Sarcoidosis Patients Research Articles

Critical ablation targets of ventricular tachycardia revealed by activation mapping with both last deflection and peak frequency annotations in a patient of cardiac sarcoidosis

Critical ablation targets of ventricular tachycardia revealed by activation mapping with both last deflection and peak frequency annotations in a patient of cardiac sarcoidosis

Evaluation of myocardial work indexes in patients with cardiac sarcoidosis

Abstract Background Cardiac involvement is associated with worse prognosis and mortality in sarcoidosis. Diagnosis often requires expensive and less available tests. Purpose The aim of this study is to evaluate whether non-invasive measurement of myocardial work by transthoracic echocardiogram has incremental value in the diagnosis of cardiac involvement compared to left ventricular (LV) global longitudinal strain (GLS). Methods This is a cross-sectional, non-blinded, single-center pilot study. Patients of both genders > 18 years old, with confirmed diagnosis of cardiac sarcoidosis according to the Heart Rhythm Society criteria, and controls consisting of individuals diagnosed with systemic sarcoidosis without cardiac involvement, were included. Patients with obesity grade 2 or higher , moderate or severe primary heart valve disease, myocardial diseases of other etiologies, established coronary artery disease, and inadequate acoustic window were excluded. All patients underwent transthoracic echocardiography and non-invasive blood pressure measurement, followed by subsequent analysis involving the construction of a pression-strain curve. The following LV indexes were calculated: GLS, global work index, global constructive work, global wasted work, and global work efficiency. ROC curves were calculated for all variables using the EasyROC online tool (v 1.3.1), and these were later compared to GLS. Confidence intervals were established by the DeLong method, and curves were compared by the Bonferroni method. A two-tailed p value of 0.05 was considered significant. Results Twenty patients with cardiac involvement and twenty patients without cardiac involvement were evaluated. The results of the variables are presented in table 1. Conclusions With exception of wasted work, all other LV myocardial work variables showed statistical correlation with cardiac involvement in sarcoidosis patients. However, there was no incremental value of myocardial work indexes compared to the isolated use of GLS.

Prevalence of cardiovascular complications and factors associated with higher case-fatality rate among hospitalized patients with sarcoidosis

Abstract Background Cardiovascular (CV) involvement is a serious complication of sarcoidosis with exaggerated morbidity and mortality. However, the prevalence of CV comorbidities and their case-fatality rate have not been established among hospitalized patients with sarcoidosis. Methods Using the National Inpatient Sample (NIS) database, hospitalized patients with a diagnosis of sarcoidosis were identified. The prevalence of each CV comorbidity and the associated case-fatality rate was determined among this population of patients. Results Data of 406,315 admission cases with a diagnosis of sarcoidosis was analyzed from 2016 to 2020. Of this, 13,950 patients (3.4%) had AMI (STEMI: 0.3% and NSTEMI: 2.3%), 121,515 patients (30%) had HF (HFrEF: 8% and HFpEF: 13%), 7,470 patients (1.8%) had CVA, 8,825 patients had sarcoid myocarditis (2.2%), 8,965 patients (5.6%) had PVD, 71,815 patients had Afib (17.7%), 46,775 patients (11.5%) had cardiorenal syndrome, and 3,905 patients (1%) developed cardiac arrest. Case-Fatality rate was the highest for sarcoidosis patients who developed cardiac arrest (61.4%), followed by STEMI (11.6%), NSTEMI (7.7%), and cardiac tamponade (7.8%). Increasing age (2% for each year), male gender (14% more than females), and black race (25%) but not economic status was associated with increased odds of death among patients with sarcoidosis. While PCI was associated with a lower mortality rate (aOR: 0.4, 95%CI:0.2-0.7, P=0.005), revascularization with CABG (aOR: 0.3, 95% CI: 0.1-1.2, P=0.08) did not reduce the mortality rate. Conclusion Atrial fibrillation, heart failure (HFpEF > HFrEF), and cardiorenal syndrome are the most common cardiovascular complications among hospitalized patents with sarcoidosis. However, case-fatality rate is significantly higher for other less prevalent cardiovascular comorbidities of sarcoidosis, which include cardiac arrest, acute myocardial infarction (STEMI > NSTEMI), and cardiac tamponade.

Sarcoid Nodule or Lung Cancer? A High-Resolution Computed Tomography-Based Retrospective Study of Pulmonary Nodules in Patients with Sarcoidosis

Background: The objective of this retrospective study was to compare the characteristics of sarcoid nodules and neoplastic nodules using high-resolution computed tomography (HRCT) in sarcoidosis patients. Methods: This is a single-center retrospective study. From 2010 to 2023, among 685 patients affected by pulmonary sarcoidosis, 23 patients developed pulmonary nodules of a suspicious malignant nature. The HRCT characteristics of biopsy-proven malignant (Group A) vs. inflammatory (Group B) nodules were analyzed and compared. Results: A significant difference was observed between the groups in terms of age (p = 0.012). With regard to HRCT features, statistical distinctions were observed in the appearance of the nodule, more frequently spiculated in the case of lung cancer (p < 0.01), in the diameter of the nodule (Group A: 23.5 mm; Group B: 12.18 mm, p < 0.02), in the median nodule density (Group A: 60.0 HU, Group B: −126.7 HU, p < 0.01), and in the number of pulmonary nodules, as a single parenchymal nodule was more frequently observed in the neoplastic patient group (p = 0.043). In Group A, the 18-PET-CT demonstrated hilar/mediastinal lymphadenopathy in 100% of cases; histology following surgery did not report any cases of malignant lymph node involvement. Conclusions: An accurate clinical evaluation and HRCT investigation are crucial for diagnosing lung cancer in patients with sarcoidosis in order to determine who requires surgical resection. The spiculated morphology of the nodule, greater size, the number of pulmonary nodules, and density using HRCT appear to correlate with the malignant nature of the lesion.

Outcomes of cardiac resynchronization therapy (CRT) in cardiac sarcoidosis patients with a range of ejection fractions.

In cardiac sarcoidosis (CS) patients, the benefit of cardiac resynchronization therapy (CRT) remains unclear. We sought to assess the short-term and long-term effects of CRT in CS patients with a range of left ventricular (LV) ejection fractions (LVEFs). Consecutive CS patients with heart failure with reduced ejection fraction (HFrEF; LVEF≤40%), mildly reduced ejection fraction (HFmrEF; LVEF 41%-49%) and preserved ejection fraction (HFpEF; LVEF≥50) treated with CRT under the care of a tertiary UK centre between 2008 and 2023 were reviewed. CRT response was defined by >5% improvement in serial LVEF. The primary endpoint was a composite of all-cause mortality, cardiac transplantation or unplanned hospitalization for decompensated heart failure. The secondary endpoint included ventricular arrhythmic events. Of the 100 patients enrolled (age 58±10years; 71% male), 63 had HFrEF, 17 had HFmrEF and 20 had HFpEF. After short-term follow-up (9.8±5.4months), HFrEF patients demonstrated significant LVEF response (P<0.01). On Kaplan-Meier analysis (follow-up 38±32months), HFrEF non-responders had significantly worse event-free survival compared with HFrEF responders for the primary (P<0.001) and secondary (P=0.001) endpoints. Despite short-term LV function improvement, CRT responders still had worse event-free survival compared with HFmrEF/HFpEF patients for the primary endpoint (P<0.001). On multivariable Cox analysis, age [hazard ratio (HR) 1.05, 95% confidence interval (CI) 1.01-1.10, P=0.008] and HFrEF CRT non-response (HR 12.33, 95% CI 2.45-61.87, P=0.002) were associated with the primary endpoint. In CS patients with HFrEF, CRT response is associated with a better long-term prognosis than non-response. However, HFrEF CRT responders still have worse long-term prognosis than HFmrEF/HFpEF patients.

Neurosarcoidosis presenting as transient ischemic attacks: A Case Report

Sarcoidosis is a multi-organ granulomatous disease of unknown etiology characterized by the presence of non-caseating granulomas. It has the potential to affect multiple organs including the nervous system. Neurosarcoidosis is present in around 5% of sarcoidosis patients. The clinical manifestations of neurosarcoidosis are heterogeneous, as granulomas can affect the brain, spinal cord and peripheral nervous system, separately or in different combinations. We report a case of neurosarcoidosis with pulmonary involvement in a young female patient presented with multiple episodes of transient ischemic attacks (TIAs). She was treated with boluses of cyclophosphamide followed by azathioprine which led to marked clinical and radiological improvement.

Elevated serum angiotensin converting enzyme correlates with specific HLA-DRB1 alleles and extrapulmonary manifestations in sarcoidosis

BackgroundGenetics influence the clinical picture in sarcoidosis, a granulomatous heterogeneous disease often accompanied by elevated serum angiotensin converting enzyme (s-ACE). We aimed to investigate if certain HLA-DRB1 alleles correlate with the levels of s-ACE, known as a marker of the granuloma burden. MethodsMedical journals of patients with sarcoidosis from a Swedish clinical registry were retrospectively examined to extract the highest recorded s-ACE value and analysed in relation to patient characteristics including phenotype [Löfgren syndrome (LS)/ non-LS], chest X-ray staging according to Scadding, treatment with immunosuppressants, presence of extrapulmonary manifestations (EPM), HLA-DRB1 alleles and prognosis (resolving vs. non-resolving disease within 2 years). Data were analysed with Fisher's exact test and Bonferroni correction was applied for HLA analyses. ResultsOf 1204 patients included, 40% had s-ACE levels above reference value. In comparison with patients with normal s-ACE, those with elevated levels were more often classified into non-LS (78% vs 59%, p < 0.001), and Scadding stage II (50% vs 38%, p < 0.001) but less often Scadding stage I (33% vs 46%, p < 0.001) and had more often EPM (45% vs 23%, p < 0.001). The patients with HLA-DRB1×04 had more often elevated s-ACE (p < 0.01) while those with HLA-DRB1×03 commonly had normal levels (p < 0.001). ConclusionsIn this retrospective study, HLA alleles associated with s-ACE levels in sarcoidosis patients, which in turn correlated with occurrence of EPM. These findings shed some new light on possible mechanisms behind differences in s-ACE levels.

Nailfold Video-Capillaroscopy in Sarcoidosis: New Perspectives and Challenges.

Nailfold video-capillaroscopy (NVC) is a non-invasive cost-effective technique involving the microscopic examination of small blood vessels of the distal nailfold with a magnification device. It provides valuable information regarding the microcirculation including anomalies such as tortuous or dilated capillaries, hemorrhages, and avascular areas, which can characterize connective tissue diseases. The utility of NVC in the diagnosis and monitoring of systemic sclerosis (SSc) has been investigated in numerous studies allowing the distinction of the specific microvascular pattern of scleroderma from different conditions other than scleroderma (non-scleroderma pattern). Sarcoidosis (SA) is a systemic inflammatory disease that can affect various organs, including the lungs, skin, and lymph nodes. The purpose of our review was to evaluate the current state of the art in the use of NVC in the diagnosis of SA, to understand the indications for its use and any consequent advantages in the management of the disease in different settings in terms of benefits for patients. We searched for the key terms "sarcoidosis" and "video-capillaroscopy" in a computerized search of Pub-Med, extending the search back in time without setting limits. We provided a critical overview of the literature, based on a precise evaluation. After our analysis, we examined the six yielded works looking for answers to our questions. Few studies have evaluated that microcirculation is often compromised in SA, with alterations in blood flow and consequent tissue damage. Basing on highlighted findings, NVC appears to be a useful tool in the initial evaluation of sarcoidosis patients. Furthermore, capillaroscopy is useful in the evaluation of the coexistence of sarcoidosis and scleroderma spectrum disorder or overlap syndromes. In conclusions, no specific pattern has been described for sarcoidosis, and further re-search is needed to fully understand the implications of nailfold capillaroscopy find-ings in this disease and to establish standardized guidelines for its use in clinical practice.

Hydroxychloroquine monotherapy in sarcoidosis: Indications, efficacy, and side effects.

In sarcoidosis which is not threatening vital internal organs such as heart, central nervous system or lungs immunomodulatory treatment, such as hydroxychloroquine can be considered. Despite its common use, limited data are available regarding effectiveness and side effects as monotherapy in sarcoidosis. Recommendations on its usage are based on expert opinion as literature is scarce. This retrospective study examines real-world data about the indications, effectivity and side effects of hydroxychloroquine monotherapy in sarcoidosis patients with no damage to the vital internal organs. Successful treatment was defined as continuation after 24 weeks without step up therapy or worsening of symptoms. Sixty patients were eligible for the study. Starting dose was 400mg/day, lowered to 200mg/day after 3 months in most patients. The predominant treatment indications were musculoskeletal 45 (75%) and cutaneous involvement 13 (22%). Thirty-three patients (55%) continued treatment after 24 weeks. Twenty-four patients (40%) mentioned side effects, mainly gastrointestinal, leading to treatment discontinuation in eleven patients (18%). No severe side effects were seen. Continuation after 24 weeks was significantly higher in patients with cutaneous involvement compared to other indications 85% vs 47% respectively (p =0.02). Treatment with hydroxychloroquine monotherapy was satisfactory in 55% of patients, especially for cutaneous involvement. However, it poses considerable non-severe side-effects.

Central Nervous System Sarcoidosis: A National-Basedregistry study.

Sarcoidosis of the central nervous system (CNS) often presents deleterious effects on affected patients. Data and available literature discussing the diagnosis and treatment of this condition are scarce and inconsistent. In this study, we aim to shed light on demographics, management, diagnostics, and clinical complications of CNS sarcoidosis patients within the United States (US) based on a nation-wide registry questionnaire. Our retrospective study was conducted based on a national registry investigating 3,835 respondents to the Foundation for Sarcoidosis Research Sarcoidosis Advanced Registry for Cures Questionnaire (FSR-SARC). This national registry data was collected during the period of June 2014 to August 2019. We performed propensity score matching, summary, univariate, and multivariate analyses to establish a comparison between the presence and absence of central nervous system sarcoidosis. We identified a total of 420/3634 (11.55%) patients having CNS sarcoidosis; 296 (70.5%) were females, 307 (73.1%) were Caucasian and 81 (19.3%) were African American. The mean (±SD) age at diagnosis of CNS sarcoidosis was 43.3 (±12) years old. Multiorgan involvement (≥3 organs) was present in 318/420 (75.7%) patients. Brain magnetic resonance imaging was the most common ancillary diagnostic modality used and reported to be abnormal 251/328 (76.5%). Corticosteroids were the most used treatment by CNS sarcoidosis patients 206/420 (49.0%) followed by cytotoxic agents 180/420 (42.9%). CNS sarcoidosis prevalence in our cohort was similar to what has been described previously. The most prevalent imaging modality used was cranial MRI. Corticosteroids were the most used medications. Lastly, CNS sarcoidosis showed a propensity to cause several clinical complications such as chronic pain syndrome and disability.

Factors Associated with Corticosteroid Adherence in Sarcoidosis.

We measured corticosteroid medication adherence (CMA) in sarcoidosis patients and analyzed if demographic and clinical factors, beliefs about medications, corticosteroid side-effects, psychosocial status, and the doctor-patient relationship were associated with corticosteroid adherence. Sarcoidosis patients receiving corticosteroids were eligible to participate. CMA was measured using the Medication Adherence Response Scale-10 (MARS-10), a validated patient reported outcome measure (PRO). Data collection included patient demographics and clinical variables to assess their sarcoidosis phenotype. The patients were administered additional PROs concerning their psychosocial status, beliefs about medication use, corticosteroid side-effects and the strength of their doctor-patient relationship. 132 patients were enrolled. Their mean prednisone dose was 9.9 ± 7.5mg/day. 75% (99/132) were adherent with corticosteroids (MARS-10 ≥ 6) and 25% (33/132) were nonadherent (MARS-10 < 6). All demographic features, education level, and annual family income were not associated with CMA. Most clinical variables including spirometry, use of additional sarcoidosis drugs, number of organs involved with sarcoidosis were not associated with CMA. Almost all PROs including a better attitude toward medication use, less psychological issues, less corticosteroid side-effects, and a stronger doctor-patient relationship were associated with better CMA. A multi-logistic regression found that patient-doctor communication and the patient's intrinsic beliefs about the use of medications remained associated with CMA. We found no significant relationship between demographic or socioeconomic factors and CMA. Few clinical factors were associated with CMA. In a univariate analysis, CMA was associated with physician-doctor communication, beliefs about medication use, psychological/emotional issues, and corticosteroid side-effects. Only the first two of these factors remained associated with CMA in a multi-logistic analysis. These data suggest that CMA is heavily influenced by sarcoidosis patient beliefs about medications, and less so by patient demographics.

Effects of Azithromycin on Blood Inflammatory Gene Expression and Cytokine Production in Sarcoidosis

IntroductionIn sarcoidosis granulomas, monocyte-derived macrophages are activated by pro-inflammatory cytokines including TNF and IL-6. Current drug treatment for sarcoidosis aims to suppress inflammation but disabling side effects can ensue. The macrolide azithromycin may be anti-inflammatory. We aimed to determine whether treatment with azithromycin affects blood inflammatory gene expression and monocyte functions in sarcoidosis.MethodsBlood samples were collected from patients with chronic pulmonary sarcoidosis enrolled in a single arm, open label clinical trial who received oral azithromycin 250 mg once daily for 3 months. Whole blood inflammatory gene expression with or without LPS stimulation was measured using a 770-mRNA panel. Phenotypic analysis and cytokine production were conducted by flow cytometry and ELISA after 24h stimulation with growth factors and TLR ligands. mTOR activity was assessed by measuring phosphorylated S6RP.ResultsDifferential gene expression analysis indicated a state of heightened myeloid cell activation in sarcoidosis. Compared with controls, sarcoidosis patients showed increased LPS responses for several cytokines and chemokines. Treatment with azithromycin had minimal effect on blood gene expression overall, but supervised clustering analysis identified several chemokine genes that were upregulated. At the protein level, azithromycin treatment increased LPS-stimulated TNF and unstimulated IL-8 production. No other cytokines showed significant changes following azithromycin. Blood neutrophil counts fell during azithromycin treatment whereas mononuclear cells remained stable. Azithromycin had no detectable effects on mTOR activity or activation markers.ConclusionBlood myeloid cells are activated in sarcoidosis, but azithromycin therapy did not suppress inflammatory gene expression or cytokine production in blood.Trial registration: EudraCT 2019-000580-24 (17 May 2019)

Clinical phenotypes of sarcoidosis using cluster analysis: a Spanish population-based cohort study.

Sarcoidosis is a clinically heterogenous disease. The objective of this study is the identification of clinical phenotypes using cluster analysis. A model-based clustering relaying on 19 clinical variables was performed in a retrospective cohort of 342 sarcoidosis patients, diagnosed and followed-up from 1999 to 2019 in a tertiary hospital at Northern Spain. Chi-square test and ANOVA were used to compare categorical and continuous variables among groups. Two-sample t-tests and the partition of Pearson's chi-square statistic were used in pairwise comparisons. The Wasfi severity score was calculated and compared among clusters. Cluster analysis identified five groups: C1 (16.1%), C2 (14.3%), C3 (24.3%), C4 (5.0%), and C5 (40.4%). Lung involvement was predominant, ranging from 55.1% (C2) to 100% (C1 and C4). Extrapulmonary involvement was significantly higher in C2 (96.4%) and C3 (98.0%). A significant lower FEV1 percent predicted was detected in C5 (90.5±21.8) versus C1 (102.0±22.9), C3 (102.3±17.6) and C4 (105.8±20.8). The cluster 5 had a lower FVC percent predicted (96.6±18.9) than others, ranging from 108.1±18.0 (C3) to 111.5±21.7 (C4). The prescription of systemic glucocorticoids and non-corticosteroid immunosuppressants was higher in the clusters 1, 3 and 5. Chronicity rates were higher in C3 (31.3%) and C5 (32.6%) compared to C1 (9.1%) and C4 (0%), as well as the Wasfi severity score values. Five phenotypes with different clinical and prognostic characteristics are proposed in our study. Cluster analysis can be a useful tool for identifying clinical patterns in a disease as heterogeneous as sarcoidosis and optimising its management.

Comprehensive microRNA analyses using vitreous humor of ocular sarcoidosis.

MicroRNAs (miRNAs) are non-coding RNAs which have attracted attention as biomarkers in a variety of diseases. However, extensive unbiased analysis of miRNA in vitreous humor of sarcoidosis patients has not been reported. In the present study, we comprehensively analyzed the dysregulated miRNAs in ocular sarcoidosis to search for potential biomarkers. This study included seven patients diagnosed with ocular sarcoidosis (five definite and two presumed). Five patients with unclassified uveitis and 24 with non-inflammatory diseases served as controls. MicroRNA expression levels in vitreous humor samples were measured by microarray, and differentially expressed miRNAs between sarcoidosis and other diseases were explored. Next, pathway enrichment analysis was performed to evaluate the functions of the dysregulated miRNAs, and machine learning was used to search for candidate biomarkers. A total of 614 upregulated miRNAs and 8 downregulated miRNAs were detected in vitreous humor of patients with ocular sarcoidosis compared with patients with unclassified uveitis and non-inflammatory diseases. Some dysregulated miRNAs were involved in the TGF-β signaling pathway. Furthermore, we identified miR-764 as the best predictor for ocular sarcoidosis using Boruta selection. In this study, comprehensive miRNA analysis of vitreous humor samples identified dysregulated miRNAs in ocular sarcoidosis. This study suggests new insights into molecular pathogenetic mechanisms of sarcoidosis and may provide useful information toward developing novel diagnostic biomarkers and therapeutic targets for sarcoidosis.

Medical Therapy and Clinical Outcomes in Cardiac Sarcoidosis Patients With Systolic Heart Failure.

Cardiac sarcoidosis (CS) may result in systolic heart failure (heart failure with reduced ejection fraction [HFrEF]), but its response to guideline-directed medical therapy (GDMT) remains uncertain. We investigated 881 patients evaluated for CS to identify those with diagnosed CS, left ventricular ejection fraction (LVEF) ≤40% at diagnosis, and follow-up echocardiogram within 11-24 months. Demographics, LVEF, GDMT as quantified by Kansas City Medical Optimization (KCMO) score, and immunosuppressive treatment were recorded. The primary outcome was a composite of event-free survival (unplanned heart failure hospitalization, left ventricular assist device [LVAD]/heart transplant, or death). Seventy-nine (9%) CS patients met the inclusion criteria (35% female, median age 57 years, mean LVEF 30.9%, median New York Heart Association class II [46%], mean number of GDMT agents 1.7, and mean KCMO score 31.8). Most (87%) were treated with immunosuppressive treatment. At follow-up (median 16 months), the mean number of GDMT agents increased to 2.2 (P=0.02), and the mean KCMO score to 70.1 (P<0.001). Mean LVEF improved to 39.9% (excluding LVAD/transplant; P<0.001) and the change in LVEF was correlated with follow-up KCMO score (P<0.001). The primary outcome occurred in 13 (16%) patients and differed by KCMO score (log-rank P<0.001), but not by immunosuppressive treatment (log-rank P=0.36). GDMT optimization is associated with better cardiac remodeling and clinical outcomes in CS patients with HFrEF.

Leveraging AI technology in sarcoidosis.

Sarcoidosis is a systemic, granulomatous disease of uncertain cause. Diagnosis may be difficult, prognosis uncertain and response to treatment unpredictable. The application of artificial intelligence to sarcoidosis may provide clinical decision support for these challenges. This review will provide an overview of current and potential future applications of artificial intelligence in sarcoidosis. The predominant application of artificial intelligence in sarcoidosis is imaging. Imaging models may differentiate sarcoidosis from other pulmonary disorders. Models, which predict survival and identify key factors relevant to prognosis are also available. The application of cluster analysis to organize sarcoidosis patients into developmental phenotypes is underway. Machine learning algorithms to evaluate the treatment response of sarcoidosis patients do not yet exist but similar models may evaluate patients with other inflammatory disease. The potential applications of artificial intelligence to sarcoidosis is vast, but there are practical limitations that warrant consideration. These include: the accessibility of data, biases in data, cost and privacy. The application of artificial intelligence in medicine is still in its early stages but models are poised to support the diagnostic and prognostic challenges in sarcoidosis patients. The predictive power of these artificial intelligence is likely to come from combining various models, trained on content-rich datasets from phenotypically heterogeneous sarcoidosis patients.

Mortality and Health Outcomes Among Patients With Sarcoidosis Treated With Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers

Sarcoidosis is a multisystem inflammatory disease where management and outcomes can vary widely. The renin-angiotensin-aldosterone system (RAAS) has been implicated in its pathogenesis, yet the impact of RAAS modulators on health outcomes in sarcoidosis remains poorly understood. How do pharmacological modulators of RAAS affect health outcomes in patients diagnosed with sarcoidosis? We conducted a large multicenter investigation using the TriNetX Research Network database. Patients included in our study were individuals diagnosed with sarcoidosis and prescribed either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB). All cohorts were matched for important covariates, and outcomes measured included mortality, cardiac and respiratory outcomes, and sepsis rates following sarcoidosis diagnosis. We observed an increased mortality risk among sarcoidosis patients prescribed ACE inhibitors compared to patients prescribed ARB therapies. Furthermore, sarcoidosis patients prescribed ACE inhibitors had worse cardiac and respiratory outcomes, and increased sepsis rates compared to the ARB cohort. Our findings suggest that ACE inhibitors and ARB's have divergent effects on outcomes in sarcoidosis patients. These findings highlight the potential pathogenic role of RAAS signaling in this disease and underscore the importance of carefully selecting RAAS modulators for individuals with sarcoidosis.

Progressive multifocal leukoencephalopathy in sarcoidosis successfully treated with pembrolizumab.

Progressive multifocal leukoencephalopathy (PML) is a severe, demyelinating disease of the central nervous system caused by JC virus infection. The disease can be seen in sarcoidosis patients without additional risk factors. Here, we present an individual with PML secondary to sarcoidosis treated with 8 doses of pembrolizumab, a Programmed Cell-Death-1 (PD-1) Immune Checkpoint Inhibitor who showed significant improvement. This report illustrates the objective clinical and radiological improvement in a patient with PML due to sarcoidosis, and suggests further study of immune checkpoint inhibitors as a potential treatment for sarcoidosis patients with PML.

Current Practices and Emerging Therapies to Optimize Heart Failure Management in Cardiac Sarcoidosis: A Systematic Review.

Cardiac sarcoidosis (CS) is a distinctive manifestation of sarcoidosis, a multisystemic inflammatory disorder that is characterized by non-necrotizing granulomas. CS can lead to arrhythmias, heart failure (HF), and sudden cardiac death. The diagnosis of CS involves imaging in the form of a two-dimensional echocardiogram, cardiac magnetic resonance imaging (MRI), an 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) scan, and an endomyocardial biopsy. Treatment of CS entails corticosteroids, immunosuppressive agents, monoclonal antibodies, and, in advanced cases, heart transplantation (HTx). This systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, focusing on HF in sarcoidosis patients. Eligibility criteria include recent (2019-2024) research papers on sarcoidosis-induced heart failure, excluding other causes. The databases searched were PubMed, Google Scholar, and ScienceDirect. From 36,755 initial articles, 2,060 remained after filtering, and 17 were selected for quality assessment. Based on quality assessment, 11 studies were included in the final review. In CS, a variety of treatment strategies can be implemented. Corticosteroids are the first-line therapeutic options, and in the majority of cases, they are very successful in controlling the disease progression. Immunosuppressive agents like methotrexate and azathioprine are used to avoid long-term steroid use. Both corticosteroids and immunosuppressives act by reducing inflammation and preventing myocardial scarring. Biological agents like infliximab and adalimumab prevent disease progression by targeting specific inflammatory pathways and are used in refractory cases. Regular HF management drugs like angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), sodium-glucose transport protein 2 (SGLT2) inhibitors, beta-blockers, and diuretics help in optimizing cardiac function. In severe cases, a left ventricular assist device (LVAD) may be required. The ultimate treatment for end-stage CS is HTx, which has to be supplemented with a strong, individualized regimen of glucocorticoids and immunosuppressives to avoid graft rejection and to control sarcoidosis. Due to a lack of standard protocols for management and limited knowledge about CS, the ideal treatment of HF is still a matter of debate. Hence, further research and clinical trials need to be performed to optimize patient outcomes.

Sarcoidosis and Emergency Hospitalization

IntroductionSarcoidosis is an idiopathic systemic granulomatosis whose evolution is self-limiting in the majority of cases. However, it can progress to organ damage that menaces the vital or functional prognosis of patients. Sarcoidosis itself, but also its comorbidities, can pose a threat to the patient, require rapid initiation of treatment and justify emergency hospitalization. Research questionWhat are the reasons and prognosis of sarcoidosis patients hospitalized in emergency ? MethodsThe objectives of our study were to describe the causes of admission, and to identify predictors of mortality in sarcoidosis patients hospitalized in emergency. This is a retrospective monocentric study. We included patients hospitalized after a stay in the emergency room or in intensive care unit (ICU) or requiring an unscheduled hospitalization after a telephone advice or a consultation, between 01/01/2017 and 07/07/2020. ResultsWe identified 154 sarcoidosis patients hospitalized in emergency, among which 14 (9%) required the ICU. There were 81 men, with a median age of 55.0 [44.0; 67.0] years. Sarcoidosis was inaugural in 20 (14%) patients. The primary reason for hospitalization was lower respiratory infections in 32 (21%) patients, followed by acute pulmonary exacerbation of sarcoidosis in 17 (11%), suspected cardiac sarcoidosis in 13 (8.4%), and neurosarcoidosis in 12 (7.7%). The median length of stay was 6 [3.00; 10.0] days. In-hospital mortality rate was 3.9%. The 2-year transplantation-free survival following hospitalization was 86,8% [95% CI 81,4- 92,5]. The factors associated with a worse transplantation-free survival were Charlson comorbidity index (HR=1.29 [95% CI=1.04-1.61]; p=0.021), pulmonary hypertension (HR=2.53 [95% CI=1.10-5.83]; p=0.029), and oxygen therapy during hospitalization (HR=4.18 [95%CI=1.55-11.29]; p=0.005). InterpretationThe overall mortality of sarcoidosis patients hospitalized in emergency is high. The presence of comorbidities and the severity of respiratory failure, as reflected by oxygen requirement, are important prognostic determinants.