Focus on Sarcoidosis
Cardiac sarcoidosis outcome differences: A comparison of patients with de novo cardiac versus known extracardiac sarcoidosis at presentationSarcoidosis is a systemic disease characterized by granulomatous inflammation. Cardiac involvement is associated with increased morbidity. However, differences in clinical characteristics and outcomes based on initial sarcoidosis organ manifestation in patients with cardiac sarcoidosis (CS) have not been described.
The association of baseline sarcoidosis measurements with 6-month outcomes that are of interest to patients: Results from the On-line Sarcoidosis Assessment Platform Study (OSAP)Cutoffs for most of the phenotypic measures used to assess sarcoidosis distinguished groups of sarcoidosis patients with differing OIPs over the subsequent 6 months. The patients’ global assessment of their disease was the most accurate of these measures.
Patterns of medication use and imaging following initial diagnosis of sarcoidosisSarcoidosis is a rare inflammatory disease with unclear natural history. Using a large, retrospective, longitudinal, population-based cohort, we sought to define its natural history in order to guide future clinical studies.
Risk of acute myocardial infarction in sarcoidosis: A population-based cohort study from SwedenDue to conflicting findings in previous studies, it remains unclear whether individuals with sarcoidosis are at a higher relative risk of acute myocardial infarction. In this cohort study, individuals with sarcoidosis and matched general population comparators were followed for acute myocardial infarction in Swedish nationwide registers. A small (20%) risk increase associated with sarcoidosis was identified, which did not markedly vary by age at diagnosis, sex, treatment status around diagnosis, and time since diagnosis.
Abnormal FeV1 and body mass index are associated with impaired cough-related quality of life in sarcoidosis patientsSarcoidosis is a granulomatous disease that mainly manifests within the lungs and may thereby impair lung function. Beyond and independently from organ impairment, sarcoidosis may affect quality of life which can be quantified by questionnaires. The Leicester Cough Questionnaire (LCQ) has been developed to assess cough-related quality of life. We analysed data from a prospectively collected cohort of sarcoidosis patients for validation of the German LCQ version. Our analyses demonstrated that LCQ values add additional information beyond routinely monitored parameters (e.g.
Ophthalmologic assessments in patients with newly diagnosed sarcoidosis: An observational study from a universal healthcare systemConsensus guidelines for the management of sarcoidosis recommend screening eye examinations for all patients, even in those without ocular symptoms. We aimed to determine the proportion of sarcoidosis patients that complete ophthalmologic evaluations and factors associated with their performance.
The impact of demographic disparities in the presentation of sarcoidosis: A multicenter prospective studyTo study how demographic differences impact disease manifestation of sarcoidosis using the WASOG tool in a large multicentric study.
Sarcoidosis: A nationwide registry-based study of incidence, prevalence and diagnostic work-upThe primary objective was to evaluate the prevalence and incidence of sarcoidosis, and secondly, to evaluate differences in incidence by age at diagnosis, gender, region, calendar year and treatment and to evaluate sarcoidosis-related diagnostic work-up.
HLA-DRB1 alleles associate with hypercalcemia in sarcoidosisThe mechanisms behind and which patients are at risk of developing sarcoidosis associated hypercalcemia (SAHC) have not been addressed. Different human leukocyte antigen (HLA) alleles associate with disease phenotypes in sarcoidosis. Insights into associations between HLA alleles, clinical phenotype and calcium levels may provide clues to mechanisms behind SAHC and help monitoring patients at risk for SAHC.
Outcomes of SARS-CoV-2 infection in patients with pulmonary sarcoidosis: A multicenter retrospective research network studyCrude COVID-19 mortality and other clinical outcome measures are poor in pulmonary sarcoidosis cohort; however, propensity-matched analyses revealed no difference in outcomes, showing that higher mortality is driven by higher burden of comorbidities.
Genomic biomarkers in chronic beryllium disease and sarcoidosisBackground Previous gene expression studies have identified genes IFNγ, TNFα, RNase 3, CXCL9, and CD55 as potential biomarkers for sarcoidosis and/or chronic beryllium disease (CBD). We hypothesized that differential expression of these genes could function as diagnostic biomarkers for sarcoidosis and CBD, and prognostic biomarkers for sarcoidosis. Study Design/Methods We performed RT-qPCR on whole blood samples from CBD (n = 132), beryllium sensitized (BeS) (n = 109), and sarcoidosis (n = 99) cases and non-diseased controls (n = 97) to determine differential expression of target genes.
Antifibrotic drugs for pulmonary sarcoidosis: A treatment in search of an indicationThe most common causes of disability and death from sarcoidosis are directly or indirectly related to complications of fibrotic lung disease . Fibrosis develops in up to 20% of pulmonary sarcoidosis patients [2,3] and may result in end-stage parenchymal lung disease . Fibrotic pulmonary sarcoidosis is associated with distortion of airways leading to airflow obstruction, bronchiectasis, and increased episodes of clinical worsening that are often related to pulmonary infections [4–7]. Sarcoidosis associated pulmonary hypertension is caused by a variety of mechanisms, but the most common of these is distortion of the pulmonary vasculature from fibrosis [8,9].
High expression of mTOR signaling in granulomatous lesions is not predictive for the clinical course of sarcoidosisSarcoidosis is a systemic granulomatous disease with a variable clinical presentation and disease course. There is still no reliable biomarker available, which assists in the diagnosis or prediction of the clinical course. According to a murine model, the expression level of the metabolic checkpoint kinase mechanistic target of Rapamycin complex 1 (mTORC1) in granulomas of sarcoidosis patients may be used as a clinical biomarker.
Current perspectives on the immunopathogenesis of sarcoidosisSarcoidosis is an inflammatory systemic disease that commonly affects the lungs or lymph nodes but can manifest in other organs. Herein, we review the latest evidence establishing how innate and adaptive immune responses contribute to the pathogenesis and clinical course of sarcoidosis. We discuss the possible role of microbial organisms as etiologic agents in sarcoidosis and the evidence supporting sarcoidosis as an autoimmune disease. We also discuss how animal and in vitro human models have advanced our understanding of the immunopathogenesis of sarcoidosis.
sIL-2R levels predict the spontaneous remission in sarcoidosisSarcoidosis is associated with a wide range of disease outcomes including spontaneous remission and progressive courses. It is necessary to identify patients with spontaneous remission without corticosteroid treatment. This study aimed to identify the markers for predicting spontaneous remission in patients with sarcoidosis.
The utility of endobronchial ultrasound-transbronchial needle aspiration in patients with suspected extra-pulmonary sarcoidosis without thoracic lymphadenopathyDiagnosis of extra-pulmonary sarcoidosis can be difficult, and a biopsy is usually required. We evaluated the utility of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) in patients with suspected extra-pulmonary sarcoidosis with thoracic lymph nodes ≤10 mm on chest computed tomography (CT) and no or minimal pulmonary infiltrates.
Clinical features and outcomes of asymptomatic pulmonary sarcoidosis. A comparative cohort studyTo evaluate the clinical characteristics and outcomes of patients with asymptomatic pulmonary sarcoidosis (APS) detected incidentally and compare them with symptomatic non-Löfgren sarcoidosis (SnLS) patients.
Predictors of mortality in fibrosing pulmonary sarcoidosisPulmonary fibrosing sarcoidosis is associated with increased mortality. This study was aimed to explore the prognosis value of a panel of parameters for predicting mortality.
Randomised, placebo-controlled trial of dexamethasone for quality of life in pulmonary sarcoidosisMany patients with pulmonary sarcoidosis experience reduced quality of life. Although oral corticosteroids are the most common agents used in sarcoidosis, very little is known on the effects on quality of life.
Breaking hearts and taking names: A case of sarcoidosis related effusive-constrictive pericarditisPericardial involvement of sarcoidosis is a rare cause for acute heart failure, and usually occurs as a result of the development of a pericardial effusion leading to cardiac tamponade. Even rarer still, is the manifestation of constrictive pericarditis. We report a case of sarcoidosis with lung, pleural, and pericardial involvement with effusive-constrictive pericarditis leading to cardiac tamponade.
Evaluating S100B as a serum biomarker for central neurosarcoidosisS100B is a calcium-binding protein found primarily in glial cells. In the setting of neuronal injury and disruption of the blood brain barrier, S100B can leak into the cerebrospinal fluid and systemic circulation.
Sarcoidosis diagnosis and treatment in Sweden: A register-based assessment of variations by region and calendar periodIn Sweden, sarcoidosis prevalence varies geographically, but it is unclear whether diagnosis and treatment patterns vary by geographical area and calendar period. We sought to investigate differences in sarcoidosis diagnosis and treatment by healthcare region and calendar period using nationwide register data.
CXCL9 and CXCL10 are differentially associated with systemic organ involvement and pulmonary disease severity in sarcoidosisSarcoidosis is a granulomatous inflammatory disease with limited blood markers to predict outcomes. The interferon-gamma (IFN-γ)-inducible chemotactic cytokines (chemokines), CXCL9 and CXCL10, are both increased in sarcoidosis patients, yet they possess important molecular differences. Our study determined if serum chemokines correlated with different aspects of disease severity.
Mortality for sarcoidosis patients on the transplant wait list in the Lung Allocation Score era: Experience from a high volume centerSarcoidosis progresses to end stage fibrotic lung disease in 10% of patients and may necessitate lung transplantation. Organ allocation is currently determined by the Lung Allocation Score (LAS), but its performance in a sarcoidosis population has not been evaluated.
Correspondence for "clinical epidemiology of familial sarcoidosis: A systematic literature review"We have read the very interesting article titled “Clinical epidemiology of familial sarcoidosis: a systematic literature review” by Drs. Terwiel and van Moorsel published recently in Respiratory medicine . The work was based on the very stringent selection of 27 articles out of a total of 459 published on sarcoidosis in order to obtain a high level of statistical quality in the evaluation of the prevalence of familial forms. This review took into account all articles published until March 2018, date of submission to Respiratory Medicine.
Correspondence for “Clinical epidemiology of familial sarcoidosis: A systematic literature review”It is with great interest that we read the article titled “Clinical epidemiology of familial sarcoidosis: A systematic literature review” by Drs. Terwiel and van Moorsel published recently in Respiratory Medicine . Their systematic review on familial sarcoidosis highlights the great heterogeneity in familial disease prevalence and in familial relative risks among published studies. They also emphasize the high heritability (>60%) of sarcoidosis.
Economic burden of incident interstitial lung disease (ILD) and the impact of comorbidity on costs of careEvidence about the economic burden related to interstitial lung diseases (ILDs) and the cost-driving factors is sparse. In the knowledge that distinct comorbidities affect the clinical course of ILDs, our study investigates their impact on costs of care within first year after diagnosis.
Serum CXCL11 correlates with pulmonary outcomes and disease burden in sarcoidosisSarcoidosis is a systemic granulomatous disease of unknown etiology that affects the lungs in 90% of patients, but has a wide range of disease manifestations and outcomes including chronic and progressive courses. Noninvasive biomarkers are needed to assess these outcomes and guide decisions for long term monitoring and treatment. Interferon-gamma (IFN-γ)-inducible chemotactic cytokines (chemokines), CXCL9, CXCL10 and CXCL11, show promise in this regard because they have been implicated in the pathogenesis of and reflect the burden of granulomatous inflammation.
Direct and indirect economic and health consequences related to sarcoidosis in Denmark: A national register-based studySarcoidosis is a systemic disease that primarily affects the younger population. Longitudinal studies of the economic burden of sarcoidosis are scarce. This study evaluates overall the economic burden of sarcoidosis in Denmark before and after initial diagnosis.
Elderly sarcoidosis: A comparative study from a 42-year single-centre experienceTo describe the clinical features and outcomes in elderly patients with sarcoidosis and to compare them with younger patients.
Quantifying the relationship between symptoms at presentation and the prognosis of sarcoidosisAlthough it is the general consensus that sarcoidosis patients who present with sarcoidosis-related symptoms have a worse outcome than patients whose disease is detected incidentally without symptoms, this premise has not been rigorously examined.
Sarcoidosis: No longer a benign disease?Sarcoidosis is a multi-system disease of unknown cause characterized by noncaseating granulomatous inflammation that results in symptoms and organ dysfunction due to persistent inflammation and fibrosis. It predominately affects the lungs in over 90% of patients, but can injure any organ in the body. Sarcoidosis can be a life-threatening disease, particularly in those with pulmonary fibrosis, pulmonary hypertension, or cardiac involvement [1,2]. Opportunistic infections may also play a role in mortality in patients on immunosuppression [2,3].
The development of sarcoidosis in patients receiving daclizumab: A case series from multiple clinical trialsSeveral 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.
Can the Sarcoidosis Health Questionnaire predict the long-term outcomes in Japanese sarcoidosis patients?The Sarcoidosis Health Questionnaire (SHQ) is the first sarcoidosis-specific health status questionnaire ever developed. Worse health status, as evaluated by the SHQ, may indicate higher risk for deterioration in the following 5 years.
Clinical epidemiology of familial sarcoidosis: A systematic literature reviewAlthough the presence of familial sarcoidosis has been confirmed, clinical and epidemiological data on its characteristics are scattered and sometimes paradoxical. The objective of this review is to assess what is known on the clinical epidemiology of familial sarcoidosis, by combining data from early case reports with recent population based data; aiming to support in clinical decision making and providing information to patients.
Sarcoidosis deaths in the United States: 1999–2016It has been over a decade since a comprehensive study has been published that has examined sarcoidosis deaths at the national level. The purpose of this study was to analyze sarcoidosis as the underlying cause of death using current national death certificate data. Results from this project can be used to evaluate and compare trends of sarcoidosis reported deaths across the U.S.
Response to Letter to Editor regarding "Sarcoidosis and IPF in the same patient-a coincidence, an association or a phenotype?"We thank Drs. Valentin, Hyde, Gomez and Patel for commenting on our recently published article “Sarcoidosis and IPF in the same patient-a coincidence, an association or a phenotype?” . Indeed, one of our objectives in reporting our observations was to provoke further interest in the scientific community regarding such patients and conduct of clinical studies in such cohorts.
Letter to the editorIt was with great interest we read the article by Dr. Collins and colleagues published in the August 2018 edition of Respiratory Medicine, titled “Sarcoidosis and IPF in the same patient-a coincidence, an association or a phenotype?” The authors describe the characteristics of a disease entity they coined “combined sarcoidosis and idiopathic pulmonary fibrosis (CSIPF)” . We appreciate the authors’ efforts to shed light on this clinical entity, which to date has sparked debate in terms of proper classification of patients who share radiographic and histopathologic features of sarcoidosis and idiopathic pulmonary fibrosis (IPF).
Sarcoidosis: A benign disease or a culture of neglect?The widespread perception that sarcoidosis is essentially a benign disease has undoubtedly contributed to a lack of investment in sarcoidosis-related public health and research initiatives. Respiratory clinicians managing both pulmonary sarcoidosis and idiopathic pulmonary fibrosis may be especially likely to subscribe to this view. Unlike most other forms of fibrotic lung disease, pulmonary sarcoidosis stabilizes with time, with or without therapy, in the majority of patients. Sarcoidosis patients with major cardiac or neurologic involvement are often managed by sub-specialists and may be under-represented in general sarcoidosis cohorts.
Combined sarcoidosis and idiopathic pulmonary fibrosis (CSIPF): Genuine disease entity, obscure clinical phenotype or diagnostic red herring?The diffuse parenchymal lung diseases (DPLDs), often collectively referred to as the interstitial lung diseases (ILDs), are a heterogeneous group of disorders that are classified together because of similar clinical, radiographic, physiologic, or pathologic manifestations . Universal features of the DPLDs include cellular proliferation, inflammation and/or fibrosis within the alveolar wall . Architectural distortion of the airways and alveoli is also frequently present. The DPLDs are categorized into those that are associated with known causes and those that are idiopathic.
Work ability before and after sarcoidosis diagnosis in SwedenInformation on how sarcoidosis affects one's ability to work is needed to clarify the burden of disease on the individual and society. Our aim was to describe the work ability of individuals with sarcoidosis before and after diagnosis compared to people without sarcoidosis.
Cardiac sarcoidosis: Diagnosis confirmation by bronchoalveolar lavage and lung biopsyThe diagnosis of cardiac sarcoidosis (CS) is difficult to ascertain due to the insensitivity of endomyocardial biopsy. Current diagnostic criteria require a positive endomyocardial biopsy or extra-cardiac biopsy with clinical features suggestive of CS. Common tests for diagnosis of pulmonary sarcoidosis include bronchoalveolar lavage (BAL), lung and mediastinal lymph node (MLN) biopsies. Our objective was to determine the diagnostic utility of these tests in patients with suspected CS and without prior history of pulmonary involvement.
Sarcoidosis and IPF in the same patient-a coincidence, an association or a phenotype?Idiopathic Pulmonary Fibrosis (IPF) and Sarcoidosis are distinct clinical entities. Fibrotic disease in pulmonary sarcoidosis is typically upper lobe predominant. In IPF fibrosis is basilar and peripheral predominant [usual interstitial pneumonia (UIP) pattern]. Sarcoidosis and UIP have rarely been observed in the same patient. We sought to characterize patients manifesting both sarcoidosis and IPF and compare clinical features and survival to that of patients with “Lone-IPF” (IPF only) and pulmonary sarcoidosis with fibrosis in a non-UIP pattern.
Monitoring cardiac sarcoidosis: The next frontierCardiac sarcoidosis is a potentially life-threatening form of the disease. Although most sarcoidosis-related deaths result from lung involvement, most of these deaths occur after years of the slow development of lung fibrosis from granulomatous inflammation [1,2]. Contrary to pulmonary sarcoidosis, cardiac sarcoidosis may cause life-threatening events and severe organ dysfunction relatively quickly because of myocardial granulomas deposited in unfortunate locations. Furthermore, myocardial sarcoid granulomas tend to progress relatively quickly to scar  that does not respond to anti-granulomatous therapy and is permanent.
Prevalence, incidence, and mortality of sarcoidosis in Korea, 2003–2015: A nationwide population-based studyThe prevalence and incidence of sarcoidosis, a granulomatous disorder involving multiple organ systems, varies among geographical regions and ethnicities. This study evaluated the incidence, prevalence, and mortality of sarcoidosis in a large nationwide population-based cohort in Korea.
Sleep disturbance and symptom burden in sarcoidosisSarcoidosis is a systemic inflammatory disease associated with myriad symptoms, including fatigue. It can affect physiological processes like sleep, leading to poor sleep quality and excessive daytime sleepiness. We hypothesized that sarcoidosis patients would report more severe sleep disturbance than healthy controls and that relationships would be found with sleep disturbance and the severity of other symptoms.
Sarcoidosis in WTC-Exposed workersWithout adequate attention to the incidence and prevalence of surveillance with diagnostic technology, and without suitable consideration of the technologic effects on what becomes detected or left unidentified, the rates of reported diseases simply represent the rates of diagnostic detection and cannot be accepted as scientific enumeration of the true incidence and prevalence of those diseases. .
Efficacy and safety of infliximab biosimilar Inflectra® in severe sarcoidosisInfliximab, a monoclonal antibody against tumor necrosis factor alpha (TNF-α) is effective third-line therapy in severe sarcoidosis. The originator product of Infliximab, Remicade®, is expensive, limiting universal access. Recently, a less expensive biosimilar of infliximab, Inflectra®, has become available, but the efficacy and tolerability has not been studied in sarcoidosis.
Effect of inhaled corticosteroids on lung function in chronic beryllium diseaseThe clinical effects of inhaled corticosteroids (ICS) on chronic beryllium disease (CBD) are unknown. Although frequently used for symptoms or disease not requiring systemic therapy, the clinical course of patients on ICS has not been evaluated.
Neutrophil gelatinase-associated lipocalin in patients with sarcoidosisNeutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein that is involved in the innate immune system and increased expression has been detected in diverse diseases. Sarcoidosis is a systemic granulomatous disorder and its clinical course and prognosis are changeable and highly divergent. This study aimed to examine the expression of NGAL in patients with sarcoidosis. In addition, we examined whether NGAL could serve as a marker of disease activity and prognosis.
Steroids for sarcoidosis: How much and for how long?Most clinicians agree that corticosteroids are the first choice for treatment for symptomatic pulmonary sarcoidosis [1,2]. Prednisone is one of the most commonly used corticosteroids, with the usual initial dose being 20–40 mg daily [3,4]. However, the specific dose and rationale for such a dose is unclear. Early studies of corticosteroids were associated with quite variable doses and duration of therapy. In some studies, 60 mg for one month and then slowly tapered for more than a year  while others gave 15 mg for three months total .
Everyday cognitive failure and depressive symptoms predict fatigue in sarcoidosis: A prospective follow-up studyFatigue is a major and disabling problem in sarcoidosis. Knowledge concerning correlates of the development of fatigue and possible interrelationships is lacking.
Endpoints in sarcoidosis: More like IPF or asthma?Sarcoidosis remains an enigmatic disease. Its cause is unknown, the indications for treatment are often unclear, and its natural history is variable. An additional important enigmatic issue that has hampered clinical sarcoidosis research is the failure to develop reliable and universally accepted clinical endpoints.
Respiratory Medicine: Focus on Sarcoidosis: Editor's welcomeWith this editorial, my Editorial Board Members and I launch the maiden voyage of Respiratory Medicine: Focus on Sarcoidosis, a companion journal of Respiratory Medicine. The journal's scope will encompass the etiology, immunopathogenesis, diagnosis, clinical manifestations, natural history, treatment, and outcomes of sarcoidosis. The journal will devote a significant amount of space to extrapulmonary sarcoidosis, in addition to pulmonary sarcoidosis.