The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue ...samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure.
Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability.
The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and 1 best practice statement. All evidence was very low quality.
The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available.
Sarcoidosis is a granulomatous disease of unknown cause, occurs worldwide and has a highly variable prevalence. The disease is typically dominant in the lungs, although it can affect virtually any ...organ and is unpredictable in its clinical course. The severity of pulmonary sarcoidosis ranges from incidentally discovered radiographic abnormalities in asymptomatic patients to a chronic progressive disease that is refractory to treatment. Mortality from sarcoidosis appears to have increased in the past three decades, with respiratory failure being the most common cause of sarcoidosis-related death. Pulmonary fibrosis, extensive disease on high-resolution chest CT, impaired lung function, and pulmonary hypertension are well established predictors of poor clinical outcomes. In patients who need systemic therapy to control their disease, corticosteroids are the most commonly used first-line treatment, with antimetabolites generally representing an alternative for patients who are unresponsive to corticosteroids or who cannot tolerate them. Indeed, corticosteroid therapy is associated with toxic effects that correlate with both the cumulative dose and duration of treatment. The scarcity of truly effective therapies and shortage of reliable predictors of the unpredictable development of disease in individual patients greatly contribute to making sarcoidosis such a difficult disease to manage.
Summary Background Both sarcoidosis and its treatment may worsen health related quality of life (HRQoL). We performed a propensity analysis of sarcoidosis-specific HRQoL patient reported outcome ...measures (PRO) to disentangle the effects of sarcoidosis and corticosteroid therapy on HRQoL in sarcoidosis outpatients. Methods Consecutive outpatient sarcoidosis patients were administered modules from two sarcoidosis-specific HRQoL PROs: the Sarcoidosis Health Questionnaire (SHQ) and the Sarcoidosis Assessment Tool (SAT). Patients were divided into those that received ≤500 mg of prednisone (PRED-LOW) versus >500 mg of prednisone (PRED-HIGH) over the previous year. SAT and SHQ scores were initially compared in the two corticosteroid groups. Then a multivariate analysis was performed using a propensity score analysis adjusted for race, age, gender and the severity of illness. Results In the unadjusted analysis, the PRED-HIGH group demonstrated the following worse HRQoL scores compared to the LOW-PRED group: SHQ Daily (p = 0.02), SAT satisfaction (p = 0.03), SAT daily activities (p = 0.03). In the propensity analysis, the following domains demonstrated worse HRQoL in the PRED-HIGH group than the PRED-LOW group: SAT fatigue (p < 0.0001), SAT daily activities (p = 0.03), SAT satisfaction (p = 0.03). All these differences exceeded the established minimum important difference for these SAT domains. The SHQ Physical score appeared to demonstrate a borderline improved HRQoL in the PRED-HIGH versus the PRED-LOW group (p = 0.05).). In a post-hoc exploratory analysis, the presence of cardiac sarcoidosis may have explained the quality of life differences between the two corticosteroid groups. Conclusions Our cohort of sarcoidosis clinic patients who received ≤500 mg of prednisone in the previous year had an improved HRQoL compared to patients receiving >500 mg on the basis of two sarcoidosis-specific PROs after adjusting for severity of illness. These data support the need to measure HRQoL in sarcoidosis trials, and suggest that the search should continue for effective alternative medications to corticosteroids.
Sarcoidosis is a complex disease with heterogeneous clinical presentations that can affect virtually any organ. Although the lung is typically the most common organ involved, combined pulmonary and ...cardiac sarcoidosis (CS) account for most of the morbidity and mortality associated with this disease. Pulmonary sarcoidosis can be asymptomatic or result in impairment in quality of life and end-stage, severe, and/or life-threatening disease. The latter outcome is seen almost exclusively in those with fibrotic pulmonary sarcoidosis, which accounts for 10% to 20% of pulmonary sarcoidosis patients. CS is problematic to diagnose and may cause significant morbidity and death from heart failure or ventricular arrhythmias. The diagnosis of CS usually requires surrogate cardiac imaging biomarkers, as endomyocardial biopsy has relatively low yield, even with directed electrophysiological mapping. Treatment of CS is often multifactorial, involving a combination of antigranulomatous therapy and pharmacotherapy for cardiac arrhythmias and/or heart failure in addition to device placement and cardiac transplantation.
Mathematical model of sarcoidosis Hao, Wenrui; Crouser, Elliott D.; Friedman, Avner
Proceedings of the National Academy of Sciences - PNAS,
11/2014, Letnik:
111, Številka:
45
Journal Article
Recenzirano
Odprti dostop
Sarcoidosis is a disease involving abnormal collection of inflammatory cells forming nodules, called granulomas. Such granulomas occur in the lung and the mediastinal lymph nodes, in the heart, and ...in other vital and nonvital organs. The origin of the disease is unknown, and there are only limited clinical data on lung tissue of patients. No current model of sarcoidosis exists. In this paper we develop a mathematical model on the dynamics of the disease in the lung and use patients' lung tissue data to validate the model. The model is used to explore potential treatments.
Pulmonary fibrosing sarcoidosis is associated with increased mortality. This study was aimed to explore the prognosis value of a panel of parameters for predicting mortality.
This retrospective study ...included 216 patients with confirmed stage 4 pulmonary sarcoidosis. Stage 4 diagnosis date served as baseline. The following information was systematically present at baseline: epidemiological characteristics; treatments; pulmonary function; composite physiologic index (CPI); systolic pulmonary artery pressure at echocardiography; pulmonary fibrosis extent, main pulmonary artery/ascending aorta diameters ratio (MPAD/AAD) and MPAD/body surface area (BSA) measured and calculated using computed tomography, Walsh's algorithm based on CPI, lung fibrosis extent and MPAD/AAD ratio, and modified Walsh's algorithm with MPAD/BSA replacing MPAD/AAD allowed to estimate good or bad prognosis profiles. The primary outcome of the study was all cause mortality and lung transplantation. The value of baseline parameters was tested as predictors of mortality using univariate and multivariate analyses.
Median follow-up was 105 months. There were 41 deaths and 5 transplantations. At multivariate analysis, survival was independently predicted by several parameters including CPI, lung fibrosis extent, pulmonary hypertension at echography or MPAD/BSA ratio, Walsh's algorithm, and geographic origin. The modified Walsh's algorithm was most highly predictive.
Survival was best predicted by geographic origin, lung fibrosis extent, PH at echography or MPAD/BSA ratio, as well as by various scores among them the modified Walsh's algorithm had very high predictive value thanks to MPAD/BSA ratio which accurately predicted mortality.
•Mortality in stage 4 sarcoidosis is associated with a CPI>40, fibrosis extent> 20% and pulmonary hypertension.•Patients native from Sub-Saharan Africa or French West Indies had a higher risk of mortality.•Replacing MPAD/AAD by MPAD/BSA in Walsh algorithm allows to accurately predict mortality.
Mortality in pulmonary sarcoidosis is highly variable and a reliable prognostic algorithm for disease staging and for guiding management decisions is needed. The objective of this study is to derive ...and test a staging system for determining prognosis in pulmonary sarcoidosis.
We identified the prognostic value of high-resolution computed tomography (HRCT) patterns and pulmonary function tests, including the composite physiological index (CPI) in patients with pulmonary sarcoidosis. We integrated prognostic physiological and HRCT variables to form a clinical staging algorithm predictive of mortality in a test cohort. The staging system was externally validated in a separate cohort by the same methods of discrimination used in the primary analysis and tested for clinical applicability by four test observers.
The test cohort included 251 patients with pulmonary sarcoidosis in the study referred to the Sarcoidosis clinic at the Royal Brompton Hospital, UK, between Jan 1, 2000, and June 30, 2010. The CPI was the strongest predictor of mortality (HR 1·04, 95% CI 1·02-1·06, p<0·0001) in the test cohort. An optimal CPI threshold of 40 units was identified (HR 4·24, 2·84-6·33, p<0·0001). The CPI40, main pulmonary artery diameter to ascending aorta diameter ratio (MPAD/AAD), and an extent of fibrosis threshold of 20% were combined to form a staging algorithm. When assessed in the validation cohort (n=252), this staging system was strikingly more predictive of mortality than any individual variable alone (HR 5·89, 2·68-10·08, p<0·0001). The staging system was successfully applied to the test and validation cohorts combined, by two radiologists and two physicians.
A clear prognostic separation of patients with pulmonary sarcoidosis is provided by a simple staging system integrating the CPI and two HRCT variables.
The objectives of this study were to compare the survival of sarcoid patients with pulmonary fibrosis with that of the general population and to determine the causes of death and the incidence of ...evolutive complications. This retrospective cohort included 142 sarcoid patients in radiographic stage IV (74 males; mean ± SD age 48.1 ± 12 yrs). Their survival was compared with that of the general French population, matched for the year and age at diagnosis of stage IV disease, sex and length of follow-up. Expected survival probabilities were calculated year-by-year on the basis of probabilities provided by official demographic data for France. Survival curves were based on the Kaplan-Meier method and compared using the log-rank test. During the follow-up period (7.1 ± 4.8 yrs), pulmonary hypertension (PH) was observed in 29.7% of cases and aspergilloma in 11.3%. Long-term oxygen therapy was required in 12%. Survival was 84.1% at 10 yrs, which was worse than for the general population (p = 0.013). 16 (11.3%) patients died from the following causes: refractory PH (n = 5), chronic respiratory insufficiency (n = 4), acute respiratory insufficiency (n = 2), haemoptysis due to aspergilloma (n = 1), heart sarcoidosis (n = 1), nocardiosis (n = 1) and unknown causes (n = 2). Survival is significantly decreased in stage IV patients. 75% of fatalities are directly attributable to respiratory causes.
To characterize the epidemiology of sarcoidosis from 1946 through 2013.
An inception cohort of patients with incident sarcoidosis from January 1, 1976, through December 31, 2013, in Olmsted County, ...Minnesota, was identified based on comprehensive individual medical record review. Inclusion required physician diagnosis supported by histopathologic confirmation, radiologic features of intrathoracic sarcoidosis, and a compatible clinical presentation. Data were collected on demographic characteristics, clinical presentation, laboratory investigations, and mortality. The data were augmented with a previously identified cohort of Olmsted County residents diagnosed as having sarcoidosis in 1946-1975. Incidence rates were age and sex adjusted to the 2010 US white population.
A total of 448 incident cases of sarcoidosis were identified (mean age, 44.2 years; 52% women). The annual incidence of sarcoidosis was 10.0 per 100,000 population. The incidence of sarcoidosis increased in women from 1950 to 1960, but otherwise there were no significant calendar year trends. However, the peak age at incidence for women shifted from 40 to 59 years in 1950 to 50 to 69 years in 2010. Similarly, the peak age at incidence for men shifted from 30 to 49 years in 1950 to 40 to 59 years in 2010. Ninety-seven percent of patients had intrathoracic involvement, but only 43% had respiratory symptoms. The overall mortality of patients with sarcoidosis was not different from that of the general population (standardized mortality ratio=0.90; 95% CI, 0.74-1.08).
Sarcoidosis occurred in approximately 10 persons per 100,000 per year. Most of the patients had intrathoracic involvement, although less than half had respiratory symptoms. Overall mortality was not different from that of the general population.
Pulmonary hypertension (PH) is a significant cause of morbidity and mortality in sarcoidosis. We established a multi-national registry of sarcoidosis associated PH (SAPH) patients.
Sarcoidosis ...patients with PH confirmed by right heart catheterization (RHC) were studied. Patients with pulmonary artery wedge pressure (PAWP) of 15 mmHg or less and a mean pulmonary artery pressure (mPAP) ≥ 25 Hg were subsequently analyzed. Data collected included hemodynamics, forced vital capacity (FVC), diffusion capacity of carbon monoxide (DLCO), chest x-ray, and 6-min walk distance (6MWD).
A total of 176 patients were analyzed. This included 84 (48%) cases identified within a year of entry into the registry and 94 (53%) with moderate to severe PH. There was a significant correlation between DLCO percent predicted (% pred) andmPAP (Rho = −0.228, p = 0.0068) and pulmonary vascular resistance (PVR) (Rho = −0.362, p < 0.0001). PVR was significantly higher in stage 4 disease than in stage 0 or 1 disease (p < 0.05 for both comparisons). About two-thirds of the SAPH patients came from the United States (US). There was a significant difference in the rate of treatment between US (67.5%) versus non-US (86%) (Chi Square 11.26, p = 0.0008) sites.
The clinical features of SAPH were similar across multiple centers in the US, Europe, and the Middle East. The severity of SAPH was related to reduced DLCO. There were treatment differences between the US and non-US centers.
•Multi-national study of 176 sarcoidosis associated pulmonary hypertension patients.•Similar clinical features across US, Europe, and Middle East.•Pulmonary vascular resistance was higher in patients with pulmonary fibrosis.•There was a correlation between DLCO and level of pulmonary hypertension.•Pulmonary hypertension was more likely to be treated in Europe than US.
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