Active Sarcoidosis Research Articles

Activation of mucosal-associated invariant T cells in the lungs of sarcoidosis patients

Although the pathogenesis of sarcoidosis is not fully understood, immunological characterization has elucidated highly polarized expression of the type 1 T helper cell response. Mucosal-associated invariant T (MAIT) cells are innate T cells that recognize bacterial riboflavin and rapidly produce cytokines such as interferon γ and tumor necrosis factor α. We prospectively evaluated the proportion of MAIT cells and the expression levels of cell surface markers in peripheral blood from 40 sarcoidosis patients and 28 healthy controls. MAIT cells in bronchoalveolar lavage fluid (BALF) were also examined in 12 sarcoidosis patients. In peripheral blood, the proportion of MAIT cells was lower (P = 0.0002), but the expression levels of CD69 and programmed death 1 on MAIT cells were higher in sarcoidosis patients than in healthy controls. Moreover, CD69 expression levels were significantly correlated with clinical biomarkers. Sarcoidosis patients with parenchymal infiltration in the lungs showed a significantly higher proportion and number of MAIT cells in BALF compared to patients without parenchymal infiltration. CD69 expression levels on MAIT cells in BALF were higher than levels in peripheral blood. The activation status of MAIT cells might reflect the disease activity of sarcoidosis. Therefore, it is a potential target for sarcoidosis treatment.

Treatment of Active Cardiac Sarcoidosis with TNF Alpha Inhibitors

Background Cardiac sarcoidosis (CS) is associated with significant morbidity and mortality including progressive heart failure and sudden cardiac death. High-dose steroid immunosuppression remains standard of care for CS but there is a lack of randomized clinical trial data. As a result, there remains significant treatment variability among specialized centers. TNF alpha inhibitors are widely used for other inflammatory diseases and are generally well tolerated. However, little data, if any, exists regarding their utility in CS. TNF alpha inhibitors are particularly attractive given the potential adverse effects of chronic glucocorticoid based immunosuppression. The purpose of this study was to explore the effectiveness of TNF alpha inhibitors in active CS. Methods We performed a retrospective analysis of patients with metabolically active CS (defined by increased FDG avidity by cardiac PET imaging) who were treated with TNF alpha inhibitors. All patients underwent follow up PET imaging. Disease activity was quantified by the number of left ventricular (LV) myocardial segments with FDG avidity (based on a 17 segment model of the LV). Adverse events related to therapy was also recorded. Results Nine patients treated with TNF alpha inhibitors were included in this analysis. Eight Patients received the TNF alpha inhibitor, infliximab, one patient received adalimumab. Eight of the nine patients had previously received prednisone for CS; four transitioned from prednisone to infliximab due to adverse effects of steroid use; three transitioned because of continued active CS despite steroid therapy; one patient exhibited recurrent cardiac FDG avidity after prednisone discontinuation and another declined steroid treatment. The number of LV myocardial segments with active CS decreased from 8.6 +/- 3.6 to 1.9 +/- 3.5 (p=0.001) after a mean treatment duration of 7 months of infliximab that represents a decline of FDG avid LV segments by 72%. There was no significant change in LV ejection fraction (45 +/- 15% to 50 +/- 11% after therapy, p=NS). Six of the nine patients had complete resolution of active CS, and two had partial improvement. One patient experienced pancytopenia felt possibly related to infliximab; no other obvious adverse events were observed. Conclusions In this retrospective cohort, TNF alpha inhibition lead to significant improvement in disease activity based on FDG PET imaging. Most patients demonstrated complete resolution of active CS with minimal adverse effects. Further investigation into the use of TNF alpha inhibitors for treating active CS is warranted.

Quantification of pulmonary disease activity in sarcoidosis measured with 18F-FDG PET/CT: SUVmax versus total lung glycolysis

Background18F-FDG PET/CT has proven to be a reliable tool for therapy monitoring in sarcoidosis. Previous PET studies investigated the SUVmax as a marker for disease activity. Total lung glycolysis (TLuG) is a new tool, quantifying the glycolysis of the entire lung. Since SUVmax represents the maximum activity in only one pixel, we hypothesize that TLuG is a more accurate marker for active pulmonary disease and predictor of response than SUVmax.MethodsIn this retrospective cohort study, 27 patients started on infliximab for refractory pulmonary sarcoidosis. Patients received infliximab intravenously monthly at a dose of 5 mg/kg. We performed a lung function test and an 18F-FDG PET/CT before initiation of infliximab and after 6 months of treatment. SUVmax and TLuG were determined in the pre- and post-scan. Change in lung function was correlated with the change in SUVmax and TLuG and was correlated to the initial SUVmax and TLuG to evaluate the predictive value of the initial metabolic activity.ResultsΔSUVmax significantly correlated with ΔFVC (r = − 0.497, p = 0.008) and with ΔFEV1 (r = − 0.467, p = 0.014). Furthermore, ΔTLuG significantly correlated with ΔFVC (r = − 0.430, p = 0.025), ΔFEV1 (r = − 0.532, p = 0.004) and ΔDLCOc (r = − 0.423, p = 0.039). Change in SUVmax and TLuG significantly correlated (r = 0.735, p < 0.001). Initial SUVmax significantly correlated with the change in FVC and DLCOc. In addition, initial TLuG significantly correlated with the change in FEV1 and DLCOc.A SUVmax > 7.5 at initiation of infliximab was predictive for 5% response in FVC, whereas SUVmax > 9.2 was predictive for 5% response in DLCOc. In addition, high TLuG > 4100 at initiation of infliximab was predictive for 5% response in FVC and FEV1 and TLuG > 4500 was predictive for response in DLCOc.ConclusionSUVmax and TLuG are equal in determining the response to infliximab in pulmonary sarcoidosis patients. Furthermore, SUVmax and TLuG at initiation of infliximab can predict change in lung function after treatment. Since TLuG is a more time-consuming tool, we recommend to use SUVmax of the lung parenchyma for response monitoring in pulmonary sarcoidosis.

Janus kinase inhibition induces disease remission in cutaneous sarcoidosis and granuloma annulare

Sarcoidosis and granuloma annulare (GA) are cutaneous granulomatous disorders that can be difficult to treat. There is evidence of underlying Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway activation in sarcoidosis, suggesting that JAK inhibition might be effective. To evaluate treatment with tofacitinib, a JAK inhibitor, in patients with recalcitrant sarcoidosis and GA. A prospective evaluation of tofacitinib in 4 consecutive patients with recalcitrant cutaneous sarcoidosis (n= 3) and generalized GA (n=1) was conducted. Immunohistochemical analysis of skin biopsy specimens from other patients with sarcoidosis (n=21) and GA (n=17) was performed to characterize patterns of JAK-STAT pathway activation. Tofacitinib resulted in a mean improvement in the baseline Cutaneous Sarcoidosis Activity and Morphology Instrument and Granuloma Annulare Scoring Index scores of 96% (standard deviation, 2%). Histologic resolution of disease was documented in all patients (3 out of 3) who had skin biopsies while receiving therapy. Constitutive STAT1 and STAT3 activation was observed in both sarcoidosis and GA, albeit in different patterns. Signal regulatory protein α may explain the differences in JAK-STAT signaling between sarcoidosis and GA. The study is limited by the small number of participants. Tofacitinib resulted in dramatic improvement in 4 patients with cutaneous sarcoidosis and GA. Larger studies are underway to better understand this effect.

Cathepsin S, a new serum biomarker of sarcoidosis discovered by transcriptome analysis of alveolar macrophages.

Development of reliable new biomarkers remains crucial to improve diagnosis and assessing disease activity in sarcoidosis. The objective of this study was to seek such markers from the gene expression signature of alveolar macrophages by transcriptome analysis. Pooled RNA extracted from alveolar macrophages from patients with active sarcoidosis and control patients was subjected to transcriptome analysis using microarrays. Expressed gene intensity in sarcoidosis relative to that in control was calculated. We measured serum cathepsin S (CTSS) concentrations in 89 healthy volunteers, 107 patients with sarcoidosis, 26 with interstitial pneumonia, 150 with pneumoconiosis, and 76 with pulmonary mycobacteriosis by the enzyme-linked immunosorbent assay. Among 12 genes with ratios higher than that of a housekeeping gene, we selected CTSS for scrutinizing protein expression in serum because of the feasibility of the protein assay. CTSS concentrations were significantly increased in sarcoidosis compared with not only controls but also all the other lung diseases. Receiver operating characteristics curve for sarcoidosis and parenchymal lung diseases revealed an area under the curve of 0.800 (95% confidence interval, 0.751-0.850; p=1.4 x 10-18) with 70% sensitivity and 78% specificity at a CTSS concentration of 15.5 ng/ml. A significant trend was identified between CTSS concentrations and the number of affected organs. Serum CTSS concentrations varied in parallel with clinical courses both spontaneously and in response to corticosteroid therapy. Epithelioid cells in granulomas were positive for immunohistochemical staining with CTSS. CTSS has the potential to be a useful biomarker in sarcoidosis.

Physical Inactivity in Pulmonary Sarcoidosis

PurposeReduced physical activity in many chronic diseases is consistently associated with increased morbidity. Little is known about physical activity in sarcoidosis. The aim of this study was to objectively assess physical activity in patients with pulmonary sarcoidosis and investigate its relationship with lung function, exercise capacity, symptom burden, and health status.MethodsPhysical activity was assessed over one week in 15 patients with pulmonary sarcoidosis and 14 age-matched healthy controls with a tri-axial accelerometer (ActivPal™) and the International Physical Activity Questionnaire (IPAQ). All participants underwent pulmonary function tests, 6-min walk test (6MWT) and completed the Fatigue Assessment Scale (FAS), Medical Research Council (MRC) Dyspnoea Scale and the King’s Sarcoidosis Questionnaire (KSQ).ResultsPatients with sarcoidosis had significantly lower daily step counts than healthy controls; mean (SD) 5624 (1875) versus 10,429 (2942) steps (p < 0.01) and a trend towards fewer sit-to-stand transitions each day (p = 0.095). Only two patients (13%) self-reported undertaking vigorous physical activity (IPAQ) compared to half of healthy individuals (p < 0.01). Daily step count was significantly associated with 6MWT distance in sarcoidosis (r = 0.634, p = 0.01), but not with forced vital capacity (r = 0.290), fatigue (r = 0.041), dyspnoea (r = −0.466) or KSQ health status (r = 0.099–0.484). Time spent upright was associated with fatigue (r = −0.630, p = 0.012) and health status (KSQ Lung scores r = 0.524, p = 0.045), and there was a significant correlation between the number of sit-to-stand transitions and MRC dyspnoea score (r = −0.527, p = 0.044).ConclusionPhysical activity is significantly reduced in sarcoidosis and is associated with reduced functional exercise capacity (6MWD). Fatigue, exertional symptoms and health status were more closely associated with time spent upright and the number of bouts of physical activity, as compared to step counts. Further studies are warranted to identify the factors that determine different physical activity profiles in sarcoidosis.

Identification of Active Sarcoidosis Using Chitotriosidase and Angiotensin-Converting Enzyme.

Activity/remission differentiation is a great challenge in the follow-up and treatment of sarcoidosis patients. Angiotensin-converting enzyme (ACE) and high sensitivity C-reactive protein (hs-CRP) were proposed as sarcoidosis biomarkers. More recently, chitotriosidase (CHITO) has been described as a better alternative. This study has the aim to evaluate the association of CHITO activity, ACE, hs-CRP or a combination of these biomarkers and to construct a clinical algorithm to differentiate between sarcoidosis activity/remission status. Forty-six patients with either active sarcoidosis or sarcoidosis in remission and 21 healthy individuals were included. ACE, hs-CRP, and CHITO were evaluated in serum samples. Comparisons of the laboratory variable means among groups were performed by linear models. The cutoff points of the biomarkers for activity/remission differentiation were calculated using the Youden's index. Biomarker cutoff points and decision tree classifier (DTC) performance were estimated by their leave-one-out cross-validation (LOOCV) accuracy (Acc), sensitivity (Se), and specificity (Sp). A 55% mean Se and a 100% mean Sp were found for CHITO, while an 88% Se and a 47% Sp were found for ACE, and a 66% Se and a 68% Sp for hs-CRP cutoff points for activity/remission differentiation. The DTC algorithm with CHITO, hs-CRP, and ACE information had an LOOCV mean Acc of 82%, Se of 78%, and Sp of 89% for sarcoidosis activity/remission differentiation. The algorithm involving CHITO, hs-CRP, and ACE could be a suitable strategy for differentiation between sarcoidosis activity/remission status.

Radiologic Manifestations of Musculoskeletal Sarcoidosis.

The purpose of this review article is to present the spectrum of abnormalities and multi-modality imaging evaluations in patients with musculoskeletal sarcoidosis. The articular manifestations of sarcoidosis are difficult to distinguish from those of the other inflammatory and degenerative arthropathies, and the muscular lesions in sarcoidosis are generally clinically silent and therefore often missed. Magnetic resonance imaging has shown these manifestations to be very common in active sarcoidosis, and should thus be included in the screening if musculoskeletal sarcoidosis is suspected. The clinician should consider magnetic resonance imaging for the evaluation of patients with sarcoidosis who have unexplained osteoarticular complaints if standard radiographs are negative. Furthermore, radiologists should include sarcoidosis in the differential diagnosis of musculoskeletal disease detected at magnetic resonance imaging in the appropriate clinical setting.

Pulmonary sarcoidosis as a cause of intermittent fever of unknown origin in a hemodialysis patient with renal cell carcinoma: A case report and literature review

Hemodialysis patients have weakened immune systems and can exhibit fever due to various causes. Herein, we describe the case of a 61-year-old hemodialysis patient who exhibited intermittent low-grade fever after a pacemaker had been implanted 2 months before due to sick sinus syndrome. She had a medical history of subcutaneous sarcoidosis and uveitis. Active pulmonary sarcoidosis was diagnosed based on elevated soluble interleukin-2 receptor, elevated lysozyme level, and gallium-67 scintigraphy uptake in hilar and mediastinal lymph nodes. She was also diagnosed with renal cell carcinoma via contrast computed tomography. However, because her C-reactive protein level remained normal, the possibility of neoplastic fever was considered low. After the initiation of prednisolone administration, her fever gradually disappeared. Her serum soluble interleukin-2 receptor and lysozyme level improved in parallel with the enlargement of the mediastinal lymph node and gallium-67 scintigraphy uptake.

IL-13-regulated Macrophage Polarization during Granuloma Formation in an In Vitro Human Sarcoidosis Model.

The mechanisms underlying abnormal granuloma formation in patients with sarcoidosis are complex and remain poorly understood. A novel in vitro human granuloma model was used to determine the molecular mechanisms of granuloma genesis in patients with sarcoidosis in response to putative disease-causing mycobacterial antigens. Peripheral blood mononuclear cells (PBMCs) from patients with active sarcoidosis and from normal, disease-free control subjects were incubated for 7 days with purified protein derivative-coated polystyrene beads. Molecular responses, as reflected by differential expression of genes, extracellular cytokine patterns, and cell surface receptor expression, were analyzed. Unbiased systems biology approaches were used to identify signaling pathways engaged during granuloma formation. Model findings were compared with human lung and mediastinal lymph node gene expression profiles. Compared with identically treated PBMCs of control subjects (n = 5), purified protein derivative-treated sarcoidosis PBMCs (n = 6) were distinguished by the formation of cellular aggregates resembling granulomas. Ingenuity Pathway Analysis of differential expression gene patterns identified molecular pathways that are primarily regulated by IL-13, which promotes alternatively activated (M2) macrophage polarization. M2 polarization was further demonstrated by immunohistochemistry performed on the in vitro sarcoidosis granuloma-like structures. IL-13-regulated gene pathways were confirmed in human sarcoidosis lung and mediastinal lymph node tissues. The in vitro human sarcoidosis granuloma model provides novel insights into early granuloma formation, particularly IL-13 regulation of molecular networks that regulate M2 macrophage polarization. M2 macrophages are predisposed to aggregation and multinucleated giant cell formation, which are characteristic features of sarcoidosis granulomas. Clinical trial registered with www.clinicaltrials.gov (NCT01857401).

Peripheral blood B cell subsets from patients with various activity of chronic sarcoidosis

Sarcoidosis is an inflammatory disease of unknown etiology, characterized by development of necrosis-free epithelioid cell granulomas, resulting in hyperactivation of various of the immune system. The role of humoral mechanisms in the pathogenesis of sarcoidosis is less studied than cell-mediated. It is necessary to study the role of activation or the anergy of the B cell development of immunity in sarcoidosis, the degree of its activity and the characteristics of the clinical course of the disease. Our study was aimed at investigating the characteristics of the B subsets in the peripheral blood of patients with chronic sarcoidosis (n = 41), depending on the activity of the disease. The control was peripheral blood samples from healthy volunteers (n = 43). Objective clinical and instrumental criteria, angiotensin converting enzyme (ACE) were used to determine the activity of the disease. Using flow cytometry analysis of peripheral blood cell B were determined based on two approaches: expression of IgD/CD38 (“Bm1-Bm5” classification) and IgD/CD27. In patients with sarcoidosis there was a significantly higher relative number of Bm2 activated naive cells (IgD + CD38 + ) than in conditionally healthy volunteers, 65.38% versus 55,66% (p < 0.001). The relative and absolute contents of eBm5 (IgD - CD38 + ) and Bm5 (IgD - CD38 + ) memory were significantly lower in the group of patients with sarcoidosis relative to the control group. Relative values: 6.59% versus 13.31%, (p < 0.001), and 3.43% versus 8.49%, (p < 0.001), respectively. It was shown that with an increased level of ACE in the peripheral blood of patients, the number of naive Bm1 (IgD + CD38 - ) was significantly reduced, r = -0.557, p < 0.001. The relative content of memory B that did not switch the class of synthesized antibodies (IgD + CD27 + ) in the group of patients was reduced to 6,25%, and in the control group — 12,95% (p<0.001). The number of memory that switched the class of synthesized antibodies (IgD - CD27 + ) was also significantly reduced in patients with sarcoidosis and amounted to 6.75% versus 16.50% in the control group (p < 0.001). In patients with high levels of ACE, there was an increase in the relative content of naive B (IgD + CD27 - ), r = 0.532, p < 0.001. An inverse relationship was established between the number of memory B (IgD + CD27 + ) and ACE levels, r = -0.565, p < 0.001. These results indicate the important role of the B cell immune response in the pathogenesis of sarcoidosis and make it possible to evaluate the characteristics of the humoral response with various degrees of disease activity.

Hybrid Imaging in Evaluation of Abdominal Sarcoidosis.

To determine the prevalence of abdominal involvement, distribution pattern and evaluate role of hybrid molecular imaging in patients with abdominal sarcoidosis. Between January 2010 and December 2011, 98 patients with chronic sarcoidosis and presence of prolonged symptoms or other findings suggestive of active disease were referred to FDG PET/CT examination. Active disease was found in 82 patients, and they all were screened for the presence of abdominal sarcoidosis on FDG PET/CT. All patients also underwent MDCT and assessment of serum ACE level. Follow up FDG PET/CT examination was done 12.3±5.4 months after the baseline. Abdominal sarcoidosis was present in 31/82 patients with active sarcoidosis. FDG uptake was present in: retroperitoneal lymph nodes (77%), liver (26%), spleen (23%), adrenal gland (3%). Majority of patients had more than two locations of disease. Usually thoracic disease was spread into the extrathoracic localizations, while isolated abdominal sarcoidosis was present in 10% of patients. After first FDG PET/CT examination therapy was changed in all patients. Eleven patients came to the follow up examination where SUVmax significantly decreased in the majority of them. Three patients had total remission, three had absence of abdominal disease but discrete findings in thorax and others had less spread disease. ACE levels did not correlate with SUVmax level. FDG PET/CT can be a useful tool for detection of abdominal sarcoidosis and in the evaluation of therapy response in these patients. Awareness of the presence of intra-abdominal sarcoidosis is important in order to prevent long-standing unrecognized disease.

QuantiFERON-TB-GOLD In-Tube in Patients with Sarcoidosis

Sarcoidosis and tuberculosis (TB) are the diseases that share many similarities. Mycobacterium tuberculosis (MTB) culture results are the gold standard for the diagnosis of TB, but false positive results are not rare. The aim was to evaluate the utility of QFT in detecting latent TB infection in a group of sarcoidosis patients with negative history of TB and negative culture/BACTEC results, and checking sarcoidosis activity influence on the QFT results. Additionally, we assessed if QFT negative result may strengthen the suspicion that positive culture/BACTEC results are false positive. 37 culture-negative and 6 culture-positive sarcoidosis patients were enrolled. On the basis of clinical and radiological data TB was considered unlikely (false-positive results). A control group consisted of age-matched subjects with excluded TB (n = 37). QuantiFERON-TB GOLD In-Tube (QIAGEN, USA) was used according to the manual. Test validity was checked basing on the results obtained from a low-risk (n = 21) and active TB group (n = 23). The frequency of positive results tended to be higher in MTB(-) sarcoidosis (24.3% vs. 13.5% for the control group, p = 0.37), but was similar to the general population. None of culture-positive sarcoidosis patients was QFT-positive. The positive results were equally distributed among patients with active and inactive sarcoidosis. QFT has been found to be the useful test for the detection of latent TB infection in sarcoidosis patients. In addition, we confirm that sarcoidosis activity does not negatively influence the result of QFT. Moreover, QFT would be proposed as a cost-saving diagnostic test providing additional diagnostic information when false positive MTB culture result in the sarcoidosis patient is highly suspected. However, in each case clinical, radiological and epidemiological data should be considered before taking the therapeutic decision.

DON’T LET THE DRY MOUTH FOOL YOU

SESSION TITLE: Signs and Symptoms of Chest Disease SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Sarcoidosis is a well-known though poorly understood disease process with a multitude of manifestations. Clinicians should be aware of the diverse manifestations, as any evidence of active sarcoidosis requires consideration for treatment. We present a case of Mikulicz syndrome, a rare presentation of sarcoidosis in which the parotid and lacrimal glands are infiltrated by granulomas with resulting dry mouth, dry eyes and occasionally recurrent fevers. CASE PRESENTATION: The patient is a thirty-seven-year-old African-American female with a history of pulmonary and dermatologic sarcoidosis. She was diagnosed after a skin biopsy revealed noncaseating granulomas in the setting of chronic dyspnea with bilateral hilar lymphadenopathy. Systemic glucocorticoids were initiated with improvement in her dyspnea and skin lesions. Over the next several years, she did not tolerate weaning attempts and experienced frequent flares requiring escalating doses of methotrexate and glucocorticoids that led to significant side effects to include diabetes, obesity and bilateral hip avascular necrosis. Ultimately, her dyspnea and cough resolved on methotrexate and her skin lesions improved with a combination of intralesional triamcinolone injections and hydroxychloroquine with successful weaning off of her steroids. However, in subsequent visits, she reported swelling in her jaw along with a dry mouth with no recurrent skin lesions or dyspnea. On exam, enlargement of the parotid and lacrimal glands was recognized as Mikulicz syndrome. As a result, adalimumab was initiated with resolution of her symptoms. DISCUSSION: Mikulicz syndrome is a rare presentation of sarcoidosis, occurring in only 2% of patients with systemic sarcoidosis. It can easily be overlooked or attributed to a different disease process such as Sjogren’s syndrome, IgG4 related disease, lymphoma, vasculitis and HIV. However, it has been associated with significant symptoms affecting quality of life and most importantly represents active disease that requires consideration of treatment. In this case, the early recognition of Mikulicz syndrome led to appropriate treatment with a TNF-alpha antagonist that otherwise may not have been started as her skin and pulmonary sarcoid was relatively quiescent. CONCLUSIONS: Sarcoidosis can present with symptoms in nearly any organ system with significant impact on treatment course and quality of life. Providers who routinely treat sarcoid should be aware of the diverse manifestations of the disease, including the relatively rare presentations like Mikulicz syndrome as they may alter treatment strategy. Reference #1: Ungprasert, Patompong, Cynthia S. Crowson, and Eric L. Matteson. "Clinical characteristics of parotid gland sarcoidosis: a population based study.” JAMA otolaryngology--head & neck surgery 142.5 (2016): 503. Reference #2: Rao, Dinesh, et al. "A Case Report of Mikulicz Syndrome.” Journal of radiology case reports 11.7 (2017): 1. DISCLOSURES: No relevant relationships by Arthur Holtzclaw, source=Web Response No relevant relationships by John Sherner, source=Web Response

Relationship between CT activity score with lung function and the serum angiotensin converting enzyme in pulmonary sarcoidosis on chest HRCT.

To address the reliability of CT activity score (CTAS) and investigate the relationships between CTAS, lung function changes after treatment and the serum angiotensin-converting enzyme (SACE) levels.Fifty-seven sarcoidosis patients underwent chest high-resolution CT (HRCT) and spirometry, as well as SACE examination, were retrospectively analyzed. Follow-up spirometry in each patient was obtained about 6 months after the initial spirometry. The correlations between CTAS and pulmonary function changes were evaluated by Spearman correlation analysis. According to SACE status, patients were divided into normal and high level 2 subgroups. Comparisons of pulmonary function parameters, HRCT abnormalities extent scores between SACE normal and high 2 subgroups were performed with the Mann–Whitney U test or Independent samples t test.CTAS demonstrated significant correlations with lung function changes (Δ%VC: ρ= 0.543, P < .001; ΔFEV1.0/FVC:ρ = 0.417, P = .001; Δ%TLC: ρ = 0.309, P = .019). In addition, worse initial lung function, larger changes of lung function, and higher extent scores of HRCT were observed in SACE high-level subgroup.The findings of this study suggest that CTAS of initial HRCT is a promising index for disease activity in pulmonary sarcoidosis to some degree. Prospective studies with large cohort designed to address further verification are warranted before wide clinical practice.

PET/CT in the Diagnosis and Workup of Sarcoidosis: Focus on Atypical Manifestations

Sarcoidosis is a multisystem disease characterized by the formation of noncaseating granulomas. Lung and intrathoracic lymph nodes are classic sites of involvement; however, sarcoidosis can affect any site in the body. The clinical course is extremely variable, and the imaging features are diverse and dependent on the affected site, degree of inflammation, and treatment the patient receives. Atypical manifestations and imaging findings can make diagnosis and/or management challenging. In addition, assessment of treatment response can be difficult in the setting of chronic disease. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT is sensitive for assessment of the inflammatory activity of sarcoidosis in any organ. Although FDG PET/CT is not included in the standard workup for sarcoidosis, there has been growing evidence that supports the value of this examination in guiding diagnosis and management. FDG PET/CT may be especially useful for assessing reversible granuloma, treatment response, disease extent, occult disease, and cardiac or osseous sarcoidosis, and determining the most suitable biopsy site. Capability to image the entire body during a single examination is advantageous in cases of systemic disease such as sarcoidosis. The authors review the use of FDG PET/CT, providing up-to-date evidence and describing various cases of sarcoidosis in which FDG PET/CT has an important role in diagnosis and/or management. They also discuss the usefulness of FDG PET/CT in cases of selective manifestations of sarcoidosis. ©RSNA, 2018.

Gallium-68 DOTA-NOC PET/CT as an alternate predictor of disease activity in sarcoidosis.

We evaluated the role of gallium-68-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide (Ga-DOTA-NOC) PET/CT in assessing sarcoidosis disease activity. Patients diagnosed with sarcoidosis underwent Ga-DOTA-NOC-PET/CT. The maximum standardized uptake value (SUVmax) at the pathological site and in the descending thoracic aorta (reference standard, SUVmed) were assessed. A SUVmax/SUVmed ratio (disease activity score) of more than one was considered a marker of active disease and was compared with the clinical symptoms and serum angiotensin-converting enzyme and computed tomography (CT) scan. The primary outcome was to assess the efficacy of the scan in estimating disease activity. Of the 39 patients enrolled in the study, 27 patients were symptomatic and the rest were asymptomatic at enrollment. Increased disease activity was present in 25 (92%) of the 27 symptomatic patients and two (16%) of the 12 asymptomatic patients. The sensitivity and specificity of the test were 92.5% (95% confidence interval=75.7-99.0) and 83.3% (95% confidence interval=51.5-97.9), respectively. Seven out of nine patients who became asymptomatic after treatment showed a significant decrease in the mean disease activity score in post-treatment scans (3.38±1.05 vs 1.20±0.82, P<0.001). Ga-DOTA-NOC PET/CT emerged as a useful tool to assess the disease activity and treatment response in patients with sarcoidosis with thoracic involvement.

Significant elevation of the levels of B-cell activating factor (BAFF) in patients with sarcoidosis.

B-cell activating factor (BAFF) plays an important role in the survival and differentiation of B-cells and production of antibodies. Recent studies show that the serum BAFF levels are elevated in patients with sarcoidosis; however, they have not studied the relationship of the finding with the clinical features of the disease. The purpose of the present study is to analyze the BAFF and to elucidate the relationship between BAFF levels and the disease activity or severity of sarcoidosis. Eighty-eight patients with sarcoidosis and 21 healthy volunteers were enrolled in the present study. The BAFF levels were measured by an enzyme-linked immunosorbent assay. To assess the disease severity, we examined the number of affected organs, Schadding stages, respiratory function impairment (RFI), and the scoring system developed by Wasfi et al. The serum BAFF levels in sarcoidosis patients were significantly higher than those in healthy volunteers (median 1553.0 vs 984.6pg/ml, p < 0.001). There were positive correlations between the serum BAFF level and disease activity markers. In addition, there were positive correlations between the BAFF levels and the disease severity score in both the serum (R = 0.367, p < 0.001) and bronchoalveolar lavage fluid (BALF) (R = 0.376, p < 0.001). This study demonstrated that the BAFF levels in both the serum and BALF were positively correlated with the disease activity markers and disease severity. BAFF may be useful as an indicator of both the disease activity and severity.

Case Study: Cardiac sarcoidosis resolved with Mycobacterium avium paratuberculosis antibiotics (MAP).

Background: The author presents a clinical history and personal case study following his diagnosis of inactive sarcoidosis in 2004, followed by an acute episode of cardiac sarcoidosis (CS) in 2012 which resulted in complete heart block, cardiac myopathy, heart failure and insertion of an implantable cardioverter defibrillator (ICD) pacemaker. Methods: Following a detailed review of the clinical and scientific literature he concluded that sarcoidosis may be a mycobacterial infection and could be treated with anti-MAP antibiotic regime (1) developed to treat Crohn's disease. Findings: After successful culture and identification of viable MAP in his blood, treatment with the MAP antibiotic regime for one year led to complete metabolic resolution of the previously avid cardiac sarcoidosis and no PET evidence of any metabolically active sarcoidosis anywhere. Such reversal of cardiac sarcoidosis has never previously been reported. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 171-177).

Results of treatment and criteria of progress of respiratory organs sarkoidosis

The aim of the work. This research work is devoted to the development of new additional criteria for the activity of inflammatory process in sarcoidosis of respiratory organs. The goal is to assess the effectiveness of performed treatment of sarcoidosis of respiratory organs by using low-cost highly-sensitive inflammatory markers. Materials and methods. The study involved 68 patients with lung sarcoidosis before and after the three-month treatment. In addition to general-clinical methods of examination, in patients with sarcoidosis we also determined the levels of TNF-α and IL-2. Results. Patients with active lung sarcoidosis had 2.61 times (p<0.05) increased level of IL-2 in bronchoalveolar lavage fluid and 9.05 times (p<0.05) increased levels in peripheral blood serum; the levels of TNF-α increased by 4.98 times (p<0.05) in bronchoalveolar lavage fluid and by 3.2 times (p<0.05) in peripheral blood serum as compared to the findings in the control group of patients. The study showed that in the group of patients, where the efficacy of the prescribed therapy was noted, the level of IL-2 decreased by 2.08 times (p<0.05) in bronchoalveolar lavage fluid and by 3.76 times (p<0.05) in peripheral blood serum, and the concentration of TNF-α decreased by 3.87 times (p<0.05) in bronchoalveolar lavage fluid and by 2.06 times in peripheral blood serum as compared to the initial indices. Conclusions. The decrease of TNF-α level in bronchoalveolar lavage fluid on the background of three-months treatment correlated (r=0.84; p<0.05) to the changes in peripheral blood serum; at the same time the decrease of TNF-α level in peripheral blood serum correlated (r=0.89; p<0.05) to the decrease of IL-2 in peripheral blood serum of patients with sarcoidosis of respiratory organs