Outcome Of Sarcoidosis Research Articles

Epidemiology and health outcomes of sarcoidosis in a universal healthcare population: a cohort study.

Sarcoidosis-related mortality appears to be rising in North America, with increasing rates in females and the elderly. We aimed to estimate trends in sarcoidosis incidence, prevalence and mortality in Ontario, Canada.We performed a cohort study using health administrative data from Ontario between 1996 and 2015. International Classification of Diseases and Ontario Health Insurance Plan codes were used for case detection. Three disease definitions were created: 1) sarcoidosis, two or more physician claims within 2 years; 2) chronic sarcoidosis, five or more physician claims within 3 years; and 3) sarcoidosis with histology, two or more physician claims with a tissue biopsy performed between claims.Overall, 18 550, 9199 and 3819 individuals with sarcoidosis, chronic sarcoidosis and sarcoidosis with histology, respectively, were identified. The prevalence of sarcoidosis was 143 per 100 000 in 2015, increasing by 116% (p<0.0001) from 1996. The increase in age-adjusted prevalence was higher in males than females (136% versus 99%; p<0.0001). The incidence of sarcoidosis declined from 7.9 to 6.8 per 100 000 between 1996 and 2014 (15% decrease; p=0.0009). A 30.3% decrease in incidence was seen among females (p<0.0001) compared with a 5.5% increase in males (p=0.47). Age- and sex-adjusted mortality rates of patients with sarcoidosis rose from 1.15% to 1.47% between 1996 and 2015 (28% increase; p=0.02), with the overall trend being nonsignificant (p=0.39). Mortality rates in patients with chronic sarcoidosis increased significantly over the study period (p=0.0008).The prevalence of sarcoidosis is rising in Ontario, with an apparent shifting trend in disease burden from females to males. Mortality is increasing in patients with chronic sarcoidosis.

Musculoskeletal and pulmonary outcomes of sarcoidosis after initial presentation of osseous involvement.

We aimed to investigate the musculoskeletal and pulmonary outcomes of patients with osseous sarcoidosis. We identified 24 patients with osseous sarcoidosis and at least one year of follow-up after diagnosis (baseline). We collected outcome data at 1-year follow-up and last follow-up. We defined a composite outcome measure; worsening considered as worsening in any of the following 4 components compared to baseline: 1) osseous sarcoidosis symptoms, 2) musculoskeletal imaging of affected bone, 3) chest imaging, or 4) pulmonary function testing (PFT). A minority of patients had a worsening composite outcome at 1-year (9/24, 38%) and last follow-up (5/24, 21%). When only considering musculoskeletal symptoms and imaging, only 25% (6/24) and 13% (3/24) of patients worsened compared to baseline at 1-year and last follow-up, respectively. Patients with a worsening composite overall outcome tended to be older at baseline than those without the outcome for both 1-year (54.3 years vs. 47.5 years, p=0.11) and last follow-up (55.0 years vs. 48.7 years; p=0.23), although these differences were non-significant. Treatment was not associated with worsening composite overall outcome at 1-year follow-up (p=0.40), but was significantly associated with decreased risk for worsening at last follow-up (p=0.05). In this retrospective cohort study of osseous sarcoidosis, most patients had a favorable outcome according to symptoms, musculoskeletal/chest imaging, and PFTs, even though only a minority were treated with glucocorticoids or DMARDs. These results suggest that the natural history of osseous sarcoidosis is often benign, although some patients experience clinical progression.

Dynamics of homeostasis and the outcome of sarcoidosis of the respiratory system in the treatment of corticosteroids

The outcome of sarcoidosis of the respiratory system is closely linked to the state of homeostasis and reactivity. Monitoring their status is possible through immunological, biochemical and hormonal studies. Within common medical institutions re-executing these studies is not always possible for a number of reasons. Therefore, the research for the availability and informative criteria of homeostasis and reactivity state was initiated at the end of XIXth century and continues until now. At the Department of Phthisiopulmonology of the First St.-Petersburg state medical University Academy I. P. Pavlov. University, new accessible and informative diagnostic criteria for estimation the state of homeostatic balance of the organism are developed. They are based on research of the general adaptation syndrome and the discovery of antistress types of adaptive reactions of the organism. In this regard, based on the leukogram evaluation following diagnostic criteria were developed and tested: leukocyte-lymphocytic index, types of adaptive reactions, entropy and redundancy of formed elements of white blood cells, extent of disturbance of homeostasis, indices of proliferation and differentiation of monocytes and reactivity types. Unfortunately, in the pulmonology clinics, they are used today only in single cases. The monitoring of homeostasis and reactivity indicators in patients with respiratory system sarcoidosis had a high working performance. It is established that in sarcoidosis the best treatment effect with corticosteroids with minimal residual changes of respiratory system took place in patients with the appropriate type of reactivity and normal range of other indicators. Pathological reactivity of an organism, especially hyporeactive and areactive types, are always accompanied by formation of pronounced residual sarcoidosis changes in the respiratory tract, which is the basis for the subsequent exacerbation (recurrence) of sarcoidosis.

Role of serum immunoglobulins for predicting sarcoidosis outcome: A cohort study.

BackgroundSarcoidosis is a systemic granulomatous disease which carries variable outcomes. Serum protein electrophoresis is an easily accessible and routinely performed examination at diagnosis, in order to search for hypergammaglobulinemia, which is frequently found, and to rule out other granulomatous diseases such as common variable immunodeficiency. We aimed to assess the impact of baseline immunoglobulin level on the outcome of sarcoidosis.MethodsWe conducted a retrospective cohort-study, at Rennes University Hospital, in which all newly diagnosed patients for whom a serum protein electrophoresis had been performed at baseline were enrolled, from 2006 to 2014. The main outcome was the need for corticosteroid treatment within 2 years from diagnosis, the secondary outcome was the occurrence of relapse among treated patients.ResultsEighty patients were included in the study, and 41.25% of them exhibited an elevated globulins rate. In univariate analysis, an elevated ACE level >70 U/l, Afro-Caribbean origin, and extra-pulmonary involvement, were associated with the need for corticosteroid treatment. In multivariate analysis, only ACE elevation (OR = 1.03, IC95% 1.01–1.05, p = 0.009) and extra-pulmonary involvement (OR = 5.8, IC95% 1.4–24, p = 0.015) were significant. Immunoglobulin level was not associated with the main outcome. Regarding the secondary outcome, none of the studied features were predictive of relapse among the 34 treated patients followed for two years.ConclusionsThere was no relation between the immunoglobulin level at diagnosis and the evolution of sarcoidosis. An elevated ACE level and the presence of initial extra-pulmonary involvement were both associated with a more severe course of the disease necessitating a corticosteroid treatment.

A Circulating MicroRNA Signature Serves as a Diagnostic and Prognostic Indicator in Sarcoidosis.

MicroRNAs (miRNAs) act as post-transcriptional regulators of gene expression. In sarcoidosis, aberrant miRNA expression may enhance immune responses mounted against an unknown antigenic agent. We tested whether a distinct miRNA signature functions as a diagnostic biomarker and explored its role as an immune modulator in sarcoidosis. The expression of miRNAs in peripheral blood mononuclear cells from subjects who met clinical and histopathologic criteria for sarcoidosis was compared with that observed in matched controls in the ACCESS (A Case Controlled Etiologic Study of Sarcoidosis) study. Signature miRNAs were determined by miRNA microarray analysis and validated by quantitative RT-PCR. Microarray analysis identified 54 mature, human feature miRNAs that were differentially expressed between the groups. Significant feature miRNAs that distinguished subjects with sarcoidosis from controls were selected by means of probabilistic models adjusted for clinical variables. Eight signature miRNAs were chosen to verify the diagnosis of sarcoidosis in a validation cohort, and distinguished subjects with sarcoidosis from controls with a positive predictive value of 88%. We identified both novel and previously described genes and molecular pathways associated with sarcoidosis as targets of these signature miRNAs. Additionally, we demonstrate that signature miRNAs (hsa-miR-150-3p and hsa-miR-342-5p) are significantly associated with reduced lymphocytes and airflow limitations, both of which are known markers of a poor prognosis. Together, these findings suggest that a circulating miRNA signature serves as a noninvasive biomarker that supports the diagnosis of sarcoidosis. Future studies will test the miRNA signature as a prognostication tool to identify unfavorable changes associated with poor clinical outcomes in sarcoidosis.

Genetic, Immunologic, and Environmental Basis of Sarcoidosis.

Sarcoidosis is a multisystem disease with tremendous heterogeneity in disease manifestations, severity, and clinical course that varies among different ethnic and racial groups. To better understand this disease and to improve the outcomes of patients, a National Heart, Lung, and Blood Institute workshop was convened to assess the current state of knowledge, gaps, and research needs across the clinical, genetic, environmental, and immunologic arenas. We also explored to what extent the interplay of the genetic, environmental, and immunologic factors could explain the different phenotypes and outcomes of patients with sarcoidosis, including the chronic phenotypes that have the greatest healthcare burden. The potential use of current genetic, epigenetic, and immunologic tools along with study approaches that integrate environmental exposures and precise clinical phenotyping were also explored. Finally, we made expert panel-based consensus recommendations for research approaches and priorities to improve our understanding of the effect of these factors on the health outcomes in sarcoidosis.

Right ventricular involvement and the extent of left ventricular enhancement with magnetic resonance predict adverse outcome in pulmonary sarcoidosis.

AimsCardiac involvement is the main determinant of poor outcomes in sarcoidosis. Right ventricular (RV) dysfunction and left ventricular (LV) late gadolinium enhancement (LGE) have been reported to be predictive of adverse outcome in non‐ischaemic cardiomyopathies. The aim of our study was to determine whether delayed RV LGE with cardiovascular magnetic resonance would be predictive of adverse events in addition to LV LGE during the long‐term follow‐up of pulmonary sarcoidosis patients.Methods and resultsEighty‐four consecutive biopsy‐proven pulmonary sarcoidosis patients were followed for a median of 56 months [38–74] after baseline delayed contrast‐enhanced cardiac magnetic resonance. The composite primary endpoint consisted of admission for congestive heart failure, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy, pacemaker implantation for high degree atrio‐ventricular block, or cardiac death. The composite secondary endpoint included all‐cause mortality in addition to the primary endpoint. RV and LV LGE were demonstrated in respectively 12 and 27 patients. Five of 10 events included in the primary endpoint occurred in the group with RV LGE. RV LGE, LV, or biventricular LGE yielded Cox hazard ratios of 8.71 [95% confidence interval (CI) 1.90–23.81], 9.22 (95% CI 1.96–43.45), and 12.09 (95% CI 3.43–42.68) for the composite primary endpoint. In a multivariate model, the predictive value of biventricular LGE for the composite primary and secondary endpoints was strongest. Kaplan–Meier event‐free survival curves were most significant for RV LGE and biventricular LGE (log rank with P < 0.001).ConclusionsBiventricular LGE at presentation is the strongest, independent predictor of adverse outcome during long‐term follow‐up. Asymptomatic myocardial scar <8% of LV mass carried a favourable long‐term outcome.

Noncoding RNAs: New Players in Pulmonary Medicine and Sarcoidosis.

Noncoding RNAs (ncRNAs) are coded by 98% of human genomic DNA. They are grouped into two major classes according to length: small ncRNAs and long ncRNAs. They regulate genome organization, stability, and physiological processes that maintain cellular homeostasis. Recently, great interest has emerged in ncRNAs because of their significant roles in the development of inflammatory diseases, including sarcoidosis. Some have been introduced as novel markers for disease activity, such as increased levels of microRNA-34a in peripheral blood mononuclear cells of patients with sarcoidosis, re-emphasizing the inflammatory component in sarcoidosis. They are also important factors in the outcome of sarcoidosis. Dysregulation of microRNA-let7f leads to overexpression of profibrotic factors and could be related to the pathogenesis of pulmonary fibrosis in patients with sarcoidosis, owing to their stimulatory effect on collagen expression and deposition. However, many unanswered questions remain about the association of ncRNAs and sarcoidosis. By understanding the functions of ncRNAs in T-helper cell type 1 and T-helper cell type 17, we may uncover the mechanism of action of those cells in sarcoidosis. Further translational research is needed to define the RNA gene fingerprint of different sarcoidosis stages.

Innate immunity in sarcoidosis pathobiology.

The immunopathogenesis of sarcoidosis is considered to involve contributions from both adaptive and innate immune responses. Although the identification of adaptive responses to candidate pathogenic antigens will elucidate mechanisms that regulate inflammation in sarcoidosis, innate mechanisms likely represent the 'missing link' to the initiation, maintenance, and resolution of noncaseating granulomatous inflammation, the hallmark feature of sarcoidosis. Furthermore, environments that expose patients to candidate pathogenic antigens for sarcoidosis also provide opportunities for engagement with innate ligands. Several studies have identified enhanced responsiveness via pattern recognition receptor pathways, potentiating the local induction of cytokines relevant to granulomatous inflammation, such as through stimulation of nucleotide-binding oligomerization domain-like receptor and Toll-like receptor pathways. These pathways contribute to the inherent properties of granulomas including, in some cases, persistent localization of pathogens and antigen. Serum amyloid A has been identified to be abundant in sarcoidosis tissues, and this promiscuous host protein can serve as an innate ligand to regulate experimental granulomatous inflammation. Nascent evidence supports a potential role for alternatively activated macrophages to direct histopathological outcomes in sarcoidosis. Innate pathways deserve further investigation as potential therapeutic targets for inhibiting granuloma formation in sarcoidosis.

PROGNOSTIC ALGORITHM FOR DISEASE FLOW IN PULMONARY AND THORACIC LYMPH NODES SARCOIDOSIS

Background: Sarcoidosis is a systemic granulomatosis commonly affecting respiratory system. Variable and often unpredictable flow of the disease provides rationale for the development of prognostic algorithm. Aim: To detect predictive parameters in pulmonary and thoracic lymph nodes sarcoidosis; to develop prognostic algorithm. Materials and methods: The results of examination of 113 patients (85 women and 28 men, 19-77 years old) with morphologically verified sarcoidosis has been assessed. Clinical manifestations, functional, radiographic (including CT numerical scores) and morphological features of the disease were analyzed against 3-year outcomes in prednisolon/hydroxychloroquine-treated or treatment-naive patients. Results: Radiographic stage, CT-pattern scores, several parameters of pulmonary function tests (DL co, RV, FEV1, FVC) and dyspnoe had the greatest prognostic significance for disease flow. Prognostic accuracy was 87.8% and increased to 94.5% after one-year dynamics of symptoms was taken into account. Therapy with systemic glu-cocorticosteroids did not influence outcomes in sarcoidosis with asymptomatic enlargement of thoracic lymph nodes. Conclusion: We have developed an algorithm for prognosis assessment in pulmonary sarcoidosis. Taking into account the results of patients follow-up significantly improves the accuracy of the prognosis.

Osteoprotegerin/sRANKL Signaling System in Pulmonary Sarcoidosis: A Bronchoalveolar Lavage Study.

Osteoprotegerin (OPG), a soluble tumor necrosis factor receptor family molecule, protects endothelial cells from apoptosis in vitro and promotes neovascularization in vivo. Angiogenesis may be crucial for the course and outcome of sarcoidosis. In this study, we evaluated the clinical usefulness of OPG and its ligand, a soluble receptor activator of nuclear factor-kappaB (sRANKL), in bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis (BBS, Besniera-Boeck-Schaumann disease). We studied 22 BBS patients and 15 healthy volunteers as a control group. The levels of OPG, sRANKL, and interleukin-18 (IL-18) were measured by the Elisa method. The BALF levels of sRANKL and IL-18 were higher in the BBS patients compared with controls [sRANKL: 2.12 (0.82-10.23) vs. 1.12 (0.79-4.39) pmol/l, p = 0.03; IL-18: 34.29 (12.50-133.70) vs. 13.05 (12.43-25.88) pg/ml, p = 0.001]. There were no significant differences between the concentration of OPG in the BBS patients and healthy controls [0.22 (0.14-0.81) vs. 0.23 (0.14-0.75) pmol/l]. In the BBS patients we found correlations between sRANKL and IL-18 in BALF (r = 0.742, p = 0.0001) and between OPG and lung diffusing capacity for carbon monoxide (DLCO) (r = -0.528, p = 0.029). Receiver-operating characteristic (ROC) curve was applied to find the cut-off for the BALF level of sRANKL (BBS vs. healthy: 1.32 pmol/l). We conclude that OPG and sRANKL may have usefulness in clinical evaluation of BBS patients.

Reliability and Validity of Cutaneous Sarcoidosis Outcome Instruments Among Dermatologists, Pulmonologists, and Rheumatologists.

Dermatologists, pulmonologists, and rheumatologists study and treat patients with sarcoidosis with cutaneous manifestations. The validity of cutaneous sarcoidosis outcome instruments for use across medical specialties remains unknown. To assess the reliability and validity of cutaneous sarcoidosis outcome instruments for use by dermatologists and nondermatologists treating sarcoidosis. We performed a cross-sectional study evaluating the use of the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) and Sarcoidosis Activity and Severity Index (SASI) to assess cutaneous sarcoidosis disease severity and the Physician's Global Assessment (PGA) as a reference instrument. Four dermatologists, 3 pulmonologists, and 4 rheumatologists evaluated facial cutaneous sarcoidosis in 13 patients treated at a cutaneous sarcoidosis clinic in a 1-day study on October 24, 2014; data analysis was performed from November through December 2014. Interrater and intrarater reliability and convergent validity, with correlation with quality-of-life measures as the secondary outcome. All instruments demonstrated excellent intrarater reliability. Interrater reliability (reported as intraclass correlation coefficient [95% CI]) was good for the CSAMI Activity scale (0.69 [0.51-0.87]) and PGA (0.66 [0.47-0.85]), weak for the CSAMI Damage scale (0.26 [0.11-0.52]), and excellent for the modified Facial SASI (0.78 [0.63-0.91]). The CSAMI Activity scale and modified Facial SASI showed moderate correlations (95% CI) with the PGA (0.67 [0.57-0.75] and 0.57 [0.45-0.66], respectively). The CSAMI Activity scale but not the modified Facial SASI showed significant correlations (95% CI) with quality-of-life instruments, such as the Dermatology Life Quality Index (Spearman rank correlation, 0.70 [0.25-0.90]) and the Skin Stigma raw score of the Sarcoidosis Assessment Tool (Pearson product moment correlation, 0.56 [0.01-0.85]). The CSAMI and SASI were reliable and valid in assessing cutaneous sarcoidosis among our diverse group of specialists. The CSAMI Activity score also correlated with quality-of-life measures and suggested construct validity. These results lend credibility to expand the use of the CSAMI and SASI by dermatologists and nondermatologists in assessing cutaneous sarcoidosis disease activity.

Racial Difference in Sarcoidosis Mortality in the United States

The clinical presentation and outcome of sarcoidosis varies by race. However, the race difference in mortality outcome remains largely unknown. We studied mortality related to sarcoidosis from 1999 through 2010 by examining data on multiple causes of death from the National Center for Health Statistics. We compared the comorbid conditions between sarcoidosis-related deaths with deaths caused by car accidents (previously healthy control subjects) and rheumatoid arthritis (chronic disease control subjects) in both African Americans and Caucasians. From 1999 through 2010, sarcoidosis was reported as an immediate cause of death in 10,348 people in the United States with a combined overall mean age-adjusted mortality rate of 2.8 per 1 million person-years. Of these, 6,285 were African American and 3,984 Caucasian. The age-adjusted mortality rate for African Americans was 12 times higher than for Caucasians. African Americans died at an earlier age than Caucasians. African Americans living in the District of Columbia and North Carolina and Caucasians living in Vermont had higher mortality rates. Although the total sarcoidosis age-adjusted mortality rate had not changed over the 12 year period studied, this rate increased for Caucasians (R = 0.747, P = .005) but not for African Americans. Compared with the control groups, pulmonary hypertension was significantly more common in individuals with sarcoidosis. This nationwide population-based study exposes a significant difference in ethnicity and sex among people dying of sarcoidosis in the United States. Pulmonary hypertension investigation should be considered in all patients with sarcoidosis, especially African Americans.

Expression of HIF-1A/VEGF/ING-4 Axis in Pulmonary Sarcoidosis.

Angiogenesis/angiostasis regulated by hypoxia inducible factor-1A (HIF-1A)/vascular endothelial growth factor (VEGF)/inhibitor of growth protein 4 (ING-4) axis may be crucial for the course and outcome of sarcoidosis. Overexpression of angiogenic factors (activation of VEGF through HIF-1A) may predispose to chronic course and lung fibrosis, whereas immunoangiostasis (related to an overexpression of inhibitory ING-4) may be involved in granuloma formation in early sarcoid inflammation, or sustained or recurrent formation of granulomas. In this work we investigated gene expression of HIF-1A, VEGF and ING-4 in bronchoalveolar fluid (BALF) cells and in peripheral blood (PB) lymphocytes of sarcoidosis patients (n=94), to better understand mechanisms of the disease and to search for its biomarkers. The relative gene expression level (RQ value) was analyzed by qPCR. The results were evaluated according to the presence of lung parenchymal involvement (radiological stage I vs. II-IV), acute vs. insidious onset, lung function tests, calcium metabolism parameters, percentage of lymphocytes (BALL%) and BAL CD4+/CD8+ in BALF, age, and gender. In BALF cells, the ING-4 and VEGF RQ values were increased, while HIF-1A expression was decreased. In PB lymphocytes all studied genes were overexpressed. Higher expression of HIF-1A in PB lymphocytes of patients with abnormal spirometry, and in BALF cells of patients with lung volume restriction was found. VEGF gene expression in BALF cells was also higher in patients with abnormal spirometry. These findings were in line with previous data on the role of HIF-1A/VEGF/ING-4 axis in the pathogenesis of sarcoidosis. Up-regulated HIF-1A and VEGF genes are linked to acknowledged negative prognostics.

Subclinical left ventricular dysfunction by echocardiographic speckle-tracking strain analysis relates to outcome in sarcoidosis.

Limited data exist on the risk of developing cardiac sarcoidosis (CS) and/or adverse events in sarcoidosis patients. Using LV global longitudinal strain (GLS), an emerging sensitive parameter of LV function, we evaluated the prevalence of subclinical cardiac dysfunction in sarcoidosis and investigated whether LVGLS predicts adverse outcomes in this population. A total of 130 patients with proven sarcoidosis undergoing echocardiography at our referral centre were identified. Following exclusion of those with evidence of CS (n = 14) or other pre-existing structural heart disease (n = 16), 100 patients (55 ± 13 years, 48% male, 90% pulmonary involvement) and 100 age- and gender-matched controls were included. LVGLS was measured by speckle-tracking analysis. The primary endpoint was a composite of all-cause mortality, heart failure hospitalization, device implantation, new arrhythmias, or future development of CS on advanced cardiac imaging modalities. LVGLS was significantly impaired in sarcoidosis patients compared with controls (-17.3 ± 2.5 vs. -20.0 ± 1.6%, P < 0.001). Overall, 27 patients (27%) reached the endpoint during a median follow-up of 35 months. On Cox proportional hazards model analysis, abnormal 24-h Holter, larger LV end-diastolic diameters, and more impaired LVGLS were significantly associated with the endpoint; however, only LVGLS remained independently associated on multivariate analysis [hazard ratio (HR) 1.4, 95% confidence interval (CI) 1.1-1.7, P = 0.006]. Patients with LVGLS less than -17.3% were significantly more likely to be free of the primary endpoint (log-rank P = 0.01). LVGLS is impaired in sarcoidosis patients, suggesting subclinical cardiac dysfunction despite the absence of conventional evidence of cardiac disease, and is independently associated with occurrence of cardiac events and/or development of CS.

Etiologic role of infectious agents.

A consensus statement found in most peer-reviewed literature on sarcoidosis is that the etiology of sarcoidosis is unknown. It is timely to review whether this statement should be revised. Many infectious agents meet the basic requirements of inducing granulomatous inflammation and immunologic responses consistent with sarcoidosis including oligoclonal expansion of CD4+ T cells, polarized Th1 and possibly Th17 responses, and dysregulated regulatory T-cell function. Studies over the past decade provide increasing and complementary data to implicate a role for infectious agents in sarcoidosis etiology. These studies used different methodologies such as polymerase chain reaction and mass spectrometry to document microbial nucleic acids and proteins in sarcoidosis tissues. Multiple studies report antigen-specific immune responses to specific microbial proteins in sarcoidosis. In aggregate, these studies provide compelling evidence that mycobacteria play a major etiologic role in sarcoidosis in the United States and Europe. Studies from Japan support a role for Propionibacteria as a major etiologic agent in the country. There is controversy over how these (or other) infectious agents cause sarcoidosis. The hypothesis that chronic sarcoidosis is caused by a viable, replicating mycobacterial or other infection has no direct pathologic, microbiologic, or clinical evidence. A novel hypothesis links microbial triggers to a sarcoidosis outcome from the accumulation of aggregated proinflammatory serum amyloid A within granulomas, providing a mechanism for chronic disease in the absence of any viable tissue infection. Further studies are needed to provide more definitive evidence for these competing hypotheses before the statement that the etiology of sarcoidosis is unknown becomes obsolete.

Effect of obesity on patient-reported outcomes in sarcoidosis

To assess the impact of high body mass index (BMI) on patient-reported outcomes in sarcoidosis patients and healthy persons. In this case-control study, we investigated symptoms of fatigue and dyspnoea, health status, BMI and spirometric tests in 184 sarcoidosis patients and the same number of sex- and age-matched healthy subjects. Fatigue was assessed using the fatigue scale (FS), dyspnoea was determined by the baseline dyspnoea index (BDI) and health status was measured using the respiratory-specific St George's Respiratory Questionnaire (SGRQ). There were significantly more subjects with increased BMI (≥25 kg/m(2)) among the sarcoidosis patients than among the healthy volunteers ((2) 37.675, P < 0.01). Sarcoidosis patients also had a greater probability of having a higher BMI (P < 0.01, OR 1.18, 95%CI 1.071.3). We found significantly lower BDI scores and forced expiratory volume in 1 s/forced vital capacity, as well as higher total SGRQ and total FS scores in sarcoidosis patients than in healthy individuals (P < 0.01 for all differences). Sarcoidosis significantly reduces patients' health status, both independently and also due to increased BMI. Reduction in BMI may contribute to improved spirometry results and health status of patients with sarcoidosis.

Long-term prognosis of the course of sarcoidosis: analysis of the literature and own experience

Aim. To evaluate the prognosis of the course of sarcoidosis in patients with a follow-up term of 10 years or more. Methods. Analysis of the literature, comparison with the data from own research. Analyzed was the data on 15 patients with sarcoidosis with the follow-up term of 10 years or more. Compared were the parameters of spirometry, blood tests, blood oxygen saturation, of the conducted treatment in the patients with remission and with a chronic course. Results. In 8 patients (53.3%) during the last follow-up visit (10 years or more after detection) noted was a stable remission (in 7 after the initial detection and in 1 after a single exacerbation). Among all the 15 patients after 10 years or more the frequency of dyspnea on exertion increased from 33.3 to 46.9%, chest pain - from 6.7 to 20%, complaints of weakness decreased from 66.7 to 53.3%, of fever - from 26.7 to 13.3%, and of cough - from 53.3 to 20%, of erythema nodosum - from 40 to 6.7%, of articular syndrome - from 60 to 20%, of splenomegaly - from 13.3 to 6.7%. When comparing the dynamics of the indicators in the subgroup with persistent remission noted was a significant decrease in the instantaneous volume rate after the exhalation of 50% of the forced vital lung capacity; blood oxygen saturation and diastolic blood pressure significantly increased, the proportion of monocytes in the leukocyte formula decreased. Registered was a significant increase in erythrocyte sedimentation rate within the physiological range. In patients with a chronic course of sarcoidosis occurred a significantly reduction of the forced vital lung capacity, of the forced expiratory volume in 1 s, of the instantaneous volume rate after exhalation of 25% of the forced vital lung capacity. Conclusion. The best prognosis had the patients, who were young adults with an acute onset, and who did not receive glucocorticoids. Pentoxifylline may improve the course and outcome of sarcoidosis.

Health status of sarcoidosis patients in baseline and in 10 years under different treatment strategies (multicenter analysis)

Summary. A multicenter (12 centers) retrospective analysis of health status of 83 sarcoidosis patients in time of diagnosis and after 10 years of treatment has been performed. In 10 years after diagnosis, 47 % of the patients had complete remission of pulmonary manifestations; mean forced spirometric values have not reduced in 10 years (excluding patients initially treated with anti-TB drugs). Patients treated with systemic steroids initially or during 10 yrs were less likely to have the complete remission (36.5 %) and more likely to have recurrent sarcoidosis course (57.1 %) compared to those not treated with systemic steroids. Pentoxifylline administration positively influenced the remission rate (71.4 %) and relapse rate in patients who had not received immunosuppressive therapy (28.6 %). A tendency has been found to positive effects of essential phospholipids on relapse rate and remission rate in sarcoidosis. Anti-TB therapy or treatment of sarcoidosis patients in TB centers negatively influenced the outcome of sarcoidosis. The results disclose an urgent need to imply new approaches to treatment of sarcoidosis, eg. anti-TNF-α drugs.

Review: Role of Genetics in Susceptibility and Outcome of Sarcoidosis

Sarcoidosis develops in genetically predisposed individuals that are exposed to unknown antigens. There is a statistically significant increased risk for the disease among family members of sarcoidosis patients, and the disease differs in different ethnic groups. It is a genetically complex disease, with many genes contributing, both as risk factors but also with an influence on the disease course. The strongest genetic associations with sarcoidosis are found within the major histocompatibility complex (MHC) [human leukocyte antigen (HLA) in humans]-region on chromosome six. This region includes, besides the HLA-class I and class-II genes, a large number of genes important for the immune response and inflammation. The well studied associations between sarcoidosis and HLA-class II molecules indicate specific antigen presentation for T helper cells, which is in agreement with the characteristic finding of lung-accumulated CD4+ T helper cells expressing a limited set of T cell receptors. Strong associations between distinct HLA-DRB1 alleles and the disease phenotype and course have been described, especially so in patient subgroups. Although a large number of genes are associated with sarcoidosis, this review focuses on gene associations and their influence on the disease phenotype, including the disease course.