , Masculino , Sarcoidose/epidemiologia , Sarcoidose/etnologia , Distribuição por Sexo
10.
Curr Opin Pulm Med ; 25(5): 497-504, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31365384

RESUMO

PURPOSE OF REVIEW: Advanced sarcoidosis is an important cause of morbidity and mortality in sarcoidosis. Over the past few years, several studies have been published clarifying the prevalence and severity of this condition. RECENT FINDINGS: Pulmonary involvement is the most common form of sarcoidosis. Increased morbidity and significant mortality is encountered in advanced lung disease. Although many sarcoidosis patients with pulmonary fibrosis have a normal life expectancy, at least 20% develop progression and may die from this complication. Sarcoidosis-associated pulmonary hypertension (SAPH) is an independent cause of death in advanced pulmonary sarcoidosis. Two large multicenter registries and a large single-center report provide more details regarding presentation and outcome of SAPH. Advanced neurologic disease is associated with significant morbidity, but not much mortality. Two large retrospective reviews demonstrated the effectiveness of infliximab in treating advanced neurosarcoidosis. Advanced cardiac sarcoidosis can lead to mortality. SUMMARY: Advanced sarcoidosis is associated with significant morbidity and some mortality. Up to a quarter of all sarcoidosis patients have one or more forms of advanced disease. These patients require closer monitoring and often multiples treatments.

11.
Curr Opin Pulm Med ; 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31343491

RESUMO

PURPOSE OF REVIEW: Advanced sarcoidosis is an important cause of morbidity and mortality in sarcoidosis. Over the past few years, several studies have been published clarifying the prevalence and severity of this condition. RECENT FINDINGS: Pulmonary involvement is the most common form of sarcoidosis. Increased morbidity and significant mortality is encountered in advanced lung disease. Although many sarcoidosis patients with pulmonary fibrosis have a normal life expectancy, at least 20% develop progression and may die from this complication. Sarcoidosis-associated pulmonary hypertension (SAPH) is an independent cause of death in advanced pulmonary sarcoidosis. Two large multicenter registries and a large single-center report provide more details regarding presentation and outcome of SAPH. Advanced neurologic disease is associated with significant morbidity, but not much mortality. Two large retrospective reviews demonstrated the effectiveness of infliximab in treating advanced neurosarcoidosis. Advanced cardiac sarcoidosis can lead to mortality. SUMMARY: Advanced sarcoidosis is associated with significant morbidity and some mortality. Up to a quarter of all sarcoidosis patients have one or more forms of advanced disease. These patients require closer monitoring and often multiples treatments.

12.
Lung ; 197(4): 427-436, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31190130

RESUMO

BACKGROUND: Sarcoidosis is a systemic disease in which the personal environment seems to drive a differentiated disease frequency and clinical expression. The main epidemiological studies suggest a key influence of potential environmentally linked exposures related to the type of occupation, the household, life style, socioeconomic status, and region of residence. OBJECTIVE: To provide an update on how sarcoidosis may be modulated by environmental factors. DATA SOURCES: We searched PubMed for epidemiological studies. SYNTHESIS: The risk of sarcoidosis is enhanced in people working in jobs related to agriculture, water, construction, metal machining, education, and health, and reduced in those working in jobs mainly centered on personal care. Studies have confirmed seasonal-related peaks of sarcoidosis incidence that follow geographical North-South and West-East gradients. Other personal factors include smoking, personal household exposures, and leisure activities. The evidence pointing to the crucial role of the environment in the etiopathogenesis of sarcoidosis is mounting rapidly. Few diseases so strongly combine geography, environment, gender, and ethnicity as key etiopathogenic factors, with susceptibility to any putative agent being modulated by the individual exposome and genome. CONCLUSION: Geoepidemiological research should focus on evaluating the combined effects of environmental and genetic factors, the identification of clusters of geographically driven exposures, and more precise measurement of all personal exposures (degree of combination, length, and level of exposure).

13.
BMJ Open Respir Res ; 6(1): e000394, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30956806

RESUMO

Introduction: Routine and international comparison of clinical outcomes enabling identification of best practices for patients with pulmonary sarcoidosis is lacking. The aim of this study was to develop a standard set of outcome measures for pulmonary sarcoidosis, using the value-based healthcare principles. Methods: Six expert clinics for interstitial lung diseases in four countries participated in a consensus-driven RAND-modified Delphi study. A mixed-method approach was applied for the identification of an outcome measures set and initial conditions for patients with pulmonary sarcoidosis. The expert team consisted of multidisciplinary professionals (n=14) from Cleveland Clinic, Cincinnati MC, Erasmus MC, Leuven UZ, Royal Brompton and St. Antonius Hospital. During a ranking process, participants were instructed to rank variables on a scale from 1 to 10 based on whether it has (1) impact of the outcome on quality of life, (2) impact of quality of care on the outcome and (3) the number of patients negatively affected by the outcome. Results: An outcome measures set was defined consisting of seven outcome measures: mortality, pulmonary function, soluble interleukin-2 receptor change as an activity biomarker, weight gain, quality of life, osteoporosis and clinical outcome status. Discussion: Collecting outcomes in pulmonary sarcoidosis internationally and the use of a broadly accepted set can enable international comparison. Differences in outcomes can potentially be used as a starting point for quality improvement initiatives.

14.
Curr Opin Neurol ; 32(3): 475-483, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30865007

RESUMO

PURPOSE OF REVIEW: Sarcoidosis is a complex disease with many faces, and the clinical manifestation and course of neurosarcoidosis are particularly variable. Although neurosarcoidosis occurs in up to 10% of sarcoidosis patients, it can lead to significant morbidity and some mortality. RECENT FINDINGS: Three criteria are usually required for a diagnosis of (neuro)sarcoidosis: clinical and radiologic manifestations, noncaseating granulomas, and no evidence of alternative disease. Recent guidelines have helped to clarify criteria for diagnosing neurosarcoidosis. No firm guidelines exist on whether, when, and how treatment should be started. Treatment depends on the presentation and distribution, extensiveness, and severity of neurosarcoidosis. As regards evidence-based treatment, only a few randomized controlled trials have been done. Hence, several aspects of (neuro)sarcoidosis management are not fully addressed by the current literature. SUMMARY: Significant advances have been made in the potential and accuracy of diagnostics for neurosarcoidosis. Treatment should be approached within the context of the patient's anticipated clinical course, avoidance of adverse drug effects, and, if necessary, from the perspective of the comprehensive management of a chronic disease. A multidisciplinary approach to the management of sarcoidosis is strongly recommended.


Assuntos
Doenças do Sistema Nervoso Central/terapia , Sarcoidose/terapia , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/psicologia , Gerenciamento Clínico , Humanos , Equipe de Assistência ao Paciente , Sarcoidose/diagnóstico , Sarcoidose/psicologia
15.
Am J Gastroenterol ; 114(8): 1238-1247, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30865014

RESUMO

Involvement of the gastrointestinal (GI) tract is an infrequent extrathoracic presentation of sarcoidosis. We reviewed 305 cases of GI involvement reported in 238 patients, in whom GI sarcoidosis was the first sign of the disease in half the cases. The disease does not affect the GI tract uniformly, with a clear oral-anal gradient (80% of reported cases involved the esophagus, stomach, and duodenum). Clinicopathological mechanisms of damage may include diffuse mucosal infiltration, endoluminal exophytic lesions, involvement of the myenteric plexus, and extrinsic compressions. Ten percent of patients presented with asymptomatic or subclinical disease found on endoscopy. The diagnosis is relevant clinically because 22% of cases reviewed presented as life threatening. In addition, initial clinical/endoscopic findings may be highly suggestive of GI cancer. The therapeutic approach is heterogeneous and included wait-and-see or symptomatic approaches, glucocorticoid/immunosuppressive therapy, and surgery. Sarcoidosis of the gut is a heterogeneous, potentially life-threatening condition that requires a multidisciplinary approach and early clinical suspicion to institute personalized therapeutic management and follow-up.

16.
Respirology ; 24(6): 531-542, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30912244

RESUMO

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the commonly used technique for pathological confirmation of clinically suspected sarcoidosis, mostly owing to its consistently high success rate in the detection of granulomas. However, other possible advantages, which are less appreciated and often poorly studied, may also contribute to the wider use of EBUS-TBNA in the future. These advantages include refinement of differential diagnoses through the study of lymph node characteristics during B-mode examination; reduction of complications associated with bronchoscopy, as well as improved triage of the specimen for ancillary studies with the use of rapid on-site evaluation; optimization of the quality of the sample through the selection of a target area for biopsy with minimal vascularity and absence of calcifications by using the colour Doppler and the B-mode; and prediction of the presence of extensive lymph node fibrosis by using the strain elastography module. Yet, limitations and possible clinical drawbacks should also be acknowledged. Indeed, due to the lack of specificity of the pathology findings in EBUS-derived samples, the diagnosis of sarcoidosis is one of the exclusion and should remain essentially clinical. The external validity of EBUS-TBNA results in sarcoidosis is questionable, as they mainly derive from studies in populations with a high disease prevalence. Finally, the risk exists that the low morbidity and high diagnostic yield of EBUS-TBNA may lead to its overuse in patients with clinical/radiological findings specific enough to secure a clinical diagnosis of sarcoidosis.

17.
ERJ Open Res ; 4(4)2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30588477

RESUMO

Sarcoidosis patient survey reveals QoL and functionality are required as core outcomes in treatment and care, along with more multidisciplinary working by clinicians and the establishment of specialist sarcoidosis centres in every European country http://ow.ly/DTvt30mQnqc.

18.
JAMA Neurol ; 75(12): 1546-1553, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30167654

RESUMO

Importance: The Neurosarcoidosis Consortium Consensus Group, an expert panel of physicians experienced in the management of patients with sarcoidosis and neurosarcoidosis, engaged in an iterative process to define neurosarcoidosis and develop a practical diagnostic approach to patients with suspected neurosarcoidosis. This panel aimed to develop a consensus clinical definition of neurosarcoidosis to enhance the clinical care of patients with suspected neurosarcoidosis and to encourage standardization of research initiatives that address this disease. Observations: The work of this collaboration included a review of the manifestations of neurosarcoidosis and the establishment of an approach to the diagnosis of this disorder. The proposed consensus diagnostic criteria, which reflect current knowledge, provide definitions for possible, probable, and definite central and peripheral nervous system sarcoidosis. The definitions emphasize the need to evaluate patients with findings suggestive of neurosarcoidosis for alternate causal factors, including infection and malignant neoplasm. Also emphasized is the need for biopsy, whenever feasible and advisable according to clinical context and affected anatomy, of nonneural tissue to document the presence of systemic sarcoidosis and support a diagnosis of probable neurosarcoidosis or of neural tissue to support a diagnosis of definite neurosarcoidosis. Conclusions and Relevance: Diverse disease presentations and lack of specificity of relevant diagnostic tests contribute to diagnostic uncertainty. This uncertainty is compounded by the absence of a pathognomonic histologic tissue examination. The diagnostic criteria we propose are designed to focus investigations on NS as accurately as possible, recognizing that multiple pathophysiologic pathways may lead to the clinical manifestations we currently term NS. Research recognizing the clinical heterogeneity of this diagnosis may open the door to identifying meaningful biologic factors that may ultimately contribute to better treatments.


Assuntos
Doenças do Sistema Nervoso Central/diagnóstico , Sistema Nervoso Central , Consenso , Guias de Prática Clínica como Assunto , Sarcoidose/diagnóstico , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/microbiologia , Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Doenças do Sistema Nervoso Central/microbiologia , Doenças do Sistema Nervoso Central/patologia , Doenças do Sistema Nervoso Central/fisiopatologia , Humanos , Sarcoidose/microbiologia , Sarcoidose/patologia , Sarcoidose/fisiopatologia
19.
Sci Transl Med ; 10(460)2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30257954

RESUMO

Pulmonary fibrosis is a progressive inflammatory disease with high mortality and limited therapeutic options. Previous genetic and immunologic investigations suggest common intersections between idiopathic pulmonary fibrosis (IPF), sarcoidosis, and murine models of pulmonary fibrosis. To identify immune responses that precede collagen deposition, we conducted molecular, immunohistochemical, and flow cytometric analysis of human and murine specimens. Immunohistochemistry revealed programmed cell death-1 (PD-1) up-regulation on IPF lymphocytes. PD-1+CD4+ T cells with reduced proliferative capacity and increased transforming growth factor-ß (TGF-ß)/interleukin-17A (IL-17A) expression were detected in IPF, sarcoidosis, and bleomycin CD4+ T cells. PD-1+ T helper 17 cells are the predominant CD4+ T cell subset expressing TGF-ß. Coculture of PD-1+CD4+ T cells with human lung fibroblasts induced collagen-1 production. Strikingly, ex vivo PD-1 pathway blockade resulted in reductions in TGF-ß and IL-17A expression from CD4+ T cells, with concomitant declines in collagen-1 production from fibroblasts. Molecular analysis demonstrated PD-1 regulation of the transcription factor STAT3 (signal transducer and activator of transcription 3). Chemical blockade of STAT3, using the inhibitor STATTIC, inhibited collagen-1 production. Both bleomycin administration to PD-1 null mice or use of antibody against programmed cell death ligand 1 (PD-L1) demonstrated significantly reduced fibrosis compared to controls. This work identifies a critical, previously unrecognized role for PD-1+CD4+ T cells in pulmonary fibrosis, supporting the use of readily available therapeutics that directly address interstitial lung disease pathophysiology.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/patologia , Interleucina-17/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Crescimento Transformador beta1/biossíntese , Regulação para Cima , Adulto , Idoso , Animais , Bleomicina , Proliferação de Células , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Feminino , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Humanos , Fibrose Pulmonar Idiopática/genética , Masculino , Camundongos , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/genética , Sarcoidose/imunologia , Sarcoidose/patologia , Células Th17/metabolismo
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