Sarcoidosis Group Research Articles

Echocardiographic evaluation of left ventricular mechanicsin sarcoidosis patients without overt heart disease: a systematic review and meta-analysis.

During the last decade, a small number of studies have used speckle tracking echocardiography (STE) to investigate sarcoidosis effect on left ventricular (LV) mechanics in patients without overt heart disease. The present systematic review and meta-analysis has been primarily designed to summarize the main findings of these studies and to examine the overall influence of sarcoidosis on LV-global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF). All echocardiographic studies assessing conventional echoDoppler parameters and myocardial strain indices in patients with extracardiac sarcoidosis (ECS) vs. healthy controls, selected from PubMed and EMBASE databases, were included. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment of Case-Control Studies. Continuous data (LV-GLS and LVEF) were pooled as a standardized mean difference (SMD) comparing sarcoidosis group with healthy controls. The overall SMDs of LV-GLS and LVEF were calculated using the random-effect model. The full-text of 13 studies with 785 ECS patients and 567 healthy controls were analyzed. Both average LVEF (60.5±6.6 vs 63.0±4.8%, P<0.001) and LV-GLS (-17.4±3.3 vs -21.0±2.7%, P<0.001) were significantly lower in ECS patients than controls. However, sarcoidosis showed a significantly larger effect on LV-GLS (SMD: -1.26, 95%CI -1.61,-0.91, P<0.001) rather than on LVEF (SMD: -0.51, 95%CI -0.83,-0.20, P=0.001). Substantial heterogeneity was found for the studies that assessed LV-GLS (I2=86.4%) and LVEF (I2=85.3%). Egger's test gave a P-value of 0.24 for LV-GLS and 0.32 for LVEF assessment, indicating no publication bias. On meta-regression analysis, none of the moderators was significantly associated with effect modification for both LV-GLS and LVEF (all P <0.05). In patients without overt heart disease, the effect of sarcoidosis on LV-GLS is significantly greater than on LVEF. STE analysis should be implemented in clinical practice for the early detection of myocardial involvement in ECS patients.

New Neutrophil Parameters in Diseases with Various Inflammatory Processes.

The neutrophils evaluation seems interesting in the initial qualifications of patients with various inflammatory processes. In this study, we presented analysis of neutrophils and new parameters of the complexity (NEUT-GI, NE-WX), maturation (IG), size (NE-FSC, NE-WZ), and neutrophil activities (NEUT-RI, NE-WY) in coronavirus disease 2019 (COVID-19), lung cancer (LC), sarcoidosis (SA), and healthy controls (HCs). Peripheral blood (PB) was collected. The new parameters were examined by the Sysmex XN-1500. The mean absolute value for the IG parameter was the highest in the LC group. The differences in NEUT-RI value between COVID-19 and the HC group were observed. No significant differences were noticed between groups in the NEUT-GI granularity parameter. Neutrophil size assessed by NE-FSC parameter was reduced in all groups compared to HCs. The values of complexity (NE-WX), fluorescence (NE-WY), and size (NE-WZ) were the lowest in the HCs, whereas the highest median proportions of NE-WX, NE-WY, and NE-WZ were in LC patients. Patients from the SA group differed significantly from the HC group only for the NE-WZ parameter. We showed the usefulness of neutrophil parameters and their reactivity, morphology, and exhaustion. A more detailed analysis of blood counts may reveal trends that indicate a disease-specific immune response.

Can computed tomography findings and radiomics analysis of mediastinal lymph nodes differentiate between sarcoidosis and lymphoma?

To assess the ability of computed tomography (CT) findings and radiomics analysis to differentiate mediastinal lymphadenopathies as sarcoidosis versus lymphoma. 94 patients with lymphoma and 97 patients with sarcoidosis, who had > 1cm mediastinal lymph node were included. Size, location of lymph nodes, and distribution of the largest lymph nodes in two groups were compared. A total of 636 lymphadenopathies in four different regions were segmented for radiomics. Lesion segmentation was semiautomatically performed with a dedicated commercial software package on chest CT images. 149 patients were grouped as a training cohort, while 42 patients who underwent CT in the oncology hospital were used for external validation. The least absolute shrinkage and selection operator (LASSO) analysis was used to perform feature selection. Using selected features, the classification performance of various data mining methods in separating groups of sarcoidosis and lymphoma was investigated. Distribution and size of lymphadenopathies were significantly different in sarcoidosis and lymphoma groups (<0.05). Radiomics and data mining methods showed excellent performance in differentiating lymph nodes of sarcoidosis and lymphoma according to both the largest lymphadenopathy and lymphadenopathies in four different mediastinal regions (AUC >0,95). Distribution and size of lymphadenopathies can help differential diagnosis in patients with sarcoidosis and lymphoma. CT radiomics analysis can discriminate the lymph nodes of sarcoidosis and lymphoma with great performance regardless of lymph node size and location and it can be used safely in the diagnosis of these diseases, which can sometimes be challenging to distinguish from each other.

Choroidal manifestations of non-ocular sarcoidosis: an enhanced depth imaging OCT study

BackgroundAlthough choroidal thickening was reported as a sign of active inflammation in ocular sarcoidosis, there has been no research on the choroidal changes in non-ocular sarcoidosis (defined as systemic sarcoidosis without overt clinical signs of ocular involvement). Therefore, this study aimed to investigate choroidal structural changes in patients with non-ocular sarcoidosis.MethodsThis retrospective case–control study was conducted at Asan Medical Center, a tertiary referral center. We evaluated 30 eyes with non-ocular sarcoidosis and their age- and spherical equivalent-matched healthy control eyes. The subfoveal choroidal thickness, area ratio (Sattler layer-choriocapillaris complex [SLCC] area to Haller layer [HL] area), and choroidal vascularity index (CVI, luminal area to choroidal area) were analyzed using enhanced depth imaging in optical coherence tomography. Systemic and ocular factors associated with the choroidal thickness were investigated.ResultsCompared with the healthy control group, the non-ocular sarcoidosis group had significantly thicker subfoveal choroid (total and all sublayers [SLCC and HL]) and lower area ratio. There were no significant differences in the CVIs at all sublayers between groups. In the non-ocular sarcoidosis group, eyes under oral steroid treatment had thinner choroid than eyes under observation. In the control group, eyes with older age and more myopic spherical equivalent had thinner choroidal thickness.ConclusionTotal and all sublayers of the subfoveal choroid were significantly thicker without significant vascularity changes in non-ocular sarcoidosis eyes than in healthy control eyes. The degree of choroidal thickening was disproportionally greater at HL than at SLCC. These characteristic choroidal changes may be the subclinical manifestations in non-ocular sarcoidosis.

Correlation of Mantoux Test and Serum Angiotensin-Converting Enzyme (ACE) Levels with Clinically and Radiologically Diagnosed Ocular Tuberculosis and Ocular Sarcoidosis

Abstract Aim: To evaluate the role of combined Mantoux test and serum angiotensin-converting enzyme (ACE) levels in the diagnosis of ocular tuberculosis (TB) and ocular sarcoidosis. Materials and Methods: A prospective and observational study including patients with bilateral granulomatous uveitis diagnosed both radiologically and clinically as ocular TB or ocular sarcoidosis within a six-month period. CT Thorax/CT abdomen was done, and findings were noted. Mantoux test and serum ACE levels were recorded, and findings were correlated. Results: The study included a total of 60 patients: 32 patients with ocular TB and 28 patients with ocular sarcoidosis. Using Mantoux test, 84.4% in the TB group tested positive and were correctly identified (sensitivity), and 96.4% in the sarcoid group tested negative and were correctly identified as sarcoidosis. Hence, the association between Mantoux test and diagnoses was statistically significant (P &lt; 0.001). In the TB group, 25 subjects had normal and seven had elevated serum ACE levels. In the sarcoidosis group, 22 subjects had elevated and six had normal serum ACE levels. Hence, 78.1% were correctly identified with normal serum ACE levels (sensitivity) in the TB group and 78.6% were identified with elevated serum ACE levels in the sarcoidosis group, and the proportion difference was statistically significant (P &lt; 0.001). Conclusion: Mantoux test and serum ACE levels are cost-effective investigations and can be used for the diagnosis of ocular TB and sarcoidosis when combined with clinical and radiological evidence. The combined use of serum ACE and Mantoux test is useful in differentiating between sarcoidosis and TB.

Quadriceps femoris muscle ultrasound in sarcoidosis: an observational case-control study.

Although loss of muscle mass may be associated with general weakness, intolerance to physical activity and fatigue, it is underestimated and poorly understood in patients with sarcoidosis. To compare the quadriceps femoris muscle (QFM) thickness measured by ultrasonography (US) between the female patients with sarcoidosis and controls, secondly to assess the correlation between the muscle strength, fatigue and QFM thickness. Observational, case-control study. Physical Medicine and Rehabilitation Department of a University Hospital. Thirty-one women with sarcoidosis and 27 healthy volunteers were included in the study. The participants were evaluated for the following outcomes: 1) handgrip strength; 2) QFM thickness measured using US; and 3) sonographic thigh adjustment ratio (STAR). The sarcoidosis group was also evaluated with the 30-second chair stand test (30s-CST) and Fatigue Severity Scale (FSS). The QFM thickness and STAR values of the patients with sarcoidosis were significantly lower than those of the controls (P=0.0001). However, no statistically significant difference was observed between the handgrip strengths of the groups (P=0.581). There was no statistically significant correlation between the STAR values and handgrip strength in the sarcoidosis group; however, there was a significant positive correlation between the STAR values and 30s-CST (r=0.467, P=0.008). Loss of muscle mass is one of the musculoskeletal conditions in patients with sarcoidosis that may be associated with nonspecific symptoms, such as general debility, intolerance to physical activity, and fatigue. In the present study, no difference was observed in hand grip strength between the groups, while we found that QFM thickness was affected in patients with sarcoidosis when compared to the controls. The ultrasonographic QFM evaluation seems to be an innovative tool which may be used at all stages of sarcoidosis patient follow-up. The grip strength is a commonly used test to detect muscle weakness, but onset of a decrease in muscle mass in the lower extremities may occur earlier. Considering the increased burden of musculoskeletal problems in this population, performing 30s-CST and sonographic QFM thickness is practical methods to identify risky patients.

The usefulness of speckle tracking echocardiography for the prediction of cardiac involvement in patients with biopsy-proven sarcoidosis.

Cardiac sarcoidosis (CS) is commonly diagnosed based on clinical criteria and abnormalities in noninvasive imaging reported in patients with biopsy-proven extracardiac sarcoidosis. Electrocardiogram and two-dimensional echocardiography have a low sensitivity for CS detection. Cardiovascular magnetic resonance imaging (CMR) and positron emission tomography (PET) have limitations in terms of cost and availability. This study aimed to assess the usefulness of left ventricular longitudinal strain, measured using two-dimensional speckle tracking echocardiography (STE), for the prediction of late gadolinium enhancement (LGE) presence in CMR in patients with biopsy-proven sarcoidosis. A total of 119 patients with biopsy-proven extracardiac sarcoidosis were divided, according to the clinical criteria proposed by the 2014 Heart Rhythm Society expert consensus statement (HRS 2014), into two groups: 43 individuals with "probable cardiac sarcoidosis", CS(+) and 76 individuals without cardiac sarcoidosis, CS (-). Data from echocardiography, CMR, 12-lead ECG and 24h Holter monitoring were analyzed. Left ventricular global longitudinal strain (LV-GLS) was slightly reduced in the entire sarcoidosis group (-18.61±2.96), no difference between the CS (+) and CS (-) subgroups was found (-18.0%±3.2% and -18.9%±2.8%, respectively; p=.223). No cut-off value for LV-GLS was identified that could predict the presence of LGE. Segmental longitudinal strain impairment partially correlated with the presence of LGE on CMR. In our cohort of sarcoidosis patients, segmental longitudinal strain proved more helpful in the diagnostic process than LV-GLS. The ultimate role of STE in the diagnosis of CS remains to be established.

Diagnostic Value of Serum KL-6 in Interstitial Lung Diseases.

To explore serum KL-6 level and investigate its diagnostic value in interstitial lung diseases (ILDs). Serum KL-6 level was measured using the chemiluminescent enzyme immunoassay. Statistical analysis was performed for determining the KL-6 concentration of each group. KL-6 level (U/mL) in the ILD group was 1388.321 ±1943.116, which was higher than that in the control group, showing a significant statistical difference. ROC curve analysis based on the receiver operating characteristic curve showed the optimal cut-off value of 402.5U/mL, sensitivity of 77.4%, specificity of 93.4%, and accuracy of 89.4%; through Chi-square test with the two groups, the positive rate of KL-6 in patients with ILD was proved to be significantly higher than that in the control group. KL-6 level was 1063.00±504.757 in the idiopathic pulmonary fibrosis (IPF) group, 1346.892 ±1827.252 in the connective tissue disease-associated interstitial lung disease (CTD-ILD) group, 467.889±288.859 in the organizing pneumonia (OP) group, 8252.333±6050.625 in the pulmonary alveolar proteinosis (PAP) group, and 359.200±392.707 in the sarcoidosis group. The rank sum test showed that the differences were statistically significant. KL-6 level was the lowest in the sarcoidosis group, followed by that in the OP group. Serum KL-6 level was confirmed to be highly sensitive, specific, and accurate in the diagnosis of ILD. Subgroup analysis showed that the KL-6 level was the lowest in the sarcoidosis group, followed by that in the OP group.

The role of serum and bronchoalveolar lavage fluid chitotriosidase activity on diagnosis, disease characteristics and prognosis of sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease with an unpredictable clinical course. Chitotriosidase is a chitinase mainly expressed by activated macrophages. Increased chitotriosidase activity has been reported in serum and bronchoalveolar lavage (BAL) of sarcoidosis patients compared to healthy controls. This study aims to evaluate the role of serum and BAL chitotriosidase activity on diagnosis, disease characteristics, and prognosis of sarcoidosis. Patients referred with suspected sarcoidosis or other interstitial lung disease were prospectively included in the study. All patients underwent bronchoscopy with BAL. Serum and BAL chitotriosidase activity, BAL differential cell counts, and lymphocyte phenotypes were determined. Sarcoidosis patients were followed up regularly. Forty-two sarcoidosis and 28 non-sarcoidosis patients were included in the study. Serum chitotriosidase activity was higher in sarcoidosis group 247.5 (2.78-461) vs 108 (2.78-272) nmol/h/mL (p< 0.001). BAL chitotriosidase activity tended to be higher in sarcoidosis group 11 (2-308) vs 6.95 (2.27-44) nmol/h/mg but was not found to be statistically significant (p= 0.11). Serum and BAL chitotriosidase activities were correlated with each other (p= 0.023, r= 0.355). No significant difference was found between the diagnostic performance of BAL CD4/CD8 ratio and serum chitotriosidase activity (p= 0.079). Serum chitotriosidase and ACE activities were correlated with each other (p= 0.004, r= 0.457). No significant difference was found between serum or BAL chitotriosidase activity and stage or extrapulmonary involvement. Serum chitotriosidase activity was higher in patients who needed systemic therapy at diagnosis (p= 0.046). However, no significant difference was found between serum or BAL chitotriosidase activities and disease progression (p= 0.395 and p= 0.723, respectively). Serum chitotriosidase activity can be helpful in the differential diagnosis of sarcoidosis with a similar diagnostic performance with BAL CD4/CD8 ratio. Although serum chitotriosidase activity at diagnosis does not predict progressive disease, it is associated with the need for systemic therapy at diagnosis. Serial chitotriosidase measurements may be useful in monitoring disease progression during follow-up.

Can TERT rs2853669 polymorphysm indicate fibrosis in sarcoidosis?

Sarcoidosis is a systemic inflammatory disease of unknown cause, characterized by the presence of non-caseating granulomas, which can affect all organs in the body, especially the lung. The fibrotic stage 4 of sarcoidosis usually does not respond adequately to treatment and may cause respiratory distress in the patient. Some telomerase gene polymorphisms have been significantly associated with lung cancer and idiopathic pulmonary fibrosis. In our study, we aimed to investigate the relationship between telomerase mutation and progression to fibrosis in patients with sarcoidosis. A total of 93 patients, including 18 males and 73 females, who were clinically and histopathologically diagnosed with sarcoidosis were included in the study. The 78 patients included in the study were classified as non-fibrotic and 15 as fibrotic sarcoidosis. In telomerase rs2853669 single nucleotide polymorphism, three genotypes, homozygous TT, homozygous CC and heterozygous TC, were determined as the genotypes of the patients. When non-fibrotic and fibrotic sarcoidosis groups were compared, no significant difference was found in terms of genotypes (p=0.76). The FEV1 (forced expiratory volume in the first second) % of the CC genotype was lower than that of the other genotypes (p=0.01). In sarcoidosis patients, telomerase rs2853669 polymorphism does not indicate progression to fibrosis, but since FEV1% was found to be lower in individuals with homozygous CC polymorphism, it is thought that it may predict loss of respiratory function. Further studies are needed to evaluate the association of telomerase polymorphisms with fibrosis in sarcoidosis.

Determination of immunological biomarkers in sarcoidosis and their relation to disease activity

Sarcoidosis is a multisystem granulomatous disease of unknown origin. Ninety percent of patients with sarcoidosis have lung involvement. The onset can be acute or non-acute and the severity of sarcoidosis ranges widely from asymptomatic patients with accidental radiographic findings to patients with severe organ involvement. This case control analytic prospective study was conducted at the Chest Clinic, Al Zahraa hospital, to assess the diagnostic value of serum soluble interleukin 2 receptor (sIL-2R), cluster of differentiation 4 (CD4)/CD8 ratio and CD103 in sarcoidosis. We investigated the value of serum sIL-2R using ELISA and blood CD103, blood CD4/CD8 ratio using flow cytometry for 30 cases of sarcoidosis in different stages and 30 control persons to detect their use as a marker for diagnosis. We found a significant increase in sIL-2R in the sarcoidosis group as compared to the control group (p˂0.0001), while there was a significant decrease in CD103/CD4 in sarcoidosis group as compared to the control group (p &lt;0.001). In conclusion, sIL-2R and CD103 can be used as diagnostic markers for sarcoidosis.

Circulating Regulatory T Cell Subsets in Patients with Sarcoidosis.

A prospective comparative study was performed in 2016-2018 (34 patients with sarcoidosis (men (67.6%), women (32.3%)) were examined). Healthy subjects-the control group (n = 40). The diagnosis of pulmonary sarcoidosis was performed according to the standard criteria. We used two ten-color combinations of antibodies for Treg immunophenotyping. The first one contained CD39-FITC, CD127-PE, CCR4-PE/Dazzle™ 594, CD25-PC5.5, CD161-PC7, CD4-APC, CD8-APC-AF700, CD3-APC/Cy7, HLA-DR-PacBlue, and CD45 RA-BV 510™, while the second consisted of CXCR3-Alexa Fluor 488, CD25-РЕ, CXCR5-РЕ/Dazzle™ 594, CCR4-PerСP/Сy5.5, CCR6-РЕ/Cy7, CD4-АPC, CD8 АPC-AF700, CD3-АPC/Cy7, CCR7-BV 421, and CD45 RA-BV 510. The flow cytometry data were analyzed by using Kaluza software v2.3. A statistical analysis was performed with Statistica 7.0 and GraphPad Prism 8 software packages. Primarily, we found that patients with sarcoidosis had decreased absolute numbers of Treg cells in circulation. We noted that the level of CCR7-expressing Tregs decreased in patients with sarcoidosis vs. the control group (65.55% (60.08; 70.60) vs. 76.93% (69.59; 79.86) with p < 0.001). We noticed that the relative numbers of CD45RA-CCR7+ Tregs decreased in patients with sarcoidosis (27.11% vs. 35.43%, p < 0.001), while the frequency of CD45 RA-CCR7- and CD45RA+ CCR7- Tregs increased compared to the control group (33.3% vs. 22.73% and 0.76% vs. 0.51% with p < 0.001 and p = 0.028, respectively). CXCR3-expressing Treg cell subsets-Th1-like CCR60078CXCR3+ Tregs and Th17.1-like CCR6+ CXCR3+ Tregs-significantly increased in patients with sarcoidosis vs. the control group (14.4% vs. 10.5% with p < 0.01 and 27.9% vs. 22.8% with p < 0.01, respectively). Furthermore, the levels of peripheral blood EM Th17-like Tregs significantly decreased in the sarcoidosis group vs. the control group (36.38% vs. 46.70% with p < 0.001). Finally, we found that CXCR5 expression was increased in CM Tregs cell subsets in patients with sarcoidosis. Our data indicated a decrease in circulating Tregs absolute numbers and several alterations in Treg cell subsets. Moreover, our results highlight the presence of increased levels of CM CXCR5+ follicular Tregs in the periphery that could be linked with the imbalance of follicular Th cell subsets and alterations in B cell, based on the immune response. The balance between the two functionally distinct Treg cell populations-Th1-like and Th17-like Tregs-could be used in sarcoidosis diagnosis and the determination of prognosis and disease outcomes. Furthermore, we want to declare that analysis of Treg numbers of phenotypes could fully characterize their functional activity in peripherally inflamed tissues.

Role of Serum Soluble Interleukin-2 Receptor Level in the Diagnosis of Sarcoidosis: A Systematic Review and Meta-Analysis.

Serum Soluble Interleukin-2 Receptor (sIL-2R) levels are used clinically as a disease activity marker for systemic sarcoidosis. Studies have investigated the diagnostic role of serum soluble interleukin-2 receptor (sIL-2R) level for sarcoidosis relative to biopsy. We performed a systematic review and meta-analysis of studies evaluating the diagnostic utility of sIL-2R. We carried out an electronic search in Medline, Embase, Google Scholar, and Cochrane databases using keyword and Medical Subject Heading (MeSH) terms: sarcoidosis and sIL-2R. Studies evaluating the sIL-2R levels as a diagnostic tool in clinically diagnosed or biopsy-proven sarcoidosis patients compared to control groups with non-sarcoidosis patients were included. Forest plots were constructed using a random effect model depicting pooled sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy. We selected ten studies comprising 1477 patients, with 592 in the sarcoidosis group and 885 in the non- sarcoidosis group. Pooled sensitivity and specificity of sIL-2R levels were 0.88 (95% CI: 0.75-0.95) and 0.87 (95% CI 0.73-0.94) respectively. Pooled negative predictive value and positive predictive value were 0.91 (95% CI 0.77-0.97) and 0.85 (95% CI 0.59-0.96) respectively with diagnostic accuracy of 0.86 (95% CI 0.71- 0.93). In addition to its utility as a marker of sarcoidosis disease activity, sIL-2R has high diagnostic accuracy. Despite the limitations of the heterogenous sarcoidosis population and different sIL-2R cutoffs, our results suggest that sIL-2R is an important biomarker that can be used to confirm sarcoidosis diagnosis in unconfirmed or unclear cases.

Microvascular damage evaluation based on nailfold videocapillarosopy in sarcoidosis.

Microvascular damage is thought to play a role in the pathogenesis of sarcoidosis. We aimed to evaluate the nailfold capillaroscopy (NVC) pattern to detect microvascular changes in patients with sarcoidosis and the relationship of capillaroscopic parameters with clinical variables and disease-related measurements. Forty-two patients with sarcoidosis and 42 age- and sex-matched patients with systemic sclerosis (SSc) and healthy individuals were included in this cross-sectional case-control study. Patients aged 18-80years who met the current American Thoracic Society criteria for sarcoidosis were included. NVC was performed by a digital microscope under a magnification of × 200. Capillary density, number of dilated, giant and neoangiogenic capillaries, capillary loop diameter, capillary shape, micro-hemorrhages, and number of avascular areas, were evaluated by an assessor who was blind to the groups allocation. Among the capillaroscopic parameters, neoangiogenesis and dilated capillaries, which can be seen in the pattern of scleroderma, were detected in patients with sarcoidosis but not significantly different from the control group (p = 0.055; p = 0.433, respectively). The rate of tortuosity and crossing capillaries of 50% and above was significantly higher in the sarcoidosis group than in SSc and healthy controls (p < 0.05). In patients with sarcoidosis, the only statistically significant finding was; forced expiratory volume (FEV1) in one second was lower in patients with a crossed capillary rate > 50% than in patients with a crossed capillary rate of less than 50% (FEV1; 87.21 ± 19.3, 102.5 ± 14.8, p = 0.04; respectively). Patients with a diagnosis of sarcoidosis have different capillaroscopic patterns. The presence of these nonspecific abnormal patterns may reflect microvascular damage in the pathophysiology of sarcoidosis. Key Points • Microvascular damage may play a role in the pathogenesis of sarcoidosis. • There may be some nonspecific abnormal findings in capillaroscopy findings in sarcoidosis. • Capillaroscopy may be valuable in reflecting sarcoidosis lung injury.

Lung Transplantation Waitlist Mortality Among Sarcoidosis Patients by Lung Allocation Score Grouping

The Lung Allocation Score (LAS) system was designed to equalize and minimize waitlist mortality among candidiates for lung transplantation. The LAS stratifies sarcoidosis patients by mean pulmonary arterial pressure (mPAP) into group A (mPAP ≤30 mm Hg) and group D (mPAP >30 mm Hg). In this study, we aimed to analyze the effect of diagnostic grouping and patient characteristics on waitlist mortality among sarcoidosis patients. This was a retrospective review of sarcoidosis lung transplantation candidates since LAS implementation in May 2005 through May 2019 in the Scientific Registry of Transplant Recipients database. We compared baseline characteristics, LAS variables, and waitlist outcomes between sarcoidosis groups A and D. We performed Kaplan-Meier survival analysis and multivariable regression to determine associations with waitlist mortality. We identified 1027 sarcoidosis candidates since LAS implementation. Of these, 385 had mPAP ≤30 mm Hg and 642 had mPAP >30 mm Hg. Waitlist mortality was 18% in sarcoidosis group D and 14% in sarcoidosis group A. Kaplan-Meier curve showed lower waitlist survival probability for sarcoidosis group D than group A (log-rank P=.0049). Functional status, oxygen requirement, and sarcoidosis group D were associated with increased waitlist mortality. Cardiac output ≥4 L/min was associated with decreased waitlist mortality. Sarcoidosis group D had lower waitlist survival than group A. Decreased survival appears driven by mPAP; sarcoidosis group D, functional status, oxygen requirement, and cardiac output had significant associations with waitlist mortality. These findings suggest that the current LAS grouping does not adequately reflect the risk for waitlist mortality among sarcoidosis group D patients.

Investigation of the value of hematological biomarkers in the clinical differential diagnosis of IgG4-RD.

IgG4- related disease (IgG4- RD) is a systemic fibroinflammatory disease whose pathogenesis has not been completely elucidated. Due to the novelty and complexity of the diagnostic criteria, it is difficult to distinguish from the diseases included in the differential diagnosis without tissue biopsy. This study aimed to discover new biomarkers that can help for disease diagnosis and its differential diagnosis by reviewing the relationships between neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). Thirty IgG4- RD, 38 granulomatous polyangiitis (GPA), and 46 sarcoidosis patients presenting to the Rheumatology Clinic meeting the criteria of 2019 American College of Rheumatology, 2012 International Chapel Hill and 1999 American Thoracic Society meeting, respectively, and 27 healthy control subjects were included. We collected data on complete blood count with automated differential values including NLR, PLR, SII, and SIRI. The SII and PLR values were significantly higher in patients with IgG4-RD compared to healthy controls, (SII median (minmax) 572 (102-5583) vs. 434 (172-897), PLR median (min-max) 130 (56.8-546) vs. 104 (57.5- 253) p < 0.001). SII value was found to have a significant positive correlation with CRP in IgG4-RD disease (r = 0.371; p = 0.043). While SII, SIRI, NLR, PLR parameters were not significant between the IgG4-RD and sarcoidosis groups, SII, SIRI, NLR, PLR were significantly higher in patients with GPA than in IgG4-RD patients (p < 0.001). This is the first study to review the SII, SIRI, NLR, and PLR in IgG4-RD. The obtained results suggest that the SII could beused as a new tool, for differential diagnosis and activity of the IgG4-RD.

Role of anti-tumor necrosis factor-alpha agents in treatment of sarcoidosis: A meta-analysis

ImportanceAnti-tumor necrosis factor-alpha agent (anti-TNF-α) is considered an effective third-line therapy for refractory sarcoidosis,studies observing the efficacy of anti-TNF-α agents show conflicting results. ObjectiveWe performed an up-to-date systemic meta-analysis to determine effectiveness and further elucidate the role of anti-TNF-α in the treatment of sarcoidosis. Data sourcesA systematic search was carried out in PubMed/Medline, EMBASE, and Cochrane Library for studies reporting the therapeutic effects of anti-TNF drugs on patients with pulmonary and extra-pulmonary sarcoidosis, published up to April 10, 2022. The study was registered in the international prospective register of systematic reviews (PROSPERO) under ID: CRD42022364614. Study selectionClinical trials written reporting the therapeutic effects of anti-TNF drugs on patients with pulmonary and extra-pulmonary sarcoidosis were included. Data extraction and synthesisStatistical analyses were performed with Comprehensive Meta-Analysis software, and the random-effects model was used. The combined overall treatment success was determined for patients with pulmonary and extrapulmonary sarcoidosis. Main outcomes and measuresOverall treatment success rate wasdefined as no disease progression or improvement in symptoms. ResultsEight clinical trial articles were included in the meta-analysis; four used Infliximab, two Etanercept, one Adalimumab, and one Ustekinumab and Golimumab. The mean age of participants was 48.5 years. The duration of drug therapy ranged from 14 to 45 weeks. We found a combined overall treatment success rate, defined as no disease progression or improvement in symptoms, of 69.9% (95% CI 35.0-90.9, I2: 70%) in the pulmonary sarcoidosis group and 74.5% (95% CI 36.3-93.7, I2: 90%) in the extrapulmonary sarcoidosis group. There was no evidence of publication bias in either group. Conclusion and relevanceTreatment of refractory sarcoidosis with anti-TNF-α agents was effective in both pulmonary and extrapulmonary sarcoidosis, with a slightly higher efficacy seen in extrapulmonary sarcoidosis. Further randomized controlled trials should be conducted to determine the effects of anti-TNF-α agents as a part of the management strategy of sarcoidosis. Patients with pulmonary sarcoidosis should be studied separately from patients with extrapulmonary sarcoidosis to adjust for confounding results.

The diagnostic utility of ultrasound elastography to differentiate tuberculosis and sarcoidosis during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).

Elastography is a non-invasive tool that may allow differentiation between benign and malignant lymph nodes during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). In tuberculosis (TB) endemic areas, clinicoradiological features of mediastinal TB and sarcoidosis often overlap, rendering an accurate diagnosis challenging. There is interest in the identification of modalities to aid in this differentiation. There are currently no published data on the utility of EBUS-elastography in differentiating between TB and sarcoidosis. Subjects undergoing EBUS-TBNA were prospectively enrolled, and elastography features were observed. Subjects with definitive diagnosis of TB or sarcoidosis were enrolled. The elastography features recorded included the three-colour classification patterns and strain ratio. We enrolled 96 subjects with a definitive diagnosis (53 with TB and 43 with sarcoidosis). Of the 27 patients in whom the lymph nodes were classified as type 1 on endobronchial ultrasound elastography colour pattern, 17 had a diagnosis of TB (62.9%), while 10 were sarcoidosis (37%). For type 2 lymph nodes, 20/45 (44.4%) were TB and 25/45 (55.6%) were sarcoidosis. Type 3 lymph nodes were TB in 16/24 (66.7%) and sarcoidosis in 8/24 (33.3%). In classifying type 1 as 'sarcoidosis' and Type 3 as 'tubercular', the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were 48.5%, 55.6%, 66.7%, 37%, and 0.51, respectively. The strain ratio (Median [IQR]) was 1.29 (0.37-5.98) in TB and 2.10 (0.83-4.52) in sarcoidosis group (P = 0.48). Ultrasound elastographic lymph node characteristics have a poor diagnostic utility to differentiate between TB and sarcoidosis during EBUS-TBNA.

Left atrial phasic volumes and functions changes in asymptomatic patients with sarcoidosis: evaluation by three-dimensional echocardiography

Background Cardiac involvement is the leading cause of morbidity and death in patients with sarcoidosis. However, many patients remain asymptomatic until the late-stage. In this study, we investigated the left atrial (LA) phasic volumes and functions changes by three-dimensional (3D) echocardiography measurements in asymptomatic patients with sarcoidosis, which has good correlation with cardiac magnetic resonance imaging. Methods In this cross-sectional study, 44 asymptomatic patients with sarcoidosis and 40 age, sex and BMI-matched healthy volunteers underwent two-dimensional (2D) and 3D-echocardiograpy. Standard echocardiographic and tissue Doppler imaging parameters were obtained. LA phasic volumes were assessed by 3D-echocardiography. From the 3D-echocardiography derived values, LA active, passive, and total emptying fraction (EF) were calculated. Results All left ventricular ejection fractions (LVEF) obtained by 2D and 3D-echocardiography were normal (≥50%). While LA diameters (33.36 ± 4.23 vs. 30.57 ± 5.43) and E/e’ septal annulus ratios (10.82 ± 1.79 vs. 9.27 ± 1.81) were significantly higher, A-wave (70.80 ± 5.81 vs. 74.51 ± 5.41) and e’septal annular velocities (6.48 ± 1.58 vs. 9.03 ± 1.63) were significantly lower in the sarcoidosis group as compared with control group, respectively. While 3D-echocardiography derived LA-minimum volume indices (LAVImin) (13.89 ± 2.75 vs. 12.23 ± 1.73) were significantly higher, 3D-echocardiography derived LA active EFs (AAEF) (30.78 ± 3.52 vs. 38.52 ± 4.75) and LA total EFs (TAEF) (47.71 ± 7.47 vs. 53.32 ± 5.81) were found to be significantly lower in the sarcoidosis group as compared with control group, respectively. Conclusion LAVImin, AAEF and TAEF calculated based on LA phasic volumes obtained by 3D-echocardiography may be promising indicators of subclinical cardiac involvement in asymptomatic patients with sarcoidosis.

Analysis of Association of Asp299Gln (rs 4986790) and Thr399Ile (rs 4986791) Polymorphisms of the &lt;i&gt;TLR4&lt;/i&gt; Gene with Risk of Developing Lung Sarcoidosis (Using the Example of Residents of Karelia)

The objective: to analyze the association of the Asp299Gln (rs 4986790) and Thr399Ile(rs 4986791) polymorphisms of the TLR4 gene with the risk of pulmonary sarcoidosis in the Russian population of the Republic of Karelia.Subjects and Methods. 253 people were examined: 122 patients diagnosed with morphologically verified sarcoidosis with lung involvement (average age – 41.00 ± 12.56 years) (Sarcoidosis Group) and 131 healthy donors (Control Group) (average age – 44.00 ± 14.23 years). All subjects in both groups considered themselves Russians by ethnicity, as reported in the survey. The distribution of alleles and genotypes by the polymorphic markers Asp299Gln (rs 4986790) and Thr399Ile (rs 4986791) of the TLR4 gene was studied in the group of patients with pulmonary sarcoidosis and the group of healthy individuals. Genotyping was carried out by PCR-RFLP.Results. There were no statistically significant differences in the distribution of allele and genotype frequencies for the Asp299Gln (rs 4986790) and Thr399Ile (rs 4986791) polymorphic markers of the TLR4 gene between the group of patients with pulmonary sarcoidosis and the control group: (χ2 = 0, df = 1, p = 0.997 и χ2 = 1.0, df = 2, p = 0.606; χ2 = 0.785, df = 1, p = 0.376 и χ2 = 0, df = 2, p = 1.0).Conclusion. The polymorphic marker Asp299Gln (rs 4986790) and Thr399Ile (rs 4986791) of the TLR4 gene is not associated with the risk of pulmonary sarcoidosis in the Russian population of the Republic of Karelia.