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The article discusses a rare subtype of idiopathic multicentric Castleman disease known as the TAFRO syndrome, characterized by thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, and organomegaly. The diagnosis of Castleman disease requires careful clinicopathological correlation, and radiographic adrenal abnormalities can serve as a diagnostic clue for TAFRO. Treatment with an interleukin-6 inhibitor is crucial to prevent morbidity and death, with rapid initiation often resulting in excellent outcomes. The case study presented in the article highlights the challenges in diagnosing and treating this rare disease, emphasizing the importance of early recognition and appropriate therapy. [Extracted from the article]

Introduction: Endobronchial ultrasound-guided transbronchial needle aspiration remains the gold standard for the diagnosis of mediastinal pathologies. Its greatest limitation has been the low diagnostic yield in lymphoproliferative disorders as well as insufficient samples for molecular testing. Transesophageal examinations using an EBUS scope have helped increase the diagnostic yield by allowing for additional biopsies of paraesophageal and intra-abdominal lesions. Similarly, the novel approach of transbronchial mediastinal cryobiopsy has further increased the yield by providing larger and better-preserved biopsies. Both complimentary techniques have shown great individual feasibility and safety. However, the feasibility of transesophageal cryobiopsies in the evaluation of mediastinal pathologies remains a subject of debate. Aim: The aim of the study was to investigate the safety and feasibility of transesophageal EBUS-guided mediastinal cryobiopsies performed at our center. Methods: We conducted a retrospective review of 30 patients who underwent mediastinal cryobiopsy through the esophagus at our institution between October 2023 and March 2024. Data on patient demographics, diagnostic yield, and complications were collected and analyzed. Results: The mean patient age was 43 years, with a gender distribution of 60% male and 40% female. The primary indications included suspicion of lymphoproliferative disorders, suspected sarcoidosis, and malignancies with paraesophageal lesions. The overall diagnostic yield was 93%. No major complications were noted in any of the patients. Conclusion: Transesophageal mediastinal cryobiopsy appears to be a promising complimentary technique for mediastinal evaluation with a relatively high diagnostic yield and favorable safety profile. However, further studies with larger cohorts are warranted to validate the findings at our institution. [ABSTRACT FROM AUTHOR]

Background: Non‐Hodgkin lymphoma (NHL) is one of the most common haematologic malignancies in the world. Despite substantial efforts to identify causes and risk factors for NHL, its aetiology is largely unclear. Autoimmune diseases have long been considered potential risk factors for NHL. We carried out Mendelian randomisation (MR) analyses to examine whether genetically predicted susceptibility to ten autoimmune diseases (Behçet's disease, coeliac disease, dermatitis herpetiformis, lupus, psoriasis, rheumatoid arthritis, sarcoidosis, Sjögren's syndrome, systemic sclerosis, and type 1 diabetes) is associated with risk of NHL. Methods: Two‐sample MR was performed using publicly available summary statistics from cohorts of European ancestry. For NHL and four NHL subtypes, we used data from UK Biobank, Kaiser Permanente cohorts, and FinnGen studies. Results: Negative associations between type 1 diabetes and sarcoidosis and the risk of NHL were observed (odds ratio [OR] 0.95, 95% confidence interval [CI]: 0.92–0.98, p = 5 × 10−3, and OR 0.92, 95% CI: 0.85–0.99, p = 2.8 × 10−2, respectively). These findings were supported by the sensitivity analyses accounting for potential pleiotropy and weak instrument bias. No significant associations were found between the other eight autoimmune diseases and NHL risk. Conclusion: These findings suggest that genetically predicted susceptibility to type 1 diabetes, and to some extent sarcoidosis, might reduce the risk of NHL. However, future studies with different datasets, approaches, and populations are warranted to further examine the potential associations between these autoimmune diseases and the risk of NHL. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Objectives: Myocarditis is an inflammatory disease of the myocardium and remains to this day a challenging diagnosis. A promising novel imaging method uses the expression of somatostatin receptors (SSTRs) on inflammatory cells to visualize myocardial inflammation. However, little is known about the histopathological correlate of SSTR imaging in different forms of myocarditis. Methods: In the present retrospective histopathological study, we systematically analysed the expression of SSTR subtype 2 (SSTR2) on inflammatory cells of 33 patients with biopsy- or explant-proven myocarditis (lymphocytic myocarditis (n = 5), giant-cell myocarditis (n = 11), and cardiac sarcoidosis (n = 17)), and in eight controls (multi-organ donors) without signs of myocardial inflammation and/or scars. Results: In all patients, immunohistochemical staining for SSTR2 was positive in areas with CD68-positive macrophages and multinucleated giant cells. Staining for SSTR2 was most prominent in the presence of multinucleated giant cells. The colocalization of both SSTR2 and CD68 on the same cell could be confirmed using immunofluorescence microscopy. Western blotting confirmed the upregulated expression of SSTR2 in cases of granulomatous inflammation (sarcoidosis) of the skeletal and heart muscle, in comparison with controls. Conclusions: In conclusion, our findings demonstrate the expression of SSTR2 on the protein level on CD68-positive macrophages and multinucleated giant cells in various forms of myocarditis, which provides a clear rationale for the diagnostic use of SSTR imaging in this patient group. [ABSTRACT FROM AUTHOR]

Purpose: Uveitis and scleritis may be caused by local or systemic infection, or associated with noninfectious systemic inflammatory autoimmune disease. This study explored the all-cause mortality following an individual's first presentation with uveitis/scleritis. Methods: A cross-sectional study was conducted on all uveitis/scleritis patients diagnosed by uveitis specialists and treated in a single tertiary referral center in New Zealand between 2006 and 2020(15y). Masquerade syndromes including intraocular lymphoma were excluded. Outcome measures: demographics, etiology of uveitis/scleritis, anatomical location and all-cause mortality. Results: 2723 subjects were identified. Median age of onset of uveitis/scleritis was 44.9 years (Range:1.5–99.5 years). 49.6% were female. Median follow-up from diagnosis of uveitis/scleritis was 8.0 years (IQR 4.1–11.6 years) with a total follow-up of 24 443.3 subject-years. The most frequent diagnosis was idiopathic disease (30.9%), HLA-B27-positive uveitis (20.0%), and sarcoidosis (4.7%). Infectious etiologies (24.1%) were most commonly from herpes zoster virus (9.3%) and toxoplasmosis (4.3%). The age-adjusted mortality rate was higher in subjects with idiopathic disease, sarcoidosis, Fuchs' uveitis syndrome, granulomatosis with polyangiitis/ANCA-associated vasculitis, toxoplasmosis, and herpes zoster virus, when compared to HLA-B27-positive uveitis. Hazard of mortality peaked in the first seven years following diagnosis, then subsequently declined. Patients with uveitis/scleritis had a significantly higher rate of mortality compared to the general New Zealand population (IRR 1.656 p = 0.017). Conclusion: Infectious etiologies of uveitis/scleritis in this cohort were high when compared to other developed nations, attributable to data from a tertiary referral center treating inpatients. Potential shared inflammatory mechanisms in the eye and other organs can lead to concurrent non-ocular disease requiring systemic treatment, impacting an individual's longevity. [ABSTRACT FROM AUTHOR]

An autoimmune component in the cause of sarcoidosis has long been debated, but population-based data on the clustering of immune-mediated diseases (IMDs) and sarcoidosis in individuals and families suggestive of shared cause are limited. Do patients with a history of IMDs have a higher risk of sarcoidosis and do IMDs cluster in families with sarcoidosis? We conducted a case-control-family study (2001-2020). Patients with sarcoidosis (N = 14,146) were identified in the Swedish National Patient Register using a previously validated definition (≥ 2 International Classification of Diseases [ICD]-coded inpatient or outpatient visits). At diagnosis, patients were matched to up to 10 control participants from the general population (N = 118,478) for birth year, sex, and residential location. Patients, control participants, and their first-degree relatives (FDRs; Multi-Generation Register) were ascertained for IMDs by means of ICD codes in the Patient Register (1968-2020). Conditional logistic regression was used to estimate ORs and 95% CIs of sarcoidosis associated with a history of IMDs in patients and control participants and in FDRs. Patients with sarcoidosis exhibited a higher prevalence of IMDs compared with control participants (7.7% vs 4.7%), especially connective tissue diseases, cytopenia, and celiac disease. Familial aggregation was observed across IMDs; the strongest association was with celiac disease (OR, 2.09; 95% CI, 1.22-3.58), followed by cytopenia (OR, 1.88; 95% CI, 0.97-3.65), thyroiditis (OR, 1.72; 95% CI, 1.14-2.60), skin psoriasis (OR, 1.70; 95% CI, 1.34-2.15), inflammatory bowel disease (OR, 1.53; 95% CI, 1.14-2.03), immune-mediated arthritis (OR, 1.49; 95% CI, 1.20-1.85), and connective tissue disease (OR, 1.39; 95% CI, 1.00-1.93). This study showed that IMDs confer a higher risk of sarcoidosis and they aggregate in families with sarcoidosis, signaling a shared cause between IMDs and sarcoidosis. Our findings warrant further evaluation of shared genetic mechanisms. [ABSTRACT FROM AUTHOR]

Sarcoidosis staging primarily has relied on the Scadding chest radiographic system, although chest CT imaging is finding increased clinical use. Whether standardized chest CT scan assessment provides additional understanding of lung function beyond Scadding stage and demographics is unknown and the focus of this study. We used National Heart, Lung, and Blood Institute study Genomics Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) cases of sarcoidosis (n = 351) with Scadding stage and chest CT scans obtained in a standardized manner. One chest radiologist scored all CT scans with a visual scoring system, with a subset read by another chest radiologist. We compared demographic features, Scadding stage and CT scan findings, and the correlation between these measures. Associations between spirometry and diffusing capacity of the lungs for carbon monoxide (D lco) results and CT scan findings and Scadding stage were determined using regression analysis (n = 318). Agreement between readers was evaluated using Cohen's κ value. CT scan features were inconsistent with Scadding stage in approximately 40% of cases. Most CT scan features assessed on visual scoring were associated negatively with lung function. Associations persisted for FEV 1 and D lco when adjusting for Scadding stage, although some CT scan feature associations with FVC became insignificant. Scadding stage was associated primarily with FEV 1 , and inclusion of CT scan features reduced significance in association between Scadding stage and lung function. Multivariable regression modeling to identify radiologic measures explaining lung function included Scadding stage for FEV 1 and FEV 1 to FVC ratio (P <. 05) and marginally for D lco (P <. 15). Combinations of CT scan measures accounted for Scadding stage for FVC. Correlations among Scadding stage and CT scan features were noted. Agreement between readers was poor to moderate for presence or absence of CT scan features and poor for degree and location of abnormality. In this study, CT scan features explained additional variability in lung function beyond Scadding stage, with some CT scan features obviating the associations between lung function and Scadding stage. Whether CT scan features, phenotypes, or endotypes could be useful for treating patients with sarcoidosis needs more study. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is there an association between premature ovarian insufficiency (POI) and severe autoimmune diseases before and after POI diagnosis? SUMMARY ANSWER Women with POI had at least one hospital-treated autoimmune disorder preceding POI diagnosis 2.6 times more often compared with matched female controls, and a 2- to 3-fold risk for these diseases for several years after POI diagnosis. WHAT IS KNOWN ALREADY It has been suggested that autoimmunity is an important factor in the pathogenesis of POI. Estimations of the prevalence of POI cases with autoimmune origin have ranged from 4% to 50%. STUDY DESIGN, SIZE, DURATION This population-based registry study included 3972 women diagnosed with spontaneous POI between 1988 and 2017 and 15 708 female population controls and used both case–control and cohort analysis. Autoimmune disease diagnoses were evaluated from childhood until the end of the year 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with POI were identified from the reimbursement registry of the Finnish Social Insurance Institution by their right to hormone replacement therapy (HRT). Four female population controls matched by age and municipality of residence were searched for each POI case to form a reference cohort. Women with a history of cancer or bilateral oophorectomy were excluded. Severe autoimmune disorder diagnoses for the years 1970–2017 were identified from the Hospital Discharge Registry. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using binary logistic regression for cases of having any, or one or more, specific autoimmune diseases preceding the index date (the date when reimbursement for HRT was granted for the POI) among women with POI as compared to controls. Standardized incidence ratios (SIR) with 95% CIs for getting diagnosed with an autoimmune disease after the index date in 3-year follow-up periods among women with POI (who did not have these diseases prior to the index date) were also calculated. The expected numbers of autoimmune disease cases were based on the incidence of first-onset severe autoimmune disease among the controls. MAIN RESULTS AND THE ROLE OF CHANCE The prevalence of having at least one severe autoimmune disease in women with POI was 5.6% (n = 233), with an OR of 2.6 (95% CI 2.2, 3.1) when compared to population controls. Women with POI had an increased prevalence of several specific autoimmune diseases prior to the index date compared to controls: polyglandular autoimmune diseases (OR 25.8, 95% CI 9.0, 74.1), Addison's disease (OR 22.9, 95% CI 7.9, 66.1), vasculitis (OR 10.2, 95% 4.3, 24.5), systemic lupus erythematosus (OR 6.3 95% CI 4.2, 20.3), rheumatoid arthritis (OR 2.3, 95% CI 1.7, 3.2), sarcoidosis (OR 2.3, 95% CI 1.2, 4.5), inflammatory bowel diseases (OR 2.2, 95% CI 1.5, 3.3), and hyperthyroidism (OR 1.9, 95% CI 1.2, 3.1); whereas the prevalence of diabetes type 1 and ankylosing spondylitis did not differ between the women with POI and the reference cohort. The SIRs for being diagnosed for the first time with a severe autoimmune disease after POI diagnosis was 2.8 (95% CI 2.3, 3.4), during the first three years after POI diagnosis, decreasing gradually to 1.3 (1.1, 1.6) after 12 years. LIMITATIONS, REASONS FOR CAUTION This study only included autoimmune disorders diagnosed in specialized health care; hence, the overall prevalence of autoimmune disorders in women with POI may be higher. WIDER IMPLICATIONS OF THE FINDINGS Severe autoimmune diseases have a strong association with POI, suggesting that immunological mechanisms play a pivotal role in POI. Future studies should focus on specific autoimmune mechanisms behind POI, from both preventive and curative perspectives. STUDY FUNDING/COMPETING INTEREST(S) This work was financially supported by Oulu University Hospital. S.M.S. received grants from the Finnish Menopause Society, the Finnish Medical Foundation, and the Juho Vainio Foundation. H.S. received grants from the Finnish Menopause Society, the Oulu Medical Research Foundation, the Finnish Research Foundation of Gynecology and Obstetrics, UniOGS graduate school, The Finnish Medical Society Duodecim, Orion Research Foundation, and the University of Oulu Scholarship Fund. M.-M.O. received a grant from the Sakari Alhopuro Foundation and the Finnish Diabetes Research Foundation. None of the funders had any involvement in the study design or its execution or reporting. The authors do not have any competing interests to report. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Searching for a reliable indicator of treatment response in sarcoidosis remains a challenge. The use of the soluble interleukin 2 receptor (sIL-2R) as a measure of disease activity has been proposed by researchers. The aim of this study was to develop a machine learning model to predict sIL-2R levels based on serum angiotensin-converting enzyme (ACE) levels of patients that can be used in evaluating lung function. This new sIL-2R prediction model combines Support Vector Regression (SVR) with the Bald Eagle Search (BES) algorithm. However, BES has only a few adjustable parameters, simple searching technique and produces consistent results all the time. In this way, the hyper-parameters of SVR are optimized by BES that eventually improved the accuracy of predicted sIL-2R values. The hybrid SVR-BES model was evaluated using a dataset consisting of medical records of patients suspected sarcoidosis focusing specifically on soluble interleukin 2 receptor (sIL-2R) levels and angiotensin converting enzyme (ACE) levels. These other methodologies include Hybrid SVR with Firefly Algorithm (SVR-FFA), Decision Tree (DT), SVR with Gray Wolf Optimization (SVR-GWO), Random Forest (RF). According to these results, Root Mean Square Error (RMSE) is 0.5615 while correlation coefficient (R) is 0.9457 thereby indicating higher accuracy compared to other methods as presented by hybrid SVR-BES model. [ABSTRACT FROM AUTHOR]

Progressive multifocal leukoencephalopathy (PML) is a rare central nervous system disease caused by JC virus (JCV) infection. Human immunodeficiency virus (HIV) infection is the greatest risk factor for PML. Other immunological diseases, including systemic sarcoidosis, have also been reported as risk factors for PML. Herein, we report a case of PML co-occurring with neurosarcoidosis. Early diagnosis using brain biopsy and appropriate therapeutic interventions achieved favorable outcomes. PML in patients with active intracranial neurosarcoidosis is extremely rare. We believe that it is important to perform brain biopsy at an early stage to allow diagnosis, even for central nervous system involvement with a progressive parenchymal lesion in patients with sarcoidosis, if PML is possible. [ABSTRACT FROM AUTHOR]

Background: Visual interpretation of PET and CMR may fail to identify cardiac sarcoidosis (CS) with high specificity. This study aimed to evaluate the role of [18F]FDG PET and late gadolinium enhancement (LGE)-CMR radiomic features in differentiating CS from another cause of myocardial inflammation, in this case patients with cardiac-related clinical symptoms following COVID-19. Methods: [18F]FDG PET and LGE-CMR were treated separately in this work. There were 35 post-COVID-19 (PC) and 40 CS datasets. Regions of interest were delineated manually around the entire left ventricle for the PET and LGE-CMR datasets. Radiomic features were then extracted. The ability of individual features to correctly identify image data as CS or PC was tested to predict the clinical classification of CS vs. PC using Mann--Whitney U-tests and logistic regression. Features were retained if the P-value was <0.00053, the AUC was >0.5, and the accuracy was >0.7. After applying the correlation test, uncorrelated features were used as a signature ( joint features) to train machine learning classifiers. For LGE-CMR analysis, to further improve the results, different classifiers were used for individual features besides logistic regression, and the results of individual features of each classifier were screened to create a signature that included all features that followed the previously mentioned criteria and used it them as input for machine learning classifiers. Results: The Mann--Whitney U-tests and logistic regression were trained on individual features to build a collection of features. For [18F]FDG PET analysis, the maximum target-to-background ratio (TBRmax) showed a high area under the curve (AUC) and accuracy with small P-values (<0.00053), but the signature performed better (AUC 0.98 and accuracy 0.91). For LGE-CMR analysis, the Gray Level Dependence Matrix (gldm)-Dependence Non-Uniformity showed good results with small error bars (accuracy 0.75 and AUC 0.87). However, by applying a Support Vector Machine classifier to individual LGE-CMR features and creating a signature, a Random Forest classifier displayed better AUC and accuracy (0.91 and 0.84, respectively). Conclusion: Using radiomic features may prove useful in identifying individuals with CS. Some features showed promising results in differentiating between PC and CS. By automating the analysis, the patient management process can be accelerated and improved. [ABSTRACT FROM AUTHOR]

To determine the potential causal association between serum lipid levels and sarcoidosis, and to investigate the potential impact of lipid lowering agents on sarcoidosis. Two-sample Mendelian randomization (TSMR) was used to investigate the association between lipid levels (including LDL-c, HDL-c, TG, and TC) and sarcoidosis risk. In addition, we used Mendelian drug target randomization (DMR) to analyze the relationship between drug targets for lowering LDL-c levels (HMGCR, PCSK9, and NPC1L1) and drug targets for lowering TG levels (LPL and APOC3) and the risk of sarcoidosis. According to the TSMR analysis, a positive correlation was observed between the serum LDL-c concentration and sarcoidosis incidence (n = 153 SNPs, OR = 1.232, 95% CI = 1.018–1.491; p = 0.031). Similarly, serum TG concentration was found to be positively associated with sarcoidosis (n = 52 SNPs, OR = 1.287, 95% CI = 1.024–1.617; p = 0.03). The DMR results demonstrated a positive correlation between PCSK9-mediated serum LDL-c levels and sarcoidosis (n = 35 SNPs, OR = 1.681, 95% CI = 1.220–2.315; p = 0.001). Similarly, serum TG levels mediated by LPL were positively associated with sarcoidosis (n = 28 SNPs, OR = 1.569, 95% CI = 1.223–2.012; p = 0.0003). This study suggested that elevated serum TG and LDL-c levels may increase the risk of sarcoidosis. PCSK9-mediated reduction of LDL-C levels (simulating the effects of PCSK9 inhibitors) and LPL-mediated reduction of TG levels (simulating the effects of LPL-related lipid lowering drugs) can decrease the risk of developing sarcoidosis. [ABSTRACT FROM AUTHOR]

Background: Although the imaging manifestations of pulmonary sarcoidosis have been described in detail in previous studies, a consensus has not been reached on the imaging presentation of non-specific interstitial pneumonia (NSIP) lookalike pattern as a distinct pattern in the diagnosis of pulmonary sarcoidosis in high-resolution computed tomography (HRCT). No cases of pulmonary sarcoidosis comorbid with NSIP have been reported. Case presentation: A 53-year-old male presented to the hospital with a five-year history of recurrent coughing up sputum and a four-year history of shortness of breath. In addition to the typical features of pulmonary sarcoidosis, the patient's HRCT also showed unexpected interstitial changes in the lower lobes of both lungs, suggesting an NSIP pattern. Histopathology of the lung tissue in this region confirmed well-formed noncaseating epithelioid granulomas and pathological modifications of NSIP. After a rigorous exclusion diagnosis combining the patient's clinical features, radiological and pathological findings, we diagnosed this patient with pulmonary sarcoidosis comorbid with NSIP. Conclusions: This suggests that NSIP may act as a rare comorbidity of pulmonary sarcoidosis thereby resulting in the patient's HRCT presenting differently from routine sarcoidosis imaging. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a multi-organ granulomatous disease of uncertain origin, characterized by the formation of non-necrotizing granulomas in various organs, including the heart. Cardiac involvement in sarcoidosis is rare, with approximately 5% of sarcoidosis patients developing clinically apparent cardiac disease, which is associated with significant morbidity and mortality. Genetically predisposed individuals develop granuloma in myocardium musculature, leading to aberrant conduction of cardiac impulses and the development of various arrhythmias. Common arrhythmias range from atrial fibrillation to ventricular tachycardia and can lead to sudden cardiac death because of ventricular fibrillation. The diagnostic challenge results from high specificity but rather limited sensitivity of endomyocardial biopsy, which is the gold standard diagnostic test, making advanced imaging techniques, such as cardiac magnetic resonance imaging and fluorine-18 fluorodeoxyglucose positron emission tomography, crucial for early detection. Management involves a complex approach with immunosuppression, antiarrhythmic medications, and catheter ablation, often supplemented by implantable cardioverter-defibrillators to prevent sudden cardiac death. In cardiac sarcoidosis, ventricular arrhythmias are common and cause high mortality. Timely intervention and management are crucial for a better prognosis. The disease's growing prevalence requires further research on refining early detection techniques and developing efficient treatment strategies for these high-risk patients. This review focuses on the etiopathogenesis of arrhythmias in cardiac sarcoidosis, diagnosis, and effective management strategies. [ABSTRACT FROM AUTHOR]

Background Sarcoidosis is a rare disease, and cardiac involvement is seen in the minority of patients. The clinical symptoms depend on the location of the noncaseating granulomas in the heart and vary from asymptomatic to atrioventricular (AV) conduction block, ventricular arrhythmia, heart failure, and sudden cardiac death. Clinically manifest cardiac sarcoidosis seldomly presents with supraventricular tachycardia. Case summary We present a case where a female patient presented with AV nodal re-entrant tachycardia as an uncommon initial presentation of cardiac sarcoidosis. Her resting electrocardiogram showed a complete left bundle branch block and first-degree AV conduction block. During hospitalization, there was continuous switching between sinus rhythm with first-degree AV block, 2:1 AV block, and AV nodal re-entrant tachycardia. Discussion It is important to be aware that cardiac sarcoidosis can rarely present with supraventricular tachycardia as initial symptom. Given the elevated risk of sudden cardiac death, early detection is crucial and all patients who require permanent pacing should be considered for implantable cardioverter-defibrillator implantation. [ABSTRACT FROM AUTHOR]

Infiltrative heart disease (InHD) is a group of diseases characterized by the deposition of abnormal substances in the heart tissue, causing diastolic, less often systolic, dysfunction of the ventricle(s). Their classification still does not exist. In 2013, the MOGE(S) classification of cardiomyopathies was published, taking into account, along with the morphological and functional characteristics of the heart, damage to other organs, the presence of genetic mutations, acquired causes (e.g., myocardial inflammation, autoimmune diseases, storage diseases, amyloidosis), etc. By analogy with it we offer the MORAL-STAGE classification for InHD. It includes ten features: morphofunctional characteristics (M), organ damage (O), risk of cardiac death (R), age of clinical presentation, age of disease-specific therapy initiation (A), localization of the infiltrative process (inside or outside the cell, L), information about the functional class heart failure and stage of infiltrative heart disease (S), treatment (T), abnormal rhythm or conduction (A), genetic or familial nature of inheritance (G), etiology of the process (E). This article summarizes the cornerstones of the MORAL-STAGE classification and its clinical relevance. In addition, new issues are discussed that can be considered in future versions of the MORAL-STAGE classification. [ABSTRACT FROM AUTHOR]

Purpose: Determining uveitis etiology is a challenge. It is based primarily on demographic data and the characteristics of eye examination. It is not clear to what extent extraocular physical signs contribute to elucidating the etiology. This study aimed to establish the contribution of the clinical extra-ophthalmological features for the assessment of the underlying etiology of uveitis. Methods: We retrospectively reviewed 1307 patients with uveitis referred to our tertiary center between 2003 and 2021. Uveitis was classified according to the Standardization of Uveitis Nomenclature. Clinical features were collected at diagnosis by internists before the etiological diagnosis was made. The main outcome description was the contribution of clinical features. Results: Clinical extra-ophthalmological features contributed to the assessment of the underlying etiology of uveitis in 363 (27.8%) patients. The joint and the skin examinations were the most useful for etiological investigations, respectively in 12.3% and 11.8% of patients. Five etiologies of uveitis accounted for 80% of the cases: sarcoidosis, HLA-B27-related uveitis, Behçet's disease, multiple sclerosis, and Vogt-Koyanagi-Harada disease. Clinical extra-ophthalmological features were particularly important in the etiological diagnosis of acute bilateral anterior uveitis and panuveitis. Conclusion: This study suggests that clinical extra-ophthalmological features are essential for the etiological diagnosis of uveitis in more than a quarter of patients. It demonstrates once again the value of collaboration between ophthalmologists and other specialists experienced in performing extra-ophthalmological clinical examinations, particularly in patients with acute bilateral anterior uveitis and panuveitis. [ABSTRACT FROM AUTHOR]

Objectives: To report and describe the characteristics and outcomes of patients with advanced atrioventricular block (AVB) in Saudi Arabia. Methods: We included consecutive patients who underwent pacemaker implantation at King Khaled University Hospital, Riyadh, Saudi Arabia, for advanced AVB, which was defined as second degree type 2 AVB, third degree AVB, and symptomatic atrial fibrillation with slow ventricular response. The variable “young patient” was defined as age of 60 or less, based on guidelines recommending cardiac sarcoidosis (CS) evaluation at this age or younger. Results: Among 100 patients (median age: 71 males, 51%), 29 (29%) were young patients. Most patients had at least one comorbidity including hypertension, diabetes, or dyslipidemia (81%). Young patients constituted 26.6% (n=21/79) of idiopathic AVB cases and only 23.8% (n=8/21) underwent CS evaluation (8/21). Conclusion: A significant proportion of AVB occurs in young patients. Yet, CS is often not ruled out. Future studies should define the yield of CS evaluation in the Saudi population when international consensus documents are followed. [ABSTRACT FROM AUTHOR]

Introduction: 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. Materials and Methods: 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. Results: Few studies have evaluated that microcirculation is often compromised in SA, with alterations in blood flow and consequent tissue damage. Discussion: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Sarcoid myositis is a rare and often debilitating extrapulmonary manifestation of sarcoidosis that can be difficult to recognize without a prior sarcoidosis diagnosis. Sarcoidosis with muscle nodules or masses as the first symptom is the least common form, occurring in approximately 0.5%–2.3% of cases. This article presents four middle‐aged female patients who initially sought medical attention for a lower limb mass. Ultrasound examinations revealed consistent characteristic changes indicative of myositis. All patients underwent ultrasound‐guided muscle biopsy and were diagnosed with sarcoidosis. Therefore, ultrasonography plays a pivotal role as the primary diagnostic tool for the early detection of sarcoid myositis. [ABSTRACT FROM AUTHOR]

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A 76-year-old male diagnosed with sarcoidosis presented with atraumatic left anterior knee pain. Initial imaging of the left lower extremity revealed an eccentrically-based lytic lesion in the mid-distal femur with cortical erosion and an additional lytic lesion in the proximal tibia. Magnetic resonance imaging (MRI) demonstrated an aggressive lesion in the proximal tibia with surrounding marrow edema, cortical breach, and erosion into the distal patellar tendon. Given concern for metastatic bone lesions, a18-fluorodeoxyglucose positron emission tomography/computed tomography scan (FDG PET/CT) was performed which demonstrated concordant hypermetabolic lytic lesions at the left mid-distal femur and the left proximal tibia, as well as hypermetabolic diffuse lymphadenopathy. The patient was presumed to have metastatic lung cancer based on the presence of lung nodules. Due to concern for impending pathologic fracture, the patient underwent open biopsy with a plan for prophylactic fixation of both lesions. Intra-operatively, however, both lesions were found to contain pus, from which cultures ultimately grew Cryptococcus neoformans. This is a case of disseminated skeletal cryptococcosis masquerading as metastatic cancer in a patient without classic risk factors for disseminated cryptococcosis (defined as extrapulmonary evidence of infection). Classically, disseminated cryptococcosis is thought to occur in severely immunocompromised patients, such as those with human immunodeficiency virus (HIV) or organ transplant recipients. This case highlights the need to maintain a high index of suspicion in patients with underlying immunocompromising conditions, including less common conditions such as sarcoid, who present with bony lesions. This case report then discusses the diagnostic evaluation and treatment of disseminated skeletal cryptococcosis. [ABSTRACT FROM AUTHOR]

Introduction: In 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. Methods: Blood 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. Results: Differential 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. Conclusion: Blood 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) [ABSTRACT FROM AUTHOR]

Sarcoidosis is a chronic granulomatous disease predominantly affecting the lungs and inducing significant morbidity and elevated mortality rate. The etiology of the disease is unknown but may involve exposure to an antigenic agent and subsequent inflammatory response resulting in granuloma formation. Various environmental and occupational risk factors have been suggested by previous observations, such as moldy environments, insecticides, and bird breeding. Our study investigated the association of air pollution with diagnosis of sarcoidosis using a case-control design. Penn State Health electronic medical records from 2005 to 2018 were examined for adult patients with (cases) and without (controls) an International Classification of Disease (ICD)-9 or −10 code for sarcoidosis. Patient addresses were geocoded and 24-hr residential-level air pollution concentrations were estimated using spatio-temporal models of particulate matter <2.5 μm (PM2.5), ozone, and PM2.5 elemental carbon (EC) and moving averages calculated. In total, 877 cases and 34,510 controls were identified. Logistic regression analysis did not identify significant associations between sarcoidosis incidence and air pollution exposure estimates. However, the odds ratio (OR) for EC for exposures occurring 7–10 years prior did approach statistical significance, and ORs exhibited an increasing trend for longer averaging periods. Data suggested a latency period of more than 6 years for PM2.5 and EC for reasons that are unclear. Overall, results for PM2.5 and EC suggest that long-term exposure to traffic-related air pollution may contribute to the development of sarcoidosis and emphasize the need for additional research and, if the present findings are substantiated, for public health interventions addressing air quality as well as increasing disease surveillance in areas with a large burden of PM2.5 and EC. [ABSTRACT FROM AUTHOR]

Introduction: In patients with cardiac sarcoidosis (CS), implantable cardioverter‐defibrillators (ICDs) are important for preventing sudden cardiac death. This study aimed to investigate sex disparities in CS patients undergoing ICD implantation. Methods: The 2016–2020 National Inpatient Sample (NIS) database compared the characteristics and outcomes of males and females with CS receiving ICDs. Results: Among 760 CS patients who underwent inpatient ICD implantation, 66.4% were male. Males were younger (55.0 vs. 56.9 years, p <.01), had higher rates of diabetes (31.7% vs. 21.6%, p <.01) and chronic kidney disease (CKD) (16.8% vs. 7.8%, p <.01) but lower prevalence of atrial fibrillation (AF) (11.9% vs. 23.5%, p <.01), sick sinus syndrome (4.0% vs. 7.8%, p =.024), ventricular fibrillation (VF) (9.9% vs. 15.7%, p =.02), and black ancestry (31.9% vs. 58.0%, p <.01). Unadjusted major adverse cardiovascular events (MACE), defined as a composite of in‐hospital death, myocardial infarction (MI), and ischemic stroke, was higher in females (11.8% vs. 6.9%, p =.024), but when adjusted for age and tCharlson Comorbidity Index (CCI), females demonstrated significantly lower odds of experiencing MACE (aOR: 0.048, 95% CI: 0.006–0.395, p =.005). Incidence of acute kidney injury (AKI) post‐ICD was significantly lower in females (15.7% vs. 23.8%, p =.01) as was the adjusted odds (aOR: 0.282, 95% CI: 0.146–0.546, p <.01). There was comparable mean length of stay and hospital charges. Conclusion: ICD utilization in CS patients is more common among males, who have a higher prevalence of diabetes and CKD but a lower prevalence of AF, sick sinus syndrome, and VF. Adjusted MACE and AKI were significantly lower in females. [ABSTRACT FROM AUTHOR]

Rationale: Sarcoidosis is a systemic granulomatous disorder associated with hypergammaglobulinemia and the presence of autoantibodies. The specific antigens initiating granulomatous inflammation in sarcoidosis are unknown, and there is no specific test available to diagnose sarcoidosis. To discover novel sarcoidosis antigens, we developed a high-throughput T7 phage display library derived from the sarcoidosis cDNA and identified numerous clones differentiating sarcoidosis from other respiratory diseases. After clone sequencing and a homology search, we identified two epitopes (cofilin μ and chain A) that specifically bind to serum IgGs of patients with sarcoidosis. Objectives: To develop and validate an epitope-specific IgG-based immunoassay specific for sarcoidosis. Methods: We chemically synthesized both immunoepitopes (cofilin μ and chain A) and generated rabbit polyclonal antibodies against both neoantigens. After extensive standardization, we developed a direct peptide ELISA and measured epitope-specific IgG in the sera of 386 subjects, including healthy control subjects (n = 100), three sarcoidosis cohorts (n = 186), pulmonary tuberculosis (n = 70), and lung cancer (n = 30). Measurements and Main Results: To develop a model to classify sarcoidosis distinctly from other groups, data were analyzed using fivefold cross-validation when adjusting for confounders. The cofilin μ IgG model yielded a mean sensitivity, specificity, and positive and negative predictive value of 0.97, 0.9, 0.9, and 0.96, respectively. Those same measures for chain A IgG antibody were 0.9, 0.83, 0.84, and 0.9, respectively. Combining both biomarkers improved the area under the curve, sensitivity, specificity, and positive and negative predictive value. Conclusions: These results provide a novel immunoassay for sarcoidosis. The discovery of two neoantigens facilitates the development of biospecific drug discovery and the sarcoidosis-specific model. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor-α (TNF- α) antagonists are considered a significant therapeutic option in the treatment of sarcoidosis. Nevertheless, their use can also paradoxically result in sarcoidosis-like reactions. Here, we present a case of a 56-year-old patient with psoriatic arthritis who after 3 months of certolizumab therapy developed pulmonary sarcoidosis. Therefore, certolizumab was discontinued and prednisone initiated. Subsequently, 4 months later a complete remission of interstitial lesions was observed. Due to insufficient control of psoriatic arthritis, upadacitinib and methotrexate were prescribed and despite initial improvement, a couple of months later a massive exacerbation of skin psoriasis occurred and the treatment was switched to secukinumab. As of today, no evidence of sarcoidosis recurrence has been noted. Drug-induced sarcoidosis-like reactions (DISR) appear to be less frequently associated with certolizumab rather than with other anti-TNF-α agents. However, specific mechanisms of this phenomenon remain unclear and require future investigation. [ABSTRACT FROM AUTHOR]

This document summarizes a study on the use of systemic corticosteroids in the treatment of granuloma annulare (GA), a skin condition. The study found that tapering off corticosteroids was associated with the progression of localized GA to generalized GA. However, the study had limitations such as a small sample size and potential recall bias. The authors recommend future studies with standardized doses and durations of corticosteroid treatment. The study was approved by the Wake Forest University Health Sciences IRB and patients provided informed consent. [Extracted from the article]

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Despite the achievements of modern medicine, tuberculosis remains one of the leading causes of mortality globally. The difficulties in differential diagnosis have particular relevance in the case of suspicion of tuberculosis with other granulomatous diseases. The most similar clinical and radiologic changes are sarcoidosis. The aim of this study is to apply mathematical modeling to determine diagnostically significant immunological parameters and an algorithm for the differential diagnosis of tuberculosis and sarcoidosis. Materials and methods: The serum samples of patients with sarcoidosis (SD) (n = 29), patients with pulmonary tuberculosis (TB) (n = 32) and the control group (n = 31) (healthy subjects) collected from 2017 to 2022 (the average age 43.4 ± 5.3 years) were examined. Circulating 'polarized' T-helper cell subsets were analyzed by multicolor flow cytometry. A symbolic regression method was used to find general mathematical relations between cell concentrations and diagnosis. The parameters of the selected model were finally fitted through multi-objective optimization applied to two conflicting indices: sensitivity to sarcoidosis and sensitivity to tuberculosis. Results: The difference in Bm2 and CD5−CD27− concentrations was found to be more significant for the differential diagnosis of sarcoidosis and tuberculosis than any individual concentrations: the combined feature Bm2 − [CD5−CD27−] differentiates sarcoidosis and tuberculosis with p < 0.00001 and AUC = 0.823. An algorithm for differential diagnosis was developed. It is based on the linear model with two variables: the first variable is the difference Bm2 − [CD5−CD27−] mentioned above, and the second is the naïve-Tregs concentration. The algorithm uses the model twice and returns "dubious" in 26.7% of cases for patients with sarcoidosis and in 16.1% of cases for patients with tuberculosis. For the remaining patients with one of these two diagnoses, its sensitivity to sarcoidosis is 90.5%, and its sensitivity to tuberculosis is 88.5%. Conclusions: A simple algorithm was developed that can distinguish, by certain immunological features, the cases in which sarcoidosis is likely to be present instead of tuberculosis. Such cases may be further investigated to rule out tuberculosis conclusively. The mathematical model underlying the algorithm is based on the analysis of "naive" T-regulatory cells and "naive" B-cells. This may be a promising approach for differential diagnosis between pulmonary sarcoidosis and pulmonary tuberculosis. The findings may be useful in the absence of clear differential diagnostic criteria between pulmonary tuberculosis and sarcoidosis. [ABSTRACT FROM AUTHOR]

Objectives: Previous observational epidemiological studies have identified a potential association between inflammatory bowel disease (IBD) and sarcoidosis. Nonetheless, the precise biological mechanisms underlying this association remain unclear. Therefore, we adopted a Mendelian randomization (MR) approach to investigate the causal relationship between IBD with genetic susceptibility to sarcoidosis, as well as to explore the potential mediating role. Methods: The genetic associations were obtained from publicly available genome-wide association studies (GWASs) of European ancestry. The IBD dataset has 31,665 cases and 33,977 controls, consisting of 13,768 individuals with ulcerative colitis (UC) and 17,897 individuals with Crohn's disease (CD). The genetic associations of sarcoidosis with 4,854 cases and 446,523 controls. A bidirectional causality between IBD and sarcoidosis was implemented to be determined by a two-sample MR approach. The inverse variance weighted (IVW) method was utilized as the main statistical method, and a series of sensitivity analyses were performed to detect heterogeneity and horizontal pleiotropy. A two-step MR approach was used to investigate whether the mediating pathway from IBD to sarcoidosis was mediated by PBC. Results: The forward MR analysis indicated that genetic predisposition to IBD was significantly linked to an increased risk of sarcoidosis (OR = 1.088, 95% CI: 1.023-1.158, pIBD-sar = 7.498e-03). Similar causal associations were observed in CD (OR = 1.082, 95% CI: 1.028-1.138, pCD-sar = 2.397e-03) and UC (OR = 1.079, 95% CI: 1.006-1.158, pUC-sar = 0.034). Reverse MR analysis revealed that genetic susceptibility to sarcoidosis was correlated with an augmented risk of CD (OR = 1.306, 95% CI: 1.110-1.537, psar-CD = 1.290e-03) but not IBD or UC. The mediation analysis via two-step MR showed that the causal influence of IBD and CD on sarcoidosis effects was partly mediated by PBC, and the mediating effect was 0.018 (95% CI: 0.005-0.031, p = 7.596e-03) with a mediated proportion of 21.397% in IBD, and 0.014 (95% CI: 0.004-0.024, p = 7.800e-03) with a mediated proportion of 17.737% in CD. Conclusions: The MR analysis provided evidence substantiating the causal effect of IBD (CD and UC) on an increased risk of sarcoidosis, with PBC playing a mediating role in IBD and CD. However, sarcoidosis only enhances the risk of developing CD, but not IBD or UC. These findings illuminate the etiology of sarcoidosis and contribute to the management of IBD patients. [ABSTRACT FROM AUTHOR]

Sarcoidosis, an enigmatic disease with unknown etiology, is characterized by inflammation and the potential involvement of various organs, predominantly the lungs and intrathoracic lymph nodes. Non-caseating granulomas can resolve spontaneously in approximately 60% of cases within 2-3 years. However, sarcoidosis-related mortality has increased. Lung fibrosis, affecting up to 20% of sarcoidosis patients, stands out as a primary cause of mortality. Traditionally, fibrosis is viewed because of prolonged inflammation, necessitating antiinflammatory treatment with systemic steroids, immunosuppressants, and anti-TNF agents to manage the disease. The recent introduction of antifibrotic drugs such as nintedanib and pirfenidone offers new avenues for treating fibrotic sarcoidosis. Nintedanib, effective in idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD), has shown promise in patients with various progressive fibrosing interstitial lung diseases (PF-ILD), including those with sarcoidosis. Pirfenidone, also effective in IPF, has demonstrated potential in managing fibrotic sarcoidosis, though results have been inconclusive due to limited participant numbers in studies. This review explores the theoretical and empirical evidence supporting the use of antifibrotics in sarcoidosis, weighing the benefits and drawbacks. While antifibrotics offer a potential therapeutic approach, further randomized controlled trials are essential to determine their efficacy in fibrotic sarcoidosis. Addressing fibrosis as a continuum of chronic inflammation, the role of antifibrotics in managing sarcoidosis remains an area requiring more in-depth research to improve patient outcomes and advance treatment paradigms. [ABSTRACT FROM AUTHOR]

Sarcoidosis and tuberculosis (TB) are two granulomatous diseases that often share overlapping clinical features, including uveitis. We measured 368 inflammation-related proteins in serum in both diseases, with and without uveitis from two distinct geographically separated cohorts: sarcoidosis from the Netherlands and TB from Indonesia. A total of 192 and 102 differentially expressed proteins were found in sarcoidosis and active pulmonary TB compared to their geographical healthy controls, respectively. While substantial overlap exists in the immune-related pathways involved in both diseases, activation of B cell activating factor (BAFF) signaling and proliferation-inducing ligand (APRIL) mediated signaling pathways was specifically associated with sarcoidosis. We identified a B-lymphocyte activation signature consisting of BAFF, TNFRSF13B/TACI, TRAF2, IKBKG, MAPK9, NFATC1, and DAPP1 that was associated with sarcoidosis, regardless of the presence of uveitis. In summary, a difference in B-lymphocyte activation is a key discriminative immunological feature between sarcoidosis/ocular sarcoidosis (OS) and TB/ocular TB (OTB). Sarcoidosis patients exhibit higher level of serum B cell activation signature compared to tuberculosis, regardless of uveitis manifestation. [ABSTRACT FROM AUTHOR]

Background: The internet is a common source of health information for patients and caregivers. To date, content and information quality of YouTube videos on sarcoidosis has not been studied. The aim of our study was to investigate the content and quality of information on sarcoidosis provided by YouTube videos. Methods: Of the first 200 results under the search term "sarcoidosis," all English-language videos with content directed at patients were included. Two independent investigators assessed the content of the videos based on 25 predefined key features (content score with 0–25 points), as well as reliability and quality (HONCode score with 0–8 points, DISCERN score with 1–5 points). Misinformation contained in the videos was described qualitatively. Results: The majority of the 85 included videos were from an academic or governmental source (n = 63, 74%), and median time since upload was 33 months (IQR 10–55). Median video duration was 8 min (IQR 3–13) and had a median of 2,044 views (IQR 504 − 13,203). Quality assessment suggested partially sufficient information: mean HONCode score was 4.4 (SD 0.9) with 91% of videos having a medium quality HONCode evaluation. Mean DISCERN score was 2.3 (SD 0.5). Video content was generally poor with a mean of 10.5 points (SD 0.6). Frequently absent key features included information on the course of disease (6%), presence of substantial geographical variation (7%), and importance of screening for extrapulmonary manifestations (11%). HONCode scores were higher in videos from academic or governmental sources (p = 0.003), particularly regarding "transparency of sponsorship" (p < 0.001). DISCERN and content scores did not differ by video category. Conclusions: Most YouTube videos present incomplete information reflected in a poor content score, especially regarding screening for extrapulmonary manifestations. Quality was partially sufficient with higher scores in videos from academic or governmental sources, but often missing references and citing specific evidence. Improving patient access to trustworthy and up to date information is needed. [ABSTRACT FROM AUTHOR]

Background/Objectives: The relationship between sarcoidosis and the occurrence of neoplasia deserves to be investigated, but this relation has been observed in different and heterogeneous populations, leading to conflicting data. To clarify the causal relationship between these two diseases, different risk factors (e.g., smoking), concurrent comorbidities, corticosteroid therapy, and metastasis development—as an expression of cancer aggressiveness—were investigated. Methods: In a retrospective study on 287 sarcoidosis outpatients at the Pneumological Department of the Gemelli Foundation (Rome, Italy) between 2000 and 2024, the diagnosis of cancer was recorded in 36 subjects (12.5%). Results: The reciprocal timeline of the diseases showed three different scenarios: (1) cancer preceding sarcoidosis or sarcoid-like reactions (63.8%); (2) cancer arising after sarcoidosis diagnosis (8.3%); and (3) sarcoidosis accompanying the onset of malignancy (27.8%). Only two subjects with sarcoidosis and cancer showed metastasis, and one of them was affected by lymphoma. Conclusions: These data suggest that granulomatous inflammation due to sarcoidosis may assume an ambivalent role as a "double-edged sword", according to the M1/M2 macrophage polarization model: it represents a protective shield, preventing the formation of metastasis through the induction of immune surveillance against cancer while, on the other hand, it can be a risk factor for carcinogenesis due to the persistence of a chronic active inflammatory status. Low-dose steroid treatment was administered in only 31.6% of the cancer–sarcoidosis subjects for less than six months to control inflammation activity, with no promotive effect on carcinogenesis observed. [ABSTRACT FROM AUTHOR]

Background/Objective: To describe the clinical features and radiological outcomes of patients with spinal cord neurosarcoidosis, treatments, and long-term follow-up for this rare disorder. Methods: A cross-sectional, retrospective medical chart review was performed for all patients with spinal cord neurosarcoidosis treated at a single center between 01/1995 and 12/2020. Radiological imaging, laboratory test results, the type of immunosuppressive therapy, and function test scores were reviewed. Results: We assessed 39 patients with spinal cord neurosarcoidosis (23 men, 16 women, mean age at presentation 46.4 years, SD 10.2 years). The mean (SD) duration of spinal cord neurosarcoidosis at data abstraction was 9.8 (6.3) years. There were 24 patients (62%) with extensive intramedullary lesions, 8 (21%) with multiple patchy intramedullary lesions, 12 (31%) with leptomeningeal involvement, and 7 (18%) with nerve root enhancement. The cervical spine was the most commonly affected region in 33 patients (85%). The most common presenting symptoms were paresthesia/neuropathic pain in 20 (51%) and weakness of extremities in 15 (38%) patients. Most patients (n = 37; 95%) had been treated with corticosteroids at symptom onset, and methotrexate was the most used immunosuppressive therapy (n = 19; 49%). Of 34 patients with follow-up magnetic resonance imaging (MRI) available, the median time to improvement per MRI was 10.8 months (95% CI, 6.1–17.0 months). Of 31 patients with MRI enhancement at presentation, 18 (58%) had complete enhancement resolution at follow-up, with a median time to resolution of 51.8 months (95% CI, 24.9–83.4 months). Patients had significantly lower pyramidal (p = 0.004) and sensory functional (p = 0.031) systems scores from presentation to the last clinic visit. Conclusions: Because spinal cord neurosarcoidosis is challenging to diagnose and no set treatment guidelines exist, clarifying patients' clinical parameters and responses to various treatments is needed to improve timely and efficient care. The incidence of spinal cord involvement in sarcoidosis in our cohort was higher than intracranial involvement and most patients had a long extensive intramedullary lesion. We also observed that most patients with spinal cord neurosarcoidosis improved clinically and radiologically after treatment; however, the resolution of MRI enhancement after immunosuppressive therapy may take years. Prospective studies of neurosarcoidosis will be crucial to address questions about effective treatment and long-term prognosis. [ABSTRACT FROM AUTHOR]

A 74-year-old woman with a history of hypertension and peripheral artery disease and a reported diagnosis of sarcoidosis presents for an episode of syncope and shortness of breath. She had a history of sarcoidosis diagnosed on chest radiography that showed lymphadenopathy. There were no associated symptoms, and she was not previously treated for sarcoidosis. She previously smoked and had quit smoking 9 years earlier. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case illustrates sarcoidosis as a potential complication of COVID‐19, highlighting the need for a comprehensive diagnostic approach, including histopathology and prolonged monitoring, to distinguish it from post‐COVID fibrosis. Further research is crucial to elucidate these associations and understand their underlying mechanisms. Severe Acute Respiratory Syndrome Coronavirus‐ 2 (SARS‐CoV‐2), a positive‐sense single‐stranded RNA virus, causes COVID‐19 and has been linked to autoimmune disorders. Sarcoidosis is a multi‐system disease that is frequently triggered by infections. It is characterized by non‐necrotizing granulomas in multiple organs. We present a case of sarcoidosis as rare sequelae of COVID‐19. A 26‐year‐old man presented with mild COVID‐19 symptoms, followed by prolonged fever and cough despite initial therapy, prompting a provisional diagnosis of post‐COVID fibrosis. A subsequent assessment at a tertiary hospital revealed dyspnea, weight loss, and abnormal chest imaging, all of which were consistent with pulmonary sarcoidosis with pulmonary tuberculosis as a differential diagnosis. A biopsy taken during bronchoscopy confirmed pulmonary sarcoidosis and treatment with inhalation steroids resulted in symptom relief, which was followed by remission with oral steroid therapy. Sarcoidosis is a systemic disease of unknown etiology, characterized by non‐necrotizing granulomas in multiple organs. It may be triggered by infections and involves an abnormal immune response. COVID‐19 can potentially initiate sarcoidosis, with both sharing common immune mechanisms. Diagnosis involves imaging and biopsy, and treatment typically includes glucocorticoids and regular monitoring. This case report emphasizes the potential link between COVID‐19 and autoimmune conditions like sarcoidosis, highlighting the need for a comprehensive diagnostic approach and long‐term observation to distinguish between sarcoidosis and post‐COVID fibrosis. [ABSTRACT FROM AUTHOR]

Purposeof Review: Cardiac sarcoidosis is an inflammatory condition that has been associated with deleterious cardiac manifestations. The diagnosis of cardiac sarcoidosis is challenging and can be guided by advanced cardiac imaging. Recent Findings: Endomyocardial biopsy lacks sensitivity in confirming a diagnosis of cardiac sarcoidosis. Studies have shown that the use of cardiac magnetic resonance imaging (MRI) and cardiac Positron Emission Testing (PET) are associated with increased sensitivity and specificity in the diagnosis of cardiac sarcoidosis. Summary: Cardiac MRI and cardiac PET CT, although distinct entities, are complimentary in the diagnosis, prognostication of major cardiac events, and aid in the treatment algorithm in patients with cardiac sarcoidosis. [ABSTRACT FROM AUTHOR]

Purpose of Review: Cardiac sarcoidosis (CS) refers to cardiac involvement in sarcoidosis and is usually associated with worse outcomes. This comprehensive review aims to elucidate the electrocardiographic (ECG) signs and features associated with CS, as well as examine modern techniques and their importance in CS evaluation. Recent Findings: The exact pathogenesis of CS is still unclear, but it stems from an abnormal immunological response triggered by environmental factors in individuals with genetic predisposition. CS presents with non-cardiac symptoms; however, conduction system abnormalities are common in patients with CS. The most common electrocardiographic (ECG) signs include atrioventricular blocks and ventricular tachyarrhythmia. Distinct patterns, such as fragmented QRS complexes, T-wave alternans, and bundle branch blocks, are critical indicators of myocardial involvement. The application of advanced ECG techniques such as signal-averaged ECG, Holter monitoring, wavelet-transformed ECG, microvolt T-wave alternans, and artificial intelligence-supported analysis holds promising outcomes for opportune detection and monitoring of CS. Summary: Timely utilisation of inexpensive and readily available ECG possesses the potential to allow early detection and intervention for CS. The integration of artificial intelligence models into ECG analysis is a promising approach for improving the ECG diagnostic accuracy and further risk stratification of patients with CS. [ABSTRACT FROM AUTHOR]

This document is a letter published in the Archives of Dermatological Research that discusses a cross-sectional analysis of the All of Us database to understand hypertrophic scars (HTS) in underrepresented groups. The study found that HTS patients were more likely to be Black, Asian, and female, while patients over 65, without health insurance, with lower education, and low income had lower odds of HTS. Patients with HTS also had a higher odds of various comorbidities. The letter includes two tables that provide information on the prevalence of certain characteristics and comorbidities in individuals with HTS compared to those without HTS. The study highlights the importance of early identification of at-risk populations and the need for improved accessibility and affordability of HTS diagnosis and treatment. [Extracted from the article]

We present a case series of eight patients with ocular tuberculosis (OTB), latent tuberculosis (TB) or sarcoidosis, some of whom were receiving anti-tumor necrosis factor alpha (anti-TNF-a) therapy for various systemic diseases. Only one patient had a positive QuantiFERON®-TB test (QFT), and only one case showed a positive acid-resistant bacilli (ARB) test result. In a third case, brain imaging provided valuable assistance. Ocular tuberculosis should not be overlooked during clinical examination, as it remains a relevant diagnosis even in nonendemic regions. Over the last decade, the use of anti-TNF-α inhibitors for treating resistant uveitis has increased significantly. Consequently, it is essential to closely monitor patients for immunosuppression and remain vigilant about the risk of TB. [ABSTRACT FROM AUTHOR]

We report two cases of sarcoidosis presenting with skin nodules as the first manifestation, without prominent respiratory symptoms. Chest CT showed multiple pulmonary nodules and lymphadenopathy. Case 1, a 47-year-old female, presented with nodules on the elbows and fingers. Dermatological examination revealed demarcated, asymptomatic red and skin-colored nodules on the right elbow, and the index finger and the little finger of the left hand, sized 0.3 to 0.9 cm in diameter. Histopathology of the left pinky finger showed normal epidermis and epithelia granuloma with fibrous encapsulated naked tubercles in the dermis. Chest CT revealed bronchitis and multiple nodules in the both lungs, mediastinal and hilar lymphadenopathy. The diagnosis was sarcoidosis. Case 2, a 44-year-old female, complained of a 3-month history of nodules on the left lower limb. Dermatological examination showed two dark red and skin-colored nodules, sized 2.0 cm x 2.0 cm and 3.0 cm x 2.0 cm, respectively, on the anterior tibia of the left lower leg. A demarcated asymptomatic skin-colored nodule was observed on the posterior left lower leg. Histopathology of the left shin revealed mild epidermal hyperplasia and superficial dermal infiltrates of epithelioid cells and multinucleated giant cells. Chest CT revealed multiple nodules in the lower lobe of the left lung, upper and middle lobes of the right lung, mosaic perfusion of both lungs, a few fibers and calcifications in the middle and lower lobes of the right lung, mediastinal lymphadenopathy with calcification. Patients was diagnosed with sarcoidosis. Both patients were treated with oral prednisone acetate at 30 mg/d for 2 months, followed by a gradual reduction in glucocorticoid dose. No new rash was found after one-year follow-up. [ABSTRACT FROM AUTHOR]

Sarcoidosis, a granulomatous disorder of unknown etiology affecting multiple organs. It is often a benign disease but can have significant morbidity and mortality when the heart is involved (often presenting with clinical manifestations such as conduction irregularities and heart failure). This study addresses a critical gap in cardiac sarcoidosis (CS) research by developing a robust animal model. The absence of a reliable animal model for cardiac sarcoidosis is a significant obstacle in advancing understanding and treatment of this condition. The proposed model utilizes carbon nanotube injection and transverse aortic constriction as stressors. Intramyocardial injection of carbon nanotubes induces histiocytes typical of sarcoid granulomas in the heart but shows limited effects on fibrosis or cardiac function. Priming the immune system with transverse aortic constriction prior to intramyocardial injection of carbon nanotubes enhances cardiac fibrosis, diminishes cardiac function, and impairs cardiac conduction. This novel, easily executable model may serve as a valuable tool for disease profiling, biomarker identification, and therapeutic exploration. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Beryllium is used widely in industry due to its favourable elemental properties. Its extraction and subsequent incorporation into alloys and composites generate hazardous fumes and dust. Chronic beryllium disease (CBD) is an occupational interstitial lung disease that clinically resembles sarcoidosis. We present a case of a 33-year-old jeweller who developed CBD from exposure to dust while grinding unfinished gemstones. While workplace protection exists for beryllium workers, the health risks in artisans are unrecognised. Most cases are diagnosed in industries primarily involved in the use of beryllium (Table I); however, in our case the exposure to beryllium was unexpected. Lymphocyte proliferation testing for beryllium is a key investigation in patients with suspected CBD. To our knowledge, this is the first reported case of CBD diagnosed in a jeweller in South Africa. [ABSTRACT FROM AUTHOR]

Sarcoids are the most frequently diagnosed dermatological tumour in horses. It is a disease that can affect various species of equids, such as donkeys, mules and zebras. This type of tumour can develop in all horse breeds, regardless of age and gender. Treatment options depend on many factors, such as the type of lesion, location, extent, owner preference and financial considerations. In the present study, we investigated the TRIM29 expression, the methylation status of its first exon and its involvement in the formation of equine sarcoids. Bisulfite sequencing PCR (BSP) was used to determine DNA methylation at CpG sites and real‐time quantitative polymerase chain reaction (qPCR) was used to detect TRIM29 expression level. Our results showed that TRIM29 is significantly downregulated in lesional samples (FC = −3.72; p < 0.001). Furthermore, TRIM29 expression was significantly correlated (R = −0.73; p < 0.001) with hypermethylation of its specific CpG sites in the first exon of this gene. Our research has demonstrated that the identification of increased methylation of CpG sequences in horse sarcoids, along with the decreased expression of the TRIM29 gene, is an important step towards understanding the molecular mechanisms underlying the disease. These findings can serve in the future as a diagnostic biomarker for horse sarcoids and help in detecting the disease. [ABSTRACT FROM AUTHOR]

Objective: To describe the radiological features of patients with headache as a presenting symptom of neurosarcoidosis. Background: Neurologic complications occur in approximately 5%–10% of patients with sarcoidosis, and approximately 50% of these patients have neurologic deficits at the time sarcoidosis is first diagnosed. A wide spectrum of central and peripheral nervous system clinical manifestations may be observed, including cranial nerve palsies, sensory and/or motor deficits, and headache. Magnetic resonance imaging (MRI) results in patients with neurosarcoidosis may include abnormal contrast enhancement, structural masses, and demyelinating lesions. Methods: This single‐center retrospective cohort study assessed patients who were diagnosed with neurosarcoidosis in an urban tertiary care center between 1995 and 2016. We included patients who had MRI results at the time of diagnosis. Patients were divided into two groups based on the presence or absence of headache as a presenting symptom. The MRI result of meningeal contrast enhancement was reviewed. Results: Of the 110 patients analyzed, 30 (27.3%) had an initial presenting symptom of headache while 80 (72.7%) did not. Patients with headache had a higher proportion of meningeal contrast enhancement on MRI (66.7% [20/30] vs. 25.0% [20/80]; p < 0.001) and leptomeningeal involvement (53.3% [16/30] vs. 7.5% [6/80], p < 0.001) compared to patients with no headache. However, those with headache had a lower proportion of spinal cord localization (13.8% [4/29] vs. 34.2% [26/76], p = 0.038) and intraparenchymal central nervous system involvement (16.7% [5/30] vs. 51.3% [41/80], p = 0.001) compared to patients with no headache. Conclusion: Patients with neurosarcoidosis who presented with headache as an initial symptom had a higher proportion of meningeal contrast enhancement seen by MRI than patients who presented with other neurological symptoms. This suggests a clinico‐radiologic link between headache and meningeal disruption in patients with neurosarcoidosis. [ABSTRACT FROM AUTHOR]